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Sedentary individuals have a significant increase in a marker of subclinical heart disease, according to a recent study. Each additional hour spent seated per day was associated with a 14% increase in the amount of coronary artery calcification seen on CT imaging.

Even for those who exercise vigorously but also spend many hours sitting, prolonged sedentary activity was independently associated with greater CAC. The effect held true even after adjustment for other known cardiac risk factors, according to Dr. Jacquelyn Kulinski of the Medical College of Wisconsin, Milwaukee, and colleagues at Dallas’ University of Texas Southwestern Medical Center. The results were released in advance of their presentation on March 15 at the annual meeting of the American College of Cardiology in San Diego.

Purestock/Thinkstock.com

Using data from wrist accelerometers in the Dallas Heart Study, a multi-ethnic, population-based sample of adults residing in Dallas, Tex., Dr. Kulinski and colleagues assessed the activity of 2,031 participants without known cardiovascular disease. The median age was 50, about 62% were female, and about half of the participants were black.

The accelerometer, worn on the nondominant hand, captured 7 consecutive days of minute-by-minute activity, and could differentiate between sedentary behavior (sitting or reclining during waking hours), nonexercise activity (such as light movement around the house or a workplace), and more vigorous, purposeful exercise. CAC was assessed via two cardiac CT scans and a standardized scoring system.

Overall, participants had an average 5 hours of sedentary time per day, with a range of 2-12 hours. Higher amounts of sedentary time were associated with being older, having a higher body mass index, and having diabetes or hypertension.

The multivariate analysis included adjustments for patient demographics, clinical characteristics, and the amount to which participants participated in moderate to vigorous physical activity. The researchers found that each additional hour of sedentary time during the day was associated with a statistically significant, 14% increase in CAC. Somewhat surprisingly, Dr. Kulinski noted, there was no association between the amount of moderate to vigorous physical activity and the amount of CAC detected.

Sedentary behavior, sometimes called “sitting disease,” has previously been identified as an independent risk factor for heart disease. These findings, she said, further bolster the concept that “lack of exercise and too much sitting are independent risk factors for CAD and death.”

Dr. Kulinski noted that although fitness is one of the strongest predictors of cardiac health and longevity, there has not been a clear demonstration that increased amounts of exercise are associated with less CAC. This has been true although CAC is an established marker of early formation of the plaque that can lead to coronary artery blockage. The present study suggests that sedentary behaviors, rather than lack of vigorous exercise, may contribute more to the development of CAC than had previously been known.

ACC Vice President Richard Chazal of Lee Memorial Health System, Fort Myers, Fla., remarked in a press briefing before the meeting that this information should be reassuring to patients. “Sometimes just moving around some, even short of a vigorous exercise program, is important,” said Dr. Chazal. “Regular exercise further reduces risk, and it may do so by a mechanism distinct from coronary artery calcification.”

“On a positive note,” Dr. Kulinski said, “reducing daily sitting time by even 1-2 hours could have a significant and positive impact on future cardiovascular health, and this should really be investigated in future studies.”

Dr. James de Lemos disclosed ties with Amgen, DiaDexus, Novo Nordisk, St. Jude Medical, Abbott Diagnostics, and Siemen’s Diagnostics. Dr. Jarrett Berry reports ties with Nihon and Merck. The remaining authors have no disclosures.

Sedentary individuals have a significant increase in a marker of subclinical heart disease, according to a recent study. Each additional hour spent seated per day was associated with a 14% increase in the amount of coronary artery calcification seen on CT imaging.

Even for those who exercise vigorously but also spend many hours sitting, prolonged sedentary activity was independently associated with greater CAC. The effect held true even after adjustment for other known cardiac risk factors, according to Dr. Jacquelyn Kulinski of the Medical College of Wisconsin, Milwaukee, and colleagues at Dallas’ University of Texas Southwestern Medical Center. The results were released in advance of their presentation on March 15 at the annual meeting of the American College of Cardiology in San Diego.

Purestock/Thinkstock.com

Using data from wrist accelerometers in the Dallas Heart Study, a multi-ethnic, population-based sample of adults residing in Dallas, Tex., Dr. Kulinski and colleagues assessed the activity of 2,031 participants without known cardiovascular disease. The median age was 50, about 62% were female, and about half of the participants were black.

The accelerometer, worn on the nondominant hand, captured 7 consecutive days of minute-by-minute activity, and could differentiate between sedentary behavior (sitting or reclining during waking hours), nonexercise activity (such as light movement around the house or a workplace), and more vigorous, purposeful exercise. CAC was assessed via two cardiac CT scans and a standardized scoring system.

Overall, participants had an average 5 hours of sedentary time per day, with a range of 2-12 hours. Higher amounts of sedentary time were associated with being older, having a higher body mass index, and having diabetes or hypertension.

The multivariate analysis included adjustments for patient demographics, clinical characteristics, and the amount to which participants participated in moderate to vigorous physical activity. The researchers found that each additional hour of sedentary time during the day was associated with a statistically significant, 14% increase in CAC. Somewhat surprisingly, Dr. Kulinski noted, there was no association between the amount of moderate to vigorous physical activity and the amount of CAC detected.

Sedentary behavior, sometimes called “sitting disease,” has previously been identified as an independent risk factor for heart disease. These findings, she said, further bolster the concept that “lack of exercise and too much sitting are independent risk factors for CAD and death.”

Dr. Kulinski noted that although fitness is one of the strongest predictors of cardiac health and longevity, there has not been a clear demonstration that increased amounts of exercise are associated with less CAC. This has been true although CAC is an established marker of early formation of the plaque that can lead to coronary artery blockage. The present study suggests that sedentary behaviors, rather than lack of vigorous exercise, may contribute more to the development of CAC than had previously been known.

ACC Vice President Richard Chazal of Lee Memorial Health System, Fort Myers, Fla., remarked in a press briefing before the meeting that this information should be reassuring to patients. “Sometimes just moving around some, even short of a vigorous exercise program, is important,” said Dr. Chazal. “Regular exercise further reduces risk, and it may do so by a mechanism distinct from coronary artery calcification.”

“On a positive note,” Dr. Kulinski said, “reducing daily sitting time by even 1-2 hours could have a significant and positive impact on future cardiovascular health, and this should really be investigated in future studies.”

Dr. James de Lemos disclosed ties with Amgen, DiaDexus, Novo Nordisk, St. Jude Medical, Abbott Diagnostics, and Siemen’s Diagnostics. Dr. Jarrett Berry reports ties with Nihon and Merck. The remaining authors have no disclosures.

Sedentary individuals have a significant increase in a marker of subclinical heart disease, according to a recent study. Each additional hour spent seated per day was associated with a 14% increase in the amount of coronary artery calcification seen on CT imaging.

Even for those who exercise vigorously but also spend many hours sitting, prolonged sedentary activity was independently associated with greater CAC. The effect held true even after adjustment for other known cardiac risk factors, according to Dr. Jacquelyn Kulinski of the Medical College of Wisconsin, Milwaukee, and colleagues at Dallas’ University of Texas Southwestern Medical Center. The results were released in advance of their presentation on March 15 at the annual meeting of the American College of Cardiology in San Diego.

Purestock/Thinkstock.com

Using data from wrist accelerometers in the Dallas Heart Study, a multi-ethnic, population-based sample of adults residing in Dallas, Tex., Dr. Kulinski and colleagues assessed the activity of 2,031 participants without known cardiovascular disease. The median age was 50, about 62% were female, and about half of the participants were black.

The accelerometer, worn on the nondominant hand, captured 7 consecutive days of minute-by-minute activity, and could differentiate between sedentary behavior (sitting or reclining during waking hours), nonexercise activity (such as light movement around the house or a workplace), and more vigorous, purposeful exercise. CAC was assessed via two cardiac CT scans and a standardized scoring system.

Overall, participants had an average 5 hours of sedentary time per day, with a range of 2-12 hours. Higher amounts of sedentary time were associated with being older, having a higher body mass index, and having diabetes or hypertension.

The multivariate analysis included adjustments for patient demographics, clinical characteristics, and the amount to which participants participated in moderate to vigorous physical activity. The researchers found that each additional hour of sedentary time during the day was associated with a statistically significant, 14% increase in CAC. Somewhat surprisingly, Dr. Kulinski noted, there was no association between the amount of moderate to vigorous physical activity and the amount of CAC detected.

Sedentary behavior, sometimes called “sitting disease,” has previously been identified as an independent risk factor for heart disease. These findings, she said, further bolster the concept that “lack of exercise and too much sitting are independent risk factors for CAD and death.”

Dr. Kulinski noted that although fitness is one of the strongest predictors of cardiac health and longevity, there has not been a clear demonstration that increased amounts of exercise are associated with less CAC. This has been true although CAC is an established marker of early formation of the plaque that can lead to coronary artery blockage. The present study suggests that sedentary behaviors, rather than lack of vigorous exercise, may contribute more to the development of CAC than had previously been known.

ACC Vice President Richard Chazal of Lee Memorial Health System, Fort Myers, Fla., remarked in a press briefing before the meeting that this information should be reassuring to patients. “Sometimes just moving around some, even short of a vigorous exercise program, is important,” said Dr. Chazal. “Regular exercise further reduces risk, and it may do so by a mechanism distinct from coronary artery calcification.”

“On a positive note,” Dr. Kulinski said, “reducing daily sitting time by even 1-2 hours could have a significant and positive impact on future cardiovascular health, and this should really be investigated in future studies.”

Dr. James de Lemos disclosed ties with Amgen, DiaDexus, Novo Nordisk, St. Jude Medical, Abbott Diagnostics, and Siemen’s Diagnostics. Dr. Jarrett Berry reports ties with Nihon and Merck. The remaining authors have no disclosures.

Balancing blood sugar in any hospitalized patient can be a tightrope walk, but it is especially challenging when patients can’t eat or are taking steroids.

These patients need a proactive approach that prevents both hyper- and hypoglycemia, both of which have long been tied to poorer outcomes in critically ill patients, Dr. Mary Korytkowski said at the annual advanced postgraduate course held by the American Diabetes Association.

All hospitalized patients should have a blood glucose test on admission. This baseline measure will determine in-hospital glycemic management, which can be fairly straightforward as long as patients are eating regularly. Things get tricky if patients can’t take any food orally and need enteral or parenteral nutrition. Glucocorticoids can also wreak havoc on blood sugars, even in nondiabetic patients.

“There is no question that [blood sugar extremes] impact outcomes, whether or not the patient has [a history of] diabetes,” said Dr. Korytkowski of the University of Pittsburgh. “The question is, what do we do about it?”

The NICE-SUGAR study determined that low-end blood sugar targets may actually be dangerous for hospitalized patients. Since its publication in 2012, glycemic goals have been increased. For non–critically ill patients, a pre-meal blood glucose level should be somewhere between 100-140 mg/dL. For critically ill patients, the goal is more generous at 110-180 mg/dL. Management should aim to sustain those levels, with as few out-of-goal fluctuations as possible.

Patients who have diabetes and are NPO (nothing by mouth) should have their scheduled nutritional insulin held, and their glucose levels maintained with basal and correction insulin, Dr. Korytkowski said. The dose of insulin glargine or insulin detemir will have to be decreased by up to 40% to stay within target; the dose of NPH insulin will probably have to be decreased by 30%-50%.

Those who are converted to NPO after getting their full insulin dose should then be put on a 5% or 10% dextrose solution, which should continue as long as they are getting insulin. “We have this written into our standing orders now,” Dr. Korytkowski said. Of course, routine blood glucose monitoring is essential here.

All patients who receive enteral or parenteral nutrition need a baseline blood glucose level and point-of-care testing regardless of their diabetes history. For those without diabetes, testing can be discontinued if blood glucose stays below 140 mg/dL for 48 hours without insulin.

Those with diabetes should get basal insulin twice a day in addition to their normal regimen, plus correction insulin doses as needed. If this regimen stabilizes glucose at 140-180 mg/dL, it can continue. If levels are above 180 mg/dL on at least two measurements within 24 hours, then adding 25%-50% to the correction insulin dose, along with the scheduled insulin, is indicated.

Steroid diabetes is not uncommon among patients who have been getting glucocorticoids for an extended time, such as those with chronic inflammatory disorders. Steroids oppose insulin action and stimulate gluconeogenesis, leading to an increase in hepatic glucose output. NPH insulin is indicated for these patients. A suggested schedule is 0.1 unit of NPH insulin for every 10 mg prednisone. For example, 0.4 U/kg per day for 40 mg prednisone; 0.3 U/kg per day for 30 mg, and so on.

Dr. Korytkowski disclosed that she is a consultant for Sanofi-Aventis.

[email protected]

On Twitter @alz_gal

Balancing blood sugar in any hospitalized patient can be a tightrope walk, but it is especially challenging when patients can’t eat or are taking steroids.

These patients need a proactive approach that prevents both hyper- and hypoglycemia, both of which have long been tied to poorer outcomes in critically ill patients, Dr. Mary Korytkowski said at the annual advanced postgraduate course held by the American Diabetes Association.

All hospitalized patients should have a blood glucose test on admission. This baseline measure will determine in-hospital glycemic management, which can be fairly straightforward as long as patients are eating regularly. Things get tricky if patients can’t take any food orally and need enteral or parenteral nutrition. Glucocorticoids can also wreak havoc on blood sugars, even in nondiabetic patients.

“There is no question that [blood sugar extremes] impact outcomes, whether or not the patient has [a history of] diabetes,” said Dr. Korytkowski of the University of Pittsburgh. “The question is, what do we do about it?”

The NICE-SUGAR study determined that low-end blood sugar targets may actually be dangerous for hospitalized patients. Since its publication in 2012, glycemic goals have been increased. For non–critically ill patients, a pre-meal blood glucose level should be somewhere between 100-140 mg/dL. For critically ill patients, the goal is more generous at 110-180 mg/dL. Management should aim to sustain those levels, with as few out-of-goal fluctuations as possible.

Patients who have diabetes and are NPO (nothing by mouth) should have their scheduled nutritional insulin held, and their glucose levels maintained with basal and correction insulin, Dr. Korytkowski said. The dose of insulin glargine or insulin detemir will have to be decreased by up to 40% to stay within target; the dose of NPH insulin will probably have to be decreased by 30%-50%.

Those who are converted to NPO after getting their full insulin dose should then be put on a 5% or 10% dextrose solution, which should continue as long as they are getting insulin. “We have this written into our standing orders now,” Dr. Korytkowski said. Of course, routine blood glucose monitoring is essential here.

All patients who receive enteral or parenteral nutrition need a baseline blood glucose level and point-of-care testing regardless of their diabetes history. For those without diabetes, testing can be discontinued if blood glucose stays below 140 mg/dL for 48 hours without insulin.

Those with diabetes should get basal insulin twice a day in addition to their normal regimen, plus correction insulin doses as needed. If this regimen stabilizes glucose at 140-180 mg/dL, it can continue. If levels are above 180 mg/dL on at least two measurements within 24 hours, then adding 25%-50% to the correction insulin dose, along with the scheduled insulin, is indicated.

Steroid diabetes is not uncommon among patients who have been getting glucocorticoids for an extended time, such as those with chronic inflammatory disorders. Steroids oppose insulin action and stimulate gluconeogenesis, leading to an increase in hepatic glucose output. NPH insulin is indicated for these patients. A suggested schedule is 0.1 unit of NPH insulin for every 10 mg prednisone. For example, 0.4 U/kg per day for 40 mg prednisone; 0.3 U/kg per day for 30 mg, and so on.

Dr. Korytkowski disclosed that she is a consultant for Sanofi-Aventis.

[email protected]

On Twitter @alz_gal

Balancing blood sugar in any hospitalized patient can be a tightrope walk, but it is especially challenging when patients can’t eat or are taking steroids.

These patients need a proactive approach that prevents both hyper- and hypoglycemia, both of which have long been tied to poorer outcomes in critically ill patients, Dr. Mary Korytkowski said at the annual advanced postgraduate course held by the American Diabetes Association.

All hospitalized patients should have a blood glucose test on admission. This baseline measure will determine in-hospital glycemic management, which can be fairly straightforward as long as patients are eating regularly. Things get tricky if patients can’t take any food orally and need enteral or parenteral nutrition. Glucocorticoids can also wreak havoc on blood sugars, even in nondiabetic patients.

“There is no question that [blood sugar extremes] impact outcomes, whether or not the patient has [a history of] diabetes,” said Dr. Korytkowski of the University of Pittsburgh. “The question is, what do we do about it?”

The NICE-SUGAR study determined that low-end blood sugar targets may actually be dangerous for hospitalized patients. Since its publication in 2012, glycemic goals have been increased. For non–critically ill patients, a pre-meal blood glucose level should be somewhere between 100-140 mg/dL. For critically ill patients, the goal is more generous at 110-180 mg/dL. Management should aim to sustain those levels, with as few out-of-goal fluctuations as possible.

Patients who have diabetes and are NPO (nothing by mouth) should have their scheduled nutritional insulin held, and their glucose levels maintained with basal and correction insulin, Dr. Korytkowski said. The dose of insulin glargine or insulin detemir will have to be decreased by up to 40% to stay within target; the dose of NPH insulin will probably have to be decreased by 30%-50%.

Those who are converted to NPO after getting their full insulin dose should then be put on a 5% or 10% dextrose solution, which should continue as long as they are getting insulin. “We have this written into our standing orders now,” Dr. Korytkowski said. Of course, routine blood glucose monitoring is essential here.

All patients who receive enteral or parenteral nutrition need a baseline blood glucose level and point-of-care testing regardless of their diabetes history. For those without diabetes, testing can be discontinued if blood glucose stays below 140 mg/dL for 48 hours without insulin.

Those with diabetes should get basal insulin twice a day in addition to their normal regimen, plus correction insulin doses as needed. If this regimen stabilizes glucose at 140-180 mg/dL, it can continue. If levels are above 180 mg/dL on at least two measurements within 24 hours, then adding 25%-50% to the correction insulin dose, along with the scheduled insulin, is indicated.

Steroid diabetes is not uncommon among patients who have been getting glucocorticoids for an extended time, such as those with chronic inflammatory disorders. Steroids oppose insulin action and stimulate gluconeogenesis, leading to an increase in hepatic glucose output. NPH insulin is indicated for these patients. A suggested schedule is 0.1 unit of NPH insulin for every 10 mg prednisone. For example, 0.4 U/kg per day for 40 mg prednisone; 0.3 U/kg per day for 30 mg, and so on.

Dr. Korytkowski disclosed that she is a consultant for Sanofi-Aventis.

[email protected]

On Twitter @alz_gal

NEW YORK–Incretin-based diabetes medications may not be as harmful to the pancreas as previously feared.

Emerging clinical data, combined with concerns about the accuracy of polyclonal GLP-1 receptor antibody staining, suggest that there may be little to no risk for either treatment-related pancreatitis or pancreatic cancer in patients with diabetes, Dr. Vanita R. Aroda said at the annual advanced postgraduate course held by the American Diabetes Association.

“No study has definitely concluded that there is a causal link, and but we should still keep the risk as something to at least be aware of,” said Dr. Aroda of the MedStar Research Institute, Hyattsville, Md. “Until we have more information, patients who have pancreatic risk factors probably shouldn’t receive the drugs.”

A number of confounders cast doubt on past studies showing a pathologic association between incretins and pancreatic adverse events. Although there are suggestive clinical data, preclinical data based on GLP-1 receptor staining is unreliable, because the polyclonal antibodies generally used don’t consistently stain GLP-1 transfected cells.

“In nontransfected cells, you would expect to see no uptake, but with two of the antibodies, you see quite a bit of uptake in nontransfected as well as transfected cells.”

A third polyclonal antibody has difficulty showing uptake in either type of cell. Only one, the monoclonal 3F52 antibody released in 2013, seems to reliably differentiate GLP1 receptors in these models.

In Dr. Aroda’s opinion, the more reliable results from the monoclonal antibody cast much doubt on all previous preclinical studies that used the polyclonal antibodies.

Nonrandomized data based on case reporting also add to the uncertainty, she said. Data in the Food and Drug Administration’s adverse events reporting system have shown a five- to six-time increased risk of incretin-associated pancreatitis and pancreatic cancer, but “even the FDA has said that spontaneous reports cannot be used to determine the true incidence rates of drug adverse events.” Issues of underreporting, lack of established background rates, and inadequate documentation of clinical details (comorbidities, concomitant medications, and medication errors) cloud the picture. Clarity will remain uncertain as long as decisions about safety are made based on such data.

Similar problems plague studies of discharge data, reflected in the fact that many of them have come to conflicting determinations. The most recent data, however, come from a meta-analysis comprising more than 1.3 million patients among nine insurance claims databases in North America and the European Union. The analysis found no increased risk of acute pancreatitis and any incretin-based therapy (Diabetes Obes. Metab. 2015;17:32-41).

Another recent meta-analysis showed that the adjusted risk of acute pancreatitis was not increased among Danes who had been treated with an incretin drug (Diabetes Care 2015 [doi:10.2337/dc13-2983])

A 2013 study of brain-dead organ donors did find a 40% increased pancreatic mass in diabetes patients treated with incretin therapy, compared to those who didn’t get it and to control patients. Treated patients also over-expressed both exocrine cell proliferation and pancreatic intraepithelial neoplasia (Diabetes 2013;62:2595-604).

“This study has been analyzed and reanalyzed,” Dr. Aroda said. “But it’s really comparing apples to oranges. Five patients with diabetes weren’t on any medication; four were on insulin and four on metformin only; and seven were on two or more agents. Age ranged from 40 to 58 years, and we know age is a big risk factor here.”

Dr. Aroda also examined individual drugs in her own extensive patient database. She found no differences in pancreatitis or cancer associated with liraglutide, exenatide, lixisenatide, or sitagliptin.

The European Medicines Agency is conducting a large evaluation of cardiovascular, cerebrovascular, renal and pancreatic events among diabetes patients taking noninsulin glucose-lowering agents.(SAFEGUARD). It will include combined data covering more than 240 million patient/years.

The National Institutes of Health is also looking at the issue with a consortium study of chronic pancreatitis and pancreatic cancer in diabetes patients.

These projects should result in a considerable amount of reliable data on the issue, Dr. Aroda said.

In the meantime, neither the American Diabetes Association, the Endocrine Society or any European agencies have changed their treatment guidelines with regard to incretin-based therapies.

Dr. Aroda had no financial disclosures.

[email protected]

On Twitter @alz_gal

NEW YORK–Incretin-based diabetes medications may not be as harmful to the pancreas as previously feared.

Emerging clinical data, combined with concerns about the accuracy of polyclonal GLP-1 receptor antibody staining, suggest that there may be little to no risk for either treatment-related pancreatitis or pancreatic cancer in patients with diabetes, Dr. Vanita R. Aroda said at the annual advanced postgraduate course held by the American Diabetes Association.

“No study has definitely concluded that there is a causal link, and but we should still keep the risk as something to at least be aware of,” said Dr. Aroda of the MedStar Research Institute, Hyattsville, Md. “Until we have more information, patients who have pancreatic risk factors probably shouldn’t receive the drugs.”

A number of confounders cast doubt on past studies showing a pathologic association between incretins and pancreatic adverse events. Although there are suggestive clinical data, preclinical data based on GLP-1 receptor staining is unreliable, because the polyclonal antibodies generally used don’t consistently stain GLP-1 transfected cells.

“In nontransfected cells, you would expect to see no uptake, but with two of the antibodies, you see quite a bit of uptake in nontransfected as well as transfected cells.”

A third polyclonal antibody has difficulty showing uptake in either type of cell. Only one, the monoclonal 3F52 antibody released in 2013, seems to reliably differentiate GLP1 receptors in these models.

In Dr. Aroda’s opinion, the more reliable results from the monoclonal antibody cast much doubt on all previous preclinical studies that used the polyclonal antibodies.

Nonrandomized data based on case reporting also add to the uncertainty, she said. Data in the Food and Drug Administration’s adverse events reporting system have shown a five- to six-time increased risk of incretin-associated pancreatitis and pancreatic cancer, but “even the FDA has said that spontaneous reports cannot be used to determine the true incidence rates of drug adverse events.” Issues of underreporting, lack of established background rates, and inadequate documentation of clinical details (comorbidities, concomitant medications, and medication errors) cloud the picture. Clarity will remain uncertain as long as decisions about safety are made based on such data.

Similar problems plague studies of discharge data, reflected in the fact that many of them have come to conflicting determinations. The most recent data, however, come from a meta-analysis comprising more than 1.3 million patients among nine insurance claims databases in North America and the European Union. The analysis found no increased risk of acute pancreatitis and any incretin-based therapy (Diabetes Obes. Metab. 2015;17:32-41).

Another recent meta-analysis showed that the adjusted risk of acute pancreatitis was not increased among Danes who had been treated with an incretin drug (Diabetes Care 2015 [doi:10.2337/dc13-2983])

A 2013 study of brain-dead organ donors did find a 40% increased pancreatic mass in diabetes patients treated with incretin therapy, compared to those who didn’t get it and to control patients. Treated patients also over-expressed both exocrine cell proliferation and pancreatic intraepithelial neoplasia (Diabetes 2013;62:2595-604).

“This study has been analyzed and reanalyzed,” Dr. Aroda said. “But it’s really comparing apples to oranges. Five patients with diabetes weren’t on any medication; four were on insulin and four on metformin only; and seven were on two or more agents. Age ranged from 40 to 58 years, and we know age is a big risk factor here.”

Dr. Aroda also examined individual drugs in her own extensive patient database. She found no differences in pancreatitis or cancer associated with liraglutide, exenatide, lixisenatide, or sitagliptin.

The European Medicines Agency is conducting a large evaluation of cardiovascular, cerebrovascular, renal and pancreatic events among diabetes patients taking noninsulin glucose-lowering agents.(SAFEGUARD). It will include combined data covering more than 240 million patient/years.

The National Institutes of Health is also looking at the issue with a consortium study of chronic pancreatitis and pancreatic cancer in diabetes patients.

These projects should result in a considerable amount of reliable data on the issue, Dr. Aroda said.

In the meantime, neither the American Diabetes Association, the Endocrine Society or any European agencies have changed their treatment guidelines with regard to incretin-based therapies.

Dr. Aroda had no financial disclosures.

[email protected]

On Twitter @alz_gal

NEW YORK–Incretin-based diabetes medications may not be as harmful to the pancreas as previously feared.

Emerging clinical data, combined with concerns about the accuracy of polyclonal GLP-1 receptor antibody staining, suggest that there may be little to no risk for either treatment-related pancreatitis or pancreatic cancer in patients with diabetes, Dr. Vanita R. Aroda said at the annual advanced postgraduate course held by the American Diabetes Association.

“No study has definitely concluded that there is a causal link, and but we should still keep the risk as something to at least be aware of,” said Dr. Aroda of the MedStar Research Institute, Hyattsville, Md. “Until we have more information, patients who have pancreatic risk factors probably shouldn’t receive the drugs.”

A number of confounders cast doubt on past studies showing a pathologic association between incretins and pancreatic adverse events. Although there are suggestive clinical data, preclinical data based on GLP-1 receptor staining is unreliable, because the polyclonal antibodies generally used don’t consistently stain GLP-1 transfected cells.

“In nontransfected cells, you would expect to see no uptake, but with two of the antibodies, you see quite a bit of uptake in nontransfected as well as transfected cells.”

A third polyclonal antibody has difficulty showing uptake in either type of cell. Only one, the monoclonal 3F52 antibody released in 2013, seems to reliably differentiate GLP1 receptors in these models.

In Dr. Aroda’s opinion, the more reliable results from the monoclonal antibody cast much doubt on all previous preclinical studies that used the polyclonal antibodies.

Nonrandomized data based on case reporting also add to the uncertainty, she said. Data in the Food and Drug Administration’s adverse events reporting system have shown a five- to six-time increased risk of incretin-associated pancreatitis and pancreatic cancer, but “even the FDA has said that spontaneous reports cannot be used to determine the true incidence rates of drug adverse events.” Issues of underreporting, lack of established background rates, and inadequate documentation of clinical details (comorbidities, concomitant medications, and medication errors) cloud the picture. Clarity will remain uncertain as long as decisions about safety are made based on such data.

Similar problems plague studies of discharge data, reflected in the fact that many of them have come to conflicting determinations. The most recent data, however, come from a meta-analysis comprising more than 1.3 million patients among nine insurance claims databases in North America and the European Union. The analysis found no increased risk of acute pancreatitis and any incretin-based therapy (Diabetes Obes. Metab. 2015;17:32-41).

Another recent meta-analysis showed that the adjusted risk of acute pancreatitis was not increased among Danes who had been treated with an incretin drug (Diabetes Care 2015 [doi:10.2337/dc13-2983])

A 2013 study of brain-dead organ donors did find a 40% increased pancreatic mass in diabetes patients treated with incretin therapy, compared to those who didn’t get it and to control patients. Treated patients also over-expressed both exocrine cell proliferation and pancreatic intraepithelial neoplasia (Diabetes 2013;62:2595-604).

“This study has been analyzed and reanalyzed,” Dr. Aroda said. “But it’s really comparing apples to oranges. Five patients with diabetes weren’t on any medication; four were on insulin and four on metformin only; and seven were on two or more agents. Age ranged from 40 to 58 years, and we know age is a big risk factor here.”

Dr. Aroda also examined individual drugs in her own extensive patient database. She found no differences in pancreatitis or cancer associated with liraglutide, exenatide, lixisenatide, or sitagliptin.

The European Medicines Agency is conducting a large evaluation of cardiovascular, cerebrovascular, renal and pancreatic events among diabetes patients taking noninsulin glucose-lowering agents.(SAFEGUARD). It will include combined data covering more than 240 million patient/years.

The National Institutes of Health is also looking at the issue with a consortium study of chronic pancreatitis and pancreatic cancer in diabetes patients.

These projects should result in a considerable amount of reliable data on the issue, Dr. Aroda said.

In the meantime, neither the American Diabetes Association, the Endocrine Society or any European agencies have changed their treatment guidelines with regard to incretin-based therapies.

Dr. Aroda had no financial disclosures.

[email protected]

On Twitter @alz_gal

SAN DIEGO – Encourage teens with metabolic syndrome to snack on nuts; it just might improve their health.

Investigators from the University of Texas Southwestern Medical Center, in Dallas, found that children who ate 12.9 g of nuts per day – the equivalent of a small handful of peanuts, almonds, walnuts, and the like 3 times a week – had less than half the risk of metabolic syndrome, compared with those who did not, when age, sex, race, household income, and daily intake of sugar, fruits, and vegetables were controlled for (odds ratio, 0.43; 95% confidence interval, 0.20-0.92). The benefit persisted up to about 50 g/day, then tapered off, perhaps because the extra calories offset the metabolic benefit.

Adolescents who ate nuts a few times a week also had lower body mass index z scores, smaller waists, lower systolic blood pressure, and higher HDL cholesterol levels. Similar benefits have been found in adults.

The data come from the 2003-2010 National Health and Nutrition Examination Survey (NHANES) of 2,233 12- to 19-year-olds; nut consumption was self-reported.

Pediatrician and lead investigator Dr. Roy Kim stressed that the correlations don’t prove cause and effect. Still, he said he now encourages his patients to eat nuts. He explained why in an interview at a meeting of the Endocrine Society.

[email protected]

SAN DIEGO – Encourage teens with metabolic syndrome to snack on nuts; it just might improve their health.

Investigators from the University of Texas Southwestern Medical Center, in Dallas, found that children who ate 12.9 g of nuts per day – the equivalent of a small handful of peanuts, almonds, walnuts, and the like 3 times a week – had less than half the risk of metabolic syndrome, compared with those who did not, when age, sex, race, household income, and daily intake of sugar, fruits, and vegetables were controlled for (odds ratio, 0.43; 95% confidence interval, 0.20-0.92). The benefit persisted up to about 50 g/day, then tapered off, perhaps because the extra calories offset the metabolic benefit.

Adolescents who ate nuts a few times a week also had lower body mass index z scores, smaller waists, lower systolic blood pressure, and higher HDL cholesterol levels. Similar benefits have been found in adults.

The data come from the 2003-2010 National Health and Nutrition Examination Survey (NHANES) of 2,233 12- to 19-year-olds; nut consumption was self-reported.

Pediatrician and lead investigator Dr. Roy Kim stressed that the correlations don’t prove cause and effect. Still, he said he now encourages his patients to eat nuts. He explained why in an interview at a meeting of the Endocrine Society.

[email protected]

SAN DIEGO – Encourage teens with metabolic syndrome to snack on nuts; it just might improve their health.

Investigators from the University of Texas Southwestern Medical Center, in Dallas, found that children who ate 12.9 g of nuts per day – the equivalent of a small handful of peanuts, almonds, walnuts, and the like 3 times a week – had less than half the risk of metabolic syndrome, compared with those who did not, when age, sex, race, household income, and daily intake of sugar, fruits, and vegetables were controlled for (odds ratio, 0.43; 95% confidence interval, 0.20-0.92). The benefit persisted up to about 50 g/day, then tapered off, perhaps because the extra calories offset the metabolic benefit.

Adolescents who ate nuts a few times a week also had lower body mass index z scores, smaller waists, lower systolic blood pressure, and higher HDL cholesterol levels. Similar benefits have been found in adults.

The data come from the 2003-2010 National Health and Nutrition Examination Survey (NHANES) of 2,233 12- to 19-year-olds; nut consumption was self-reported.

Pediatrician and lead investigator Dr. Roy Kim stressed that the correlations don’t prove cause and effect. Still, he said he now encourages his patients to eat nuts. He explained why in an interview at a meeting of the Endocrine Society.

[email protected]

HUNTINGTON BEACH, CALIF. – The way pioneering researcher Dr. Mark S. Gold sees it, food addiction is akin to dependence on alcohol, nicotine, and other drugs, and the earlier clinicians intervene and treat, the better.

“The evidence that sugar and other constituents of food can be an addiction is quite good, especially if you think about binging, craving, withdrawal, cross-sensitization, increased consumption, and drive for the ‘drug’ in a classic manner,” Dr. Gold said at the annual meeting of the American College of Psychiatrists. “If you focus on dopamine, sugar and food would be a drug. There’s anticipatory dopamine release if you’re presented with dessert, even after a huge meal, for example.”

Just as gambling, sex, and work can be addicting and result in a pathologic attachment, one’s drive for certain foods can lead to loss of control and/or continued use despite serious consequences such as the development of type 2 diabetes or knee and joint disease tied to weight gain. In the case of sugar, for example, “not only does it stimulate its own taking [in the form of] self-administration, loss of self-control, and binging, it can produce withdrawal as if the person is taking opiates,” said Dr. Gold, coauthor of “Food and Addiction: A Comprehensive Handbook” (New York: Oxford University Press, 2012) and the former chair of the department of psychiatry at the University of Florida, Jacksonville. “There’s an indirect opiate effect if naloxone (Narcan) produces withdrawal after sugar self-administration.”

And while obesity is currently the nation’s No. 2 health problem behind tobacco and secondhand smoke, it will be No. 1 soon, predicted Dr. Gold, a psychiatrist who has spent more than 40 years developing models for understanding the effects of tobacco, opiates, cocaine, other drugs, and food on the brain and behavior (Physiol. Behav. 2011;104:157-61).He pointed to a recent comparison of data from the Medical Expenditure Panel Survey between 2000 and 2010, which suggests that obesity “is going to bankrupt the health system because, as compared to tobacco, where death and disability tend to occur in the last 7 years of a person’s life, obesity is an unwanted gift to the health system that keeps on giving, with type 2 diabetes and other complications,” he said. “Now, bariatric surgery is the fastest-growing operation in the United States, and it’s been successful in treating teenagers. Two-thirds of Americans now qualify for obesity treatment.”

He went on to note that Americans are “conditioned by fast food,” and cited potential addictive factors as a nutritionally imbalanced prenatal diet, child rearing, genetics, and lack of exercise. “We [Americans] eat abnormally fast,” Dr. Gold added. “Our group has shown in functional imaging that it takes about 12 minutes for a thin person’s brain to get the food signal. It takes 25 minutes for an obese person to get the signal. So if the obese person goes into a fast food restaurant” and starts eating, that person gets back in line because he’s still hungry.

When first meeting a patient with a suspected food addiction, he advises clinicians to measure the person’s body mass index and to administer the Yale Food Addiction Scale, “which is easy to use,” he said. “Think about intervening and treating people when they have a BMI of 25 or greater, rather than just when they have a pre–bariatric surgery evaluation. One size doesn’t fit all when it comes to treatment.

“It’s important to have a careful look [at what’s causing their obesity]. It could be due to a thyroid condition or to a medication they’re taking.”

In addition to early intervention, “you want cognitive-behavioral treatment, new psychopharmacologic treatment where relevant, and group treatment rather than individualized treatment alone. The food addiction model is leading to a new way of thinking and new pharmacological treatment based on addiction research.”

Dr. Gold reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

HUNTINGTON BEACH, CALIF. – The way pioneering researcher Dr. Mark S. Gold sees it, food addiction is akin to dependence on alcohol, nicotine, and other drugs, and the earlier clinicians intervene and treat, the better.

“The evidence that sugar and other constituents of food can be an addiction is quite good, especially if you think about binging, craving, withdrawal, cross-sensitization, increased consumption, and drive for the ‘drug’ in a classic manner,” Dr. Gold said at the annual meeting of the American College of Psychiatrists. “If you focus on dopamine, sugar and food would be a drug. There’s anticipatory dopamine release if you’re presented with dessert, even after a huge meal, for example.”

Just as gambling, sex, and work can be addicting and result in a pathologic attachment, one’s drive for certain foods can lead to loss of control and/or continued use despite serious consequences such as the development of type 2 diabetes or knee and joint disease tied to weight gain. In the case of sugar, for example, “not only does it stimulate its own taking [in the form of] self-administration, loss of self-control, and binging, it can produce withdrawal as if the person is taking opiates,” said Dr. Gold, coauthor of “Food and Addiction: A Comprehensive Handbook” (New York: Oxford University Press, 2012) and the former chair of the department of psychiatry at the University of Florida, Jacksonville. “There’s an indirect opiate effect if naloxone (Narcan) produces withdrawal after sugar self-administration.”

And while obesity is currently the nation’s No. 2 health problem behind tobacco and secondhand smoke, it will be No. 1 soon, predicted Dr. Gold, a psychiatrist who has spent more than 40 years developing models for understanding the effects of tobacco, opiates, cocaine, other drugs, and food on the brain and behavior (Physiol. Behav. 2011;104:157-61).He pointed to a recent comparison of data from the Medical Expenditure Panel Survey between 2000 and 2010, which suggests that obesity “is going to bankrupt the health system because, as compared to tobacco, where death and disability tend to occur in the last 7 years of a person’s life, obesity is an unwanted gift to the health system that keeps on giving, with type 2 diabetes and other complications,” he said. “Now, bariatric surgery is the fastest-growing operation in the United States, and it’s been successful in treating teenagers. Two-thirds of Americans now qualify for obesity treatment.”

He went on to note that Americans are “conditioned by fast food,” and cited potential addictive factors as a nutritionally imbalanced prenatal diet, child rearing, genetics, and lack of exercise. “We [Americans] eat abnormally fast,” Dr. Gold added. “Our group has shown in functional imaging that it takes about 12 minutes for a thin person’s brain to get the food signal. It takes 25 minutes for an obese person to get the signal. So if the obese person goes into a fast food restaurant” and starts eating, that person gets back in line because he’s still hungry.

When first meeting a patient with a suspected food addiction, he advises clinicians to measure the person’s body mass index and to administer the Yale Food Addiction Scale, “which is easy to use,” he said. “Think about intervening and treating people when they have a BMI of 25 or greater, rather than just when they have a pre–bariatric surgery evaluation. One size doesn’t fit all when it comes to treatment.

“It’s important to have a careful look [at what’s causing their obesity]. It could be due to a thyroid condition or to a medication they’re taking.”

In addition to early intervention, “you want cognitive-behavioral treatment, new psychopharmacologic treatment where relevant, and group treatment rather than individualized treatment alone. The food addiction model is leading to a new way of thinking and new pharmacological treatment based on addiction research.”

Dr. Gold reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

HUNTINGTON BEACH, CALIF. – The way pioneering researcher Dr. Mark S. Gold sees it, food addiction is akin to dependence on alcohol, nicotine, and other drugs, and the earlier clinicians intervene and treat, the better.

“The evidence that sugar and other constituents of food can be an addiction is quite good, especially if you think about binging, craving, withdrawal, cross-sensitization, increased consumption, and drive for the ‘drug’ in a classic manner,” Dr. Gold said at the annual meeting of the American College of Psychiatrists. “If you focus on dopamine, sugar and food would be a drug. There’s anticipatory dopamine release if you’re presented with dessert, even after a huge meal, for example.”

Just as gambling, sex, and work can be addicting and result in a pathologic attachment, one’s drive for certain foods can lead to loss of control and/or continued use despite serious consequences such as the development of type 2 diabetes or knee and joint disease tied to weight gain. In the case of sugar, for example, “not only does it stimulate its own taking [in the form of] self-administration, loss of self-control, and binging, it can produce withdrawal as if the person is taking opiates,” said Dr. Gold, coauthor of “Food and Addiction: A Comprehensive Handbook” (New York: Oxford University Press, 2012) and the former chair of the department of psychiatry at the University of Florida, Jacksonville. “There’s an indirect opiate effect if naloxone (Narcan) produces withdrawal after sugar self-administration.”

And while obesity is currently the nation’s No. 2 health problem behind tobacco and secondhand smoke, it will be No. 1 soon, predicted Dr. Gold, a psychiatrist who has spent more than 40 years developing models for understanding the effects of tobacco, opiates, cocaine, other drugs, and food on the brain and behavior (Physiol. Behav. 2011;104:157-61).He pointed to a recent comparison of data from the Medical Expenditure Panel Survey between 2000 and 2010, which suggests that obesity “is going to bankrupt the health system because, as compared to tobacco, where death and disability tend to occur in the last 7 years of a person’s life, obesity is an unwanted gift to the health system that keeps on giving, with type 2 diabetes and other complications,” he said. “Now, bariatric surgery is the fastest-growing operation in the United States, and it’s been successful in treating teenagers. Two-thirds of Americans now qualify for obesity treatment.”

He went on to note that Americans are “conditioned by fast food,” and cited potential addictive factors as a nutritionally imbalanced prenatal diet, child rearing, genetics, and lack of exercise. “We [Americans] eat abnormally fast,” Dr. Gold added. “Our group has shown in functional imaging that it takes about 12 minutes for a thin person’s brain to get the food signal. It takes 25 minutes for an obese person to get the signal. So if the obese person goes into a fast food restaurant” and starts eating, that person gets back in line because he’s still hungry.

When first meeting a patient with a suspected food addiction, he advises clinicians to measure the person’s body mass index and to administer the Yale Food Addiction Scale, “which is easy to use,” he said. “Think about intervening and treating people when they have a BMI of 25 or greater, rather than just when they have a pre–bariatric surgery evaluation. One size doesn’t fit all when it comes to treatment.

“It’s important to have a careful look [at what’s causing their obesity]. It could be due to a thyroid condition or to a medication they’re taking.”

In addition to early intervention, “you want cognitive-behavioral treatment, new psychopharmacologic treatment where relevant, and group treatment rather than individualized treatment alone. The food addiction model is leading to a new way of thinking and new pharmacological treatment based on addiction research.”

Dr. Gold reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

Reductions in abdominal obesity were similar in patients who exercised for fixed amounts of time at different levels of intensity, but significantly greater than non-exercise controls, Dr. Robert Ross and co-authors at the Queen’s University School of Kinesiology and Health Studies, Kingston, Ontario, reported.

© Digital Vision/Thinkstock

In a study of 300 abdominally obese adults, reductions in waist circumference were greater in all three exercise groups — low-amount, low-intensity (-3.9 cm; p < .001); high-amount, low-intensity (-4.6 cm; p < .001); and high-amount, high intensity (-4.6 cm; p < .001) — than in controls, but did not significantly differ between groups. However, 2-hour reductions in glucose level were significantly higher in the high-amount, high-intensity exercise group (-0.7 mmol/L; p = .027) compared with the controls than in all other groups, the investigators reported.

The study results are “encouraging and provide treatment options for clinicians who seek lifestyle-based strategies for reducing abdominal obesity in adults at increased health risk,” Dr. Ross and his colleagues wrote in the paper.

Read the full article at: http://www.annals.org/article.aspx?doi=10.7326/M14-1189.

Reductions in abdominal obesity were similar in patients who exercised for fixed amounts of time at different levels of intensity, but significantly greater than non-exercise controls, Dr. Robert Ross and co-authors at the Queen’s University School of Kinesiology and Health Studies, Kingston, Ontario, reported.

© Digital Vision/Thinkstock

In a study of 300 abdominally obese adults, reductions in waist circumference were greater in all three exercise groups — low-amount, low-intensity (-3.9 cm; p < .001); high-amount, low-intensity (-4.6 cm; p < .001); and high-amount, high intensity (-4.6 cm; p < .001) — than in controls, but did not significantly differ between groups. However, 2-hour reductions in glucose level were significantly higher in the high-amount, high-intensity exercise group (-0.7 mmol/L; p = .027) compared with the controls than in all other groups, the investigators reported.

The study results are “encouraging and provide treatment options for clinicians who seek lifestyle-based strategies for reducing abdominal obesity in adults at increased health risk,” Dr. Ross and his colleagues wrote in the paper.

Read the full article at: http://www.annals.org/article.aspx?doi=10.7326/M14-1189.

Reductions in abdominal obesity were similar in patients who exercised for fixed amounts of time at different levels of intensity, but significantly greater than non-exercise controls, Dr. Robert Ross and co-authors at the Queen’s University School of Kinesiology and Health Studies, Kingston, Ontario, reported.

© Digital Vision/Thinkstock

In a study of 300 abdominally obese adults, reductions in waist circumference were greater in all three exercise groups — low-amount, low-intensity (-3.9 cm; p < .001); high-amount, low-intensity (-4.6 cm; p < .001); and high-amount, high intensity (-4.6 cm; p < .001) — than in controls, but did not significantly differ between groups. However, 2-hour reductions in glucose level were significantly higher in the high-amount, high-intensity exercise group (-0.7 mmol/L; p = .027) compared with the controls than in all other groups, the investigators reported.

The study results are “encouraging and provide treatment options for clinicians who seek lifestyle-based strategies for reducing abdominal obesity in adults at increased health risk,” Dr. Ross and his colleagues wrote in the paper.

Read the full article at: http://www.annals.org/article.aspx?doi=10.7326/M14-1189.

SAN DIEGO – Maternal glycemia was associated with anthropometric measures of obesity in offspring during childhood, but not with childhood body mass index, fasting glucose, or insulin resistance in a secondary analysis of a long-term follow-up study of women with mild gestational diabetes mellitus.

Baseline maternal body mass index (BMI), maternal weight gain, and Hispanic ethnicity, however, were consistently related to childhood BMI (P < .01) in the study of 236 children born to women who had untreated mild gestational diabetes mellitus (GDM) and 480 children whose mothers had a normal oral glucose tolerance test during pregnancy.

Courtesy Ohio State University

The findings underscore the importance of reducing obesity prior to pregnancy, and suggest that obesity reduction efforts should be emphasized in clinical practice, Dr. Mark B. Landon said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

“The obesity epidemic certainly has not spared the pediatric population,” said Dr. Landon, chair of obstetrics and gynecology at the Ohio State University in Columbus.

And a serious concern is that overweight and obesity are associated with a downstream risk of both metabolic and cardiovascular abnormalities into adulthood, he added.

Hispanic ethnicity and maternal BMI were also associated with childhood homeostatic model assessment-insulin resistance (HOMA-IR), and Hispanic ethnicity was associated with fasting glucose, Dr. Landon reported on behalf of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

There was a significant correlation between fasting, 1-hour, 2-hour, and 3-hour maternal glucose and subscapular/triceps skin fold ratio (Spearman correlation coefficients, 0.10, 0.08, 0.11, and 0.12, respectively). Similar correlations were seen between maternal glucose and HOMA-IR, and maternal glucose and sum of skin folds.

Fasting maternal glucose and fasting child glucose were also significantly correlated (Spearman correlation coefficients, 0.09).

On multivariable regression analysis – after controlling for maternal and neonatal factors – the only significant correlations between maternal glycemia and childhood outcomes were for 1-hour, 2-hour, and 3-hour maternal glucose measures, sum of skin folds, and subscapular/triceps skin fold ratio, he said.

Study subjects were the offspring of women who underwent a 3-hour oral glucose tolerance test between 27 and 31 weeks’ gestation, and childhood outcomes were assessed between the ages of 5 and 10 years.

Prior to the widespread recognition of the concept of fetal programming over 3 decades ago, Dr. Norbert Freinkel proposed that mild forms of diabetes, such as GDM, might exaggerate the normal dependency of the fetus on maternal fuels and that the concept of teratogenesis should be expanded to include alterations which could have long-range effects on behavioral, anthropometric, and metabolic functions, Dr. Landon said.

Multiple subsequent studies have demonstrated a link between in utero exposure to maternal hyperglycemia and the development of obesity in childhood – findings that are independent of both birth weight and maternal obesity.

©moodboard/ thinkstockphotos.com

A 2013 study showed that GDM was associated with both overweight status in childhood and childhood obesity (Diabet. Med. 2013;30:1449-56). Also, the landmark Hyperglycemia and Adverse Pregnancy Outcomes study showed that with increasing maternal glucose levels lower than the threshold for GDM diagnosis, the frequency of large-for-gestational-age infants increased proportionately – and this risk also remained after adjustment for maternal BMI and other confounders (N. Engl. J. Med. 2008;358:1991-2002).

“We have similarly reported a monotonic relationship between maternal glucose levels and the frequency of large-for-gestational-age infants in a secondary analysis from the Mild GDM Network randomized controlled trial. Recognizing that maternal glycemia clearly contributes to fetal growth, we sought to determine in this analysis whether the degree of maternal glucose tolerance during pregnancy affects the risk of childhood obesity and metabolic dysfunction,” Dr. Landon said.

Although the findings do not address the potential long-term effects of more significant hyperglycemia during pregnancy, they do confirm that maternal obesity has a greater impact on childhood obesity risk than exposure to mild hyperglycemia during pregnancy, he said in an interview.

Dr. Landon reported having no financial disclosures.

SAN DIEGO – Maternal glycemia was associated with anthropometric measures of obesity in offspring during childhood, but not with childhood body mass index, fasting glucose, or insulin resistance in a secondary analysis of a long-term follow-up study of women with mild gestational diabetes mellitus.

Baseline maternal body mass index (BMI), maternal weight gain, and Hispanic ethnicity, however, were consistently related to childhood BMI (P < .01) in the study of 236 children born to women who had untreated mild gestational diabetes mellitus (GDM) and 480 children whose mothers had a normal oral glucose tolerance test during pregnancy.

Courtesy Ohio State University

The findings underscore the importance of reducing obesity prior to pregnancy, and suggest that obesity reduction efforts should be emphasized in clinical practice, Dr. Mark B. Landon said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

“The obesity epidemic certainly has not spared the pediatric population,” said Dr. Landon, chair of obstetrics and gynecology at the Ohio State University in Columbus.

And a serious concern is that overweight and obesity are associated with a downstream risk of both metabolic and cardiovascular abnormalities into adulthood, he added.

Hispanic ethnicity and maternal BMI were also associated with childhood homeostatic model assessment-insulin resistance (HOMA-IR), and Hispanic ethnicity was associated with fasting glucose, Dr. Landon reported on behalf of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

There was a significant correlation between fasting, 1-hour, 2-hour, and 3-hour maternal glucose and subscapular/triceps skin fold ratio (Spearman correlation coefficients, 0.10, 0.08, 0.11, and 0.12, respectively). Similar correlations were seen between maternal glucose and HOMA-IR, and maternal glucose and sum of skin folds.

Fasting maternal glucose and fasting child glucose were also significantly correlated (Spearman correlation coefficients, 0.09).

On multivariable regression analysis – after controlling for maternal and neonatal factors – the only significant correlations between maternal glycemia and childhood outcomes were for 1-hour, 2-hour, and 3-hour maternal glucose measures, sum of skin folds, and subscapular/triceps skin fold ratio, he said.

Study subjects were the offspring of women who underwent a 3-hour oral glucose tolerance test between 27 and 31 weeks’ gestation, and childhood outcomes were assessed between the ages of 5 and 10 years.

Prior to the widespread recognition of the concept of fetal programming over 3 decades ago, Dr. Norbert Freinkel proposed that mild forms of diabetes, such as GDM, might exaggerate the normal dependency of the fetus on maternal fuels and that the concept of teratogenesis should be expanded to include alterations which could have long-range effects on behavioral, anthropometric, and metabolic functions, Dr. Landon said.

Multiple subsequent studies have demonstrated a link between in utero exposure to maternal hyperglycemia and the development of obesity in childhood – findings that are independent of both birth weight and maternal obesity.

©moodboard/ thinkstockphotos.com

A 2013 study showed that GDM was associated with both overweight status in childhood and childhood obesity (Diabet. Med. 2013;30:1449-56). Also, the landmark Hyperglycemia and Adverse Pregnancy Outcomes study showed that with increasing maternal glucose levels lower than the threshold for GDM diagnosis, the frequency of large-for-gestational-age infants increased proportionately – and this risk also remained after adjustment for maternal BMI and other confounders (N. Engl. J. Med. 2008;358:1991-2002).

“We have similarly reported a monotonic relationship between maternal glucose levels and the frequency of large-for-gestational-age infants in a secondary analysis from the Mild GDM Network randomized controlled trial. Recognizing that maternal glycemia clearly contributes to fetal growth, we sought to determine in this analysis whether the degree of maternal glucose tolerance during pregnancy affects the risk of childhood obesity and metabolic dysfunction,” Dr. Landon said.

Although the findings do not address the potential long-term effects of more significant hyperglycemia during pregnancy, they do confirm that maternal obesity has a greater impact on childhood obesity risk than exposure to mild hyperglycemia during pregnancy, he said in an interview.

Dr. Landon reported having no financial disclosures.

SAN DIEGO – Maternal glycemia was associated with anthropometric measures of obesity in offspring during childhood, but not with childhood body mass index, fasting glucose, or insulin resistance in a secondary analysis of a long-term follow-up study of women with mild gestational diabetes mellitus.

Baseline maternal body mass index (BMI), maternal weight gain, and Hispanic ethnicity, however, were consistently related to childhood BMI (P < .01) in the study of 236 children born to women who had untreated mild gestational diabetes mellitus (GDM) and 480 children whose mothers had a normal oral glucose tolerance test during pregnancy.

Courtesy Ohio State University

The findings underscore the importance of reducing obesity prior to pregnancy, and suggest that obesity reduction efforts should be emphasized in clinical practice, Dr. Mark B. Landon said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

“The obesity epidemic certainly has not spared the pediatric population,” said Dr. Landon, chair of obstetrics and gynecology at the Ohio State University in Columbus.

And a serious concern is that overweight and obesity are associated with a downstream risk of both metabolic and cardiovascular abnormalities into adulthood, he added.

Hispanic ethnicity and maternal BMI were also associated with childhood homeostatic model assessment-insulin resistance (HOMA-IR), and Hispanic ethnicity was associated with fasting glucose, Dr. Landon reported on behalf of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

There was a significant correlation between fasting, 1-hour, 2-hour, and 3-hour maternal glucose and subscapular/triceps skin fold ratio (Spearman correlation coefficients, 0.10, 0.08, 0.11, and 0.12, respectively). Similar correlations were seen between maternal glucose and HOMA-IR, and maternal glucose and sum of skin folds.

Fasting maternal glucose and fasting child glucose were also significantly correlated (Spearman correlation coefficients, 0.09).

On multivariable regression analysis – after controlling for maternal and neonatal factors – the only significant correlations between maternal glycemia and childhood outcomes were for 1-hour, 2-hour, and 3-hour maternal glucose measures, sum of skin folds, and subscapular/triceps skin fold ratio, he said.

Study subjects were the offspring of women who underwent a 3-hour oral glucose tolerance test between 27 and 31 weeks’ gestation, and childhood outcomes were assessed between the ages of 5 and 10 years.

Prior to the widespread recognition of the concept of fetal programming over 3 decades ago, Dr. Norbert Freinkel proposed that mild forms of diabetes, such as GDM, might exaggerate the normal dependency of the fetus on maternal fuels and that the concept of teratogenesis should be expanded to include alterations which could have long-range effects on behavioral, anthropometric, and metabolic functions, Dr. Landon said.

Multiple subsequent studies have demonstrated a link between in utero exposure to maternal hyperglycemia and the development of obesity in childhood – findings that are independent of both birth weight and maternal obesity.

©moodboard/ thinkstockphotos.com

A 2013 study showed that GDM was associated with both overweight status in childhood and childhood obesity (Diabet. Med. 2013;30:1449-56). Also, the landmark Hyperglycemia and Adverse Pregnancy Outcomes study showed that with increasing maternal glucose levels lower than the threshold for GDM diagnosis, the frequency of large-for-gestational-age infants increased proportionately – and this risk also remained after adjustment for maternal BMI and other confounders (N. Engl. J. Med. 2008;358:1991-2002).

“We have similarly reported a monotonic relationship between maternal glucose levels and the frequency of large-for-gestational-age infants in a secondary analysis from the Mild GDM Network randomized controlled trial. Recognizing that maternal glycemia clearly contributes to fetal growth, we sought to determine in this analysis whether the degree of maternal glucose tolerance during pregnancy affects the risk of childhood obesity and metabolic dysfunction,” Dr. Landon said.

Although the findings do not address the potential long-term effects of more significant hyperglycemia during pregnancy, they do confirm that maternal obesity has a greater impact on childhood obesity risk than exposure to mild hyperglycemia during pregnancy, he said in an interview.

Dr. Landon reported having no financial disclosures.