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Temper enthusiasm for long-term treatment with bisphosphonates?
Women treated with oral bisphosphonate drugs for osteoporosis for 5 years get no additional benefit – in terms of hip fracture risk – if the treatment is extended for another 5 years, new research shows.
“We found that hip fracture risk in women did not differ if women stopped bisphosphonate use after 5 years or stayed on the medication for 10 years,” coauthor Joan C. Lo, MD, Kaiser Permanente Northern California, Oakland, said in an interview.
The new study, published Dec. 7 in JAMA Network Open, did show a small benefit in continuing the treatment through 7 years vs. 5 years, but it wasn’t clear if this was significant.
“Whether there is a benefit to staying on the drug for 7 years needs to be further studied in randomized trials,” Dr. Lo stressed.
It is well established that oral bisphosphonates are effective in reducing the risk for fracture within the first 3-5 years of treatment; however, evidence on the effects of treatment beyond 5 years is lacking.
The most recent guidance from the American Society of Bone and Mineral Research (ASBMR) on the issue, which were released in 2015, recommends continuation of bisphosphonates beyond 5 years for high-risk patients, but it recommends a “drug holiday” for low-risk patients.
Study adds important new evidence
However, that guidance acknowledges that data are limited regarding long-term use. This large new study adds important new evidence to the discussion, Robert A. Adler, MD, who was a member of the ASBMR Task Force for the recent guidance, said in an interview.
“[With the lack of recent research,] this new study from Kaiser Permanente is of great interest,” said Dr. Adler, chief of endocrinology and metabolism at Central Virginia Veterans Affairs Health Care System and professor of internal medicine and of epidemiology at Virginia Commonwealth University, Richmond.
“It is new data and suggests we might temper our enthusiasm for long-term treatment with bisphosphonates,” he said.
“Importantly, it is the first large observational trial and is closer to a real-world setting than a randomized controlled trial,” he said.
But, Dr. Adler emphasized: “The take-home message is that while this suggests that patients can probably be given a drug holiday for a couple of years ... they should be retested, and if they appear to be at an increased risk of fracture, they probably should restart again.
“Osteoporosis is a chronic disorder,” he emphasized. “It isn’t cured by any of our treatments, and as people get older, they are at a higher fracture risk.
“So we really need to follow our patients for a lifetime and reassess their fracture risk every couple of years – whether they are still on therapy or on a drug holiday.”
Possible that 7 years is better than 5 but remains to be proven
The new study involved data from Kaiser Permanente Northern and Southern California on 29,685 women who had completed 5 years of treatment with oral bisphosphonates, including alendronate, risedronate, or ibandronate, between 2002 and 2014.
Among the women, 11,105 (37%) continued taking the drugs beyond 5 years to 7 years, and 2,725 (9.2%) completed a total of 10 years of treatment.
Their median age was 71. Among those for whom bone mineral density data were available, 37% had osteoporosis after the first 5 years of treatment.
During these 5 years of treatment, 507 hip fractures occurred.
The cumulative incidence of hip fracture among for those who discontinued study therapy at entry, i.e., those who underwent treatment for 5 years, was 23.0 per 1,000 individuals.
After 7 years of treatment, the rate was 20.8 per 1000. For those who continued therapy for 10 years, the rate was 26.8 per 1000 individuals.
The rate in the 7-year treatment group was based on patients taking a 6-month drug holiday after the initial 5 years, but the results are hard to interpret, Dr. Lo said.
“It’s possible that 7 years is better than 5, but this is not a randomized trial, and some of the data analyses done in the study suggest more research should be done to look at a benefit after 7 years.
“At the end of the day, doctors and women need to decide at 5 years what an individual woman’s risk fracture risk is and determine if she should stay on the drug longer,” Dr. Lo emphasized.
Limitations: Subgroups not identified, adherence hard to assess
The uncertainty of any benefit of treatment with bisphosphonates beyond 5 years is further reflected in U.S. recommendations – the Food and Drug Administration has concluded on the basis of pooled data from the extension phase of major clinical trials that any advantages of treatment beyond 3-5 years are unclear.
Key limitations of the current study include the fact that the incidence of hip fracture was not evaluated in low-risk vs. high-risk subgroups; therefore, “these findings may not be applicable to older women at higher risk of osteoporotic fracture,” the authors wrote.
Furthermore, the study did not assess outcomes of fractures other than hip fractures, such as vertebral fractures, they noted.
Dr. Adler pointed out that another limitation is that adherence in the trial was defined as taking 60% of prescribed pills.
“I think this is the biggest weakness with the study,” he said. “Particularly with medications like oral bisphosphonates that don’t really make patients feel any different, it’s a real challenge to make sure patients continue to take these drugs properly.”
The findings should give some reassurance for patients who take a break from the drugs after 5 years. However, reassessment of their risk is critical, Dr. Adler reiterated.
The study was supported by a grant from the National Institute on Aging and the National Institute of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health. The authors and Adler have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Women treated with oral bisphosphonate drugs for osteoporosis for 5 years get no additional benefit – in terms of hip fracture risk – if the treatment is extended for another 5 years, new research shows.
“We found that hip fracture risk in women did not differ if women stopped bisphosphonate use after 5 years or stayed on the medication for 10 years,” coauthor Joan C. Lo, MD, Kaiser Permanente Northern California, Oakland, said in an interview.
The new study, published Dec. 7 in JAMA Network Open, did show a small benefit in continuing the treatment through 7 years vs. 5 years, but it wasn’t clear if this was significant.
“Whether there is a benefit to staying on the drug for 7 years needs to be further studied in randomized trials,” Dr. Lo stressed.
It is well established that oral bisphosphonates are effective in reducing the risk for fracture within the first 3-5 years of treatment; however, evidence on the effects of treatment beyond 5 years is lacking.
The most recent guidance from the American Society of Bone and Mineral Research (ASBMR) on the issue, which were released in 2015, recommends continuation of bisphosphonates beyond 5 years for high-risk patients, but it recommends a “drug holiday” for low-risk patients.
Study adds important new evidence
However, that guidance acknowledges that data are limited regarding long-term use. This large new study adds important new evidence to the discussion, Robert A. Adler, MD, who was a member of the ASBMR Task Force for the recent guidance, said in an interview.
“[With the lack of recent research,] this new study from Kaiser Permanente is of great interest,” said Dr. Adler, chief of endocrinology and metabolism at Central Virginia Veterans Affairs Health Care System and professor of internal medicine and of epidemiology at Virginia Commonwealth University, Richmond.
“It is new data and suggests we might temper our enthusiasm for long-term treatment with bisphosphonates,” he said.
“Importantly, it is the first large observational trial and is closer to a real-world setting than a randomized controlled trial,” he said.
But, Dr. Adler emphasized: “The take-home message is that while this suggests that patients can probably be given a drug holiday for a couple of years ... they should be retested, and if they appear to be at an increased risk of fracture, they probably should restart again.
“Osteoporosis is a chronic disorder,” he emphasized. “It isn’t cured by any of our treatments, and as people get older, they are at a higher fracture risk.
“So we really need to follow our patients for a lifetime and reassess their fracture risk every couple of years – whether they are still on therapy or on a drug holiday.”
Possible that 7 years is better than 5 but remains to be proven
The new study involved data from Kaiser Permanente Northern and Southern California on 29,685 women who had completed 5 years of treatment with oral bisphosphonates, including alendronate, risedronate, or ibandronate, between 2002 and 2014.
Among the women, 11,105 (37%) continued taking the drugs beyond 5 years to 7 years, and 2,725 (9.2%) completed a total of 10 years of treatment.
Their median age was 71. Among those for whom bone mineral density data were available, 37% had osteoporosis after the first 5 years of treatment.
During these 5 years of treatment, 507 hip fractures occurred.
The cumulative incidence of hip fracture among for those who discontinued study therapy at entry, i.e., those who underwent treatment for 5 years, was 23.0 per 1,000 individuals.
After 7 years of treatment, the rate was 20.8 per 1000. For those who continued therapy for 10 years, the rate was 26.8 per 1000 individuals.
The rate in the 7-year treatment group was based on patients taking a 6-month drug holiday after the initial 5 years, but the results are hard to interpret, Dr. Lo said.
“It’s possible that 7 years is better than 5, but this is not a randomized trial, and some of the data analyses done in the study suggest more research should be done to look at a benefit after 7 years.
“At the end of the day, doctors and women need to decide at 5 years what an individual woman’s risk fracture risk is and determine if she should stay on the drug longer,” Dr. Lo emphasized.
Limitations: Subgroups not identified, adherence hard to assess
The uncertainty of any benefit of treatment with bisphosphonates beyond 5 years is further reflected in U.S. recommendations – the Food and Drug Administration has concluded on the basis of pooled data from the extension phase of major clinical trials that any advantages of treatment beyond 3-5 years are unclear.
Key limitations of the current study include the fact that the incidence of hip fracture was not evaluated in low-risk vs. high-risk subgroups; therefore, “these findings may not be applicable to older women at higher risk of osteoporotic fracture,” the authors wrote.
Furthermore, the study did not assess outcomes of fractures other than hip fractures, such as vertebral fractures, they noted.
Dr. Adler pointed out that another limitation is that adherence in the trial was defined as taking 60% of prescribed pills.
“I think this is the biggest weakness with the study,” he said. “Particularly with medications like oral bisphosphonates that don’t really make patients feel any different, it’s a real challenge to make sure patients continue to take these drugs properly.”
The findings should give some reassurance for patients who take a break from the drugs after 5 years. However, reassessment of their risk is critical, Dr. Adler reiterated.
The study was supported by a grant from the National Institute on Aging and the National Institute of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health. The authors and Adler have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Women treated with oral bisphosphonate drugs for osteoporosis for 5 years get no additional benefit – in terms of hip fracture risk – if the treatment is extended for another 5 years, new research shows.
“We found that hip fracture risk in women did not differ if women stopped bisphosphonate use after 5 years or stayed on the medication for 10 years,” coauthor Joan C. Lo, MD, Kaiser Permanente Northern California, Oakland, said in an interview.
The new study, published Dec. 7 in JAMA Network Open, did show a small benefit in continuing the treatment through 7 years vs. 5 years, but it wasn’t clear if this was significant.
“Whether there is a benefit to staying on the drug for 7 years needs to be further studied in randomized trials,” Dr. Lo stressed.
It is well established that oral bisphosphonates are effective in reducing the risk for fracture within the first 3-5 years of treatment; however, evidence on the effects of treatment beyond 5 years is lacking.
The most recent guidance from the American Society of Bone and Mineral Research (ASBMR) on the issue, which were released in 2015, recommends continuation of bisphosphonates beyond 5 years for high-risk patients, but it recommends a “drug holiday” for low-risk patients.
Study adds important new evidence
However, that guidance acknowledges that data are limited regarding long-term use. This large new study adds important new evidence to the discussion, Robert A. Adler, MD, who was a member of the ASBMR Task Force for the recent guidance, said in an interview.
“[With the lack of recent research,] this new study from Kaiser Permanente is of great interest,” said Dr. Adler, chief of endocrinology and metabolism at Central Virginia Veterans Affairs Health Care System and professor of internal medicine and of epidemiology at Virginia Commonwealth University, Richmond.
“It is new data and suggests we might temper our enthusiasm for long-term treatment with bisphosphonates,” he said.
“Importantly, it is the first large observational trial and is closer to a real-world setting than a randomized controlled trial,” he said.
But, Dr. Adler emphasized: “The take-home message is that while this suggests that patients can probably be given a drug holiday for a couple of years ... they should be retested, and if they appear to be at an increased risk of fracture, they probably should restart again.
“Osteoporosis is a chronic disorder,” he emphasized. “It isn’t cured by any of our treatments, and as people get older, they are at a higher fracture risk.
“So we really need to follow our patients for a lifetime and reassess their fracture risk every couple of years – whether they are still on therapy or on a drug holiday.”
Possible that 7 years is better than 5 but remains to be proven
The new study involved data from Kaiser Permanente Northern and Southern California on 29,685 women who had completed 5 years of treatment with oral bisphosphonates, including alendronate, risedronate, or ibandronate, between 2002 and 2014.
Among the women, 11,105 (37%) continued taking the drugs beyond 5 years to 7 years, and 2,725 (9.2%) completed a total of 10 years of treatment.
Their median age was 71. Among those for whom bone mineral density data were available, 37% had osteoporosis after the first 5 years of treatment.
During these 5 years of treatment, 507 hip fractures occurred.
The cumulative incidence of hip fracture among for those who discontinued study therapy at entry, i.e., those who underwent treatment for 5 years, was 23.0 per 1,000 individuals.
After 7 years of treatment, the rate was 20.8 per 1000. For those who continued therapy for 10 years, the rate was 26.8 per 1000 individuals.
The rate in the 7-year treatment group was based on patients taking a 6-month drug holiday after the initial 5 years, but the results are hard to interpret, Dr. Lo said.
“It’s possible that 7 years is better than 5, but this is not a randomized trial, and some of the data analyses done in the study suggest more research should be done to look at a benefit after 7 years.
“At the end of the day, doctors and women need to decide at 5 years what an individual woman’s risk fracture risk is and determine if she should stay on the drug longer,” Dr. Lo emphasized.
Limitations: Subgroups not identified, adherence hard to assess
The uncertainty of any benefit of treatment with bisphosphonates beyond 5 years is further reflected in U.S. recommendations – the Food and Drug Administration has concluded on the basis of pooled data from the extension phase of major clinical trials that any advantages of treatment beyond 3-5 years are unclear.
Key limitations of the current study include the fact that the incidence of hip fracture was not evaluated in low-risk vs. high-risk subgroups; therefore, “these findings may not be applicable to older women at higher risk of osteoporotic fracture,” the authors wrote.
Furthermore, the study did not assess outcomes of fractures other than hip fractures, such as vertebral fractures, they noted.
Dr. Adler pointed out that another limitation is that adherence in the trial was defined as taking 60% of prescribed pills.
“I think this is the biggest weakness with the study,” he said. “Particularly with medications like oral bisphosphonates that don’t really make patients feel any different, it’s a real challenge to make sure patients continue to take these drugs properly.”
The findings should give some reassurance for patients who take a break from the drugs after 5 years. However, reassessment of their risk is critical, Dr. Adler reiterated.
The study was supported by a grant from the National Institute on Aging and the National Institute of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health. The authors and Adler have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Teenage bone density declines following sleeve gastrectomy
Adolescents who undergo sleeve gastrectomy have lower bone density and higher bone marrow fat at 1 year following surgery, new research shows.
“It’s almost paradoxical,” Miriam Bredella, MD, of Massachusetts General Hospital in Boston, told Medscape Medical News. “Despite marked loss of body fat, these children have more fat in their bones and decreased bone density.”
She explained that the dissected part of the stomach is filled with anabolic cells that are important for building bone mass. “When those cells are cut out, the body cannot produce the hormones for building up bone.” It’s a malabsorption problem, she added. “Cutting out parts of the stomach or gut leads to less absorption.”
It is well known that bariatric surgery in adults has long-term effects on bone, she said, but this is the first time it has been studied in children.
“Nobody thinks about bone loss in children, but it’s extremely important,” Bredella reports. “The adolescent years up to age 25 are when we accrue bone density, so if something happens during this critical time, it can lead to weak bones later in life.” In the case of these adolescents, peak bone mass is never reached.
To investigate the effects of sleeve gastrectomy on bone density and marrow adipose tissue in extremely obese teenagers, researchers at Massachusetts General Hospital and Harvard Medical School recruited 52 adolescents with a mean body mass index (BMI) of 45. They measured volumetric bone mineral density using quantitative computer tomography (QCT) of the lumbar spine.
“We used QCT instead of DEXA [dual energy x-ray absorptiometry] scan because it isn’t affected by changes in soft tissue; it’s less susceptible to extreme changes in body weight,” Bredella said. “With DEXA scan there are too many artifacts.”
Half of the group (n = 26) underwent surgery. At 1 year, those who underwent surgery lost an average of 34 kg (75 lb). Adolescents in the control group lost an average of 0.2 kg (0.5 lb) (P < .0001).
Both groups repeated the QCT scan at the 1-year follow-up. Researchers found a decrease in bone density in those who underwent sleeve gastrectomy vs. controls (P = .046).
In her presentation, Bredella showed the QCT of the L2 spine in a 17-year old female before surgery and 12 months later. Her volumetric bone mineral density decreased from 183 mg/cm3 to 146 mg/cm3.
“Sleeve gastrectomy in children is bad for bones,” Bradella said. “You have to take care of your bones. This is something people are not thinking about and it probably won’t be a problem when they’re young but will likely affect these patients with osteoporosis when they are older.”
Patients need to be aware of this, she warns, and take steps to combat the bone loss. “Drinking milk, taking vitamin D, and doing weight-bearing exercise may help increase the bone density,” she said.
The increased fat in the bone is also concerning, she said. “Increased fat in the bone is a phenomenon that we see in anorexic patients,” Bredella explained.
The body appears to store the fat in bone in case of need later on, she explained. “We know that in severe states of malnutrition the body has the ability to metabolize the fat in the bones.”
The obesity epidemic in America has given way to a 100-fold increase in sleeve gastrectomy procedures in teenagers between 2005 and 2014. “These patients need this surgery so they don›t die of cardiac arrest or diabetes,” she said. “But we need to make sure they get their bone mineral density checked frequently.”
“The results of this study are important,” Marc Michalsky, MD, Nationwide Children’s Hospital, Columbus, Ohio, told Medscape Medical News. “But they need to be put into context.”
“There is an impetus and argument to support bariatric surgery as it offers a significant reduction in BMI and an associated reversal and complete amelioration of obesity related diseases.”
What this study doesn’t address, he said, is whether this population will experience an increase in bone density-related fractures down the road.
“These results are a snapshot in time — a picture of one postoperative time point,” Michalsky pointed out. “Are we seeing a process that represents continued change in bone mineralization? It’s not unreasonable to assume that the radiological findings here may lead to real clinical impact, but we don’t know.”
Bredella and Michalsky have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Adolescents who undergo sleeve gastrectomy have lower bone density and higher bone marrow fat at 1 year following surgery, new research shows.
“It’s almost paradoxical,” Miriam Bredella, MD, of Massachusetts General Hospital in Boston, told Medscape Medical News. “Despite marked loss of body fat, these children have more fat in their bones and decreased bone density.”
She explained that the dissected part of the stomach is filled with anabolic cells that are important for building bone mass. “When those cells are cut out, the body cannot produce the hormones for building up bone.” It’s a malabsorption problem, she added. “Cutting out parts of the stomach or gut leads to less absorption.”
It is well known that bariatric surgery in adults has long-term effects on bone, she said, but this is the first time it has been studied in children.
“Nobody thinks about bone loss in children, but it’s extremely important,” Bredella reports. “The adolescent years up to age 25 are when we accrue bone density, so if something happens during this critical time, it can lead to weak bones later in life.” In the case of these adolescents, peak bone mass is never reached.
To investigate the effects of sleeve gastrectomy on bone density and marrow adipose tissue in extremely obese teenagers, researchers at Massachusetts General Hospital and Harvard Medical School recruited 52 adolescents with a mean body mass index (BMI) of 45. They measured volumetric bone mineral density using quantitative computer tomography (QCT) of the lumbar spine.
“We used QCT instead of DEXA [dual energy x-ray absorptiometry] scan because it isn’t affected by changes in soft tissue; it’s less susceptible to extreme changes in body weight,” Bredella said. “With DEXA scan there are too many artifacts.”
Half of the group (n = 26) underwent surgery. At 1 year, those who underwent surgery lost an average of 34 kg (75 lb). Adolescents in the control group lost an average of 0.2 kg (0.5 lb) (P < .0001).
Both groups repeated the QCT scan at the 1-year follow-up. Researchers found a decrease in bone density in those who underwent sleeve gastrectomy vs. controls (P = .046).
In her presentation, Bredella showed the QCT of the L2 spine in a 17-year old female before surgery and 12 months later. Her volumetric bone mineral density decreased from 183 mg/cm3 to 146 mg/cm3.
“Sleeve gastrectomy in children is bad for bones,” Bradella said. “You have to take care of your bones. This is something people are not thinking about and it probably won’t be a problem when they’re young but will likely affect these patients with osteoporosis when they are older.”
Patients need to be aware of this, she warns, and take steps to combat the bone loss. “Drinking milk, taking vitamin D, and doing weight-bearing exercise may help increase the bone density,” she said.
The increased fat in the bone is also concerning, she said. “Increased fat in the bone is a phenomenon that we see in anorexic patients,” Bredella explained.
The body appears to store the fat in bone in case of need later on, she explained. “We know that in severe states of malnutrition the body has the ability to metabolize the fat in the bones.”
The obesity epidemic in America has given way to a 100-fold increase in sleeve gastrectomy procedures in teenagers between 2005 and 2014. “These patients need this surgery so they don›t die of cardiac arrest or diabetes,” she said. “But we need to make sure they get their bone mineral density checked frequently.”
“The results of this study are important,” Marc Michalsky, MD, Nationwide Children’s Hospital, Columbus, Ohio, told Medscape Medical News. “But they need to be put into context.”
“There is an impetus and argument to support bariatric surgery as it offers a significant reduction in BMI and an associated reversal and complete amelioration of obesity related diseases.”
What this study doesn’t address, he said, is whether this population will experience an increase in bone density-related fractures down the road.
“These results are a snapshot in time — a picture of one postoperative time point,” Michalsky pointed out. “Are we seeing a process that represents continued change in bone mineralization? It’s not unreasonable to assume that the radiological findings here may lead to real clinical impact, but we don’t know.”
Bredella and Michalsky have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Adolescents who undergo sleeve gastrectomy have lower bone density and higher bone marrow fat at 1 year following surgery, new research shows.
“It’s almost paradoxical,” Miriam Bredella, MD, of Massachusetts General Hospital in Boston, told Medscape Medical News. “Despite marked loss of body fat, these children have more fat in their bones and decreased bone density.”
She explained that the dissected part of the stomach is filled with anabolic cells that are important for building bone mass. “When those cells are cut out, the body cannot produce the hormones for building up bone.” It’s a malabsorption problem, she added. “Cutting out parts of the stomach or gut leads to less absorption.”
It is well known that bariatric surgery in adults has long-term effects on bone, she said, but this is the first time it has been studied in children.
“Nobody thinks about bone loss in children, but it’s extremely important,” Bredella reports. “The adolescent years up to age 25 are when we accrue bone density, so if something happens during this critical time, it can lead to weak bones later in life.” In the case of these adolescents, peak bone mass is never reached.
To investigate the effects of sleeve gastrectomy on bone density and marrow adipose tissue in extremely obese teenagers, researchers at Massachusetts General Hospital and Harvard Medical School recruited 52 adolescents with a mean body mass index (BMI) of 45. They measured volumetric bone mineral density using quantitative computer tomography (QCT) of the lumbar spine.
“We used QCT instead of DEXA [dual energy x-ray absorptiometry] scan because it isn’t affected by changes in soft tissue; it’s less susceptible to extreme changes in body weight,” Bredella said. “With DEXA scan there are too many artifacts.”
Half of the group (n = 26) underwent surgery. At 1 year, those who underwent surgery lost an average of 34 kg (75 lb). Adolescents in the control group lost an average of 0.2 kg (0.5 lb) (P < .0001).
Both groups repeated the QCT scan at the 1-year follow-up. Researchers found a decrease in bone density in those who underwent sleeve gastrectomy vs. controls (P = .046).
In her presentation, Bredella showed the QCT of the L2 spine in a 17-year old female before surgery and 12 months later. Her volumetric bone mineral density decreased from 183 mg/cm3 to 146 mg/cm3.
“Sleeve gastrectomy in children is bad for bones,” Bradella said. “You have to take care of your bones. This is something people are not thinking about and it probably won’t be a problem when they’re young but will likely affect these patients with osteoporosis when they are older.”
Patients need to be aware of this, she warns, and take steps to combat the bone loss. “Drinking milk, taking vitamin D, and doing weight-bearing exercise may help increase the bone density,” she said.
The increased fat in the bone is also concerning, she said. “Increased fat in the bone is a phenomenon that we see in anorexic patients,” Bredella explained.
The body appears to store the fat in bone in case of need later on, she explained. “We know that in severe states of malnutrition the body has the ability to metabolize the fat in the bones.”
The obesity epidemic in America has given way to a 100-fold increase in sleeve gastrectomy procedures in teenagers between 2005 and 2014. “These patients need this surgery so they don›t die of cardiac arrest or diabetes,” she said. “But we need to make sure they get their bone mineral density checked frequently.”
“The results of this study are important,” Marc Michalsky, MD, Nationwide Children’s Hospital, Columbus, Ohio, told Medscape Medical News. “But they need to be put into context.”
“There is an impetus and argument to support bariatric surgery as it offers a significant reduction in BMI and an associated reversal and complete amelioration of obesity related diseases.”
What this study doesn’t address, he said, is whether this population will experience an increase in bone density-related fractures down the road.
“These results are a snapshot in time — a picture of one postoperative time point,” Michalsky pointed out. “Are we seeing a process that represents continued change in bone mineralization? It’s not unreasonable to assume that the radiological findings here may lead to real clinical impact, but we don’t know.”
Bredella and Michalsky have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Oral steroids plus PPIs increase osteoporotic fracture risk in RA patients
Rheumatoid arthritis patients who are on both oral glucocorticoids (CGs) and proton pump inhibitors (PPIs) have an increased risk of osteoporotic fractures, according to a retrospective study of RA patients in the United Kingdom.
“Considering the increasing life expectancies and high consumption of PPIs among elderly patients, fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs,” wrote Shahab Abtahi, MD, of Maastricht (Netherlands) University Medical Centre and colleagues. The study was published in Annals of the Rheumatic Diseases.
To determine if concomitant use of the two medications – both already associated with osteoporotic fractures – would lead to a notable increase in fracture risk, the researchers conducted a population-based cohort study of RA patients aged 50 years or older who were diagnosed during 1997-2017. Patient data was gathered via the Clinical Practice Research Datalink, a primary care database of millions of U.K. medical records.
Patients with a recent history of GC/PPI use or those with a previous osteoporotic fracture were excluded from the study. Osteoporotic fractures were defined as fractures of the hip, vertebrae, humerus, forearm, pelvis, or rib. The study population included 12,351 patients, roughly two-thirds of whom were women, with a mean age of 68 years. Of the population, 4,254 patients were concomitant users of oral GCs and PPIs, compared with 3,138 patients who were not on either medication.
Among all patients, 1,411 osteoporotic fractures occurred, 264 of which occurred in the concomitant users group. After adjustments for age and sex, patients on both medications had a higher risk of fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.65-2.27), compared to patients on oral GCs alone (aHR, 1.34; 95% CI, 1.12-1.59) or PPIs alone (aHR, 1.32; 95% CI, 1.14-1.54). After full adjustment, concomitant users again had a higher risk of fracture (aHR, 1.60; 95% CI, 1.35-1.89).
Regarding specific types of breaks, the concomitant users had a notably higher risk of hip (aHR, 1.45; 95% CI, 1.11-1.91), vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and rib fractures (aHR, 4.03; 95% CI, 2.13-7.63). No increased risk was found for either humerus or forearm fractures. The risk of fracture did not rise for concomitant users who had either increasing daily doses of PPI or a longer duration of use.
The authors noted their study’s potential limitations, including having access to data on prescriptions only, not the actual use of medication, and a lack of information in the medical records regarding biologic therapies or certain indicators of RA disease activity. In addition, there was a likelihood that some patients who were improving might have stopped taking the drugs and lessened their risk of fracture, though the researchers attempted to account for this by “adjusting our analyses for six indicators of RA severity, including analgesics and csDMARDs.”
Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.
SOURCE: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.
Rheumatoid arthritis patients who are on both oral glucocorticoids (CGs) and proton pump inhibitors (PPIs) have an increased risk of osteoporotic fractures, according to a retrospective study of RA patients in the United Kingdom.
“Considering the increasing life expectancies and high consumption of PPIs among elderly patients, fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs,” wrote Shahab Abtahi, MD, of Maastricht (Netherlands) University Medical Centre and colleagues. The study was published in Annals of the Rheumatic Diseases.
To determine if concomitant use of the two medications – both already associated with osteoporotic fractures – would lead to a notable increase in fracture risk, the researchers conducted a population-based cohort study of RA patients aged 50 years or older who were diagnosed during 1997-2017. Patient data was gathered via the Clinical Practice Research Datalink, a primary care database of millions of U.K. medical records.
Patients with a recent history of GC/PPI use or those with a previous osteoporotic fracture were excluded from the study. Osteoporotic fractures were defined as fractures of the hip, vertebrae, humerus, forearm, pelvis, or rib. The study population included 12,351 patients, roughly two-thirds of whom were women, with a mean age of 68 years. Of the population, 4,254 patients were concomitant users of oral GCs and PPIs, compared with 3,138 patients who were not on either medication.
Among all patients, 1,411 osteoporotic fractures occurred, 264 of which occurred in the concomitant users group. After adjustments for age and sex, patients on both medications had a higher risk of fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.65-2.27), compared to patients on oral GCs alone (aHR, 1.34; 95% CI, 1.12-1.59) or PPIs alone (aHR, 1.32; 95% CI, 1.14-1.54). After full adjustment, concomitant users again had a higher risk of fracture (aHR, 1.60; 95% CI, 1.35-1.89).
Regarding specific types of breaks, the concomitant users had a notably higher risk of hip (aHR, 1.45; 95% CI, 1.11-1.91), vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and rib fractures (aHR, 4.03; 95% CI, 2.13-7.63). No increased risk was found for either humerus or forearm fractures. The risk of fracture did not rise for concomitant users who had either increasing daily doses of PPI or a longer duration of use.
The authors noted their study’s potential limitations, including having access to data on prescriptions only, not the actual use of medication, and a lack of information in the medical records regarding biologic therapies or certain indicators of RA disease activity. In addition, there was a likelihood that some patients who were improving might have stopped taking the drugs and lessened their risk of fracture, though the researchers attempted to account for this by “adjusting our analyses for six indicators of RA severity, including analgesics and csDMARDs.”
Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.
SOURCE: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.
Rheumatoid arthritis patients who are on both oral glucocorticoids (CGs) and proton pump inhibitors (PPIs) have an increased risk of osteoporotic fractures, according to a retrospective study of RA patients in the United Kingdom.
“Considering the increasing life expectancies and high consumption of PPIs among elderly patients, fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs,” wrote Shahab Abtahi, MD, of Maastricht (Netherlands) University Medical Centre and colleagues. The study was published in Annals of the Rheumatic Diseases.
To determine if concomitant use of the two medications – both already associated with osteoporotic fractures – would lead to a notable increase in fracture risk, the researchers conducted a population-based cohort study of RA patients aged 50 years or older who were diagnosed during 1997-2017. Patient data was gathered via the Clinical Practice Research Datalink, a primary care database of millions of U.K. medical records.
Patients with a recent history of GC/PPI use or those with a previous osteoporotic fracture were excluded from the study. Osteoporotic fractures were defined as fractures of the hip, vertebrae, humerus, forearm, pelvis, or rib. The study population included 12,351 patients, roughly two-thirds of whom were women, with a mean age of 68 years. Of the population, 4,254 patients were concomitant users of oral GCs and PPIs, compared with 3,138 patients who were not on either medication.
Among all patients, 1,411 osteoporotic fractures occurred, 264 of which occurred in the concomitant users group. After adjustments for age and sex, patients on both medications had a higher risk of fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.65-2.27), compared to patients on oral GCs alone (aHR, 1.34; 95% CI, 1.12-1.59) or PPIs alone (aHR, 1.32; 95% CI, 1.14-1.54). After full adjustment, concomitant users again had a higher risk of fracture (aHR, 1.60; 95% CI, 1.35-1.89).
Regarding specific types of breaks, the concomitant users had a notably higher risk of hip (aHR, 1.45; 95% CI, 1.11-1.91), vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and rib fractures (aHR, 4.03; 95% CI, 2.13-7.63). No increased risk was found for either humerus or forearm fractures. The risk of fracture did not rise for concomitant users who had either increasing daily doses of PPI or a longer duration of use.
The authors noted their study’s potential limitations, including having access to data on prescriptions only, not the actual use of medication, and a lack of information in the medical records regarding biologic therapies or certain indicators of RA disease activity. In addition, there was a likelihood that some patients who were improving might have stopped taking the drugs and lessened their risk of fracture, though the researchers attempted to account for this by “adjusting our analyses for six indicators of RA severity, including analgesics and csDMARDs.”
Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.
SOURCE: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.
FROM ANNALS OF RHEUMATIC DISEASES
Endocrine-disrupting plastics pose growing health threat
Many types of plastics pose an unrecognized threat to human health by leaching endocrine-disrupting chemicals, and a new report from the Endocrine Society and the International Pollutants Elimination Network presents their dangers and risks.
Written in a consumer-friendly form designed to guide public interest groups and policy makers, the report also can be used by clinicians to inform discussions with patients about the potential dangers of plastics and how they can reduce their exposure to endocrine-disrupting chemicals.
The report, Plastics, EDCs, & Health, defines endocrine-disrupting chemicals (EDCs) as “an exogenous chemical, or mixture of chemicals, that interferes with any aspect of hormone action.” Hormones in the body must be released at specific times, and therefore interference with their normal activity can have profound effects on health in areas including growth and reproductive development, according to the report.
The available data show “more and more information about the different chemicals and the different effects they are having,” said lead author, Jodi Flaws, PhD, of the University of Illinois at Urbana-Champaign, in a virtual press conference accompanying the release of the report.
Although numerous EDCs have been identified, a recent study suggested that many potentially dangerous chemical additives remain unknown because they are identified as confidential or simply not well described, the report authors said. In addition, creation of more plastic products will likely lead to increased exposure to EDCs and make health problems worse, said report coauthor Pauliina Damdimopoulou, PhD, of the Karolinska Institutet in Stockholm.
Lesser-known EDCs populate consumer products
Most consumers are aware of bisphenol A and phthalates as known EDCs, said Dr. Flaws, but the report identifies other lesser-known EDCs including per- and polyfluoroalkyl substances (PFAS), dioxins, flame retardants, and UV stabilizers.
For example, PFAS have been used for decades in a range of consumer products including stain resistant clothes, fast food wrappers, carpet and furniture treatments, cookware, and firefighting foams, according to the report. Consequently, PFAS have become common in many water sources including surface water, drinking water, and ground water because of how they are disposed. “Consumption of fish and other aquatic creatures caught in waterways contaminated with PFAS also poses heightened risks due to bioaccumulation of persistent chemicals in these animals,” the report authors noted. Human exposures to PFAS have been documented in urine, serum, plasma, placenta, umbilical cord, breast milk, and fetal tissues, they added.
Brominated flame retardants are another lesser-known EDC highlighted in the report. These chemical additives are used in plastics such as electronics cases to reduce the spread of fire, as well as in furniture foam and other building materials, the authors wrote. UV stabilizers, which also have been linked to health problems, often are used in manufacturing cars and other machinery.
Microplastics create large risk
Microplastics, defined as plastic particles less than 5 mm in diameter, are another source of exposure to EDCs that is not well publicized, according to the report. Plastic waste disposal often leads to the release of microplastics, which can infiltrate soil and water. Plastic waste is often dumped or burned; outdoor burning of plastic causes emission of dioxins into the air and ground.
“Not only do microplastics contain endogenous chemical additives, which are not bound to the microplastic and can leach out of the microplastic and expose the population, they can also bind and accumulate toxic chemicals from the surrounding environment such as sea water and sediment,” the report authors said.
Recycling is not an easy answer, either. Often more chemicals are created and released during the process of using plastics to make other plastics, according to the report.
Overall, more awareness of the potential for increased exposure to EDCs and support of strategies to seek out alternatives to hazardous chemicals is needed at the global level, the authors wrote. For example, the European Union has proposed a chemicals strategy that includes improved classification of EDCs and banning identified EDCs in consumer products.
New data support ongoing dangers
“It was important to produce the report at this time because several new studies came out on the effects of EDCs from plastics on human health,” Dr. Flaws said in an interview. “Further, there was not previously a single source that brought together all the information in a manner that was targeted towards the public, policy makers, and others,” she said.
Dr. Flaws said that what has surprised her most in the recent research is the fact that plastics contain such a range of chemicals and EDCs.
“A good take-home message [from the report] is that plastics can contain endocrine-disrupting chemicals that can interfere with normal hormones and lead to adverse health outcomes,” she said. “I suggest limiting the use of plastics as much as possible. I know this is very hard to do, so if someone needs to use plastic, they should not heat food or drink in plastic containers,” she emphasized. Individuals also can limit reuse of plastics over and over,” she said. “Heating and repeated use/washing often causes plastics to leach EDCs into food and drink that we then get into our bodies.”
Additional research is needed to understand the mechanisms by which EDCs from plastics cause damage, Dr. Flaws emphasized. “Given that it is not possible to eliminate plastics at this time, if we understood mechanisms of action, we could develop ways to prevent toxicity or treat EDC-induced adverse health outcomes,” she said. “We also need research designed to develop plastics or ‘green materials’ that do not contain endocrine disruptors and do not cause health problems or damage the environment,” she noted.
The report was produced as a joint effort of the Endocrine Society and International Pollutants Elimination Network. The report authors had no financial conflicts to disclose.
Many types of plastics pose an unrecognized threat to human health by leaching endocrine-disrupting chemicals, and a new report from the Endocrine Society and the International Pollutants Elimination Network presents their dangers and risks.
Written in a consumer-friendly form designed to guide public interest groups and policy makers, the report also can be used by clinicians to inform discussions with patients about the potential dangers of plastics and how they can reduce their exposure to endocrine-disrupting chemicals.
The report, Plastics, EDCs, & Health, defines endocrine-disrupting chemicals (EDCs) as “an exogenous chemical, or mixture of chemicals, that interferes with any aspect of hormone action.” Hormones in the body must be released at specific times, and therefore interference with their normal activity can have profound effects on health in areas including growth and reproductive development, according to the report.
The available data show “more and more information about the different chemicals and the different effects they are having,” said lead author, Jodi Flaws, PhD, of the University of Illinois at Urbana-Champaign, in a virtual press conference accompanying the release of the report.
Although numerous EDCs have been identified, a recent study suggested that many potentially dangerous chemical additives remain unknown because they are identified as confidential or simply not well described, the report authors said. In addition, creation of more plastic products will likely lead to increased exposure to EDCs and make health problems worse, said report coauthor Pauliina Damdimopoulou, PhD, of the Karolinska Institutet in Stockholm.
Lesser-known EDCs populate consumer products
Most consumers are aware of bisphenol A and phthalates as known EDCs, said Dr. Flaws, but the report identifies other lesser-known EDCs including per- and polyfluoroalkyl substances (PFAS), dioxins, flame retardants, and UV stabilizers.
For example, PFAS have been used for decades in a range of consumer products including stain resistant clothes, fast food wrappers, carpet and furniture treatments, cookware, and firefighting foams, according to the report. Consequently, PFAS have become common in many water sources including surface water, drinking water, and ground water because of how they are disposed. “Consumption of fish and other aquatic creatures caught in waterways contaminated with PFAS also poses heightened risks due to bioaccumulation of persistent chemicals in these animals,” the report authors noted. Human exposures to PFAS have been documented in urine, serum, plasma, placenta, umbilical cord, breast milk, and fetal tissues, they added.
Brominated flame retardants are another lesser-known EDC highlighted in the report. These chemical additives are used in plastics such as electronics cases to reduce the spread of fire, as well as in furniture foam and other building materials, the authors wrote. UV stabilizers, which also have been linked to health problems, often are used in manufacturing cars and other machinery.
Microplastics create large risk
Microplastics, defined as plastic particles less than 5 mm in diameter, are another source of exposure to EDCs that is not well publicized, according to the report. Plastic waste disposal often leads to the release of microplastics, which can infiltrate soil and water. Plastic waste is often dumped or burned; outdoor burning of plastic causes emission of dioxins into the air and ground.
“Not only do microplastics contain endogenous chemical additives, which are not bound to the microplastic and can leach out of the microplastic and expose the population, they can also bind and accumulate toxic chemicals from the surrounding environment such as sea water and sediment,” the report authors said.
Recycling is not an easy answer, either. Often more chemicals are created and released during the process of using plastics to make other plastics, according to the report.
Overall, more awareness of the potential for increased exposure to EDCs and support of strategies to seek out alternatives to hazardous chemicals is needed at the global level, the authors wrote. For example, the European Union has proposed a chemicals strategy that includes improved classification of EDCs and banning identified EDCs in consumer products.
New data support ongoing dangers
“It was important to produce the report at this time because several new studies came out on the effects of EDCs from plastics on human health,” Dr. Flaws said in an interview. “Further, there was not previously a single source that brought together all the information in a manner that was targeted towards the public, policy makers, and others,” she said.
Dr. Flaws said that what has surprised her most in the recent research is the fact that plastics contain such a range of chemicals and EDCs.
“A good take-home message [from the report] is that plastics can contain endocrine-disrupting chemicals that can interfere with normal hormones and lead to adverse health outcomes,” she said. “I suggest limiting the use of plastics as much as possible. I know this is very hard to do, so if someone needs to use plastic, they should not heat food or drink in plastic containers,” she emphasized. Individuals also can limit reuse of plastics over and over,” she said. “Heating and repeated use/washing often causes plastics to leach EDCs into food and drink that we then get into our bodies.”
Additional research is needed to understand the mechanisms by which EDCs from plastics cause damage, Dr. Flaws emphasized. “Given that it is not possible to eliminate plastics at this time, if we understood mechanisms of action, we could develop ways to prevent toxicity or treat EDC-induced adverse health outcomes,” she said. “We also need research designed to develop plastics or ‘green materials’ that do not contain endocrine disruptors and do not cause health problems or damage the environment,” she noted.
The report was produced as a joint effort of the Endocrine Society and International Pollutants Elimination Network. The report authors had no financial conflicts to disclose.
Many types of plastics pose an unrecognized threat to human health by leaching endocrine-disrupting chemicals, and a new report from the Endocrine Society and the International Pollutants Elimination Network presents their dangers and risks.
Written in a consumer-friendly form designed to guide public interest groups and policy makers, the report also can be used by clinicians to inform discussions with patients about the potential dangers of plastics and how they can reduce their exposure to endocrine-disrupting chemicals.
The report, Plastics, EDCs, & Health, defines endocrine-disrupting chemicals (EDCs) as “an exogenous chemical, or mixture of chemicals, that interferes with any aspect of hormone action.” Hormones in the body must be released at specific times, and therefore interference with their normal activity can have profound effects on health in areas including growth and reproductive development, according to the report.
The available data show “more and more information about the different chemicals and the different effects they are having,” said lead author, Jodi Flaws, PhD, of the University of Illinois at Urbana-Champaign, in a virtual press conference accompanying the release of the report.
Although numerous EDCs have been identified, a recent study suggested that many potentially dangerous chemical additives remain unknown because they are identified as confidential or simply not well described, the report authors said. In addition, creation of more plastic products will likely lead to increased exposure to EDCs and make health problems worse, said report coauthor Pauliina Damdimopoulou, PhD, of the Karolinska Institutet in Stockholm.
Lesser-known EDCs populate consumer products
Most consumers are aware of bisphenol A and phthalates as known EDCs, said Dr. Flaws, but the report identifies other lesser-known EDCs including per- and polyfluoroalkyl substances (PFAS), dioxins, flame retardants, and UV stabilizers.
For example, PFAS have been used for decades in a range of consumer products including stain resistant clothes, fast food wrappers, carpet and furniture treatments, cookware, and firefighting foams, according to the report. Consequently, PFAS have become common in many water sources including surface water, drinking water, and ground water because of how they are disposed. “Consumption of fish and other aquatic creatures caught in waterways contaminated with PFAS also poses heightened risks due to bioaccumulation of persistent chemicals in these animals,” the report authors noted. Human exposures to PFAS have been documented in urine, serum, plasma, placenta, umbilical cord, breast milk, and fetal tissues, they added.
Brominated flame retardants are another lesser-known EDC highlighted in the report. These chemical additives are used in plastics such as electronics cases to reduce the spread of fire, as well as in furniture foam and other building materials, the authors wrote. UV stabilizers, which also have been linked to health problems, often are used in manufacturing cars and other machinery.
Microplastics create large risk
Microplastics, defined as plastic particles less than 5 mm in diameter, are another source of exposure to EDCs that is not well publicized, according to the report. Plastic waste disposal often leads to the release of microplastics, which can infiltrate soil and water. Plastic waste is often dumped or burned; outdoor burning of plastic causes emission of dioxins into the air and ground.
“Not only do microplastics contain endogenous chemical additives, which are not bound to the microplastic and can leach out of the microplastic and expose the population, they can also bind and accumulate toxic chemicals from the surrounding environment such as sea water and sediment,” the report authors said.
Recycling is not an easy answer, either. Often more chemicals are created and released during the process of using plastics to make other plastics, according to the report.
Overall, more awareness of the potential for increased exposure to EDCs and support of strategies to seek out alternatives to hazardous chemicals is needed at the global level, the authors wrote. For example, the European Union has proposed a chemicals strategy that includes improved classification of EDCs and banning identified EDCs in consumer products.
New data support ongoing dangers
“It was important to produce the report at this time because several new studies came out on the effects of EDCs from plastics on human health,” Dr. Flaws said in an interview. “Further, there was not previously a single source that brought together all the information in a manner that was targeted towards the public, policy makers, and others,” she said.
Dr. Flaws said that what has surprised her most in the recent research is the fact that plastics contain such a range of chemicals and EDCs.
“A good take-home message [from the report] is that plastics can contain endocrine-disrupting chemicals that can interfere with normal hormones and lead to adverse health outcomes,” she said. “I suggest limiting the use of plastics as much as possible. I know this is very hard to do, so if someone needs to use plastic, they should not heat food or drink in plastic containers,” she emphasized. Individuals also can limit reuse of plastics over and over,” she said. “Heating and repeated use/washing often causes plastics to leach EDCs into food and drink that we then get into our bodies.”
Additional research is needed to understand the mechanisms by which EDCs from plastics cause damage, Dr. Flaws emphasized. “Given that it is not possible to eliminate plastics at this time, if we understood mechanisms of action, we could develop ways to prevent toxicity or treat EDC-induced adverse health outcomes,” she said. “We also need research designed to develop plastics or ‘green materials’ that do not contain endocrine disruptors and do not cause health problems or damage the environment,” she noted.
The report was produced as a joint effort of the Endocrine Society and International Pollutants Elimination Network. The report authors had no financial conflicts to disclose.
Sac/val heart failure benefit extends to diabetes patients
The beneficial effects of sacubitril/valsartan on reverse cardiac remodeling in patients with heart failure and reduced ejection fraction have been well established, but those benefits haven’t been as clearly demonstrated to carry over to HFrEF patients who also have type 2 diabetes mellitus (T2DM).
Now, a post-hoc analysis of a pivotal clinical trial reports that those benefits do extend to patients with HFrEF and T2DM.
“It’s really not about a Sophie’s choice of whether you give this or that drug in these patients,” said corresponding author Javed Butler, MD, MPH, MBA. “We really ought to be giving all of these drugs – the angiotensin receptor neprilysin inhibitors (ARNIs) and sodium-glucose transporter 2 (SGLT-2) inhibitors – to our patients for the best outcomes.”
The post-hoc analysis, published in JACC: Heart Failure, evaluated 361 patients with T2DM who were enrolled in the PROVE-HF trial of sac/val therapy for HF, published in JAMA.
PROVE-HF evaluated biomarkers, myocardial remodeling, and outcomes through a year of treatment with sac/val. The primary endpoint was the level of changes in natriuretic peptide (NT-proBNP) concentrations, left-ventricle ejection fraction (LVEF) and overall Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 scores through 12 months of treatment.
The post hoc study reported that baseline NT-proBNP concentrations were higher in the DM patients (854 pg/mL vs. 706 pg/mL), but at 12 months those levels were 513 and 441 pg/mL, respectively.
LVEF changed similarly from baseline to 12 months in both groups: from 28.3% to 37% in the DM patients and from 28.1% to 38.34% in non-DM patients. Overall KCCQ-23 scores improved similarly in both groups, but longitudinal analyses found modestly higher gains in the T2DM group, 9.3 vs. 8.6 points (P = .07).
“The real reason I wanted to do this study is that I’m a huge fan of all the SGLT-2 inhibitors, and I’m very involved in those trials, and there is right now so much momentum behind SGLT-2 inhibitors that I don’t want people to forget that ARNI is still the base therapy for HF,” said Dr. Butler, chair of cardiovascular research and the department of medicine at the University of Mississippi in Jackson.
He noted that the size of the diabetes cohort in PROVE-HF “is a nonissue” for evaluating power of the post hoc analysis because it tracked key measures in the study population continuously at eight intervals over the 12 months.
The analysis further demonstrates the synergistic effects of ARNI and SGLT-2 inhibitors in patients with T2DM and HF that were also reported in the PARADIGM-HF study, Dr. Butler said.
“We have sort of moved on, saying that SGLT-2 inhibitors have a benefit on the heart, but the reverse is also true: ARNIs are still heart failure drugs, and we don’t think of them as diabetes drugs, but the PARADIGM-HF data showed that there was a substantial reduction in hemoglobin A1c in those who had diabetes,” he said.
The researchers noted that an absence of a control group may contribute to an overestimation of reverse cardiac remodeling in the T2DM patients, and that the PROVE-HF study wasn’t prospectively powered to delineate differences in how sac/val therapy affected patients with or without diabetes. “Future investigations seeking to evaluate differences by T2DM status after sacubitril/valsartan initiation may use our findings to plan prospective sample sizes,” the researchers wrote.
Dr. Butler disclosed financial relationships with Abbott, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, CVRx, Eli Lilly, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Sequana, StealthPeptide and Vifor. Lead author Muhammad Shahzeb Khan, MD, MSc, a professor at the University of Mississippi, has no relevant financial relationships to disclose.
SOURCE: Kahn MS et al. JACC: HF. 2020 Dec 9. doi: 10.1016/j.jchf.2020.09.014.
The beneficial effects of sacubitril/valsartan on reverse cardiac remodeling in patients with heart failure and reduced ejection fraction have been well established, but those benefits haven’t been as clearly demonstrated to carry over to HFrEF patients who also have type 2 diabetes mellitus (T2DM).
Now, a post-hoc analysis of a pivotal clinical trial reports that those benefits do extend to patients with HFrEF and T2DM.
“It’s really not about a Sophie’s choice of whether you give this or that drug in these patients,” said corresponding author Javed Butler, MD, MPH, MBA. “We really ought to be giving all of these drugs – the angiotensin receptor neprilysin inhibitors (ARNIs) and sodium-glucose transporter 2 (SGLT-2) inhibitors – to our patients for the best outcomes.”
The post-hoc analysis, published in JACC: Heart Failure, evaluated 361 patients with T2DM who were enrolled in the PROVE-HF trial of sac/val therapy for HF, published in JAMA.
PROVE-HF evaluated biomarkers, myocardial remodeling, and outcomes through a year of treatment with sac/val. The primary endpoint was the level of changes in natriuretic peptide (NT-proBNP) concentrations, left-ventricle ejection fraction (LVEF) and overall Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 scores through 12 months of treatment.
The post hoc study reported that baseline NT-proBNP concentrations were higher in the DM patients (854 pg/mL vs. 706 pg/mL), but at 12 months those levels were 513 and 441 pg/mL, respectively.
LVEF changed similarly from baseline to 12 months in both groups: from 28.3% to 37% in the DM patients and from 28.1% to 38.34% in non-DM patients. Overall KCCQ-23 scores improved similarly in both groups, but longitudinal analyses found modestly higher gains in the T2DM group, 9.3 vs. 8.6 points (P = .07).
“The real reason I wanted to do this study is that I’m a huge fan of all the SGLT-2 inhibitors, and I’m very involved in those trials, and there is right now so much momentum behind SGLT-2 inhibitors that I don’t want people to forget that ARNI is still the base therapy for HF,” said Dr. Butler, chair of cardiovascular research and the department of medicine at the University of Mississippi in Jackson.
He noted that the size of the diabetes cohort in PROVE-HF “is a nonissue” for evaluating power of the post hoc analysis because it tracked key measures in the study population continuously at eight intervals over the 12 months.
The analysis further demonstrates the synergistic effects of ARNI and SGLT-2 inhibitors in patients with T2DM and HF that were also reported in the PARADIGM-HF study, Dr. Butler said.
“We have sort of moved on, saying that SGLT-2 inhibitors have a benefit on the heart, but the reverse is also true: ARNIs are still heart failure drugs, and we don’t think of them as diabetes drugs, but the PARADIGM-HF data showed that there was a substantial reduction in hemoglobin A1c in those who had diabetes,” he said.
The researchers noted that an absence of a control group may contribute to an overestimation of reverse cardiac remodeling in the T2DM patients, and that the PROVE-HF study wasn’t prospectively powered to delineate differences in how sac/val therapy affected patients with or without diabetes. “Future investigations seeking to evaluate differences by T2DM status after sacubitril/valsartan initiation may use our findings to plan prospective sample sizes,” the researchers wrote.
Dr. Butler disclosed financial relationships with Abbott, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, CVRx, Eli Lilly, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Sequana, StealthPeptide and Vifor. Lead author Muhammad Shahzeb Khan, MD, MSc, a professor at the University of Mississippi, has no relevant financial relationships to disclose.
SOURCE: Kahn MS et al. JACC: HF. 2020 Dec 9. doi: 10.1016/j.jchf.2020.09.014.
The beneficial effects of sacubitril/valsartan on reverse cardiac remodeling in patients with heart failure and reduced ejection fraction have been well established, but those benefits haven’t been as clearly demonstrated to carry over to HFrEF patients who also have type 2 diabetes mellitus (T2DM).
Now, a post-hoc analysis of a pivotal clinical trial reports that those benefits do extend to patients with HFrEF and T2DM.
“It’s really not about a Sophie’s choice of whether you give this or that drug in these patients,” said corresponding author Javed Butler, MD, MPH, MBA. “We really ought to be giving all of these drugs – the angiotensin receptor neprilysin inhibitors (ARNIs) and sodium-glucose transporter 2 (SGLT-2) inhibitors – to our patients for the best outcomes.”
The post-hoc analysis, published in JACC: Heart Failure, evaluated 361 patients with T2DM who were enrolled in the PROVE-HF trial of sac/val therapy for HF, published in JAMA.
PROVE-HF evaluated biomarkers, myocardial remodeling, and outcomes through a year of treatment with sac/val. The primary endpoint was the level of changes in natriuretic peptide (NT-proBNP) concentrations, left-ventricle ejection fraction (LVEF) and overall Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 scores through 12 months of treatment.
The post hoc study reported that baseline NT-proBNP concentrations were higher in the DM patients (854 pg/mL vs. 706 pg/mL), but at 12 months those levels were 513 and 441 pg/mL, respectively.
LVEF changed similarly from baseline to 12 months in both groups: from 28.3% to 37% in the DM patients and from 28.1% to 38.34% in non-DM patients. Overall KCCQ-23 scores improved similarly in both groups, but longitudinal analyses found modestly higher gains in the T2DM group, 9.3 vs. 8.6 points (P = .07).
“The real reason I wanted to do this study is that I’m a huge fan of all the SGLT-2 inhibitors, and I’m very involved in those trials, and there is right now so much momentum behind SGLT-2 inhibitors that I don’t want people to forget that ARNI is still the base therapy for HF,” said Dr. Butler, chair of cardiovascular research and the department of medicine at the University of Mississippi in Jackson.
He noted that the size of the diabetes cohort in PROVE-HF “is a nonissue” for evaluating power of the post hoc analysis because it tracked key measures in the study population continuously at eight intervals over the 12 months.
The analysis further demonstrates the synergistic effects of ARNI and SGLT-2 inhibitors in patients with T2DM and HF that were also reported in the PARADIGM-HF study, Dr. Butler said.
“We have sort of moved on, saying that SGLT-2 inhibitors have a benefit on the heart, but the reverse is also true: ARNIs are still heart failure drugs, and we don’t think of them as diabetes drugs, but the PARADIGM-HF data showed that there was a substantial reduction in hemoglobin A1c in those who had diabetes,” he said.
The researchers noted that an absence of a control group may contribute to an overestimation of reverse cardiac remodeling in the T2DM patients, and that the PROVE-HF study wasn’t prospectively powered to delineate differences in how sac/val therapy affected patients with or without diabetes. “Future investigations seeking to evaluate differences by T2DM status after sacubitril/valsartan initiation may use our findings to plan prospective sample sizes,” the researchers wrote.
Dr. Butler disclosed financial relationships with Abbott, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, CVRx, Eli Lilly, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Sequana, StealthPeptide and Vifor. Lead author Muhammad Shahzeb Khan, MD, MSc, a professor at the University of Mississippi, has no relevant financial relationships to disclose.
SOURCE: Kahn MS et al. JACC: HF. 2020 Dec 9. doi: 10.1016/j.jchf.2020.09.014.
FROM JACC: HEART FAILURE
FDA approves liraglutide for adolescents with obesity
The Food and Drug Administration’s new indication for liraglutide (Saxenda) for weight loss in adolescents with obesity, announced on Dec. 4, received welcome as a milestone for advancing a field that’s seen no new drug options since 2003 and boosted by 50% the list of agents indicated for weight loss in this age group.
But liraglutide’s track record in adolescents in the key study published earlier in 2020 left some experts unconvinced that liraglutide’s modest effects would have much impact on blunting the expanding cohort of teens who are obese.
“Until now, we’ve had phentermine and orlistat with FDA approval” for adolescents with obesity, and phentermine’s label specifies only patients older than 16 years. “It’s important that the FDA deemed liraglutide’s benefits greater than its risks for adolescents,” said Aaron S. Kelly, PhD, leader of the 82-week, multicenter, randomized study of liraglutide in 251 adolescents with obesity that directly led to the FDA’s action.
“We have results from a strong, published randomized trial, and the green light from the FDA, and that should give clinicians reassurance and confidence to use liraglutide clinically,” said Dr. Kelly, professor of pediatrics and codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota in Minneapolis.
An ‘unimpressive’ drop in BMI
Sonia Caprio, MD, had a more skeptical take on liraglutide’s role with its new indication: “Approval of higher-dose liraglutide is an improvement that reflects a willingness to accept adolescent obesity as a disease that needs treatment with pharmacological agents. However, the study, published in New England Journal of Medicine, was not impressive in terms of weight loss, and more importantly liraglutide was not associated with any significant changes in metabolic markers” such as insulin resistance, high-sensitivity C-reactive protein, lipoproteins and triglycerides, and hemoglobin A1c.
The observed average 5% drop in body mass index seen after a year on liraglutide treatment, compared with baseline and relative to no average change from baseline in the placebo arm, was “totally insufficient, and will not diminish any of the metabolic complications in youth with obesity,” commented Dr. Caprio, an endocrinologist and professor of pediatrics at Yale University in New Haven, Conn.
Results from the study led by Dr. Kelly also showed that liraglutide for 56 weeks cut BMI by 5% in 43% of patients, and by 10% in 26%, compared with respective rates of 19% and 8% among those in the placebo-control arm. He took a more expansive view of the potential benefits from weight loss of the caliber demonstrated by liraglutide in the study.
“In general, we wait too long with obesity in children; the earlier the intervention the better. A 3% or 4% reduction in BMI at 12 or 13 years old can pay big dividends down the road” when a typical adolescent trajectory of steadily rising weight can be flattened, he said in an interview.
Bariatric and metabolic surgery, although highly effective and usually safe, is seen by many clinicians, patients, and families as an “intervention of last resort,” and its very low level of uptake in adolescents bears witness to that reputation. It also creates an important niche for safe and effective drugs to fill as an adjunct to lifestyle changes, which are often ineffective when used by themselves. Liraglutide’s main mechanism for weight loss is depressing hunger, Dr. Kelly noted.
Existing meds have limitations
The existing medical treatments, orlistat and phentermine, both have significant drawbacks that limit their use. Orlistat (Xenical, Alli), FDA approved for adolescents 12-16 years old since 2003, limits intestinal fat absorption and as a result often produces unwanted GI effects. Phentermine’s approval for older adolescents dates from 1959 and has a weak evidence base, its label limits it to “short-term” use that’s generally taken to mean a maximum of 12 weeks. And, as a stimulant, phentermine has often been regarded as potentially dangerous, although Dr. Kelly noted that stimulants are well-accepted treatments for other disorders in children and adolescents.
“The earlier we treat obesity in youth, the better, given that it tends to track into adulthood,” agreed Dr. Caprio. “However, it remains to be seen whether weight reduction with a pharmacological agent is going to help prevent the intractable trajectories of weight and its complications. So far, it looks like surgery may be more efficacious,” she said in an interview.
Another drawback for the near future with liraglutide will likely be its cost for many patients, more than $10,000/year at full retail prices for the weight-loss formulation, given that insurers have had a poor record of covering the drug for this indication in adults, both Dr. Caprio and Dr. Kelly noted.
Compliance with liraglutide is also important. Dr. Kelly’s study followed patients for their first 26 weeks off treatment after 56 weeks on the drug, and showed that on average weights rebounded to virtually baseline levels by 6 months after treatment stopped.
Obesity treatment lasts a lifetime
“Obesity is a chronic disease, that requires chronic treatment, just like hypertension,” Dr. Kelly stressed, and cited the rebound seen in his study when liraglutide stopped as further proof of that concept. “All obesity treatment is lifelong,” he maintained.
He highlighted the importance of clinicians discussing with adolescent patients and their families the prospect of potentially remaining on liraglutide treatment for years to maintain weight loss. His experience with the randomized study convinced him that many adolescents with obesity are amenable to daily subcutaneous injection using the pen device that liraglutide comes in, but he acknowledged that some teens find this off-putting.
For the near term, Dr. Kelly foresaw liraglutide treatment of adolescents as something that will mostly be administered to patients who seek care at centers that specialize in obesity management. “I’ll think we’ll eventually see it move to more primary care settings, but that will be down the road.”
The study of liraglutide in adolescents was sponsored by Novo Nordisk, the company that markets liraglutide (Saxenda). Dr. Kelly has been a consultant to Novo Nordisk and also to Orexigen Therapeutics, Vivus, and WW, and he has received research funding from AstraZeneca. Dr. Caprio had no disclosures.
The Food and Drug Administration’s new indication for liraglutide (Saxenda) for weight loss in adolescents with obesity, announced on Dec. 4, received welcome as a milestone for advancing a field that’s seen no new drug options since 2003 and boosted by 50% the list of agents indicated for weight loss in this age group.
But liraglutide’s track record in adolescents in the key study published earlier in 2020 left some experts unconvinced that liraglutide’s modest effects would have much impact on blunting the expanding cohort of teens who are obese.
“Until now, we’ve had phentermine and orlistat with FDA approval” for adolescents with obesity, and phentermine’s label specifies only patients older than 16 years. “It’s important that the FDA deemed liraglutide’s benefits greater than its risks for adolescents,” said Aaron S. Kelly, PhD, leader of the 82-week, multicenter, randomized study of liraglutide in 251 adolescents with obesity that directly led to the FDA’s action.
“We have results from a strong, published randomized trial, and the green light from the FDA, and that should give clinicians reassurance and confidence to use liraglutide clinically,” said Dr. Kelly, professor of pediatrics and codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota in Minneapolis.
An ‘unimpressive’ drop in BMI
Sonia Caprio, MD, had a more skeptical take on liraglutide’s role with its new indication: “Approval of higher-dose liraglutide is an improvement that reflects a willingness to accept adolescent obesity as a disease that needs treatment with pharmacological agents. However, the study, published in New England Journal of Medicine, was not impressive in terms of weight loss, and more importantly liraglutide was not associated with any significant changes in metabolic markers” such as insulin resistance, high-sensitivity C-reactive protein, lipoproteins and triglycerides, and hemoglobin A1c.
The observed average 5% drop in body mass index seen after a year on liraglutide treatment, compared with baseline and relative to no average change from baseline in the placebo arm, was “totally insufficient, and will not diminish any of the metabolic complications in youth with obesity,” commented Dr. Caprio, an endocrinologist and professor of pediatrics at Yale University in New Haven, Conn.
Results from the study led by Dr. Kelly also showed that liraglutide for 56 weeks cut BMI by 5% in 43% of patients, and by 10% in 26%, compared with respective rates of 19% and 8% among those in the placebo-control arm. He took a more expansive view of the potential benefits from weight loss of the caliber demonstrated by liraglutide in the study.
“In general, we wait too long with obesity in children; the earlier the intervention the better. A 3% or 4% reduction in BMI at 12 or 13 years old can pay big dividends down the road” when a typical adolescent trajectory of steadily rising weight can be flattened, he said in an interview.
Bariatric and metabolic surgery, although highly effective and usually safe, is seen by many clinicians, patients, and families as an “intervention of last resort,” and its very low level of uptake in adolescents bears witness to that reputation. It also creates an important niche for safe and effective drugs to fill as an adjunct to lifestyle changes, which are often ineffective when used by themselves. Liraglutide’s main mechanism for weight loss is depressing hunger, Dr. Kelly noted.
Existing meds have limitations
The existing medical treatments, orlistat and phentermine, both have significant drawbacks that limit their use. Orlistat (Xenical, Alli), FDA approved for adolescents 12-16 years old since 2003, limits intestinal fat absorption and as a result often produces unwanted GI effects. Phentermine’s approval for older adolescents dates from 1959 and has a weak evidence base, its label limits it to “short-term” use that’s generally taken to mean a maximum of 12 weeks. And, as a stimulant, phentermine has often been regarded as potentially dangerous, although Dr. Kelly noted that stimulants are well-accepted treatments for other disorders in children and adolescents.
“The earlier we treat obesity in youth, the better, given that it tends to track into adulthood,” agreed Dr. Caprio. “However, it remains to be seen whether weight reduction with a pharmacological agent is going to help prevent the intractable trajectories of weight and its complications. So far, it looks like surgery may be more efficacious,” she said in an interview.
Another drawback for the near future with liraglutide will likely be its cost for many patients, more than $10,000/year at full retail prices for the weight-loss formulation, given that insurers have had a poor record of covering the drug for this indication in adults, both Dr. Caprio and Dr. Kelly noted.
Compliance with liraglutide is also important. Dr. Kelly’s study followed patients for their first 26 weeks off treatment after 56 weeks on the drug, and showed that on average weights rebounded to virtually baseline levels by 6 months after treatment stopped.
Obesity treatment lasts a lifetime
“Obesity is a chronic disease, that requires chronic treatment, just like hypertension,” Dr. Kelly stressed, and cited the rebound seen in his study when liraglutide stopped as further proof of that concept. “All obesity treatment is lifelong,” he maintained.
He highlighted the importance of clinicians discussing with adolescent patients and their families the prospect of potentially remaining on liraglutide treatment for years to maintain weight loss. His experience with the randomized study convinced him that many adolescents with obesity are amenable to daily subcutaneous injection using the pen device that liraglutide comes in, but he acknowledged that some teens find this off-putting.
For the near term, Dr. Kelly foresaw liraglutide treatment of adolescents as something that will mostly be administered to patients who seek care at centers that specialize in obesity management. “I’ll think we’ll eventually see it move to more primary care settings, but that will be down the road.”
The study of liraglutide in adolescents was sponsored by Novo Nordisk, the company that markets liraglutide (Saxenda). Dr. Kelly has been a consultant to Novo Nordisk and also to Orexigen Therapeutics, Vivus, and WW, and he has received research funding from AstraZeneca. Dr. Caprio had no disclosures.
The Food and Drug Administration’s new indication for liraglutide (Saxenda) for weight loss in adolescents with obesity, announced on Dec. 4, received welcome as a milestone for advancing a field that’s seen no new drug options since 2003 and boosted by 50% the list of agents indicated for weight loss in this age group.
But liraglutide’s track record in adolescents in the key study published earlier in 2020 left some experts unconvinced that liraglutide’s modest effects would have much impact on blunting the expanding cohort of teens who are obese.
“Until now, we’ve had phentermine and orlistat with FDA approval” for adolescents with obesity, and phentermine’s label specifies only patients older than 16 years. “It’s important that the FDA deemed liraglutide’s benefits greater than its risks for adolescents,” said Aaron S. Kelly, PhD, leader of the 82-week, multicenter, randomized study of liraglutide in 251 adolescents with obesity that directly led to the FDA’s action.
“We have results from a strong, published randomized trial, and the green light from the FDA, and that should give clinicians reassurance and confidence to use liraglutide clinically,” said Dr. Kelly, professor of pediatrics and codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota in Minneapolis.
An ‘unimpressive’ drop in BMI
Sonia Caprio, MD, had a more skeptical take on liraglutide’s role with its new indication: “Approval of higher-dose liraglutide is an improvement that reflects a willingness to accept adolescent obesity as a disease that needs treatment with pharmacological agents. However, the study, published in New England Journal of Medicine, was not impressive in terms of weight loss, and more importantly liraglutide was not associated with any significant changes in metabolic markers” such as insulin resistance, high-sensitivity C-reactive protein, lipoproteins and triglycerides, and hemoglobin A1c.
The observed average 5% drop in body mass index seen after a year on liraglutide treatment, compared with baseline and relative to no average change from baseline in the placebo arm, was “totally insufficient, and will not diminish any of the metabolic complications in youth with obesity,” commented Dr. Caprio, an endocrinologist and professor of pediatrics at Yale University in New Haven, Conn.
Results from the study led by Dr. Kelly also showed that liraglutide for 56 weeks cut BMI by 5% in 43% of patients, and by 10% in 26%, compared with respective rates of 19% and 8% among those in the placebo-control arm. He took a more expansive view of the potential benefits from weight loss of the caliber demonstrated by liraglutide in the study.
“In general, we wait too long with obesity in children; the earlier the intervention the better. A 3% or 4% reduction in BMI at 12 or 13 years old can pay big dividends down the road” when a typical adolescent trajectory of steadily rising weight can be flattened, he said in an interview.
Bariatric and metabolic surgery, although highly effective and usually safe, is seen by many clinicians, patients, and families as an “intervention of last resort,” and its very low level of uptake in adolescents bears witness to that reputation. It also creates an important niche for safe and effective drugs to fill as an adjunct to lifestyle changes, which are often ineffective when used by themselves. Liraglutide’s main mechanism for weight loss is depressing hunger, Dr. Kelly noted.
Existing meds have limitations
The existing medical treatments, orlistat and phentermine, both have significant drawbacks that limit their use. Orlistat (Xenical, Alli), FDA approved for adolescents 12-16 years old since 2003, limits intestinal fat absorption and as a result often produces unwanted GI effects. Phentermine’s approval for older adolescents dates from 1959 and has a weak evidence base, its label limits it to “short-term” use that’s generally taken to mean a maximum of 12 weeks. And, as a stimulant, phentermine has often been regarded as potentially dangerous, although Dr. Kelly noted that stimulants are well-accepted treatments for other disorders in children and adolescents.
“The earlier we treat obesity in youth, the better, given that it tends to track into adulthood,” agreed Dr. Caprio. “However, it remains to be seen whether weight reduction with a pharmacological agent is going to help prevent the intractable trajectories of weight and its complications. So far, it looks like surgery may be more efficacious,” she said in an interview.
Another drawback for the near future with liraglutide will likely be its cost for many patients, more than $10,000/year at full retail prices for the weight-loss formulation, given that insurers have had a poor record of covering the drug for this indication in adults, both Dr. Caprio and Dr. Kelly noted.
Compliance with liraglutide is also important. Dr. Kelly’s study followed patients for their first 26 weeks off treatment after 56 weeks on the drug, and showed that on average weights rebounded to virtually baseline levels by 6 months after treatment stopped.
Obesity treatment lasts a lifetime
“Obesity is a chronic disease, that requires chronic treatment, just like hypertension,” Dr. Kelly stressed, and cited the rebound seen in his study when liraglutide stopped as further proof of that concept. “All obesity treatment is lifelong,” he maintained.
He highlighted the importance of clinicians discussing with adolescent patients and their families the prospect of potentially remaining on liraglutide treatment for years to maintain weight loss. His experience with the randomized study convinced him that many adolescents with obesity are amenable to daily subcutaneous injection using the pen device that liraglutide comes in, but he acknowledged that some teens find this off-putting.
For the near term, Dr. Kelly foresaw liraglutide treatment of adolescents as something that will mostly be administered to patients who seek care at centers that specialize in obesity management. “I’ll think we’ll eventually see it move to more primary care settings, but that will be down the road.”
The study of liraglutide in adolescents was sponsored by Novo Nordisk, the company that markets liraglutide (Saxenda). Dr. Kelly has been a consultant to Novo Nordisk and also to Orexigen Therapeutics, Vivus, and WW, and he has received research funding from AstraZeneca. Dr. Caprio had no disclosures.
Natural history of adrenal incidentalomas with and without mild autonomous cortisol excess
Background: Studies have suggested that adrenal incidentalomas may increase risk of cardiometabolic disease in patients. Guidelines for repeat imaging and hormonal assessment of adrenal incidentalomas are inconsistent because of inadequate studies.
Study design: Systematic review and meta-analysis.
Setting: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched.
Synopsis: Of 1,139 studies screened; 32 met inclusion criteria: adult patients with adrenal adenoma who had 12 or more months of follow-up and outcomes of interest. Larger adrenal adenomas were less likely to have significant change in size on repeat imaging than did smaller tumors. There was no malignant transformation observed. Development of Cushing syndrome was seen in 6 of 2,745 patients. Cardiometabolic comorbid conditions were common in both MACE and NFAT patients with hypertension being the most frequently reported (64% and 58.2% respectively). Worsening of dyslipidemia was observed in both groups. Weight gain and the development of type 2 diabetes occurred more frequently in MACE than in NFAT patients (21.0% vs. 8.7%). In 1,356 patients, all-cause mortality was 11.2% (95% confidence interval, 9.5%-13.0%) for both groups over a mean follow-up of 56.3 months. Cardiovascular events accounted for 43.2% deaths. Limitations included the small number of patients in the studies assessed and the inconsistent definition of outcomes.
Bottom line: Patients with adrenal adenomas should be counseled on modifying cardiovascular risk factors whereas tumor growth, change in hormone production, and malignant transformation are less concerning based on the studies included.
Citation: Elhassan YS et al. Natural history of adrenal incidentalomas with and without mild autonomous cortisol excess: A systematic review and meta-analysis. Ann Intern Med. 2019 Jun 25;121:107-16.
Dr. Thompson is a hospitalist and assistant professor of medicine in the division of general internal medicine at Saint Louis University School of Medicine.
Background: Studies have suggested that adrenal incidentalomas may increase risk of cardiometabolic disease in patients. Guidelines for repeat imaging and hormonal assessment of adrenal incidentalomas are inconsistent because of inadequate studies.
Study design: Systematic review and meta-analysis.
Setting: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched.
Synopsis: Of 1,139 studies screened; 32 met inclusion criteria: adult patients with adrenal adenoma who had 12 or more months of follow-up and outcomes of interest. Larger adrenal adenomas were less likely to have significant change in size on repeat imaging than did smaller tumors. There was no malignant transformation observed. Development of Cushing syndrome was seen in 6 of 2,745 patients. Cardiometabolic comorbid conditions were common in both MACE and NFAT patients with hypertension being the most frequently reported (64% and 58.2% respectively). Worsening of dyslipidemia was observed in both groups. Weight gain and the development of type 2 diabetes occurred more frequently in MACE than in NFAT patients (21.0% vs. 8.7%). In 1,356 patients, all-cause mortality was 11.2% (95% confidence interval, 9.5%-13.0%) for both groups over a mean follow-up of 56.3 months. Cardiovascular events accounted for 43.2% deaths. Limitations included the small number of patients in the studies assessed and the inconsistent definition of outcomes.
Bottom line: Patients with adrenal adenomas should be counseled on modifying cardiovascular risk factors whereas tumor growth, change in hormone production, and malignant transformation are less concerning based on the studies included.
Citation: Elhassan YS et al. Natural history of adrenal incidentalomas with and without mild autonomous cortisol excess: A systematic review and meta-analysis. Ann Intern Med. 2019 Jun 25;121:107-16.
Dr. Thompson is a hospitalist and assistant professor of medicine in the division of general internal medicine at Saint Louis University School of Medicine.
Background: Studies have suggested that adrenal incidentalomas may increase risk of cardiometabolic disease in patients. Guidelines for repeat imaging and hormonal assessment of adrenal incidentalomas are inconsistent because of inadequate studies.
Study design: Systematic review and meta-analysis.
Setting: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched.
Synopsis: Of 1,139 studies screened; 32 met inclusion criteria: adult patients with adrenal adenoma who had 12 or more months of follow-up and outcomes of interest. Larger adrenal adenomas were less likely to have significant change in size on repeat imaging than did smaller tumors. There was no malignant transformation observed. Development of Cushing syndrome was seen in 6 of 2,745 patients. Cardiometabolic comorbid conditions were common in both MACE and NFAT patients with hypertension being the most frequently reported (64% and 58.2% respectively). Worsening of dyslipidemia was observed in both groups. Weight gain and the development of type 2 diabetes occurred more frequently in MACE than in NFAT patients (21.0% vs. 8.7%). In 1,356 patients, all-cause mortality was 11.2% (95% confidence interval, 9.5%-13.0%) for both groups over a mean follow-up of 56.3 months. Cardiovascular events accounted for 43.2% deaths. Limitations included the small number of patients in the studies assessed and the inconsistent definition of outcomes.
Bottom line: Patients with adrenal adenomas should be counseled on modifying cardiovascular risk factors whereas tumor growth, change in hormone production, and malignant transformation are less concerning based on the studies included.
Citation: Elhassan YS et al. Natural history of adrenal incidentalomas with and without mild autonomous cortisol excess: A systematic review and meta-analysis. Ann Intern Med. 2019 Jun 25;121:107-16.
Dr. Thompson is a hospitalist and assistant professor of medicine in the division of general internal medicine at Saint Louis University School of Medicine.
To D or not to D? Vitamin D doesn’t reduce falls in older adults
Higher doses of vitamin D supplementation not only show no benefit in the prevention of falls in older adults at increased risk of falling, compared with the lowest doses, but they appear to increase the risk, new research shows.
Based on the findings, supplemental vitamin D above the minimum dose of 200 IU/day likely has little benefit, lead author Lawrence J. Appel, MD, MPH, told this news organization.
“In the absence of any benefit of 1,000 IU/day versus 2,000 IU/day [of vitamin D supplementation] on falls, along with the potential for harm from doses above 1,000 IU/day, it is hard to recommend a dose above 200 IU/day in older-aged persons, unless there is a compelling reason,” asserted Dr. Appel, director of the Welch Center for Prevention, Epidemiology, and Clinical Research at Johns Hopkins Bloomberg School of Public Health in Baltimore.
“More is not always better – and it may even be worse,” when it comes to vitamin D’s role in the prevention of falls, he said.
The research, published in Annals of Internal Medicine, adds important evidence in the ongoing struggle to prevent falls, says Bruce R. Troen, MD, in an accompanying editorial.
“Falls and their deleterious consequences remain a substantial risk for older adults and a huge challenge for health care teams,” writes Dr. Troen, a physician-investigator with the Veterans Affairs Western New York Healthcare System.
However, commenting in an interview, Dr. Troen cautions: “There are many epidemiological studies that are correlative, not causative, that do show a likelihood for benefit [with vitamin D supplementation]. … Therefore, there’s no reason for clinicians to discontinue vitamin D in individuals because of this study.”
“If you’re monitoring an older adult who is frail and has multiple comorbidities, you want to know what their vitamin D level is [and] provide them an appropriate supplement if needed,” he emphasized.
Some guidelines already reflect the lack of evidence of any role of vitamin D supplementation in the prevention of falls, including those of the 2018 U.S. Preventive Services Task Force, which, in a reversal of its 2012 recommendation, now does not recommend vitamin D supplementation for fall prevention in older persons without osteoporosis or vitamin D deficiency, Dr. Appel and colleagues note.
No prevention of falls regardless of baseline vitamin D
As part of STURDY (Study to understand fall reduction and vitamin D in you), Dr. Appel and colleagues enrolled 688 community-dwelling participants who had an elevated risk of falling, defined as a serum 25-hydroxyvitamin D [25(OH)D] level of 25 to 72.5 nmol/L (10-29 ng/dL).
Participants were a mean age of 77.2 years and had a mean total 25(OH)D level of 55.3 nmol/L at enrollment.
They were randomized to one of four doses of vitamin D3, including 200 IU/day (the control group), or 1,000, 2,000, or 4,000 IU/day.
The highest doses were found to be associated with worse – not better – outcomes including a shorter time to hospitalization or death, compared with the 1,000-IU/day group. The higher-dose groups were therefore switched to a dose of 1,000 IU/day or lower, and all participants were followed for up to 2 years.
Overall, 63% experienced falls over the course of the study, which, though high, was consistent with the study’s criteria of participants having an elevated fall risk.
Of the 667 participants who completed the trial, no benefit in prevention of falling was seen across any of the doses, compared with the control group dose of 200 IU/day, regardless of participants’ baseline vitamin D levels.
Safety analyses showed that even in the 1,000-IU/day group, a higher risk of first serious fall and first fall with hospitalization was seen compared with the 200-IU/day group.
A limitation is that the study did not have a placebo group, however, “200 IU/day is a very small dose, probably homeopathic,” Dr. Appel said. “It was likely close to a placebo,” he said.
Caveats: comorbidities, subgroups
In his editorial, Dr. Troen notes other studies, including VITAL (Vitamin D and Omega-3 Trial) also found no reduction in falls with higher vitamin D doses; however, that study did not show any significant risks with the higher doses.
He adds that the current study lacks information on subsets of participants.
“We don’t have enough information about the existing comorbidities and medications that these people are on to be able to pull back the layers. Maybe there is a subgroup that should not be getting 4,000 IU, whereas another subgroup may not be harmed and you may decide that patient can benefit,” he said.
Furthermore, the trial doesn’t address groups such as nursing home residents.
“I have, for instance, 85-year-olds with vitamin D levels of maybe 20 nmol/L with multiple medical issues, but levels that low were not included in the study, so this is a tricky business, but the bottom line is first, do no harm,” he said.
“We really need trials that factor in the multiple different aspects so we can come up, hopefully, with a holistic and interdisciplinary approach, which is usually the best way to optimize care for frail older adults,” he concluded.
The study received funding from the National Institute of Aging.
A version of this article originally appeared on Medscape.com.
Higher doses of vitamin D supplementation not only show no benefit in the prevention of falls in older adults at increased risk of falling, compared with the lowest doses, but they appear to increase the risk, new research shows.
Based on the findings, supplemental vitamin D above the minimum dose of 200 IU/day likely has little benefit, lead author Lawrence J. Appel, MD, MPH, told this news organization.
“In the absence of any benefit of 1,000 IU/day versus 2,000 IU/day [of vitamin D supplementation] on falls, along with the potential for harm from doses above 1,000 IU/day, it is hard to recommend a dose above 200 IU/day in older-aged persons, unless there is a compelling reason,” asserted Dr. Appel, director of the Welch Center for Prevention, Epidemiology, and Clinical Research at Johns Hopkins Bloomberg School of Public Health in Baltimore.
“More is not always better – and it may even be worse,” when it comes to vitamin D’s role in the prevention of falls, he said.
The research, published in Annals of Internal Medicine, adds important evidence in the ongoing struggle to prevent falls, says Bruce R. Troen, MD, in an accompanying editorial.
“Falls and their deleterious consequences remain a substantial risk for older adults and a huge challenge for health care teams,” writes Dr. Troen, a physician-investigator with the Veterans Affairs Western New York Healthcare System.
However, commenting in an interview, Dr. Troen cautions: “There are many epidemiological studies that are correlative, not causative, that do show a likelihood for benefit [with vitamin D supplementation]. … Therefore, there’s no reason for clinicians to discontinue vitamin D in individuals because of this study.”
“If you’re monitoring an older adult who is frail and has multiple comorbidities, you want to know what their vitamin D level is [and] provide them an appropriate supplement if needed,” he emphasized.
Some guidelines already reflect the lack of evidence of any role of vitamin D supplementation in the prevention of falls, including those of the 2018 U.S. Preventive Services Task Force, which, in a reversal of its 2012 recommendation, now does not recommend vitamin D supplementation for fall prevention in older persons without osteoporosis or vitamin D deficiency, Dr. Appel and colleagues note.
No prevention of falls regardless of baseline vitamin D
As part of STURDY (Study to understand fall reduction and vitamin D in you), Dr. Appel and colleagues enrolled 688 community-dwelling participants who had an elevated risk of falling, defined as a serum 25-hydroxyvitamin D [25(OH)D] level of 25 to 72.5 nmol/L (10-29 ng/dL).
Participants were a mean age of 77.2 years and had a mean total 25(OH)D level of 55.3 nmol/L at enrollment.
They were randomized to one of four doses of vitamin D3, including 200 IU/day (the control group), or 1,000, 2,000, or 4,000 IU/day.
The highest doses were found to be associated with worse – not better – outcomes including a shorter time to hospitalization or death, compared with the 1,000-IU/day group. The higher-dose groups were therefore switched to a dose of 1,000 IU/day or lower, and all participants were followed for up to 2 years.
Overall, 63% experienced falls over the course of the study, which, though high, was consistent with the study’s criteria of participants having an elevated fall risk.
Of the 667 participants who completed the trial, no benefit in prevention of falling was seen across any of the doses, compared with the control group dose of 200 IU/day, regardless of participants’ baseline vitamin D levels.
Safety analyses showed that even in the 1,000-IU/day group, a higher risk of first serious fall and first fall with hospitalization was seen compared with the 200-IU/day group.
A limitation is that the study did not have a placebo group, however, “200 IU/day is a very small dose, probably homeopathic,” Dr. Appel said. “It was likely close to a placebo,” he said.
Caveats: comorbidities, subgroups
In his editorial, Dr. Troen notes other studies, including VITAL (Vitamin D and Omega-3 Trial) also found no reduction in falls with higher vitamin D doses; however, that study did not show any significant risks with the higher doses.
He adds that the current study lacks information on subsets of participants.
“We don’t have enough information about the existing comorbidities and medications that these people are on to be able to pull back the layers. Maybe there is a subgroup that should not be getting 4,000 IU, whereas another subgroup may not be harmed and you may decide that patient can benefit,” he said.
Furthermore, the trial doesn’t address groups such as nursing home residents.
“I have, for instance, 85-year-olds with vitamin D levels of maybe 20 nmol/L with multiple medical issues, but levels that low were not included in the study, so this is a tricky business, but the bottom line is first, do no harm,” he said.
“We really need trials that factor in the multiple different aspects so we can come up, hopefully, with a holistic and interdisciplinary approach, which is usually the best way to optimize care for frail older adults,” he concluded.
The study received funding from the National Institute of Aging.
A version of this article originally appeared on Medscape.com.
Higher doses of vitamin D supplementation not only show no benefit in the prevention of falls in older adults at increased risk of falling, compared with the lowest doses, but they appear to increase the risk, new research shows.
Based on the findings, supplemental vitamin D above the minimum dose of 200 IU/day likely has little benefit, lead author Lawrence J. Appel, MD, MPH, told this news organization.
“In the absence of any benefit of 1,000 IU/day versus 2,000 IU/day [of vitamin D supplementation] on falls, along with the potential for harm from doses above 1,000 IU/day, it is hard to recommend a dose above 200 IU/day in older-aged persons, unless there is a compelling reason,” asserted Dr. Appel, director of the Welch Center for Prevention, Epidemiology, and Clinical Research at Johns Hopkins Bloomberg School of Public Health in Baltimore.
“More is not always better – and it may even be worse,” when it comes to vitamin D’s role in the prevention of falls, he said.
The research, published in Annals of Internal Medicine, adds important evidence in the ongoing struggle to prevent falls, says Bruce R. Troen, MD, in an accompanying editorial.
“Falls and their deleterious consequences remain a substantial risk for older adults and a huge challenge for health care teams,” writes Dr. Troen, a physician-investigator with the Veterans Affairs Western New York Healthcare System.
However, commenting in an interview, Dr. Troen cautions: “There are many epidemiological studies that are correlative, not causative, that do show a likelihood for benefit [with vitamin D supplementation]. … Therefore, there’s no reason for clinicians to discontinue vitamin D in individuals because of this study.”
“If you’re monitoring an older adult who is frail and has multiple comorbidities, you want to know what their vitamin D level is [and] provide them an appropriate supplement if needed,” he emphasized.
Some guidelines already reflect the lack of evidence of any role of vitamin D supplementation in the prevention of falls, including those of the 2018 U.S. Preventive Services Task Force, which, in a reversal of its 2012 recommendation, now does not recommend vitamin D supplementation for fall prevention in older persons without osteoporosis or vitamin D deficiency, Dr. Appel and colleagues note.
No prevention of falls regardless of baseline vitamin D
As part of STURDY (Study to understand fall reduction and vitamin D in you), Dr. Appel and colleagues enrolled 688 community-dwelling participants who had an elevated risk of falling, defined as a serum 25-hydroxyvitamin D [25(OH)D] level of 25 to 72.5 nmol/L (10-29 ng/dL).
Participants were a mean age of 77.2 years and had a mean total 25(OH)D level of 55.3 nmol/L at enrollment.
They were randomized to one of four doses of vitamin D3, including 200 IU/day (the control group), or 1,000, 2,000, or 4,000 IU/day.
The highest doses were found to be associated with worse – not better – outcomes including a shorter time to hospitalization or death, compared with the 1,000-IU/day group. The higher-dose groups were therefore switched to a dose of 1,000 IU/day or lower, and all participants were followed for up to 2 years.
Overall, 63% experienced falls over the course of the study, which, though high, was consistent with the study’s criteria of participants having an elevated fall risk.
Of the 667 participants who completed the trial, no benefit in prevention of falling was seen across any of the doses, compared with the control group dose of 200 IU/day, regardless of participants’ baseline vitamin D levels.
Safety analyses showed that even in the 1,000-IU/day group, a higher risk of first serious fall and first fall with hospitalization was seen compared with the 200-IU/day group.
A limitation is that the study did not have a placebo group, however, “200 IU/day is a very small dose, probably homeopathic,” Dr. Appel said. “It was likely close to a placebo,” he said.
Caveats: comorbidities, subgroups
In his editorial, Dr. Troen notes other studies, including VITAL (Vitamin D and Omega-3 Trial) also found no reduction in falls with higher vitamin D doses; however, that study did not show any significant risks with the higher doses.
He adds that the current study lacks information on subsets of participants.
“We don’t have enough information about the existing comorbidities and medications that these people are on to be able to pull back the layers. Maybe there is a subgroup that should not be getting 4,000 IU, whereas another subgroup may not be harmed and you may decide that patient can benefit,” he said.
Furthermore, the trial doesn’t address groups such as nursing home residents.
“I have, for instance, 85-year-olds with vitamin D levels of maybe 20 nmol/L with multiple medical issues, but levels that low were not included in the study, so this is a tricky business, but the bottom line is first, do no harm,” he said.
“We really need trials that factor in the multiple different aspects so we can come up, hopefully, with a holistic and interdisciplinary approach, which is usually the best way to optimize care for frail older adults,” he concluded.
The study received funding from the National Institute of Aging.
A version of this article originally appeared on Medscape.com.
Major depression linked to insulin resistance
Individuals experiencing a current episode of major depressive disorder (MDD) are significantly more likely to have insulin resistance (IR), research shows.
Investigators found patients with MDD were 51% more likely to have IR, compared with their counterparts without depressive disorder. In addition, in individuals experiencing current depression, IR was also associated with depression severity and depression chronicity.
“We learned two things from this study – first, that insulin resistance was associated with being in a depressive episode and with the severity of that episode,” Kathleen Watson, PhD, a postdoctoral research fellow in the department of psychiatry, Stanford (Calif.) University, told this news organization. “Second, we learned that we can estimate insulin resistance using a surrogate measure that is clinically accessible – the triglyceride/HDL ratio.”
The study was published online Dec. 2 in JAMA Psychiatry.
Targeted approach
Many studies have linked MDD and IR. However, said Dr. Watson, “We did not have much description of the nature of this relationship.” She added that her team wanted to gain a better understanding of how IR relates to depression characteristics, such as remission status, severity, and chronicity.
Characterizing these associations will “represent a critical step at better phenotyping, a prelude to longitudinal studies, and a more targeted approach to the treatment of MDD,” the authors note.
For the study, the researchers drew on data from the Netherlands Study of Depression and Anxiety, a longitudinal Dutch study of adults that “describes the course and consequences of depressive and anxiety disorders.”
The study included 1,269 study participants with current MDD (n = 536), remitted MDD (n = 394), and control participants without a history of MDD (n = 339).
In addition to investigating the association between MDD and IR, the researchers also wanted to understand “whether using different surrogate IR measures has consistent association with MDD.” IR was determined using two surrogate markers – the quantitative insulin sensitivity check index (QUICKI) and the triglyceride to high-density lipoprotein ratio. Participants in the bottom quartile of the QUICKI were categorized as IR, while all other participants were categorized as being “insulin sensitive.”
The second surrogate IR measure – the triglyceride-HDL ratio – is an index based on fasting blood sample measurements, in which the determination of IR was based on sex-specific cut points (female ratio, IR > 1.9; male ratio, IR > 2.8).
Depression was determined based on the Composite International Diagnostic Interview (version 2.1), while depression severity was based on the Inventory of Depression Symptomatology. “Chronicity” was defined as depression during the preceding 4 years and was measured using the life chart review.
State vs. trait
Insulin resistance was associated with current, but not with remitted, MDD (odds ratio, 1.51; 95% confidence interval, 1.08-2.12 and OR, 1.14; 95% CI, 0.79-1.64, respectively).
In a model adjusted for age, sex, education, partner status, smoking status, and alcohol consumption, IR, as assessed by both measures, was linked to depression severity – but only the triglyceride-HDL ratio yielded an association between IR and depression chronicity.
IR was not associated with depression severity or chronicity in remitted MDD on either measure.
The findings – specifically the association between current, but not remitted, MDD – suggest that “IR is a state, rather than a trait, biomarker of depression,” the authors note.
“There are many plausible mechanisms between IR and MDD,” said Dr. Watson. “Some hypotheses for the link include inflammations, alterations to the hypothalamic-pituitary-adrenal axis, and changes in health behavior.
“Understanding these nuances helped us to lay the foundation for future research, including asking whether IR can lead to the development of MDD,” she added.
Finally, and ways to target them with potential treatments or interventions.
Shared biological mechanisms?
Commenting on the study in an interview, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto and head of the Mood Disorders Psychopharmacology Unit, said the results “suggest that a subpopulation of people with depression have what might be referred to as ‘metabolic syndrome type II’ – the depression is a consequence of abnormal metabolic processes.”
The results also suggest “maybe metabolic markers can be used as biomarkers of disease presence vs. absence,” said Dr. McIntyre, who is also the chairman and executive director of the Brain and Cognition Discovery Foundation, Toronto, and was not involved with the study.
Also commenting on the study, Andrea Fagiolini, MD, professor of psychiatry, University of Siena (Italy), said depression, metabolic, and inflammatory diseases “likely share some common biological mechanism, as they share risk factors such as unhealthy diet, unhealthy lifestyles, and frequent exposure to physical and psychological distress.”
It is “possible that treatment of depression improves IR; conversely, it is possible that lifestyle programs or medications that are able to improve IR may improve depressive symptoms,” suggested Dr. Fagiolini, who was not involved with the study. “It remains to be established which symptoms of depression are most involved in this correlation and whether their improvement precedes or follows the improvement in IR,” he noted.
The Netherlands Study of Depression and Anxiety is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development and is supported by several participating universities and mental health care organizations. Dr. Watson has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. McIntyre reported research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from multiple pharmaceutical companies. Dr. McIntyre is also CEO of AltMed. Dr. Fagiolini has served or is currently serving as consultant or speaker for or is a research grant recipient from multiple pharmaceutical companies.
A version of this article originally appeared on Medscape.com.
Individuals experiencing a current episode of major depressive disorder (MDD) are significantly more likely to have insulin resistance (IR), research shows.
Investigators found patients with MDD were 51% more likely to have IR, compared with their counterparts without depressive disorder. In addition, in individuals experiencing current depression, IR was also associated with depression severity and depression chronicity.
“We learned two things from this study – first, that insulin resistance was associated with being in a depressive episode and with the severity of that episode,” Kathleen Watson, PhD, a postdoctoral research fellow in the department of psychiatry, Stanford (Calif.) University, told this news organization. “Second, we learned that we can estimate insulin resistance using a surrogate measure that is clinically accessible – the triglyceride/HDL ratio.”
The study was published online Dec. 2 in JAMA Psychiatry.
Targeted approach
Many studies have linked MDD and IR. However, said Dr. Watson, “We did not have much description of the nature of this relationship.” She added that her team wanted to gain a better understanding of how IR relates to depression characteristics, such as remission status, severity, and chronicity.
Characterizing these associations will “represent a critical step at better phenotyping, a prelude to longitudinal studies, and a more targeted approach to the treatment of MDD,” the authors note.
For the study, the researchers drew on data from the Netherlands Study of Depression and Anxiety, a longitudinal Dutch study of adults that “describes the course and consequences of depressive and anxiety disorders.”
The study included 1,269 study participants with current MDD (n = 536), remitted MDD (n = 394), and control participants without a history of MDD (n = 339).
In addition to investigating the association between MDD and IR, the researchers also wanted to understand “whether using different surrogate IR measures has consistent association with MDD.” IR was determined using two surrogate markers – the quantitative insulin sensitivity check index (QUICKI) and the triglyceride to high-density lipoprotein ratio. Participants in the bottom quartile of the QUICKI were categorized as IR, while all other participants were categorized as being “insulin sensitive.”
The second surrogate IR measure – the triglyceride-HDL ratio – is an index based on fasting blood sample measurements, in which the determination of IR was based on sex-specific cut points (female ratio, IR > 1.9; male ratio, IR > 2.8).
Depression was determined based on the Composite International Diagnostic Interview (version 2.1), while depression severity was based on the Inventory of Depression Symptomatology. “Chronicity” was defined as depression during the preceding 4 years and was measured using the life chart review.
State vs. trait
Insulin resistance was associated with current, but not with remitted, MDD (odds ratio, 1.51; 95% confidence interval, 1.08-2.12 and OR, 1.14; 95% CI, 0.79-1.64, respectively).
In a model adjusted for age, sex, education, partner status, smoking status, and alcohol consumption, IR, as assessed by both measures, was linked to depression severity – but only the triglyceride-HDL ratio yielded an association between IR and depression chronicity.
IR was not associated with depression severity or chronicity in remitted MDD on either measure.
The findings – specifically the association between current, but not remitted, MDD – suggest that “IR is a state, rather than a trait, biomarker of depression,” the authors note.
“There are many plausible mechanisms between IR and MDD,” said Dr. Watson. “Some hypotheses for the link include inflammations, alterations to the hypothalamic-pituitary-adrenal axis, and changes in health behavior.
“Understanding these nuances helped us to lay the foundation for future research, including asking whether IR can lead to the development of MDD,” she added.
Finally, and ways to target them with potential treatments or interventions.
Shared biological mechanisms?
Commenting on the study in an interview, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto and head of the Mood Disorders Psychopharmacology Unit, said the results “suggest that a subpopulation of people with depression have what might be referred to as ‘metabolic syndrome type II’ – the depression is a consequence of abnormal metabolic processes.”
The results also suggest “maybe metabolic markers can be used as biomarkers of disease presence vs. absence,” said Dr. McIntyre, who is also the chairman and executive director of the Brain and Cognition Discovery Foundation, Toronto, and was not involved with the study.
Also commenting on the study, Andrea Fagiolini, MD, professor of psychiatry, University of Siena (Italy), said depression, metabolic, and inflammatory diseases “likely share some common biological mechanism, as they share risk factors such as unhealthy diet, unhealthy lifestyles, and frequent exposure to physical and psychological distress.”
It is “possible that treatment of depression improves IR; conversely, it is possible that lifestyle programs or medications that are able to improve IR may improve depressive symptoms,” suggested Dr. Fagiolini, who was not involved with the study. “It remains to be established which symptoms of depression are most involved in this correlation and whether their improvement precedes or follows the improvement in IR,” he noted.
The Netherlands Study of Depression and Anxiety is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development and is supported by several participating universities and mental health care organizations. Dr. Watson has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. McIntyre reported research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from multiple pharmaceutical companies. Dr. McIntyre is also CEO of AltMed. Dr. Fagiolini has served or is currently serving as consultant or speaker for or is a research grant recipient from multiple pharmaceutical companies.
A version of this article originally appeared on Medscape.com.
Individuals experiencing a current episode of major depressive disorder (MDD) are significantly more likely to have insulin resistance (IR), research shows.
Investigators found patients with MDD were 51% more likely to have IR, compared with their counterparts without depressive disorder. In addition, in individuals experiencing current depression, IR was also associated with depression severity and depression chronicity.
“We learned two things from this study – first, that insulin resistance was associated with being in a depressive episode and with the severity of that episode,” Kathleen Watson, PhD, a postdoctoral research fellow in the department of psychiatry, Stanford (Calif.) University, told this news organization. “Second, we learned that we can estimate insulin resistance using a surrogate measure that is clinically accessible – the triglyceride/HDL ratio.”
The study was published online Dec. 2 in JAMA Psychiatry.
Targeted approach
Many studies have linked MDD and IR. However, said Dr. Watson, “We did not have much description of the nature of this relationship.” She added that her team wanted to gain a better understanding of how IR relates to depression characteristics, such as remission status, severity, and chronicity.
Characterizing these associations will “represent a critical step at better phenotyping, a prelude to longitudinal studies, and a more targeted approach to the treatment of MDD,” the authors note.
For the study, the researchers drew on data from the Netherlands Study of Depression and Anxiety, a longitudinal Dutch study of adults that “describes the course and consequences of depressive and anxiety disorders.”
The study included 1,269 study participants with current MDD (n = 536), remitted MDD (n = 394), and control participants without a history of MDD (n = 339).
In addition to investigating the association between MDD and IR, the researchers also wanted to understand “whether using different surrogate IR measures has consistent association with MDD.” IR was determined using two surrogate markers – the quantitative insulin sensitivity check index (QUICKI) and the triglyceride to high-density lipoprotein ratio. Participants in the bottom quartile of the QUICKI were categorized as IR, while all other participants were categorized as being “insulin sensitive.”
The second surrogate IR measure – the triglyceride-HDL ratio – is an index based on fasting blood sample measurements, in which the determination of IR was based on sex-specific cut points (female ratio, IR > 1.9; male ratio, IR > 2.8).
Depression was determined based on the Composite International Diagnostic Interview (version 2.1), while depression severity was based on the Inventory of Depression Symptomatology. “Chronicity” was defined as depression during the preceding 4 years and was measured using the life chart review.
State vs. trait
Insulin resistance was associated with current, but not with remitted, MDD (odds ratio, 1.51; 95% confidence interval, 1.08-2.12 and OR, 1.14; 95% CI, 0.79-1.64, respectively).
In a model adjusted for age, sex, education, partner status, smoking status, and alcohol consumption, IR, as assessed by both measures, was linked to depression severity – but only the triglyceride-HDL ratio yielded an association between IR and depression chronicity.
IR was not associated with depression severity or chronicity in remitted MDD on either measure.
The findings – specifically the association between current, but not remitted, MDD – suggest that “IR is a state, rather than a trait, biomarker of depression,” the authors note.
“There are many plausible mechanisms between IR and MDD,” said Dr. Watson. “Some hypotheses for the link include inflammations, alterations to the hypothalamic-pituitary-adrenal axis, and changes in health behavior.
“Understanding these nuances helped us to lay the foundation for future research, including asking whether IR can lead to the development of MDD,” she added.
Finally, and ways to target them with potential treatments or interventions.
Shared biological mechanisms?
Commenting on the study in an interview, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto and head of the Mood Disorders Psychopharmacology Unit, said the results “suggest that a subpopulation of people with depression have what might be referred to as ‘metabolic syndrome type II’ – the depression is a consequence of abnormal metabolic processes.”
The results also suggest “maybe metabolic markers can be used as biomarkers of disease presence vs. absence,” said Dr. McIntyre, who is also the chairman and executive director of the Brain and Cognition Discovery Foundation, Toronto, and was not involved with the study.
Also commenting on the study, Andrea Fagiolini, MD, professor of psychiatry, University of Siena (Italy), said depression, metabolic, and inflammatory diseases “likely share some common biological mechanism, as they share risk factors such as unhealthy diet, unhealthy lifestyles, and frequent exposure to physical and psychological distress.”
It is “possible that treatment of depression improves IR; conversely, it is possible that lifestyle programs or medications that are able to improve IR may improve depressive symptoms,” suggested Dr. Fagiolini, who was not involved with the study. “It remains to be established which symptoms of depression are most involved in this correlation and whether their improvement precedes or follows the improvement in IR,” he noted.
The Netherlands Study of Depression and Anxiety is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development and is supported by several participating universities and mental health care organizations. Dr. Watson has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. McIntyre reported research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from multiple pharmaceutical companies. Dr. McIntyre is also CEO of AltMed. Dr. Fagiolini has served or is currently serving as consultant or speaker for or is a research grant recipient from multiple pharmaceutical companies.
A version of this article originally appeared on Medscape.com.
Prioritize COVID-19 vaccination in both types of diabetes, say docs
The risk for increased COVID-19 severity in people with type 1 diabetes appears similar to that of type 2 diabetes, contrary to some official advice from the Centers for Disease Control and Prevention. The new finding indicates that people with both types should be priority for receiving a vaccine, investigators say.
The study is the first to prospectively evaluate both inpatients and outpatients and to examine COVID-19 severity factors in addition to death in people with type 1 and type 2 diabetes separately, and was published online Dec. 2 in Diabetes Care.
Among the patients, who were seen at Vanderbilt University Medical Center in Nashville, Tenn., between March and August of 2020, those with both type 1 and type 2 diabetes had between a three- and fourfold greater risk for COVID-19 hospitalization and greater illness severity compared with people without diabetes after adjustments for age, race, and a number of other risk factors.
This finding is important since as of Dec. 1, 2020, the CDC has classified the diabetes types differently in terms of underlying medical conditions that increase the risk for severe COVID-19.
Adults of any age with type 2 diabetes are considered “at increased risk of severe illness” from the virus that causes COVID-19 whereas the CDC says those with type 1 “might be at an increased risk.”
Lead author of the new paper Justin M. Gregory, MD, said in an interview: “I think this needs revision based on the current evidence. I think the data presented in our study and that of Barron et al. in Lancet Endocrinology 2020 indicate the need to place type 1 diabetes at parity with type 2 diabetes.
“These studies indicate both conditions carry an adjusted odds ratio of three to four when compared with people without diabetes for hospitalization, illness severity, and mortality,” he stressed.
Vaccines look promising for patients with diabetes
There were no phase 3 vaccine data available for the vaccine at the time that Dr. Gregory, of the Ian M. Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University, Nashville, Tenn., and colleagues were writing their manuscript in late summer, so the article does not mention this.
But now, Dr. Gregory said, “Based on the initial press releases from Pfizer and Moderna, I am now optimistic that these vaccines might mitigate the excess morbidity and mortality from COVID-19 experienced by patients with diabetes.
“I am eager to see what we learn on December 10 and 17 [the scheduled dates for the meetings of the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee to review the Pfizer and Moderna vaccines, respectively].”
But with the winter pandemic surge in the meantime, “Our investigation suggests that as COVID-19 hospitalizations rise, patients with both type 1 and 2 diabetes will comprise a disproportionately higher number of those admissions and, once hospitalized, demonstrate a greater degree of illness severity,” he and his colleagues said.
“In light of these data, we call on our colleagues to emphasize the importance of social distancing measures and hand hygiene, with particular emphasis on patients with diabetes, including those in the most vulnerable communities whom our study affirms will face the most severe impact.”
After adjustments, excess severity risk similar for both diabetes types
The new study data came from electronic health records at Vanderbilt University Medical Center, comprising 137 primary care, urgent care, and hospital facilities where patients were tested for SARS-CoV-2 regardless of the reason for their visit.
Between March 17 and August 7, 2020, 6,451 patients tested positive for COVID-19. Of those, 273 had type 2 diabetes and 40 had type 1 diabetes.
Children younger than 18 years accounted for 20% of those with type 1 diabetes and 9.4% of those without diabetes, but none of the type 2 group. The group with type 2 diabetes was considerably older than the type 1 diabetes and no-diabetes groups, 58 years versus 37 and 33 years, respectively.
Before adjustment for baseline characteristics that differed between groups, patients with type 1 diabetes appeared to have a risk for hospitalization and greater illness severity that was intermediate between the group with no diabetes and the group with type 2 diabetes, the researchers said.
But after adjustment for age, race, sex, hypertension, smoking, and body mass index, people with type 1 diabetes had odds ratios of 3.90 for hospitalization and 3.35 for greater illness severity, which was similar to risk in type 2 diabetes (3.36 and 3.42, respectively), compared to those without diabetes.
Deep dive explores COVID-19 severity risk factors in type 1 diabetes
The investigators then conducted a detailed chart review for 37 of the 40 patients with type 1 diabetes and phone surveys with 15 of them.
The majority (28) had not been hospitalized, and only one was hospitalized for diabetic ketoacidosis (DKA) within 14 days of positive SARS-CoV-2 testing.
This contrasts with a report from the T1D Exchange, in which nearly half of 33 patients with type 1 diabetes and COVID-19 had been hospitalized with DKA. The reason for the discrepancy may be that more severe patients would more likely be referred to the T1D Exchange Registry, Dr. Gregory and colleagues hypothesized.
Clinical factors associated with COVID-19 severity (P < .05) in their study included a prior hypertension diagnosis, higher hemoglobin A1c, at least one prior DKA admission in the past year, and not using a continuous glucose monitor (CGM).
Hospitalizations were twice as likely and illness severity nearly twice as great among those with type 1 diabetes who were Black versus White. Just 8% of those with private insurance were hospitalized, compared with 60% of those with public insurance and 67% with no insurance (P = .001).
“Whereas previous reports have indicated proportionally higher rates of hospitalizations from COVID-19 among Black patients and those with public insurance, this study is the first to show a similar finding in the population with type 1 diabetes,” Dr. Gregory and colleagues wrote.
Only 9% of patients using a CGM were hospitalized versus 47% who used blood glucose meters (P < .016). Similarly, hospitalizations occurred in 6% using an insulin pump versus 33% using multiple daily injections (P < .085).
“Our analysis cannot exclude the possibility that greater amounts of diabetes technology use are a surrogate for higher socioeconomic status,” they noted.
This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, JDRF, and the Appleby Foundation. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The risk for increased COVID-19 severity in people with type 1 diabetes appears similar to that of type 2 diabetes, contrary to some official advice from the Centers for Disease Control and Prevention. The new finding indicates that people with both types should be priority for receiving a vaccine, investigators say.
The study is the first to prospectively evaluate both inpatients and outpatients and to examine COVID-19 severity factors in addition to death in people with type 1 and type 2 diabetes separately, and was published online Dec. 2 in Diabetes Care.
Among the patients, who were seen at Vanderbilt University Medical Center in Nashville, Tenn., between March and August of 2020, those with both type 1 and type 2 diabetes had between a three- and fourfold greater risk for COVID-19 hospitalization and greater illness severity compared with people without diabetes after adjustments for age, race, and a number of other risk factors.
This finding is important since as of Dec. 1, 2020, the CDC has classified the diabetes types differently in terms of underlying medical conditions that increase the risk for severe COVID-19.
Adults of any age with type 2 diabetes are considered “at increased risk of severe illness” from the virus that causes COVID-19 whereas the CDC says those with type 1 “might be at an increased risk.”
Lead author of the new paper Justin M. Gregory, MD, said in an interview: “I think this needs revision based on the current evidence. I think the data presented in our study and that of Barron et al. in Lancet Endocrinology 2020 indicate the need to place type 1 diabetes at parity with type 2 diabetes.
“These studies indicate both conditions carry an adjusted odds ratio of three to four when compared with people without diabetes for hospitalization, illness severity, and mortality,” he stressed.
Vaccines look promising for patients with diabetes
There were no phase 3 vaccine data available for the vaccine at the time that Dr. Gregory, of the Ian M. Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University, Nashville, Tenn., and colleagues were writing their manuscript in late summer, so the article does not mention this.
But now, Dr. Gregory said, “Based on the initial press releases from Pfizer and Moderna, I am now optimistic that these vaccines might mitigate the excess morbidity and mortality from COVID-19 experienced by patients with diabetes.
“I am eager to see what we learn on December 10 and 17 [the scheduled dates for the meetings of the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee to review the Pfizer and Moderna vaccines, respectively].”
But with the winter pandemic surge in the meantime, “Our investigation suggests that as COVID-19 hospitalizations rise, patients with both type 1 and 2 diabetes will comprise a disproportionately higher number of those admissions and, once hospitalized, demonstrate a greater degree of illness severity,” he and his colleagues said.
“In light of these data, we call on our colleagues to emphasize the importance of social distancing measures and hand hygiene, with particular emphasis on patients with diabetes, including those in the most vulnerable communities whom our study affirms will face the most severe impact.”
After adjustments, excess severity risk similar for both diabetes types
The new study data came from electronic health records at Vanderbilt University Medical Center, comprising 137 primary care, urgent care, and hospital facilities where patients were tested for SARS-CoV-2 regardless of the reason for their visit.
Between March 17 and August 7, 2020, 6,451 patients tested positive for COVID-19. Of those, 273 had type 2 diabetes and 40 had type 1 diabetes.
Children younger than 18 years accounted for 20% of those with type 1 diabetes and 9.4% of those without diabetes, but none of the type 2 group. The group with type 2 diabetes was considerably older than the type 1 diabetes and no-diabetes groups, 58 years versus 37 and 33 years, respectively.
Before adjustment for baseline characteristics that differed between groups, patients with type 1 diabetes appeared to have a risk for hospitalization and greater illness severity that was intermediate between the group with no diabetes and the group with type 2 diabetes, the researchers said.
But after adjustment for age, race, sex, hypertension, smoking, and body mass index, people with type 1 diabetes had odds ratios of 3.90 for hospitalization and 3.35 for greater illness severity, which was similar to risk in type 2 diabetes (3.36 and 3.42, respectively), compared to those without diabetes.
Deep dive explores COVID-19 severity risk factors in type 1 diabetes
The investigators then conducted a detailed chart review for 37 of the 40 patients with type 1 diabetes and phone surveys with 15 of them.
The majority (28) had not been hospitalized, and only one was hospitalized for diabetic ketoacidosis (DKA) within 14 days of positive SARS-CoV-2 testing.
This contrasts with a report from the T1D Exchange, in which nearly half of 33 patients with type 1 diabetes and COVID-19 had been hospitalized with DKA. The reason for the discrepancy may be that more severe patients would more likely be referred to the T1D Exchange Registry, Dr. Gregory and colleagues hypothesized.
Clinical factors associated with COVID-19 severity (P < .05) in their study included a prior hypertension diagnosis, higher hemoglobin A1c, at least one prior DKA admission in the past year, and not using a continuous glucose monitor (CGM).
Hospitalizations were twice as likely and illness severity nearly twice as great among those with type 1 diabetes who were Black versus White. Just 8% of those with private insurance were hospitalized, compared with 60% of those with public insurance and 67% with no insurance (P = .001).
“Whereas previous reports have indicated proportionally higher rates of hospitalizations from COVID-19 among Black patients and those with public insurance, this study is the first to show a similar finding in the population with type 1 diabetes,” Dr. Gregory and colleagues wrote.
Only 9% of patients using a CGM were hospitalized versus 47% who used blood glucose meters (P < .016). Similarly, hospitalizations occurred in 6% using an insulin pump versus 33% using multiple daily injections (P < .085).
“Our analysis cannot exclude the possibility that greater amounts of diabetes technology use are a surrogate for higher socioeconomic status,” they noted.
This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, JDRF, and the Appleby Foundation. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The risk for increased COVID-19 severity in people with type 1 diabetes appears similar to that of type 2 diabetes, contrary to some official advice from the Centers for Disease Control and Prevention. The new finding indicates that people with both types should be priority for receiving a vaccine, investigators say.
The study is the first to prospectively evaluate both inpatients and outpatients and to examine COVID-19 severity factors in addition to death in people with type 1 and type 2 diabetes separately, and was published online Dec. 2 in Diabetes Care.
Among the patients, who were seen at Vanderbilt University Medical Center in Nashville, Tenn., between March and August of 2020, those with both type 1 and type 2 diabetes had between a three- and fourfold greater risk for COVID-19 hospitalization and greater illness severity compared with people without diabetes after adjustments for age, race, and a number of other risk factors.
This finding is important since as of Dec. 1, 2020, the CDC has classified the diabetes types differently in terms of underlying medical conditions that increase the risk for severe COVID-19.
Adults of any age with type 2 diabetes are considered “at increased risk of severe illness” from the virus that causes COVID-19 whereas the CDC says those with type 1 “might be at an increased risk.”
Lead author of the new paper Justin M. Gregory, MD, said in an interview: “I think this needs revision based on the current evidence. I think the data presented in our study and that of Barron et al. in Lancet Endocrinology 2020 indicate the need to place type 1 diabetes at parity with type 2 diabetes.
“These studies indicate both conditions carry an adjusted odds ratio of three to four when compared with people without diabetes for hospitalization, illness severity, and mortality,” he stressed.
Vaccines look promising for patients with diabetes
There were no phase 3 vaccine data available for the vaccine at the time that Dr. Gregory, of the Ian M. Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University, Nashville, Tenn., and colleagues were writing their manuscript in late summer, so the article does not mention this.
But now, Dr. Gregory said, “Based on the initial press releases from Pfizer and Moderna, I am now optimistic that these vaccines might mitigate the excess morbidity and mortality from COVID-19 experienced by patients with diabetes.
“I am eager to see what we learn on December 10 and 17 [the scheduled dates for the meetings of the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee to review the Pfizer and Moderna vaccines, respectively].”
But with the winter pandemic surge in the meantime, “Our investigation suggests that as COVID-19 hospitalizations rise, patients with both type 1 and 2 diabetes will comprise a disproportionately higher number of those admissions and, once hospitalized, demonstrate a greater degree of illness severity,” he and his colleagues said.
“In light of these data, we call on our colleagues to emphasize the importance of social distancing measures and hand hygiene, with particular emphasis on patients with diabetes, including those in the most vulnerable communities whom our study affirms will face the most severe impact.”
After adjustments, excess severity risk similar for both diabetes types
The new study data came from electronic health records at Vanderbilt University Medical Center, comprising 137 primary care, urgent care, and hospital facilities where patients were tested for SARS-CoV-2 regardless of the reason for their visit.
Between March 17 and August 7, 2020, 6,451 patients tested positive for COVID-19. Of those, 273 had type 2 diabetes and 40 had type 1 diabetes.
Children younger than 18 years accounted for 20% of those with type 1 diabetes and 9.4% of those without diabetes, but none of the type 2 group. The group with type 2 diabetes was considerably older than the type 1 diabetes and no-diabetes groups, 58 years versus 37 and 33 years, respectively.
Before adjustment for baseline characteristics that differed between groups, patients with type 1 diabetes appeared to have a risk for hospitalization and greater illness severity that was intermediate between the group with no diabetes and the group with type 2 diabetes, the researchers said.
But after adjustment for age, race, sex, hypertension, smoking, and body mass index, people with type 1 diabetes had odds ratios of 3.90 for hospitalization and 3.35 for greater illness severity, which was similar to risk in type 2 diabetes (3.36 and 3.42, respectively), compared to those without diabetes.
Deep dive explores COVID-19 severity risk factors in type 1 diabetes
The investigators then conducted a detailed chart review for 37 of the 40 patients with type 1 diabetes and phone surveys with 15 of them.
The majority (28) had not been hospitalized, and only one was hospitalized for diabetic ketoacidosis (DKA) within 14 days of positive SARS-CoV-2 testing.
This contrasts with a report from the T1D Exchange, in which nearly half of 33 patients with type 1 diabetes and COVID-19 had been hospitalized with DKA. The reason for the discrepancy may be that more severe patients would more likely be referred to the T1D Exchange Registry, Dr. Gregory and colleagues hypothesized.
Clinical factors associated with COVID-19 severity (P < .05) in their study included a prior hypertension diagnosis, higher hemoglobin A1c, at least one prior DKA admission in the past year, and not using a continuous glucose monitor (CGM).
Hospitalizations were twice as likely and illness severity nearly twice as great among those with type 1 diabetes who were Black versus White. Just 8% of those with private insurance were hospitalized, compared with 60% of those with public insurance and 67% with no insurance (P = .001).
“Whereas previous reports have indicated proportionally higher rates of hospitalizations from COVID-19 among Black patients and those with public insurance, this study is the first to show a similar finding in the population with type 1 diabetes,” Dr. Gregory and colleagues wrote.
Only 9% of patients using a CGM were hospitalized versus 47% who used blood glucose meters (P < .016). Similarly, hospitalizations occurred in 6% using an insulin pump versus 33% using multiple daily injections (P < .085).
“Our analysis cannot exclude the possibility that greater amounts of diabetes technology use are a surrogate for higher socioeconomic status,” they noted.
This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, JDRF, and the Appleby Foundation. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.