Diabetes Hub

Interventions that included computerized clinical decision support (CDS) for pediatric clinicians in combination with individualized family coaching yielded greater reductions in children’s BMI scores than did CDS alone or usual care, investigators have reported.

In a cluster-randomized clinical trial published in JAMA Pediatrics, researchers examined data from 549 children aged 6-12 years with a BMI at the 95% percentile or higher from 14 primary care practices. A total of 194 children were enrolled in the CDS arm, 171 in the CDS plus parental coaching arm, and 184 in the usual care arm, with follow-up visits occurring 1 year later. Changes to BMI score were assessed with the Healthcare Effectiveness Data and Information Set (HEDIS) measures for obesity.

Compared with the usual care arm, BMI increased less in children in the CDS arm during 1 year (−0.51). The CDS plus parental coaching arm had a smaller magnitude of effect on BMI (−0.34), the authors wrote.

The greatest improvements in BMI were among those patients who received both interventions and had the highest fidelity to intervention protocol, noted lead author Dr. Elsie M. Taveras, a pediatrician at Massachusetts General Hospital for Children in Boston.

Read the full article in JAMA Pediatrics: (DOI:10.1001/jamapediatrics.2015.0182.)

Interventions that included computerized clinical decision support (CDS) for pediatric clinicians in combination with individualized family coaching yielded greater reductions in children’s BMI scores than did CDS alone or usual care, investigators have reported.

In a cluster-randomized clinical trial published in JAMA Pediatrics, researchers examined data from 549 children aged 6-12 years with a BMI at the 95% percentile or higher from 14 primary care practices. A total of 194 children were enrolled in the CDS arm, 171 in the CDS plus parental coaching arm, and 184 in the usual care arm, with follow-up visits occurring 1 year later. Changes to BMI score were assessed with the Healthcare Effectiveness Data and Information Set (HEDIS) measures for obesity.

Compared with the usual care arm, BMI increased less in children in the CDS arm during 1 year (−0.51). The CDS plus parental coaching arm had a smaller magnitude of effect on BMI (−0.34), the authors wrote.

The greatest improvements in BMI were among those patients who received both interventions and had the highest fidelity to intervention protocol, noted lead author Dr. Elsie M. Taveras, a pediatrician at Massachusetts General Hospital for Children in Boston.

Read the full article in JAMA Pediatrics: (DOI:10.1001/jamapediatrics.2015.0182.)

Interventions that included computerized clinical decision support (CDS) for pediatric clinicians in combination with individualized family coaching yielded greater reductions in children’s BMI scores than did CDS alone or usual care, investigators have reported.

In a cluster-randomized clinical trial published in JAMA Pediatrics, researchers examined data from 549 children aged 6-12 years with a BMI at the 95% percentile or higher from 14 primary care practices. A total of 194 children were enrolled in the CDS arm, 171 in the CDS plus parental coaching arm, and 184 in the usual care arm, with follow-up visits occurring 1 year later. Changes to BMI score were assessed with the Healthcare Effectiveness Data and Information Set (HEDIS) measures for obesity.

Compared with the usual care arm, BMI increased less in children in the CDS arm during 1 year (−0.51). The CDS plus parental coaching arm had a smaller magnitude of effect on BMI (−0.34), the authors wrote.

The greatest improvements in BMI were among those patients who received both interventions and had the highest fidelity to intervention protocol, noted lead author Dr. Elsie M. Taveras, a pediatrician at Massachusetts General Hospital for Children in Boston.

Read the full article in JAMA Pediatrics: (DOI:10.1001/jamapediatrics.2015.0182.)

Adolescents with type 1 diabetes experienced more rapid gastric emptying time than did healthy controls, which was linked to greater postprandial rises in blood glucose, a new study has found.

The prospective case-control study in 30 adolescents with type 1 diabetes showed a median half-emptying time of 78 minutes, compared with 109 minutes in controls (P = .2), while the postprandial increase in blood glucose strongly correlated with gastric half-emptying time, according to a paper published online April 14 in the Journal of Clinical Endocrinology and Metabolism.

The findings are in contrast with studies in adults which have previously shown that delayed gastric emptying time affects a significant number of adults with type 1 diabetes. But this current study did show that, as with adults, fasting hyperglycemia was linked to slower gastric emptying and increased upper gastrointestinal symptoms (J. Clin. Endocrinol. Metab. 2015 April 14 [doi:10.1210/jc.2015-1055]).

“Our results suggest that therapies that modify the rate of gastric emptying may be of particular benefit in optimizing postprandial glycaemia in adolescents with type 1 diabetes, and should be investigated further,” wrote Dr. Shiree J. Perano of the University of Adelaide (Australia) and her coauthors.

The study was supported by a McLeod Foundation fellowship, SA, and an Australian Pediatric Endocrine Care grant from Pfizer pharmaceuticals. Two authors declared funding, advisory board memberships, and honoraria from pharmaceutical companies. No other conflicts of interest were declared.

Adolescents with type 1 diabetes experienced more rapid gastric emptying time than did healthy controls, which was linked to greater postprandial rises in blood glucose, a new study has found.

The prospective case-control study in 30 adolescents with type 1 diabetes showed a median half-emptying time of 78 minutes, compared with 109 minutes in controls (P = .2), while the postprandial increase in blood glucose strongly correlated with gastric half-emptying time, according to a paper published online April 14 in the Journal of Clinical Endocrinology and Metabolism.

The findings are in contrast with studies in adults which have previously shown that delayed gastric emptying time affects a significant number of adults with type 1 diabetes. But this current study did show that, as with adults, fasting hyperglycemia was linked to slower gastric emptying and increased upper gastrointestinal symptoms (J. Clin. Endocrinol. Metab. 2015 April 14 [doi:10.1210/jc.2015-1055]).

“Our results suggest that therapies that modify the rate of gastric emptying may be of particular benefit in optimizing postprandial glycaemia in adolescents with type 1 diabetes, and should be investigated further,” wrote Dr. Shiree J. Perano of the University of Adelaide (Australia) and her coauthors.

The study was supported by a McLeod Foundation fellowship, SA, and an Australian Pediatric Endocrine Care grant from Pfizer pharmaceuticals. Two authors declared funding, advisory board memberships, and honoraria from pharmaceutical companies. No other conflicts of interest were declared.

Adolescents with type 1 diabetes experienced more rapid gastric emptying time than did healthy controls, which was linked to greater postprandial rises in blood glucose, a new study has found.

The prospective case-control study in 30 adolescents with type 1 diabetes showed a median half-emptying time of 78 minutes, compared with 109 minutes in controls (P = .2), while the postprandial increase in blood glucose strongly correlated with gastric half-emptying time, according to a paper published online April 14 in the Journal of Clinical Endocrinology and Metabolism.

The findings are in contrast with studies in adults which have previously shown that delayed gastric emptying time affects a significant number of adults with type 1 diabetes. But this current study did show that, as with adults, fasting hyperglycemia was linked to slower gastric emptying and increased upper gastrointestinal symptoms (J. Clin. Endocrinol. Metab. 2015 April 14 [doi:10.1210/jc.2015-1055]).

“Our results suggest that therapies that modify the rate of gastric emptying may be of particular benefit in optimizing postprandial glycaemia in adolescents with type 1 diabetes, and should be investigated further,” wrote Dr. Shiree J. Perano of the University of Adelaide (Australia) and her coauthors.

The study was supported by a McLeod Foundation fellowship, SA, and an Australian Pediatric Endocrine Care grant from Pfizer pharmaceuticals. Two authors declared funding, advisory board memberships, and honoraria from pharmaceutical companies. No other conflicts of interest were declared.

SILVER SPRING, MD.– Alogliptin’s cardiovascular risk profile is acceptably safe for high-risk patients with type 2 diabetes, a Food and Drug Administration advisory panel has unanimously agreed.

At a meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee on April 14, panelists reviewed the results of the results of a large cardiovascular outcomes study of the dipeptidyl peptidase-4 (DPP-4) inhibitor, the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) study, an international, randomized, double-blind, placebo-controlled trial of about 5,400 people with type 2 diabetes and established cardiovascular disease.

The FDA is requiring CV outcomes trials for all type 2 diabetes drugs, including those in development, and issued a guidance for industry for these trials in December 2008, which states that the trials should evaluate the major adverse cardiovascular event (MACE) incidence in patients at increased risk for CVD and that a 30% or greater excess CV risk over placebo should be excluded to meet the criteria for acceptable CV safety.

Alogliptin, marketed as Nesina by Takeda Pharmaceutical USA, was approved in January 2013. It also is combined with metformin (Kazano) and with pioglitazone (Oseni). The EXAMINE study, which was underway at the time of approval, enrolled people who had an acute coronary syndrome event (acute MI or unstable angina requiring hospitalization) within 15-90 days of enrollment.

Over a median follow-up of 1.5 years, there was no increase in the MACE composite endpoint of CV death, nonfatal MI, and nonfatal stroke among those on alogliptin (11.3%), compared with those on placebo (11.8%), for a hazard ratio of 0.96 – meeting the FDA criteria for CV safety (N. Engl. J. Med. 2013;369:1327-35).

Some of the issues raised with the study included a lower-than-planned proportion of patients enrolled in the United States and Canada – less than 16% of the total – and a subgroup analysis showing that, in the North American patients, the MACE rate among those on alogliptin was elevated compared with placebo (HR, 1.28). The FDA reviewers said that the North American population had some characteristics that might explain this difference.

Another finding discussed was the higher number of hospitalizations for heart failure in patients on alogliptin (106) than for those on placebo (89), for a rate of 2.6 vs. 2.3 cases per 100 patient-years (HR, 1.19), according to the FDA. In the CV outcomes study of another DPP-4 inhibitor, saxagliptin, which the panel reviewed earlier in the day, there was a similar signal for an increased risk of heart failure hospitalizations associated with the drug.

Panelists, however, said they were not convinced that the geographic differences represented a real effect, which they said could be due to chance and did not affect the overall results – although they would have preferred to have more people from the United States enrolled in the study. Panelists also were not overly concerned about the risk of heart failure, but they pointed out that the risk of heart failure risk should be monitored in patients on the drug because of the signal seen with saxagliptin. Several panelists said that they suspected that heart failure may turn out to be a class effect. CV outcomes trials for the two other approved DPP-4 inhibitors – sitagliptin (Januvia) and linagliptin (Tradjenta) – are ongoing.

“It’s clear that the trial achieved its primary objective in a manner consistent with the 2008 guidelines,” said one of the panelists, Dr. Thomas Wang, director of the division of cardiovascular medicine at Vanderbilt University, Nashville, Tenn. Although there were some limitations of the study, such as the low proportion of U.S. participants and the relatively short duration of follow-up, “these limitations do not come close to negating the conclusion” regarding the cardiovascular risk profile, he commented.

In another vote, 13 of the 16 panelists said that the new safety information should be added to the alogliptin prescribing information. “This trial represented a huge effort and we know a lot about the outcomes related to this drug now,” and that information should be included in the label, said one of the panelists, Dr. Susan Heckbert, professor in the department of epidemiology, University of Washington, Seattle.

Three panelists voted not to add any information to the label. The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest

[email protected]

SILVER SPRING, MD.– Alogliptin’s cardiovascular risk profile is acceptably safe for high-risk patients with type 2 diabetes, a Food and Drug Administration advisory panel has unanimously agreed.

At a meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee on April 14, panelists reviewed the results of the results of a large cardiovascular outcomes study of the dipeptidyl peptidase-4 (DPP-4) inhibitor, the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) study, an international, randomized, double-blind, placebo-controlled trial of about 5,400 people with type 2 diabetes and established cardiovascular disease.

The FDA is requiring CV outcomes trials for all type 2 diabetes drugs, including those in development, and issued a guidance for industry for these trials in December 2008, which states that the trials should evaluate the major adverse cardiovascular event (MACE) incidence in patients at increased risk for CVD and that a 30% or greater excess CV risk over placebo should be excluded to meet the criteria for acceptable CV safety.

Alogliptin, marketed as Nesina by Takeda Pharmaceutical USA, was approved in January 2013. It also is combined with metformin (Kazano) and with pioglitazone (Oseni). The EXAMINE study, which was underway at the time of approval, enrolled people who had an acute coronary syndrome event (acute MI or unstable angina requiring hospitalization) within 15-90 days of enrollment.

Over a median follow-up of 1.5 years, there was no increase in the MACE composite endpoint of CV death, nonfatal MI, and nonfatal stroke among those on alogliptin (11.3%), compared with those on placebo (11.8%), for a hazard ratio of 0.96 – meeting the FDA criteria for CV safety (N. Engl. J. Med. 2013;369:1327-35).

Some of the issues raised with the study included a lower-than-planned proportion of patients enrolled in the United States and Canada – less than 16% of the total – and a subgroup analysis showing that, in the North American patients, the MACE rate among those on alogliptin was elevated compared with placebo (HR, 1.28). The FDA reviewers said that the North American population had some characteristics that might explain this difference.

Another finding discussed was the higher number of hospitalizations for heart failure in patients on alogliptin (106) than for those on placebo (89), for a rate of 2.6 vs. 2.3 cases per 100 patient-years (HR, 1.19), according to the FDA. In the CV outcomes study of another DPP-4 inhibitor, saxagliptin, which the panel reviewed earlier in the day, there was a similar signal for an increased risk of heart failure hospitalizations associated with the drug.

Panelists, however, said they were not convinced that the geographic differences represented a real effect, which they said could be due to chance and did not affect the overall results – although they would have preferred to have more people from the United States enrolled in the study. Panelists also were not overly concerned about the risk of heart failure, but they pointed out that the risk of heart failure risk should be monitored in patients on the drug because of the signal seen with saxagliptin. Several panelists said that they suspected that heart failure may turn out to be a class effect. CV outcomes trials for the two other approved DPP-4 inhibitors – sitagliptin (Januvia) and linagliptin (Tradjenta) – are ongoing.

“It’s clear that the trial achieved its primary objective in a manner consistent with the 2008 guidelines,” said one of the panelists, Dr. Thomas Wang, director of the division of cardiovascular medicine at Vanderbilt University, Nashville, Tenn. Although there were some limitations of the study, such as the low proportion of U.S. participants and the relatively short duration of follow-up, “these limitations do not come close to negating the conclusion” regarding the cardiovascular risk profile, he commented.

In another vote, 13 of the 16 panelists said that the new safety information should be added to the alogliptin prescribing information. “This trial represented a huge effort and we know a lot about the outcomes related to this drug now,” and that information should be included in the label, said one of the panelists, Dr. Susan Heckbert, professor in the department of epidemiology, University of Washington, Seattle.

Three panelists voted not to add any information to the label. The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest

[email protected]

SILVER SPRING, MD.– Alogliptin’s cardiovascular risk profile is acceptably safe for high-risk patients with type 2 diabetes, a Food and Drug Administration advisory panel has unanimously agreed.

At a meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee on April 14, panelists reviewed the results of the results of a large cardiovascular outcomes study of the dipeptidyl peptidase-4 (DPP-4) inhibitor, the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) study, an international, randomized, double-blind, placebo-controlled trial of about 5,400 people with type 2 diabetes and established cardiovascular disease.

The FDA is requiring CV outcomes trials for all type 2 diabetes drugs, including those in development, and issued a guidance for industry for these trials in December 2008, which states that the trials should evaluate the major adverse cardiovascular event (MACE) incidence in patients at increased risk for CVD and that a 30% or greater excess CV risk over placebo should be excluded to meet the criteria for acceptable CV safety.

Alogliptin, marketed as Nesina by Takeda Pharmaceutical USA, was approved in January 2013. It also is combined with metformin (Kazano) and with pioglitazone (Oseni). The EXAMINE study, which was underway at the time of approval, enrolled people who had an acute coronary syndrome event (acute MI or unstable angina requiring hospitalization) within 15-90 days of enrollment.

Over a median follow-up of 1.5 years, there was no increase in the MACE composite endpoint of CV death, nonfatal MI, and nonfatal stroke among those on alogliptin (11.3%), compared with those on placebo (11.8%), for a hazard ratio of 0.96 – meeting the FDA criteria for CV safety (N. Engl. J. Med. 2013;369:1327-35).

Some of the issues raised with the study included a lower-than-planned proportion of patients enrolled in the United States and Canada – less than 16% of the total – and a subgroup analysis showing that, in the North American patients, the MACE rate among those on alogliptin was elevated compared with placebo (HR, 1.28). The FDA reviewers said that the North American population had some characteristics that might explain this difference.

Another finding discussed was the higher number of hospitalizations for heart failure in patients on alogliptin (106) than for those on placebo (89), for a rate of 2.6 vs. 2.3 cases per 100 patient-years (HR, 1.19), according to the FDA. In the CV outcomes study of another DPP-4 inhibitor, saxagliptin, which the panel reviewed earlier in the day, there was a similar signal for an increased risk of heart failure hospitalizations associated with the drug.

Panelists, however, said they were not convinced that the geographic differences represented a real effect, which they said could be due to chance and did not affect the overall results – although they would have preferred to have more people from the United States enrolled in the study. Panelists also were not overly concerned about the risk of heart failure, but they pointed out that the risk of heart failure risk should be monitored in patients on the drug because of the signal seen with saxagliptin. Several panelists said that they suspected that heart failure may turn out to be a class effect. CV outcomes trials for the two other approved DPP-4 inhibitors – sitagliptin (Januvia) and linagliptin (Tradjenta) – are ongoing.

“It’s clear that the trial achieved its primary objective in a manner consistent with the 2008 guidelines,” said one of the panelists, Dr. Thomas Wang, director of the division of cardiovascular medicine at Vanderbilt University, Nashville, Tenn. Although there were some limitations of the study, such as the low proportion of U.S. participants and the relatively short duration of follow-up, “these limitations do not come close to negating the conclusion” regarding the cardiovascular risk profile, he commented.

In another vote, 13 of the 16 panelists said that the new safety information should be added to the alogliptin prescribing information. “This trial represented a huge effort and we know a lot about the outcomes related to this drug now,” and that information should be included in the label, said one of the panelists, Dr. Susan Heckbert, professor in the department of epidemiology, University of Washington, Seattle.

Three panelists voted not to add any information to the label. The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest

[email protected]

SILVER SPRING, MD.– Results of a large postmarketing study evaluating the cardiovascular safety of saxagliptin in a high-risk population provided reassuring evidence about the drug’s overall cardiovascular risk, although a signal for heart failure hospitalizations associated with the drug was a concern, according to a Food and Drug Administration advisory panel.

At a meeting on April 14, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-1, with one abstention, that the results of the SAVOR (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus) trial showed that the use of saxagliptin in patients with type 2 diabetes had an acceptable cardiovascular risk profile. However, the panelists were concerned about the signal for an increased risk of hospitalizations for heart failure associated with saxagliptin in the study, which they agreed should be studied further. Nearly all of the panelists also voted that the safety data, including the heart failure finding and an imbalance in all-cause mortality among those on saxagliptin arm of the study, be added to the drug’s prescribing information.

Deepak Chitnis/Frontline Medical News

Approved in 2009, saxagliptin, a dipeptidyl peptidase–4 (DPP4) inhibitor, is indicated “as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings” and is marketed as Onglyza by AstraZeneca. A fixed-dose combination of saxagliptin with extended-release metformin (Kombiglyze XR) was approved in 2010. The FDA panel votes apply to both products.

The FDA is requiring that manufacturers conduct CV outcomes trials for all type 2 diabetes drugs in patients at high risk for cardiovascular disease (CVD), and in December 2008, issued a guidance document for industry, outlining the requirements for these studies, which included showing that the CVD risk, based on a major adverse cardiovascular event (MACE) endpoint, is not increased by more than 30% compared to placebo.

AstraZeneca conducted SAVOR, a prospective, randomized, double-blind, placebo-controlled study of nearly 16,500 people with type 2 diabetes, who had or were at risk of CVD, comparing saxagliptin to placebo, on top of standard treatment (N. Engl. J. Med. 2013;369:1317-26). After a median follow-up of about 2 years, the incidence of MACE (a composite of cardiovascular death, nonfatal MI, and nonfatal ischemic stroke) was identical in both groups, at 7.4%, with a hazard ratio of 1.0, meeting the FDA criteria for cardiovascular safety as outlined in the guidance, according to the company. Saxagliptin was not superior to placebo in reducing the MACE events, another primary objective of the study.

Unexpectedly, hospitalization for heart failure (HF), a component of the secondary composite endpoint, was increased among those treated with saxagliptin (hazard ratio, 1.27). There was also a “numerical imbalance” in all-cause mortality between groups, with 17 deaths in the saxagliptin patients vs. 11 in the placebo group (HR, 1.11).

However, deaths caused by heart failure were balanced between those on saxagliptin and those on placebo, and no possible mechanism for the HF finding could be identified, according to AstraZeneca, which is planning a mechanistic study to evaluate the effects of saxagliptin on volume, neurohormonal changes, and cardiac function. The company has proposed that the HF finding be addressed by adding this information to the prescribing information.

The cardiovascular safety results were reassuring, said Dr. Morris Schambelan, a panelist and professor emeritus of medicine in the division of endocrinology at the University of California, San Francisco, but like others on the committee, added that he believes the heart failure signal was real and that providing clinicians with information in the drug’s label to help predict those at higher risk in would be helpful.

Several panelists were somewhat concerned about the all-cause mortality finding, which is a strong endpoint, and therefore cannot be ruled out, they said. But they also pointed out that follow-up was relatively short for a drug that is used long term and that the results should be applied cautiously to patients at lower risk than were those enrolled in the trial.

The FDA usually follows the recommendations of its advisory panel members. Panelists had no relevant disclosures.

CV outcomes trials for other approved DPP4 inhibitors approved for type 2 diabetes – sitagliptin (Januvia) and linagliptin (Tradjenta) – are ongoing. The panel review of the CV outcomes trial for another DPP4 inhibitor approved, alogliptin (Nesina), followed the meeting on saxagliptin.

[email protected]

SILVER SPRING, MD.– Results of a large postmarketing study evaluating the cardiovascular safety of saxagliptin in a high-risk population provided reassuring evidence about the drug’s overall cardiovascular risk, although a signal for heart failure hospitalizations associated with the drug was a concern, according to a Food and Drug Administration advisory panel.

At a meeting on April 14, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-1, with one abstention, that the results of the SAVOR (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus) trial showed that the use of saxagliptin in patients with type 2 diabetes had an acceptable cardiovascular risk profile. However, the panelists were concerned about the signal for an increased risk of hospitalizations for heart failure associated with saxagliptin in the study, which they agreed should be studied further. Nearly all of the panelists also voted that the safety data, including the heart failure finding and an imbalance in all-cause mortality among those on saxagliptin arm of the study, be added to the drug’s prescribing information.

Deepak Chitnis/Frontline Medical News

Approved in 2009, saxagliptin, a dipeptidyl peptidase–4 (DPP4) inhibitor, is indicated “as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings” and is marketed as Onglyza by AstraZeneca. A fixed-dose combination of saxagliptin with extended-release metformin (Kombiglyze XR) was approved in 2010. The FDA panel votes apply to both products.

The FDA is requiring that manufacturers conduct CV outcomes trials for all type 2 diabetes drugs in patients at high risk for cardiovascular disease (CVD), and in December 2008, issued a guidance document for industry, outlining the requirements for these studies, which included showing that the CVD risk, based on a major adverse cardiovascular event (MACE) endpoint, is not increased by more than 30% compared to placebo.

AstraZeneca conducted SAVOR, a prospective, randomized, double-blind, placebo-controlled study of nearly 16,500 people with type 2 diabetes, who had or were at risk of CVD, comparing saxagliptin to placebo, on top of standard treatment (N. Engl. J. Med. 2013;369:1317-26). After a median follow-up of about 2 years, the incidence of MACE (a composite of cardiovascular death, nonfatal MI, and nonfatal ischemic stroke) was identical in both groups, at 7.4%, with a hazard ratio of 1.0, meeting the FDA criteria for cardiovascular safety as outlined in the guidance, according to the company. Saxagliptin was not superior to placebo in reducing the MACE events, another primary objective of the study.

Unexpectedly, hospitalization for heart failure (HF), a component of the secondary composite endpoint, was increased among those treated with saxagliptin (hazard ratio, 1.27). There was also a “numerical imbalance” in all-cause mortality between groups, with 17 deaths in the saxagliptin patients vs. 11 in the placebo group (HR, 1.11).

However, deaths caused by heart failure were balanced between those on saxagliptin and those on placebo, and no possible mechanism for the HF finding could be identified, according to AstraZeneca, which is planning a mechanistic study to evaluate the effects of saxagliptin on volume, neurohormonal changes, and cardiac function. The company has proposed that the HF finding be addressed by adding this information to the prescribing information.

The cardiovascular safety results were reassuring, said Dr. Morris Schambelan, a panelist and professor emeritus of medicine in the division of endocrinology at the University of California, San Francisco, but like others on the committee, added that he believes the heart failure signal was real and that providing clinicians with information in the drug’s label to help predict those at higher risk in would be helpful.

Several panelists were somewhat concerned about the all-cause mortality finding, which is a strong endpoint, and therefore cannot be ruled out, they said. But they also pointed out that follow-up was relatively short for a drug that is used long term and that the results should be applied cautiously to patients at lower risk than were those enrolled in the trial.

The FDA usually follows the recommendations of its advisory panel members. Panelists had no relevant disclosures.

CV outcomes trials for other approved DPP4 inhibitors approved for type 2 diabetes – sitagliptin (Januvia) and linagliptin (Tradjenta) – are ongoing. The panel review of the CV outcomes trial for another DPP4 inhibitor approved, alogliptin (Nesina), followed the meeting on saxagliptin.

[email protected]

SILVER SPRING, MD.– Results of a large postmarketing study evaluating the cardiovascular safety of saxagliptin in a high-risk population provided reassuring evidence about the drug’s overall cardiovascular risk, although a signal for heart failure hospitalizations associated with the drug was a concern, according to a Food and Drug Administration advisory panel.

At a meeting on April 14, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-1, with one abstention, that the results of the SAVOR (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus) trial showed that the use of saxagliptin in patients with type 2 diabetes had an acceptable cardiovascular risk profile. However, the panelists were concerned about the signal for an increased risk of hospitalizations for heart failure associated with saxagliptin in the study, which they agreed should be studied further. Nearly all of the panelists also voted that the safety data, including the heart failure finding and an imbalance in all-cause mortality among those on saxagliptin arm of the study, be added to the drug’s prescribing information.

Deepak Chitnis/Frontline Medical News

Approved in 2009, saxagliptin, a dipeptidyl peptidase–4 (DPP4) inhibitor, is indicated “as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings” and is marketed as Onglyza by AstraZeneca. A fixed-dose combination of saxagliptin with extended-release metformin (Kombiglyze XR) was approved in 2010. The FDA panel votes apply to both products.

The FDA is requiring that manufacturers conduct CV outcomes trials for all type 2 diabetes drugs in patients at high risk for cardiovascular disease (CVD), and in December 2008, issued a guidance document for industry, outlining the requirements for these studies, which included showing that the CVD risk, based on a major adverse cardiovascular event (MACE) endpoint, is not increased by more than 30% compared to placebo.

AstraZeneca conducted SAVOR, a prospective, randomized, double-blind, placebo-controlled study of nearly 16,500 people with type 2 diabetes, who had or were at risk of CVD, comparing saxagliptin to placebo, on top of standard treatment (N. Engl. J. Med. 2013;369:1317-26). After a median follow-up of about 2 years, the incidence of MACE (a composite of cardiovascular death, nonfatal MI, and nonfatal ischemic stroke) was identical in both groups, at 7.4%, with a hazard ratio of 1.0, meeting the FDA criteria for cardiovascular safety as outlined in the guidance, according to the company. Saxagliptin was not superior to placebo in reducing the MACE events, another primary objective of the study.

Unexpectedly, hospitalization for heart failure (HF), a component of the secondary composite endpoint, was increased among those treated with saxagliptin (hazard ratio, 1.27). There was also a “numerical imbalance” in all-cause mortality between groups, with 17 deaths in the saxagliptin patients vs. 11 in the placebo group (HR, 1.11).

However, deaths caused by heart failure were balanced between those on saxagliptin and those on placebo, and no possible mechanism for the HF finding could be identified, according to AstraZeneca, which is planning a mechanistic study to evaluate the effects of saxagliptin on volume, neurohormonal changes, and cardiac function. The company has proposed that the HF finding be addressed by adding this information to the prescribing information.

The cardiovascular safety results were reassuring, said Dr. Morris Schambelan, a panelist and professor emeritus of medicine in the division of endocrinology at the University of California, San Francisco, but like others on the committee, added that he believes the heart failure signal was real and that providing clinicians with information in the drug’s label to help predict those at higher risk in would be helpful.

Several panelists were somewhat concerned about the all-cause mortality finding, which is a strong endpoint, and therefore cannot be ruled out, they said. But they also pointed out that follow-up was relatively short for a drug that is used long term and that the results should be applied cautiously to patients at lower risk than were those enrolled in the trial.

The FDA usually follows the recommendations of its advisory panel members. Panelists had no relevant disclosures.

CV outcomes trials for other approved DPP4 inhibitors approved for type 2 diabetes – sitagliptin (Januvia) and linagliptin (Tradjenta) – are ongoing. The panel review of the CV outcomes trial for another DPP4 inhibitor approved, alogliptin (Nesina), followed the meeting on saxagliptin.

[email protected]

SAN DIEGO – A series of reports in 2014 from several independent groups implicated heart failure as a trigger of type 2 diabetes; findings from several of the analyses also suggested that relief of congestion can result in rapid resolution of the diabetes.

The best way to manage new-onset diabetes in heart failure patients is to “minimize the congestion,” and to “try to achieve as good control of the heart failure as possible,” said Dr. Maya Guglin during a talk at the annual meeting of the American College of Cardiology, in which she laid out the evidence for this newly recognized form of type 2 diabetes. In a review she published in 2014, Dr. Guglin coined the term “cardiogenic diabetes” to describe the condition (Heart Fail. Rev. 2014;19:595-602).

Dr. Guglin traced the data trail for cardiogenic diabetes starting in a 2011 retrospective study of 15 patients with advanced heart failure who received a left ventricular assist device (LVAD) at Columbia University in New York (Eur. J. Heart Fail. 2011;13:195-9). These 15, about a third of the 43 total LVAD recipients at Columbia at the time, had been diagnosed with type 2 diabetes for an average of 6 years before receiving the device. Just before they got their device, their average hemoglobin A_1c (HbA_1c) level was 7.7%, and their average fasting plasma glucose level was 158 mg/dL. An average of 4 months later, their mean HbA_1c had dropped to 6%, and their mean fasting glucose had fallen to 104 mg/dL. Six patients were completely off any diabetes medication. All this occurred while patients had a small increase in their body mass index, which Dr. Guglin attributed to their better physical condition and improved appetite.

Last year, another four reports appeared from four independent, U.S. heart failure groups with results that mirrored the Columbia experience. Dr. Guglin and her associates at the University of Kentucky, Lexington, reported their experience with 50 patients who received an LVAD during 2002-2012 and had type 2 diabetes just before they received a device, with an average HbA_1c of 7.6%. Three months after LVAD placement, their average HbA_1c had dropped to 5.7%, and 9-12 months after device placement, their average HbA_1c level was 5.3% (ASAIO J. 2014;60:290-3). As in the Columbia series, these improvements in hyperglycemia occurred without any significant change in body mass index.

Dr. Guglin also cited similar findings in 50 LVAD patients treated at the University of Rochester (N.Y.)(ASAIO J. 2014;60:675-80), 28 LVAD patients at Penn State Medical College in Hershey, Pa. (Heart Surg. Forum 2014;17:E98-102), and 66 LVAD patients from the University of Illinois in Chicago (Eur. J. Heart Fail. 2014;16:1120-4). In these reports type 2 diabetes existed in roughly a quarter to a third of patients with advanced heart failure who qualified for an LVAD just prior to the time they received the device.

Dr. Guglin also cited two epidemiologic analyses with complementary findings on the risk for incident diabetes faced by heart failure patients. She and her associates reviewed data from 3,165 elderly Americans free from diabetes enrolled in the Cardiovascular Health Study. This cohort included 80 patients with heart failure and 3,085 without heart failure. During 3-4 years of follow-up, 6% of the heart failure patients developed new-onset diabetes, and an additional 10% developed new-onset impaired fasting glucose. In contrast, these incidence rates were 1.5% and 5%, respectively, in the enrollees without heart failure at baseline. In an analysis that controlled for several demographic and biomedical factors, heart failure linked with a statistically significant, 2.4-fold increased risk for the development of diabetes (Cardiology 2014;129:84-92).

And a Danish nationwide cohort study of more than 99,000 residents discharged from a first-time hospitalization for heart failure during 1997-2010 showed a statistically significant link between heart failure severity and an increased rate of development of incident diabetes using diuretic treatment dosage as a surrogate measure of heart failure severity (Diabetologia 2014;57:1595-1600).

The apparent impact of LVAD placement on type 2 diabetes contrasts with what happens in patients who receive a heart transplant, where this association has not been seen. Dr. Guglin suggested that may be because of the immunosuppression with steroids that heart transplant recipients receive, treatment that also prevents diabetes resolution, she said.

“It all boils down to congestion,” Dr. Guglin said in an interview. “Control congestion as much as possible to control the diabetes.”

Dr. Guglin had no relevant financial disclosures.

[email protected]

On Twitter @mitchelzoler

SAN DIEGO – A series of reports in 2014 from several independent groups implicated heart failure as a trigger of type 2 diabetes; findings from several of the analyses also suggested that relief of congestion can result in rapid resolution of the diabetes.

The best way to manage new-onset diabetes in heart failure patients is to “minimize the congestion,” and to “try to achieve as good control of the heart failure as possible,” said Dr. Maya Guglin during a talk at the annual meeting of the American College of Cardiology, in which she laid out the evidence for this newly recognized form of type 2 diabetes. In a review she published in 2014, Dr. Guglin coined the term “cardiogenic diabetes” to describe the condition (Heart Fail. Rev. 2014;19:595-602).

Dr. Guglin traced the data trail for cardiogenic diabetes starting in a 2011 retrospective study of 15 patients with advanced heart failure who received a left ventricular assist device (LVAD) at Columbia University in New York (Eur. J. Heart Fail. 2011;13:195-9). These 15, about a third of the 43 total LVAD recipients at Columbia at the time, had been diagnosed with type 2 diabetes for an average of 6 years before receiving the device. Just before they got their device, their average hemoglobin A_1c (HbA_1c) level was 7.7%, and their average fasting plasma glucose level was 158 mg/dL. An average of 4 months later, their mean HbA_1c had dropped to 6%, and their mean fasting glucose had fallen to 104 mg/dL. Six patients were completely off any diabetes medication. All this occurred while patients had a small increase in their body mass index, which Dr. Guglin attributed to their better physical condition and improved appetite.

Last year, another four reports appeared from four independent, U.S. heart failure groups with results that mirrored the Columbia experience. Dr. Guglin and her associates at the University of Kentucky, Lexington, reported their experience with 50 patients who received an LVAD during 2002-2012 and had type 2 diabetes just before they received a device, with an average HbA_1c of 7.6%. Three months after LVAD placement, their average HbA_1c had dropped to 5.7%, and 9-12 months after device placement, their average HbA_1c level was 5.3% (ASAIO J. 2014;60:290-3). As in the Columbia series, these improvements in hyperglycemia occurred without any significant change in body mass index.

Dr. Guglin also cited similar findings in 50 LVAD patients treated at the University of Rochester (N.Y.)(ASAIO J. 2014;60:675-80), 28 LVAD patients at Penn State Medical College in Hershey, Pa. (Heart Surg. Forum 2014;17:E98-102), and 66 LVAD patients from the University of Illinois in Chicago (Eur. J. Heart Fail. 2014;16:1120-4). In these reports type 2 diabetes existed in roughly a quarter to a third of patients with advanced heart failure who qualified for an LVAD just prior to the time they received the device.

Dr. Guglin also cited two epidemiologic analyses with complementary findings on the risk for incident diabetes faced by heart failure patients. She and her associates reviewed data from 3,165 elderly Americans free from diabetes enrolled in the Cardiovascular Health Study. This cohort included 80 patients with heart failure and 3,085 without heart failure. During 3-4 years of follow-up, 6% of the heart failure patients developed new-onset diabetes, and an additional 10% developed new-onset impaired fasting glucose. In contrast, these incidence rates were 1.5% and 5%, respectively, in the enrollees without heart failure at baseline. In an analysis that controlled for several demographic and biomedical factors, heart failure linked with a statistically significant, 2.4-fold increased risk for the development of diabetes (Cardiology 2014;129:84-92).

And a Danish nationwide cohort study of more than 99,000 residents discharged from a first-time hospitalization for heart failure during 1997-2010 showed a statistically significant link between heart failure severity and an increased rate of development of incident diabetes using diuretic treatment dosage as a surrogate measure of heart failure severity (Diabetologia 2014;57:1595-1600).

The apparent impact of LVAD placement on type 2 diabetes contrasts with what happens in patients who receive a heart transplant, where this association has not been seen. Dr. Guglin suggested that may be because of the immunosuppression with steroids that heart transplant recipients receive, treatment that also prevents diabetes resolution, she said.

“It all boils down to congestion,” Dr. Guglin said in an interview. “Control congestion as much as possible to control the diabetes.”

Dr. Guglin had no relevant financial disclosures.

[email protected]

On Twitter @mitchelzoler

SAN DIEGO – A series of reports in 2014 from several independent groups implicated heart failure as a trigger of type 2 diabetes; findings from several of the analyses also suggested that relief of congestion can result in rapid resolution of the diabetes.

The best way to manage new-onset diabetes in heart failure patients is to “minimize the congestion,” and to “try to achieve as good control of the heart failure as possible,” said Dr. Maya Guglin during a talk at the annual meeting of the American College of Cardiology, in which she laid out the evidence for this newly recognized form of type 2 diabetes. In a review she published in 2014, Dr. Guglin coined the term “cardiogenic diabetes” to describe the condition (Heart Fail. Rev. 2014;19:595-602).

Dr. Guglin traced the data trail for cardiogenic diabetes starting in a 2011 retrospective study of 15 patients with advanced heart failure who received a left ventricular assist device (LVAD) at Columbia University in New York (Eur. J. Heart Fail. 2011;13:195-9). These 15, about a third of the 43 total LVAD recipients at Columbia at the time, had been diagnosed with type 2 diabetes for an average of 6 years before receiving the device. Just before they got their device, their average hemoglobin A_1c (HbA_1c) level was 7.7%, and their average fasting plasma glucose level was 158 mg/dL. An average of 4 months later, their mean HbA_1c had dropped to 6%, and their mean fasting glucose had fallen to 104 mg/dL. Six patients were completely off any diabetes medication. All this occurred while patients had a small increase in their body mass index, which Dr. Guglin attributed to their better physical condition and improved appetite.

Last year, another four reports appeared from four independent, U.S. heart failure groups with results that mirrored the Columbia experience. Dr. Guglin and her associates at the University of Kentucky, Lexington, reported their experience with 50 patients who received an LVAD during 2002-2012 and had type 2 diabetes just before they received a device, with an average HbA_1c of 7.6%. Three months after LVAD placement, their average HbA_1c had dropped to 5.7%, and 9-12 months after device placement, their average HbA_1c level was 5.3% (ASAIO J. 2014;60:290-3). As in the Columbia series, these improvements in hyperglycemia occurred without any significant change in body mass index.

Dr. Guglin also cited similar findings in 50 LVAD patients treated at the University of Rochester (N.Y.)(ASAIO J. 2014;60:675-80), 28 LVAD patients at Penn State Medical College in Hershey, Pa. (Heart Surg. Forum 2014;17:E98-102), and 66 LVAD patients from the University of Illinois in Chicago (Eur. J. Heart Fail. 2014;16:1120-4). In these reports type 2 diabetes existed in roughly a quarter to a third of patients with advanced heart failure who qualified for an LVAD just prior to the time they received the device.

Dr. Guglin also cited two epidemiologic analyses with complementary findings on the risk for incident diabetes faced by heart failure patients. She and her associates reviewed data from 3,165 elderly Americans free from diabetes enrolled in the Cardiovascular Health Study. This cohort included 80 patients with heart failure and 3,085 without heart failure. During 3-4 years of follow-up, 6% of the heart failure patients developed new-onset diabetes, and an additional 10% developed new-onset impaired fasting glucose. In contrast, these incidence rates were 1.5% and 5%, respectively, in the enrollees without heart failure at baseline. In an analysis that controlled for several demographic and biomedical factors, heart failure linked with a statistically significant, 2.4-fold increased risk for the development of diabetes (Cardiology 2014;129:84-92).

And a Danish nationwide cohort study of more than 99,000 residents discharged from a first-time hospitalization for heart failure during 1997-2010 showed a statistically significant link between heart failure severity and an increased rate of development of incident diabetes using diuretic treatment dosage as a surrogate measure of heart failure severity (Diabetologia 2014;57:1595-1600).

The apparent impact of LVAD placement on type 2 diabetes contrasts with what happens in patients who receive a heart transplant, where this association has not been seen. Dr. Guglin suggested that may be because of the immunosuppression with steroids that heart transplant recipients receive, treatment that also prevents diabetes resolution, she said.

“It all boils down to congestion,” Dr. Guglin said in an interview. “Control congestion as much as possible to control the diabetes.”

Dr. Guglin had no relevant financial disclosures.

[email protected]

On Twitter @mitchelzoler

Insulin glargine therapy was associated with significantly greater reductions in liver fat burden in patients with type 2 diabetes than was liraglutide, judging from the findings of a prospective randomized controlled trial.

Both treatments significantly improved glycosylated hemoglobin. However, neither led to a significant change in liver fat fraction, as measured with magnetic resonance spectroscopy (MRS), according to a study published online March 26 in Diabetes Care.

Wavebreakmedia Ltd

Researchers randomized 35 patients, whose type 2 diabetes was inadequately controlled on either metformin monotherapy or combination therapy, to 12 weeks therapy starting with 10 IU of subcutaneous insulin glargine daily or a starting dose of 0.6 mg of subcutaneous liraglutide, titrated to 1.8 mg or the maximal tolerated dose.

Patients on insulin glargine showed significant reductions in MRS-based liver proton density fat fraction (13.8% to 10.6%; P = .005), and MRI-based liver volume (2,010.6 mL to 1,858.7 mL; P = .01) and total liver fat index (304.4 vs. 209.3%; P = .01).

They also showed a trend toward a decreased MRS-based liver proton density fat fraction (12.6% to 9.9%; P = 0.06).

However patients treated with liraglutide showed no significant changes in any of these indexes (Diabetes Care 2015, March 26 [doi:10.2337/dc14-2548]).

While insulin is associated with weight gain and may be lipogenic, previous imaging studies have actually showed a reduction in liver fat with insulin therapy.

“The mechanisms by which insulin therapy may reduce liver fat include inhibition of lipolysis, which may reduce free fatty acid flux to the liver and decreased production of endogenous insulin passing through the liver to stimulate hepatic lipogenesis,” wrote Dr. An Tang, from the University of Montreal, and coauthors.

At the same time, GLP-1 agonists such as liraglutide promote weight loss and were thought to decrease liver fat by increasing fatty acid uptake and very low density–lipoprotein transport.

However, the study failed to find any significant change in biomarkers of liver fat burden among those patients randomized to liraglutide.

“It is possible that the postprandial increase in insulin secretion in the portal circulation and the decrease in glucagon secretion induced by the GLP-1 analogs could favor lipogenesis and therefore explain the lack of effect of liraglutide on hepatic steatosis observed in the current study,” the authors wrote.

The study found that patients taking liraglutide showed a significant reduction in body mass index or BMI (31.3 to 30.1 kg/m²; P = .008) while those on insulin glargine did not (31.2 to 31.3 kg/m²; P = .92).

“Interestingly, the improvement in BMI in patients randomized to liraglutide therapy was not associated with concomitant changes in the liver fat burden,” they wrote.

They noted a similar rate of adverse events in the insulin glargine and liraglutide groups.

The authors said that while the study’s short duration may have worked against liraglutide, because its impact on BMI may have had a longer term impact on liver fat fraction, they argued it was enough to address the primary end point.

“This reduction in liver fat burden on insulin therapy is reassuring and important because many patients with type 2 diabetes and NALFD [nonalcoholic fatty liver disease] have to be treated with insulin to achieve adequate glycemic control,” the authors wrote.

The study was supported by the Radiological Society of North America Research and Education Foundation, and Diabète Québec. Authors reported grants, honorarium, personal fees, and research funds from private industry.

Insulin glargine therapy was associated with significantly greater reductions in liver fat burden in patients with type 2 diabetes than was liraglutide, judging from the findings of a prospective randomized controlled trial.

Both treatments significantly improved glycosylated hemoglobin. However, neither led to a significant change in liver fat fraction, as measured with magnetic resonance spectroscopy (MRS), according to a study published online March 26 in Diabetes Care.

Wavebreakmedia Ltd

Researchers randomized 35 patients, whose type 2 diabetes was inadequately controlled on either metformin monotherapy or combination therapy, to 12 weeks therapy starting with 10 IU of subcutaneous insulin glargine daily or a starting dose of 0.6 mg of subcutaneous liraglutide, titrated to 1.8 mg or the maximal tolerated dose.

Patients on insulin glargine showed significant reductions in MRS-based liver proton density fat fraction (13.8% to 10.6%; P = .005), and MRI-based liver volume (2,010.6 mL to 1,858.7 mL; P = .01) and total liver fat index (304.4 vs. 209.3%; P = .01).

They also showed a trend toward a decreased MRS-based liver proton density fat fraction (12.6% to 9.9%; P = 0.06).

However patients treated with liraglutide showed no significant changes in any of these indexes (Diabetes Care 2015, March 26 [doi:10.2337/dc14-2548]).

While insulin is associated with weight gain and may be lipogenic, previous imaging studies have actually showed a reduction in liver fat with insulin therapy.

“The mechanisms by which insulin therapy may reduce liver fat include inhibition of lipolysis, which may reduce free fatty acid flux to the liver and decreased production of endogenous insulin passing through the liver to stimulate hepatic lipogenesis,” wrote Dr. An Tang, from the University of Montreal, and coauthors.

At the same time, GLP-1 agonists such as liraglutide promote weight loss and were thought to decrease liver fat by increasing fatty acid uptake and very low density–lipoprotein transport.

However, the study failed to find any significant change in biomarkers of liver fat burden among those patients randomized to liraglutide.

“It is possible that the postprandial increase in insulin secretion in the portal circulation and the decrease in glucagon secretion induced by the GLP-1 analogs could favor lipogenesis and therefore explain the lack of effect of liraglutide on hepatic steatosis observed in the current study,” the authors wrote.

The study found that patients taking liraglutide showed a significant reduction in body mass index or BMI (31.3 to 30.1 kg/m²; P = .008) while those on insulin glargine did not (31.2 to 31.3 kg/m²; P = .92).

“Interestingly, the improvement in BMI in patients randomized to liraglutide therapy was not associated with concomitant changes in the liver fat burden,” they wrote.

They noted a similar rate of adverse events in the insulin glargine and liraglutide groups.

The authors said that while the study’s short duration may have worked against liraglutide, because its impact on BMI may have had a longer term impact on liver fat fraction, they argued it was enough to address the primary end point.

“This reduction in liver fat burden on insulin therapy is reassuring and important because many patients with type 2 diabetes and NALFD [nonalcoholic fatty liver disease] have to be treated with insulin to achieve adequate glycemic control,” the authors wrote.

The study was supported by the Radiological Society of North America Research and Education Foundation, and Diabète Québec. Authors reported grants, honorarium, personal fees, and research funds from private industry.

Insulin glargine therapy was associated with significantly greater reductions in liver fat burden in patients with type 2 diabetes than was liraglutide, judging from the findings of a prospective randomized controlled trial.

Both treatments significantly improved glycosylated hemoglobin. However, neither led to a significant change in liver fat fraction, as measured with magnetic resonance spectroscopy (MRS), according to a study published online March 26 in Diabetes Care.

Wavebreakmedia Ltd

Researchers randomized 35 patients, whose type 2 diabetes was inadequately controlled on either metformin monotherapy or combination therapy, to 12 weeks therapy starting with 10 IU of subcutaneous insulin glargine daily or a starting dose of 0.6 mg of subcutaneous liraglutide, titrated to 1.8 mg or the maximal tolerated dose.

Patients on insulin glargine showed significant reductions in MRS-based liver proton density fat fraction (13.8% to 10.6%; P = .005), and MRI-based liver volume (2,010.6 mL to 1,858.7 mL; P = .01) and total liver fat index (304.4 vs. 209.3%; P = .01).

They also showed a trend toward a decreased MRS-based liver proton density fat fraction (12.6% to 9.9%; P = 0.06).

However patients treated with liraglutide showed no significant changes in any of these indexes (Diabetes Care 2015, March 26 [doi:10.2337/dc14-2548]).

While insulin is associated with weight gain and may be lipogenic, previous imaging studies have actually showed a reduction in liver fat with insulin therapy.

“The mechanisms by which insulin therapy may reduce liver fat include inhibition of lipolysis, which may reduce free fatty acid flux to the liver and decreased production of endogenous insulin passing through the liver to stimulate hepatic lipogenesis,” wrote Dr. An Tang, from the University of Montreal, and coauthors.

At the same time, GLP-1 agonists such as liraglutide promote weight loss and were thought to decrease liver fat by increasing fatty acid uptake and very low density–lipoprotein transport.

However, the study failed to find any significant change in biomarkers of liver fat burden among those patients randomized to liraglutide.

“It is possible that the postprandial increase in insulin secretion in the portal circulation and the decrease in glucagon secretion induced by the GLP-1 analogs could favor lipogenesis and therefore explain the lack of effect of liraglutide on hepatic steatosis observed in the current study,” the authors wrote.

The study found that patients taking liraglutide showed a significant reduction in body mass index or BMI (31.3 to 30.1 kg/m²; P = .008) while those on insulin glargine did not (31.2 to 31.3 kg/m²; P = .92).

“Interestingly, the improvement in BMI in patients randomized to liraglutide therapy was not associated with concomitant changes in the liver fat burden,” they wrote.

They noted a similar rate of adverse events in the insulin glargine and liraglutide groups.

The authors said that while the study’s short duration may have worked against liraglutide, because its impact on BMI may have had a longer term impact on liver fat fraction, they argued it was enough to address the primary end point.

“This reduction in liver fat burden on insulin therapy is reassuring and important because many patients with type 2 diabetes and NALFD [nonalcoholic fatty liver disease] have to be treated with insulin to achieve adequate glycemic control,” the authors wrote.

The study was supported by the Radiological Society of North America Research and Education Foundation, and Diabète Québec. Authors reported grants, honorarium, personal fees, and research funds from private industry.

A relatively rare genetic variant in the CCND2 gene halves the risk of type 2 diabetes by improving insulin secretion and sensitivity, but it does not appear to impact insulin processing, new data suggest.

In an effort to replicate earlier work that identified a low-frequency variant at CCND2 associated with lower risk of type 2 diabetes, enhanced insulin response to a glucose challenge, higher height and, paradoxically, higher body mass index, researchers examined associations between the variant and type 2 diabetes in 29,956 European individuals, finding a 51% lower incidence of type 2 diabetes among carriers of the allele, which ranged in frequency from 1.51% to 2.14%, according to a paper published online March 24 in Diabetes.

©ktsimage/Thinkstock.com

Individuals with the variant had significantly improved insulin secretion in response to a glucose challenge test, a higher disposition index of beta-cell function, as well as being significantly taller and of slightly greater BMI than controls (Diabetes 2015 [doi:10.2337/db14-1456]).

“The associations with improved disposition index and insulinogenic index but smaller effects with the Matsuda index, in up to 13,181 individuals, show that the protective diabetes effect operates primarily through a mechanism of relatively favorable insulin secretory response to a glucose challenge and to lower blood sugar more effectively than noncarriers,” wrote Dr. Hanieh Yaghootkar of the University of Exeter (England) and coauthors.

“Our best estimate of the effect of the variant on BMI suggests that the effect is smaller than reported in the original publication due to index event bias. Further studies are needed to establish the size of the BMI association. Our data, together with the original finding, show a mechanism through improved insulin secretion which results in lower fasting glucose levels, lower 2-hour OGTT glucose levels, and a lower risk of type 2 diabetes. Combining all data including 19,586 type 2 diabetes cases and 83,554 controls from the original study and our study provides evidence that carrying this variant reduces the risk of type 2 diabetes by approximately 50% relative to noncarriers,” the investigators wrote.

The study was supported by European Research Council, the Wellcome Trust, the University of Exeter Medical School, Novo Nordisk, and various government agencies, universities, and nonprofit organizations. There were no conflicts of interest declared.

A relatively rare genetic variant in the CCND2 gene halves the risk of type 2 diabetes by improving insulin secretion and sensitivity, but it does not appear to impact insulin processing, new data suggest.

In an effort to replicate earlier work that identified a low-frequency variant at CCND2 associated with lower risk of type 2 diabetes, enhanced insulin response to a glucose challenge, higher height and, paradoxically, higher body mass index, researchers examined associations between the variant and type 2 diabetes in 29,956 European individuals, finding a 51% lower incidence of type 2 diabetes among carriers of the allele, which ranged in frequency from 1.51% to 2.14%, according to a paper published online March 24 in Diabetes.

©ktsimage/Thinkstock.com

Individuals with the variant had significantly improved insulin secretion in response to a glucose challenge test, a higher disposition index of beta-cell function, as well as being significantly taller and of slightly greater BMI than controls (Diabetes 2015 [doi:10.2337/db14-1456]).

“The associations with improved disposition index and insulinogenic index but smaller effects with the Matsuda index, in up to 13,181 individuals, show that the protective diabetes effect operates primarily through a mechanism of relatively favorable insulin secretory response to a glucose challenge and to lower blood sugar more effectively than noncarriers,” wrote Dr. Hanieh Yaghootkar of the University of Exeter (England) and coauthors.

“Our best estimate of the effect of the variant on BMI suggests that the effect is smaller than reported in the original publication due to index event bias. Further studies are needed to establish the size of the BMI association. Our data, together with the original finding, show a mechanism through improved insulin secretion which results in lower fasting glucose levels, lower 2-hour OGTT glucose levels, and a lower risk of type 2 diabetes. Combining all data including 19,586 type 2 diabetes cases and 83,554 controls from the original study and our study provides evidence that carrying this variant reduces the risk of type 2 diabetes by approximately 50% relative to noncarriers,” the investigators wrote.

The study was supported by European Research Council, the Wellcome Trust, the University of Exeter Medical School, Novo Nordisk, and various government agencies, universities, and nonprofit organizations. There were no conflicts of interest declared.

A relatively rare genetic variant in the CCND2 gene halves the risk of type 2 diabetes by improving insulin secretion and sensitivity, but it does not appear to impact insulin processing, new data suggest.

In an effort to replicate earlier work that identified a low-frequency variant at CCND2 associated with lower risk of type 2 diabetes, enhanced insulin response to a glucose challenge, higher height and, paradoxically, higher body mass index, researchers examined associations between the variant and type 2 diabetes in 29,956 European individuals, finding a 51% lower incidence of type 2 diabetes among carriers of the allele, which ranged in frequency from 1.51% to 2.14%, according to a paper published online March 24 in Diabetes.

©ktsimage/Thinkstock.com

Individuals with the variant had significantly improved insulin secretion in response to a glucose challenge test, a higher disposition index of beta-cell function, as well as being significantly taller and of slightly greater BMI than controls (Diabetes 2015 [doi:10.2337/db14-1456]).

“The associations with improved disposition index and insulinogenic index but smaller effects with the Matsuda index, in up to 13,181 individuals, show that the protective diabetes effect operates primarily through a mechanism of relatively favorable insulin secretory response to a glucose challenge and to lower blood sugar more effectively than noncarriers,” wrote Dr. Hanieh Yaghootkar of the University of Exeter (England) and coauthors.

“Our best estimate of the effect of the variant on BMI suggests that the effect is smaller than reported in the original publication due to index event bias. Further studies are needed to establish the size of the BMI association. Our data, together with the original finding, show a mechanism through improved insulin secretion which results in lower fasting glucose levels, lower 2-hour OGTT glucose levels, and a lower risk of type 2 diabetes. Combining all data including 19,586 type 2 diabetes cases and 83,554 controls from the original study and our study provides evidence that carrying this variant reduces the risk of type 2 diabetes by approximately 50% relative to noncarriers,” the investigators wrote.

The study was supported by European Research Council, the Wellcome Trust, the University of Exeter Medical School, Novo Nordisk, and various government agencies, universities, and nonprofit organizations. There were no conflicts of interest declared.

Low-income women with preschool-aged children regard food cravings and food addiction as common behavior, but view food cravings with humor and not something to be resisted, according to Nipher M. Malika and her associates.

Study participants viewed food craving as a strong desire for food and as an acceptable behavior that did needed to be neither changed nor resisted. In fact, food cravings were viewed as a source of humor in nearly all of the interviews conducted by the investigators. In contrast, food addiction was treated as much more serious and distinct from food cravings, and was viewed as a behavioral failing rather than a moral one. Participants considered it possible for children to have food addictions but only if parents indulged their children’s cravings.

Previous efforts at reducing food cravings focused on strategies based on mindfulness and the assumption that people attempt to resist cravings. However, the study’s results “suggest that these intervention approaches may not be effective for obesity prevention in some demographic groups such as the low-income women we interviewed,” the investigators said.

Find the full study in Eating Behaviors (doi:10.1016/j.eatbeh.2015.03.005).

Low-income women with preschool-aged children regard food cravings and food addiction as common behavior, but view food cravings with humor and not something to be resisted, according to Nipher M. Malika and her associates.

Study participants viewed food craving as a strong desire for food and as an acceptable behavior that did needed to be neither changed nor resisted. In fact, food cravings were viewed as a source of humor in nearly all of the interviews conducted by the investigators. In contrast, food addiction was treated as much more serious and distinct from food cravings, and was viewed as a behavioral failing rather than a moral one. Participants considered it possible for children to have food addictions but only if parents indulged their children’s cravings.

Previous efforts at reducing food cravings focused on strategies based on mindfulness and the assumption that people attempt to resist cravings. However, the study’s results “suggest that these intervention approaches may not be effective for obesity prevention in some demographic groups such as the low-income women we interviewed,” the investigators said.

Find the full study in Eating Behaviors (doi:10.1016/j.eatbeh.2015.03.005).

Low-income women with preschool-aged children regard food cravings and food addiction as common behavior, but view food cravings with humor and not something to be resisted, according to Nipher M. Malika and her associates.

Study participants viewed food craving as a strong desire for food and as an acceptable behavior that did needed to be neither changed nor resisted. In fact, food cravings were viewed as a source of humor in nearly all of the interviews conducted by the investigators. In contrast, food addiction was treated as much more serious and distinct from food cravings, and was viewed as a behavioral failing rather than a moral one. Participants considered it possible for children to have food addictions but only if parents indulged their children’s cravings.

Previous efforts at reducing food cravings focused on strategies based on mindfulness and the assumption that people attempt to resist cravings. However, the study’s results “suggest that these intervention approaches may not be effective for obesity prevention in some demographic groups such as the low-income women we interviewed,” the investigators said.

Find the full study in Eating Behaviors (doi:10.1016/j.eatbeh.2015.03.005).

Current evidence supports the efficacy of only 2 of the 141 commercial or proprietary weight-loss programs available in the United States: Weight Watchers and Jenny Craig, according to a report published online April 6 in Annals of Internal Medicine.

Physicians are increasingly called upon to refer patients to high-intensity weight-loss programs, given provisions in the Affordable Care Act and a recent joint clinical practice guideline from the American Heart Association, the American College of Cardiology, and the Obesity Society. But there are no recommendations about the relative merits of such programs. To help clinicians assess their efficacy, investigators performed a comprehensive review of the literature.

©wragg/iStockphoto.com

They included only programs that stressed nutrition and behavioral counseling or social support, with or without a physical activity component, because these elements have been identified as essential to weight loss. This excluded popular programs such as Ornish and Zone, and winnowed the mass of evaluable weight-loss programs to 32. Further restricting their analysis to randomized clinical trials of at least 12 weeks’ duration excluded programs such as South Beach and Ideal Protein, and reduced the analysis to 11 programs assessed in 45 studies, said Dr. Kimberly A. Gudzune, of Johns Hopkins University, Baltimore, and her associates.

The primary efficacy outcome was mean percentage of weight loss at 1 year, compared with control conditions. Pooled results from six trials showed Weight Watchers resulted in a 2.6% greater weight loss, and pooled results from three trials showed Jenny Craig resulted in a 4.9% greater weight loss. NutriSystem showed “promising” short-term results, but no studies assessed its efficacy beyond the 3-month mark. The data on all other programs, including Medifast, SlimFast, HMR, Optifast, Atkins, Biggest Loser Club, eDiets, and Lose It!, were either insufficient or of questionable quality, the investigators said (Ann. Intern. Med. 2015 April 6 [doi:10.7326/M14-2238]).

“Given these findings, it may be reasonable for clinicians to refer patients to Weight Watchers or Jenny Craig, especially if they lack the time, training, or ancillary staff to deliver behavioral counseling in their practices,” Dr. Gudzune and her associates said.

Current evidence supports the efficacy of only 2 of the 141 commercial or proprietary weight-loss programs available in the United States: Weight Watchers and Jenny Craig, according to a report published online April 6 in Annals of Internal Medicine.

Physicians are increasingly called upon to refer patients to high-intensity weight-loss programs, given provisions in the Affordable Care Act and a recent joint clinical practice guideline from the American Heart Association, the American College of Cardiology, and the Obesity Society. But there are no recommendations about the relative merits of such programs. To help clinicians assess their efficacy, investigators performed a comprehensive review of the literature.

©wragg/iStockphoto.com

They included only programs that stressed nutrition and behavioral counseling or social support, with or without a physical activity component, because these elements have been identified as essential to weight loss. This excluded popular programs such as Ornish and Zone, and winnowed the mass of evaluable weight-loss programs to 32. Further restricting their analysis to randomized clinical trials of at least 12 weeks’ duration excluded programs such as South Beach and Ideal Protein, and reduced the analysis to 11 programs assessed in 45 studies, said Dr. Kimberly A. Gudzune, of Johns Hopkins University, Baltimore, and her associates.

The primary efficacy outcome was mean percentage of weight loss at 1 year, compared with control conditions. Pooled results from six trials showed Weight Watchers resulted in a 2.6% greater weight loss, and pooled results from three trials showed Jenny Craig resulted in a 4.9% greater weight loss. NutriSystem showed “promising” short-term results, but no studies assessed its efficacy beyond the 3-month mark. The data on all other programs, including Medifast, SlimFast, HMR, Optifast, Atkins, Biggest Loser Club, eDiets, and Lose It!, were either insufficient or of questionable quality, the investigators said (Ann. Intern. Med. 2015 April 6 [doi:10.7326/M14-2238]).

“Given these findings, it may be reasonable for clinicians to refer patients to Weight Watchers or Jenny Craig, especially if they lack the time, training, or ancillary staff to deliver behavioral counseling in their practices,” Dr. Gudzune and her associates said.

Current evidence supports the efficacy of only 2 of the 141 commercial or proprietary weight-loss programs available in the United States: Weight Watchers and Jenny Craig, according to a report published online April 6 in Annals of Internal Medicine.

Physicians are increasingly called upon to refer patients to high-intensity weight-loss programs, given provisions in the Affordable Care Act and a recent joint clinical practice guideline from the American Heart Association, the American College of Cardiology, and the Obesity Society. But there are no recommendations about the relative merits of such programs. To help clinicians assess their efficacy, investigators performed a comprehensive review of the literature.

©wragg/iStockphoto.com

They included only programs that stressed nutrition and behavioral counseling or social support, with or without a physical activity component, because these elements have been identified as essential to weight loss. This excluded popular programs such as Ornish and Zone, and winnowed the mass of evaluable weight-loss programs to 32. Further restricting their analysis to randomized clinical trials of at least 12 weeks’ duration excluded programs such as South Beach and Ideal Protein, and reduced the analysis to 11 programs assessed in 45 studies, said Dr. Kimberly A. Gudzune, of Johns Hopkins University, Baltimore, and her associates.

The primary efficacy outcome was mean percentage of weight loss at 1 year, compared with control conditions. Pooled results from six trials showed Weight Watchers resulted in a 2.6% greater weight loss, and pooled results from three trials showed Jenny Craig resulted in a 4.9% greater weight loss. NutriSystem showed “promising” short-term results, but no studies assessed its efficacy beyond the 3-month mark. The data on all other programs, including Medifast, SlimFast, HMR, Optifast, Atkins, Biggest Loser Club, eDiets, and Lose It!, were either insufficient or of questionable quality, the investigators said (Ann. Intern. Med. 2015 April 6 [doi:10.7326/M14-2238]).

“Given these findings, it may be reasonable for clinicians to refer patients to Weight Watchers or Jenny Craig, especially if they lack the time, training, or ancillary staff to deliver behavioral counseling in their practices,” Dr. Gudzune and her associates said.

Optimal control of glucose, blood pressure, LDL cholesterol, and smoking in adults with diabetes could result in substantial reductions of cardiovascular risk, according to results from a large cohort study of diabetes patients with and without underlying cardiovascular disease.

CV events and deaths associated with inadequate control of any of these four modifiable risk factors were about 11% and 3%, respectively, for subjects with baseline CVD, and 34% and 7%, respectively, for those without it.

Though risk was much higher for those with CVD, as expected, more attention to these traditional CVD risk factors in all diabetic patients – with or without CVD – would significantly reduce CVD-related morbidity and mortality, investigators concluded.

For their research, published online in Diabetes Care, epidemiologist Gabriela Vasquez-Benitez, Ph.D., of the Health Partners Institute for Education and Research in Minneapolis and her associates identified 859,617 patients with diabetes (31% with CVD) receiving treatment at a network of 11 U.S. health centers for 6 months or more, with mean follow-up of 5 years. About half of patients were female, and 45% were white. Risk factors were defined as LDL-C ≥100 mg/dL, glycosylated hemoglobin (HbA_1c) ≥7%, blood pressure ≥140/90 mm Hg, or smoking.

Dr. Vasquez-Benitez and associates used a regression analysis to quantify the contributions each risk factor made to CVD risk and type of CV event in both patient groups.

In patients without CVD (n = 593,167), the vast majority had HbA_1c, BP, and LDL-C not at goal or were current smokers. Inadequately controlled LDL cholesterol was associated with 19.6% of myocardial infarction or acute coronary syndrome (95% confidence interval, 18.7-20.5), and 13.7% of strokes. Smoking was associated with 3.8% of all CV events, while inadequately controlled blood pressure was associated with 11.6% of strokes. Dr. Vasquez-Benitez and colleagues found an increased CV risk for HbA_1c above 9%, but no increased risk for HbA_1c of 7%-7.9%, compared with 6.5%-6.9%. This finding supports current guidelines recommending HbA_1c targets below 7% or 8% for patients with diabetes, according to the investigators (Diab. Care 2015 Feb. 20 [doi:10.2337/dc14-1877]).

In subjects with diabetes and CVD, 7% of stroke was found attributable to inadequate blood pressure control and 5.9% to poor glycemic control. Smoking was the only factor seen associated with an increase in all-cause mortality in this patient group, with 2.6% of deaths seen linked to smoking.

Dr. Vasquez-Benitez and her colleagues noted in their analysis that a substantial share of risk could not be attributed to the modifiable factors investigated in their study, raising the possibility that “unidentified genetic, metabolic, or psychosocial risk factors may affect risk.”

The investigators noted as limitations of their study the fact that risk factors and comorbidities were assessed at baseline and may have changed during follow-up, and that data were obtained from routine care settings with varying time intervals. Patients with type I diabetes may have been included in the cohort due to difficulties distinguishing diabetes types in patient records, they said.

The study was funded by the Agency for Healthcare Research & Quality. None of its authors reported conflicts of interest.

Optimal control of glucose, blood pressure, LDL cholesterol, and smoking in adults with diabetes could result in substantial reductions of cardiovascular risk, according to results from a large cohort study of diabetes patients with and without underlying cardiovascular disease.

CV events and deaths associated with inadequate control of any of these four modifiable risk factors were about 11% and 3%, respectively, for subjects with baseline CVD, and 34% and 7%, respectively, for those without it.

Though risk was much higher for those with CVD, as expected, more attention to these traditional CVD risk factors in all diabetic patients – with or without CVD – would significantly reduce CVD-related morbidity and mortality, investigators concluded.

For their research, published online in Diabetes Care, epidemiologist Gabriela Vasquez-Benitez, Ph.D., of the Health Partners Institute for Education and Research in Minneapolis and her associates identified 859,617 patients with diabetes (31% with CVD) receiving treatment at a network of 11 U.S. health centers for 6 months or more, with mean follow-up of 5 years. About half of patients were female, and 45% were white. Risk factors were defined as LDL-C ≥100 mg/dL, glycosylated hemoglobin (HbA_1c) ≥7%, blood pressure ≥140/90 mm Hg, or smoking.

Dr. Vasquez-Benitez and associates used a regression analysis to quantify the contributions each risk factor made to CVD risk and type of CV event in both patient groups.

In patients without CVD (n = 593,167), the vast majority had HbA_1c, BP, and LDL-C not at goal or were current smokers. Inadequately controlled LDL cholesterol was associated with 19.6% of myocardial infarction or acute coronary syndrome (95% confidence interval, 18.7-20.5), and 13.7% of strokes. Smoking was associated with 3.8% of all CV events, while inadequately controlled blood pressure was associated with 11.6% of strokes. Dr. Vasquez-Benitez and colleagues found an increased CV risk for HbA_1c above 9%, but no increased risk for HbA_1c of 7%-7.9%, compared with 6.5%-6.9%. This finding supports current guidelines recommending HbA_1c targets below 7% or 8% for patients with diabetes, according to the investigators (Diab. Care 2015 Feb. 20 [doi:10.2337/dc14-1877]).

In subjects with diabetes and CVD, 7% of stroke was found attributable to inadequate blood pressure control and 5.9% to poor glycemic control. Smoking was the only factor seen associated with an increase in all-cause mortality in this patient group, with 2.6% of deaths seen linked to smoking.

Dr. Vasquez-Benitez and her colleagues noted in their analysis that a substantial share of risk could not be attributed to the modifiable factors investigated in their study, raising the possibility that “unidentified genetic, metabolic, or psychosocial risk factors may affect risk.”

The investigators noted as limitations of their study the fact that risk factors and comorbidities were assessed at baseline and may have changed during follow-up, and that data were obtained from routine care settings with varying time intervals. Patients with type I diabetes may have been included in the cohort due to difficulties distinguishing diabetes types in patient records, they said.

The study was funded by the Agency for Healthcare Research & Quality. None of its authors reported conflicts of interest.

Optimal control of glucose, blood pressure, LDL cholesterol, and smoking in adults with diabetes could result in substantial reductions of cardiovascular risk, according to results from a large cohort study of diabetes patients with and without underlying cardiovascular disease.

CV events and deaths associated with inadequate control of any of these four modifiable risk factors were about 11% and 3%, respectively, for subjects with baseline CVD, and 34% and 7%, respectively, for those without it.

Though risk was much higher for those with CVD, as expected, more attention to these traditional CVD risk factors in all diabetic patients – with or without CVD – would significantly reduce CVD-related morbidity and mortality, investigators concluded.

For their research, published online in Diabetes Care, epidemiologist Gabriela Vasquez-Benitez, Ph.D., of the Health Partners Institute for Education and Research in Minneapolis and her associates identified 859,617 patients with diabetes (31% with CVD) receiving treatment at a network of 11 U.S. health centers for 6 months or more, with mean follow-up of 5 years. About half of patients were female, and 45% were white. Risk factors were defined as LDL-C ≥100 mg/dL, glycosylated hemoglobin (HbA_1c) ≥7%, blood pressure ≥140/90 mm Hg, or smoking.

Dr. Vasquez-Benitez and associates used a regression analysis to quantify the contributions each risk factor made to CVD risk and type of CV event in both patient groups.

In patients without CVD (n = 593,167), the vast majority had HbA_1c, BP, and LDL-C not at goal or were current smokers. Inadequately controlled LDL cholesterol was associated with 19.6% of myocardial infarction or acute coronary syndrome (95% confidence interval, 18.7-20.5), and 13.7% of strokes. Smoking was associated with 3.8% of all CV events, while inadequately controlled blood pressure was associated with 11.6% of strokes. Dr. Vasquez-Benitez and colleagues found an increased CV risk for HbA_1c above 9%, but no increased risk for HbA_1c of 7%-7.9%, compared with 6.5%-6.9%. This finding supports current guidelines recommending HbA_1c targets below 7% or 8% for patients with diabetes, according to the investigators (Diab. Care 2015 Feb. 20 [doi:10.2337/dc14-1877]).

In subjects with diabetes and CVD, 7% of stroke was found attributable to inadequate blood pressure control and 5.9% to poor glycemic control. Smoking was the only factor seen associated with an increase in all-cause mortality in this patient group, with 2.6% of deaths seen linked to smoking.

Dr. Vasquez-Benitez and her colleagues noted in their analysis that a substantial share of risk could not be attributed to the modifiable factors investigated in their study, raising the possibility that “unidentified genetic, metabolic, or psychosocial risk factors may affect risk.”

The investigators noted as limitations of their study the fact that risk factors and comorbidities were assessed at baseline and may have changed during follow-up, and that data were obtained from routine care settings with varying time intervals. Patients with type I diabetes may have been included in the cohort due to difficulties distinguishing diabetes types in patient records, they said.

The study was funded by the Agency for Healthcare Research & Quality. None of its authors reported conflicts of interest.