American Diabetes Association (ADA): Annual Scientific Sessions 2011

SAN DIEGO – Depression is a significant independent predictor of increased mortality and may increase the risk of subsequent macrovascular events in adults with type 2 diabetes, according to a data analysis.

The findings underscore the importance of detecting and effectively managing depression in people with type 2 diabetes, concluded Dr. Patrick J. O’Connor, a family physician who is a senior clinical investigator at HealthPartners Research Foundation, Minneapolis.

The findings were based on an analysis of 2,053 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study’s HRQL (Health-Related Quality of Life) investigation, all of whom completed the 9-item depression measure from the Patient Health Questionnaire (PHQ-9) at baseline and at 12, 36, and 48 months.

"The PHQ-9 exam is not a face-to-face mental health exam with a psychiatrist; it is nine questions on a piece of paper, so it’s good but it’s not perfect," Dr. O’Connor said at the annual scientific sessions of the American Diabetes Association. A score of 10 or more on the PHQ-9 has a sensitivity of 77% and a specificity of 94% for the diagnosis of major depression.

The researchers measured depression in three different ways: having a PHQ-9 score of 10 or greater (indicating moderate to major depression); scoring 2-3 points on five of the items (considered major depression), and scoring 2 or more points on three or four of the items (considered minor depression).

Cox proportional hazard regression modeling was used to estimate hazard ratios for the impact of depression status on ACCORD’s clinical end points: the primary composite outcome (cardiovascular death, or nonfatal heart attack or stroke), the macrovascular composite outcome (cardiovascular death, nonfatal heart attack or stroke, or heart failure), and the microvascular composite outcome (progression of retinopathy, nephropathy, and neuropathy).

The mean age of study participants was 62 years, and 39% were women. Of the 2,053 patients, 712 (35%) reported a history of depression at baseline. Compared with those who reported no history of depression, those who did were more likely to be women (46% vs. 36%, respectively), to be smokers (17% vs. 11%), to have a higher mean hemoglobin A_1c level (8.4% vs. 8.2%), and to require insulin (41% vs. 33%).

About a third (30%) of the study participants scored 10 or more on the PHQ-9, which indicated moderate to major depression; 15% were considered to have major depression and 18% minor depression. After adjustment for numerous factors (including age, sex, race, coronary heart disease and heart failure status, HbA_1c levels, lipid levels, blood pressure, body mass index, and smoking status), total mortality was significantly increased both in those with a PHQ-9 score of 10 or more (hazard ratio, 1.84), and major depression (HR, 2.24), but not in those with minor depression (HR, 1.14).

"This shows that depression status is an independent predictor of mortality, even after you adjust for cardiovascular risk factors," Dr. O’Connor commented.

The relationship of major depression to ACCORD’s macrovascular outcome reached borderline statistical significance (HR, 1.42), but major depression was not significantly related to ACCORD’s primary composite outcome (HR, 1.53) or to ACCORD’s microvascular composite outcome (HR, 0.93).

The study’s primary investigator was Dr. Mark D. Sullivan, professor of psychiatry at the University of Washington, Seattle.

Dr. O’Connor said that he had no relevant conflicts of interest.

SAN DIEGO – Depression is a significant independent predictor of increased mortality and may increase the risk of subsequent macrovascular events in adults with type 2 diabetes, according to a data analysis.

The findings underscore the importance of detecting and effectively managing depression in people with type 2 diabetes, concluded Dr. Patrick J. O’Connor, a family physician who is a senior clinical investigator at HealthPartners Research Foundation, Minneapolis.

The findings were based on an analysis of 2,053 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study’s HRQL (Health-Related Quality of Life) investigation, all of whom completed the 9-item depression measure from the Patient Health Questionnaire (PHQ-9) at baseline and at 12, 36, and 48 months.

"The PHQ-9 exam is not a face-to-face mental health exam with a psychiatrist; it is nine questions on a piece of paper, so it’s good but it’s not perfect," Dr. O’Connor said at the annual scientific sessions of the American Diabetes Association. A score of 10 or more on the PHQ-9 has a sensitivity of 77% and a specificity of 94% for the diagnosis of major depression.

The researchers measured depression in three different ways: having a PHQ-9 score of 10 or greater (indicating moderate to major depression); scoring 2-3 points on five of the items (considered major depression), and scoring 2 or more points on three or four of the items (considered minor depression).

Cox proportional hazard regression modeling was used to estimate hazard ratios for the impact of depression status on ACCORD’s clinical end points: the primary composite outcome (cardiovascular death, or nonfatal heart attack or stroke), the macrovascular composite outcome (cardiovascular death, nonfatal heart attack or stroke, or heart failure), and the microvascular composite outcome (progression of retinopathy, nephropathy, and neuropathy).

The mean age of study participants was 62 years, and 39% were women. Of the 2,053 patients, 712 (35%) reported a history of depression at baseline. Compared with those who reported no history of depression, those who did were more likely to be women (46% vs. 36%, respectively), to be smokers (17% vs. 11%), to have a higher mean hemoglobin A_1c level (8.4% vs. 8.2%), and to require insulin (41% vs. 33%).

About a third (30%) of the study participants scored 10 or more on the PHQ-9, which indicated moderate to major depression; 15% were considered to have major depression and 18% minor depression. After adjustment for numerous factors (including age, sex, race, coronary heart disease and heart failure status, HbA_1c levels, lipid levels, blood pressure, body mass index, and smoking status), total mortality was significantly increased both in those with a PHQ-9 score of 10 or more (hazard ratio, 1.84), and major depression (HR, 2.24), but not in those with minor depression (HR, 1.14).

"This shows that depression status is an independent predictor of mortality, even after you adjust for cardiovascular risk factors," Dr. O’Connor commented.

The relationship of major depression to ACCORD’s macrovascular outcome reached borderline statistical significance (HR, 1.42), but major depression was not significantly related to ACCORD’s primary composite outcome (HR, 1.53) or to ACCORD’s microvascular composite outcome (HR, 0.93).

The study’s primary investigator was Dr. Mark D. Sullivan, professor of psychiatry at the University of Washington, Seattle.

Dr. O’Connor said that he had no relevant conflicts of interest.

SAN DIEGO – Depression is a significant independent predictor of increased mortality and may increase the risk of subsequent macrovascular events in adults with type 2 diabetes, according to a data analysis.

The findings underscore the importance of detecting and effectively managing depression in people with type 2 diabetes, concluded Dr. Patrick J. O’Connor, a family physician who is a senior clinical investigator at HealthPartners Research Foundation, Minneapolis.

The findings were based on an analysis of 2,053 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study’s HRQL (Health-Related Quality of Life) investigation, all of whom completed the 9-item depression measure from the Patient Health Questionnaire (PHQ-9) at baseline and at 12, 36, and 48 months.

"The PHQ-9 exam is not a face-to-face mental health exam with a psychiatrist; it is nine questions on a piece of paper, so it’s good but it’s not perfect," Dr. O’Connor said at the annual scientific sessions of the American Diabetes Association. A score of 10 or more on the PHQ-9 has a sensitivity of 77% and a specificity of 94% for the diagnosis of major depression.

The researchers measured depression in three different ways: having a PHQ-9 score of 10 or greater (indicating moderate to major depression); scoring 2-3 points on five of the items (considered major depression), and scoring 2 or more points on three or four of the items (considered minor depression).

Cox proportional hazard regression modeling was used to estimate hazard ratios for the impact of depression status on ACCORD’s clinical end points: the primary composite outcome (cardiovascular death, or nonfatal heart attack or stroke), the macrovascular composite outcome (cardiovascular death, nonfatal heart attack or stroke, or heart failure), and the microvascular composite outcome (progression of retinopathy, nephropathy, and neuropathy).

The mean age of study participants was 62 years, and 39% were women. Of the 2,053 patients, 712 (35%) reported a history of depression at baseline. Compared with those who reported no history of depression, those who did were more likely to be women (46% vs. 36%, respectively), to be smokers (17% vs. 11%), to have a higher mean hemoglobin A_1c level (8.4% vs. 8.2%), and to require insulin (41% vs. 33%).

About a third (30%) of the study participants scored 10 or more on the PHQ-9, which indicated moderate to major depression; 15% were considered to have major depression and 18% minor depression. After adjustment for numerous factors (including age, sex, race, coronary heart disease and heart failure status, HbA_1c levels, lipid levels, blood pressure, body mass index, and smoking status), total mortality was significantly increased both in those with a PHQ-9 score of 10 or more (hazard ratio, 1.84), and major depression (HR, 2.24), but not in those with minor depression (HR, 1.14).

"This shows that depression status is an independent predictor of mortality, even after you adjust for cardiovascular risk factors," Dr. O’Connor commented.

The relationship of major depression to ACCORD’s macrovascular outcome reached borderline statistical significance (HR, 1.42), but major depression was not significantly related to ACCORD’s primary composite outcome (HR, 1.53) or to ACCORD’s microvascular composite outcome (HR, 0.93).

The study’s primary investigator was Dr. Mark D. Sullivan, professor of psychiatry at the University of Washington, Seattle.

Dr. O’Connor said that he had no relevant conflicts of interest.

SAN DIEGO – Hearing impairment was more than twice as likely in adults with diabetes, compared with adults without diabetes in a meta-analysis of 13 observational studies.

Screening for hearing impairment for patients with diabetes may improve their ability to communicate and their quality of life, the investigators suggested.

Age-related hearing loss had been found associated with diabetes, but the study may be the first to quantify the strength of that association, Dr. Hirohito Sone, Chika Horikawa, and their associates reported at the annual Scientific Sessions of the American Diabetes Association.

The findings suggest that diabetes contributes to the progression of hearing impairment, though the biological or pathological mechanisms of this are not known, said Dr. Sone, professor of medicine at the University of Tsukuba Mito Medical Center, Ibaraki, Japan, where Ms. Horikawa also is based. They speculated that neuropathy or vascular disease may contribute to the hearing loss.

Eight of the 13 studies were conducted in Asia and five in Western countries. A total of 20,061 participants were included, 7,797 of whom had diabetes. Nine studies focused on the general population and four focused on hospital-based patients.

The studies looked for nonidiopathic progressive hearing impairment that was not due to noise or heredity. Hearing impairment was defined by cutoff values of pure-tone thresholds measured at a frequency range that included 2,000 Hz. Three of the studies matched patients with and without diabetes by age and sex.

Overall, diabetes was associated with a doubling in the odds of developing hearing impairment, the meta-analysis found. The risk was higher for younger adults or hospital-based patients.

Hearing impairment was three times more common in adults younger than 60 years with diabetes, compared with those without diabetes. Hospital-based patients had nearly a fourfold increased risk for hearing impairment if they had diabetes.

In all subsets of participants, there was a positive association between diabetes and hearing impairment.

Further research is needed to determine whether hearing impairment is a complication of diabetes. Research might focus on potential relationships between diabetes severity or duration and the likelihood of hearing impairment, whether people with diabetes have an earlier onset of age-related hearing impairment, and whether good glycemic control might prevent the progression of hearing loss.

The investigators reported having no conflicts of interest.

SAN DIEGO – Hearing impairment was more than twice as likely in adults with diabetes, compared with adults without diabetes in a meta-analysis of 13 observational studies.

Screening for hearing impairment for patients with diabetes may improve their ability to communicate and their quality of life, the investigators suggested.

Age-related hearing loss had been found associated with diabetes, but the study may be the first to quantify the strength of that association, Dr. Hirohito Sone, Chika Horikawa, and their associates reported at the annual Scientific Sessions of the American Diabetes Association.

The findings suggest that diabetes contributes to the progression of hearing impairment, though the biological or pathological mechanisms of this are not known, said Dr. Sone, professor of medicine at the University of Tsukuba Mito Medical Center, Ibaraki, Japan, where Ms. Horikawa also is based. They speculated that neuropathy or vascular disease may contribute to the hearing loss.

Eight of the 13 studies were conducted in Asia and five in Western countries. A total of 20,061 participants were included, 7,797 of whom had diabetes. Nine studies focused on the general population and four focused on hospital-based patients.

The studies looked for nonidiopathic progressive hearing impairment that was not due to noise or heredity. Hearing impairment was defined by cutoff values of pure-tone thresholds measured at a frequency range that included 2,000 Hz. Three of the studies matched patients with and without diabetes by age and sex.

Overall, diabetes was associated with a doubling in the odds of developing hearing impairment, the meta-analysis found. The risk was higher for younger adults or hospital-based patients.

Hearing impairment was three times more common in adults younger than 60 years with diabetes, compared with those without diabetes. Hospital-based patients had nearly a fourfold increased risk for hearing impairment if they had diabetes.

In all subsets of participants, there was a positive association between diabetes and hearing impairment.

Further research is needed to determine whether hearing impairment is a complication of diabetes. Research might focus on potential relationships between diabetes severity or duration and the likelihood of hearing impairment, whether people with diabetes have an earlier onset of age-related hearing impairment, and whether good glycemic control might prevent the progression of hearing loss.

The investigators reported having no conflicts of interest.

SAN DIEGO – Hearing impairment was more than twice as likely in adults with diabetes, compared with adults without diabetes in a meta-analysis of 13 observational studies.

Screening for hearing impairment for patients with diabetes may improve their ability to communicate and their quality of life, the investigators suggested.

Age-related hearing loss had been found associated with diabetes, but the study may be the first to quantify the strength of that association, Dr. Hirohito Sone, Chika Horikawa, and their associates reported at the annual Scientific Sessions of the American Diabetes Association.

The findings suggest that diabetes contributes to the progression of hearing impairment, though the biological or pathological mechanisms of this are not known, said Dr. Sone, professor of medicine at the University of Tsukuba Mito Medical Center, Ibaraki, Japan, where Ms. Horikawa also is based. They speculated that neuropathy or vascular disease may contribute to the hearing loss.

Eight of the 13 studies were conducted in Asia and five in Western countries. A total of 20,061 participants were included, 7,797 of whom had diabetes. Nine studies focused on the general population and four focused on hospital-based patients.

The studies looked for nonidiopathic progressive hearing impairment that was not due to noise or heredity. Hearing impairment was defined by cutoff values of pure-tone thresholds measured at a frequency range that included 2,000 Hz. Three of the studies matched patients with and without diabetes by age and sex.

Overall, diabetes was associated with a doubling in the odds of developing hearing impairment, the meta-analysis found. The risk was higher for younger adults or hospital-based patients.

Hearing impairment was three times more common in adults younger than 60 years with diabetes, compared with those without diabetes. Hospital-based patients had nearly a fourfold increased risk for hearing impairment if they had diabetes.

In all subsets of participants, there was a positive association between diabetes and hearing impairment.

Further research is needed to determine whether hearing impairment is a complication of diabetes. Research might focus on potential relationships between diabetes severity or duration and the likelihood of hearing impairment, whether people with diabetes have an earlier onset of age-related hearing impairment, and whether good glycemic control might prevent the progression of hearing loss.

The investigators reported having no conflicts of interest.

SAN DIEGO – The patient-centered medical home is beginning to demonstrate a positive impact on patients with diabetes, results from a national analysis showed.

"A lot of this has not been published yet, but we see improvements in several diabetes care measures of quality, and cost savings as well," Dr. Robert A. Gabbay said at the annual scientific sessions of the American Diabetes Association. "Stay tuned, because this is coming to a primary care practice near you. It’s catching on everywhere."

A new model for primary care, the patient-centered medical home (PCMH), involves a "more coordinated care system, enhances access for patients, and fosters team-based care, distributing the care amongst the team within the practice," explained Dr. Gabbay, who directs the Penn State Hershey Institute for Diabetes and Obesity. "At the foundation of all this is a payment reform system that helps to reimburse at a higher rate for all of these coordinated activities."

He described diabetes as a natural target for the PCMH because it’s a high-cost disease, it’s highly prevalent, and there are established, measurable evidence-based quality goals that clinicians generally agree upon. "The diabetes community has had early recognition of many of the key concepts of the medical home, such as population management, use of registries, supporting patients in their own self-management, and team-based care," he said.

More than 40 diabetes-focused PCMH demonstration projects are currently under way nationally, Dr. Gabbay said. He provided a progress report from projects launched by three large integrated health systems:

– Group Health Cooperative, Seattle: Improvements of 51%-59% in its bundled "composite quality score" of diabetes measures for 9,200 patients in the first 2 years, reductions in emergency department and inpatient admissions, and a return of $1.50 for every dollar invested in the PCMH after 21 months.

– Geisinger Health System, Danville, Pa.: First-year improvements in the proportion of patients with an HbA_1c of less than 7.0% (from 32% to 35%); blood pressure of less than 130/80 mm Hg (from 40% to 44%); and the "diabetic bundle," a measure of nine diabetes indicators (from 2% to 7%).

– HealthPartners, Minneapolis: Improvements in the bundled measures of HbA_1c, blood pressure, low-density lipoprotein (LDL) cholesterol, aspirin use, and tobacco cessation over a 4-year period (from 4% to 25%).

State initiatives have also shown improvements, said Dr. Gabbay, who is also professor of medicine at the Pennsylvania State University. For example, an assessment of 11,900 patients served by 25 of the 150 practices in a Pennsylvania-based medical home initiative launched in 2010 showed reductions in the proportion of patients with an HbA_1c of greater than 9.0% (–6%), as well as improvements in the proportion of patients with systolic blood pressure of less than 130 mm Hg (12%), LDL less than 130 mg/dL (12%), those setting self-management goals (38%), foot examinations (25%), eye examinations (18%), and diabetic nephropathy screening (13%).

In a Rhode Island initiative, providers reported improvements after 2 years in the proportion of patients achieving an HbA_1c of less than 7.0% (from 33% to 40%), blood pressure of less than 130/80 mm Hg (from 18% to 40%), and LDL of less than 100 mg/dL (from 27% to 42%).

In the meantime, initiatives in Colorado and North Carolina have both met National Committee for Quality Assurance benchmarks for diabetes care, as well as reductions in emergency department and inpatient admissions.

The most frequently used approaches to transform to a PCMH, Dr. Gabbay said, are implementing patient registries, upgrading electronic health records, improving care management, participating in learning collaboratives, and practice coaching.

"In Pennsylvania, it’s been very much driven by the chronic care model, which has a much stronger evidence base in terms of improving quality of care," he said. That state’s initiative also includes monthly outcome data reporting and multipayer financial incentives.

Dr. Gabbay said that he had no relevant financial disclosures to make.

SAN DIEGO – The patient-centered medical home is beginning to demonstrate a positive impact on patients with diabetes, results from a national analysis showed.

"A lot of this has not been published yet, but we see improvements in several diabetes care measures of quality, and cost savings as well," Dr. Robert A. Gabbay said at the annual scientific sessions of the American Diabetes Association. "Stay tuned, because this is coming to a primary care practice near you. It’s catching on everywhere."

A new model for primary care, the patient-centered medical home (PCMH), involves a "more coordinated care system, enhances access for patients, and fosters team-based care, distributing the care amongst the team within the practice," explained Dr. Gabbay, who directs the Penn State Hershey Institute for Diabetes and Obesity. "At the foundation of all this is a payment reform system that helps to reimburse at a higher rate for all of these coordinated activities."

He described diabetes as a natural target for the PCMH because it’s a high-cost disease, it’s highly prevalent, and there are established, measurable evidence-based quality goals that clinicians generally agree upon. "The diabetes community has had early recognition of many of the key concepts of the medical home, such as population management, use of registries, supporting patients in their own self-management, and team-based care," he said.

More than 40 diabetes-focused PCMH demonstration projects are currently under way nationally, Dr. Gabbay said. He provided a progress report from projects launched by three large integrated health systems:

– Group Health Cooperative, Seattle: Improvements of 51%-59% in its bundled "composite quality score" of diabetes measures for 9,200 patients in the first 2 years, reductions in emergency department and inpatient admissions, and a return of $1.50 for every dollar invested in the PCMH after 21 months.

– Geisinger Health System, Danville, Pa.: First-year improvements in the proportion of patients with an HbA_1c of less than 7.0% (from 32% to 35%); blood pressure of less than 130/80 mm Hg (from 40% to 44%); and the "diabetic bundle," a measure of nine diabetes indicators (from 2% to 7%).

– HealthPartners, Minneapolis: Improvements in the bundled measures of HbA_1c, blood pressure, low-density lipoprotein (LDL) cholesterol, aspirin use, and tobacco cessation over a 4-year period (from 4% to 25%).

State initiatives have also shown improvements, said Dr. Gabbay, who is also professor of medicine at the Pennsylvania State University. For example, an assessment of 11,900 patients served by 25 of the 150 practices in a Pennsylvania-based medical home initiative launched in 2010 showed reductions in the proportion of patients with an HbA_1c of greater than 9.0% (–6%), as well as improvements in the proportion of patients with systolic blood pressure of less than 130 mm Hg (12%), LDL less than 130 mg/dL (12%), those setting self-management goals (38%), foot examinations (25%), eye examinations (18%), and diabetic nephropathy screening (13%).

In a Rhode Island initiative, providers reported improvements after 2 years in the proportion of patients achieving an HbA_1c of less than 7.0% (from 33% to 40%), blood pressure of less than 130/80 mm Hg (from 18% to 40%), and LDL of less than 100 mg/dL (from 27% to 42%).

In the meantime, initiatives in Colorado and North Carolina have both met National Committee for Quality Assurance benchmarks for diabetes care, as well as reductions in emergency department and inpatient admissions.

The most frequently used approaches to transform to a PCMH, Dr. Gabbay said, are implementing patient registries, upgrading electronic health records, improving care management, participating in learning collaboratives, and practice coaching.

"In Pennsylvania, it’s been very much driven by the chronic care model, which has a much stronger evidence base in terms of improving quality of care," he said. That state’s initiative also includes monthly outcome data reporting and multipayer financial incentives.

Dr. Gabbay said that he had no relevant financial disclosures to make.

SAN DIEGO – The patient-centered medical home is beginning to demonstrate a positive impact on patients with diabetes, results from a national analysis showed.

"A lot of this has not been published yet, but we see improvements in several diabetes care measures of quality, and cost savings as well," Dr. Robert A. Gabbay said at the annual scientific sessions of the American Diabetes Association. "Stay tuned, because this is coming to a primary care practice near you. It’s catching on everywhere."

A new model for primary care, the patient-centered medical home (PCMH), involves a "more coordinated care system, enhances access for patients, and fosters team-based care, distributing the care amongst the team within the practice," explained Dr. Gabbay, who directs the Penn State Hershey Institute for Diabetes and Obesity. "At the foundation of all this is a payment reform system that helps to reimburse at a higher rate for all of these coordinated activities."

He described diabetes as a natural target for the PCMH because it’s a high-cost disease, it’s highly prevalent, and there are established, measurable evidence-based quality goals that clinicians generally agree upon. "The diabetes community has had early recognition of many of the key concepts of the medical home, such as population management, use of registries, supporting patients in their own self-management, and team-based care," he said.

More than 40 diabetes-focused PCMH demonstration projects are currently under way nationally, Dr. Gabbay said. He provided a progress report from projects launched by three large integrated health systems:

– Group Health Cooperative, Seattle: Improvements of 51%-59% in its bundled "composite quality score" of diabetes measures for 9,200 patients in the first 2 years, reductions in emergency department and inpatient admissions, and a return of $1.50 for every dollar invested in the PCMH after 21 months.

– Geisinger Health System, Danville, Pa.: First-year improvements in the proportion of patients with an HbA_1c of less than 7.0% (from 32% to 35%); blood pressure of less than 130/80 mm Hg (from 40% to 44%); and the "diabetic bundle," a measure of nine diabetes indicators (from 2% to 7%).

– HealthPartners, Minneapolis: Improvements in the bundled measures of HbA_1c, blood pressure, low-density lipoprotein (LDL) cholesterol, aspirin use, and tobacco cessation over a 4-year period (from 4% to 25%).

State initiatives have also shown improvements, said Dr. Gabbay, who is also professor of medicine at the Pennsylvania State University. For example, an assessment of 11,900 patients served by 25 of the 150 practices in a Pennsylvania-based medical home initiative launched in 2010 showed reductions in the proportion of patients with an HbA_1c of greater than 9.0% (–6%), as well as improvements in the proportion of patients with systolic blood pressure of less than 130 mm Hg (12%), LDL less than 130 mg/dL (12%), those setting self-management goals (38%), foot examinations (25%), eye examinations (18%), and diabetic nephropathy screening (13%).

In a Rhode Island initiative, providers reported improvements after 2 years in the proportion of patients achieving an HbA_1c of less than 7.0% (from 33% to 40%), blood pressure of less than 130/80 mm Hg (from 18% to 40%), and LDL of less than 100 mg/dL (from 27% to 42%).

In the meantime, initiatives in Colorado and North Carolina have both met National Committee for Quality Assurance benchmarks for diabetes care, as well as reductions in emergency department and inpatient admissions.

The most frequently used approaches to transform to a PCMH, Dr. Gabbay said, are implementing patient registries, upgrading electronic health records, improving care management, participating in learning collaboratives, and practice coaching.

"In Pennsylvania, it’s been very much driven by the chronic care model, which has a much stronger evidence base in terms of improving quality of care," he said. That state’s initiative also includes monthly outcome data reporting and multipayer financial incentives.

Dr. Gabbay said that he had no relevant financial disclosures to make.

SAN DIEGO – Life expectancy of patients with type 1 diabetes has improved dramatically since 1950, results from a long-term prospective study have shown.

According to the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study, life expectancy at birth for those diagnosed with type 1 diabetes during 1965-1980 was 68.8 years, or about 4 years less than that of a comparable cohort of the U.S. general population, while life expectancy for those diagnosed during 1950-1964 was 53.4 years, or about 18 years less than that of a comparable cohort of the general population.

"Individuals with childhood-onset diabetes do not represent a major insurance risk and should be minimally penalized, if at all, in terms of life insurance and other mortality-based decisions," Dr. Trevor J. Orchard said at the annual scientific sessions of the American Diabetes Association.

While numerous other studies have shown that mortality in type 1 diabetes has been decreasing in recent decades, "how this currently translates into improved life expectancy in the United States was not clear," said Dr. Orchard, professor of epidemiology, pediatrics, and medicine at the University of Pittsburgh.

The objective of the current study was to compare the life expectancy among two different cohorts of patients enrolled in the Pittsburgh EDC Study, which is a prospective study of childhood-onset type 1 diabetes. Of the 933 patients, 390 were diagnosed or seen within 1 year of diagnosis at Children’s Hospital of Pittsburgh during 1950-1964 (cohort 1), while 543 were diagnosed or seen within a year of diagnosis during 1965-1980 (cohort 2). Half of the participants were female, and their mean age at diagnosis was 8 years. All were followed through 2009.

To ascertain mortality, the researchers used death certificates and hospital, autopsy, and coroner reports. They used Kaplan-Meier curves and the log-rank statistic to determine differences in survival benefits between the cohorts, and constructed abridged life tables to calculate life expectancy.

Dr. Orchard reported that the 30-year mortality for patients in cohort 1 was 35% compared with 12% for those in cohort 2, a statistically significant difference. Similarly, the life expectancy at birth for those in cohort 1 was estimated to be 53.4 years compared with 68.8 years for those in cohort 2, a difference of about 15 years (P less than .0001). This persisted regardless of sex or pubertal status at diagnosis of diabetes.

The life expectancy of cohort 2 is 3.6 years less than that estimated for a comparable cohort of the U.S. general population (72.4 years), Dr. Orchard said, while the life expectancy of cohort 1 is about 18 years less than that of a comparable cohort of the general population (71.5 years).

Reasons for the improvement in life expectancy between the two cohorts are multifactorial, he said, including the development of blood glucose self-monitoring and the use of the hemoglobin A_1c test, which was not available in cohort 1.

"It’s difficult to partition the exact reasons for the changes, but the major improvement in terms of complications has been in renal disease," Dr. Orchard said. "Cardiovascular disease is not improving in these patients as dramatically as renal disease."

Dr. Orchard disclosed that he is a consultant for AstraZeneca and Abbott Laboratories, received research support from VeraLight, and has inherited Bristol-Myers Squibb stock

SAN DIEGO – Life expectancy of patients with type 1 diabetes has improved dramatically since 1950, results from a long-term prospective study have shown.

According to the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study, life expectancy at birth for those diagnosed with type 1 diabetes during 1965-1980 was 68.8 years, or about 4 years less than that of a comparable cohort of the U.S. general population, while life expectancy for those diagnosed during 1950-1964 was 53.4 years, or about 18 years less than that of a comparable cohort of the general population.

"Individuals with childhood-onset diabetes do not represent a major insurance risk and should be minimally penalized, if at all, in terms of life insurance and other mortality-based decisions," Dr. Trevor J. Orchard said at the annual scientific sessions of the American Diabetes Association.

While numerous other studies have shown that mortality in type 1 diabetes has been decreasing in recent decades, "how this currently translates into improved life expectancy in the United States was not clear," said Dr. Orchard, professor of epidemiology, pediatrics, and medicine at the University of Pittsburgh.

The objective of the current study was to compare the life expectancy among two different cohorts of patients enrolled in the Pittsburgh EDC Study, which is a prospective study of childhood-onset type 1 diabetes. Of the 933 patients, 390 were diagnosed or seen within 1 year of diagnosis at Children’s Hospital of Pittsburgh during 1950-1964 (cohort 1), while 543 were diagnosed or seen within a year of diagnosis during 1965-1980 (cohort 2). Half of the participants were female, and their mean age at diagnosis was 8 years. All were followed through 2009.

To ascertain mortality, the researchers used death certificates and hospital, autopsy, and coroner reports. They used Kaplan-Meier curves and the log-rank statistic to determine differences in survival benefits between the cohorts, and constructed abridged life tables to calculate life expectancy.

Dr. Orchard reported that the 30-year mortality for patients in cohort 1 was 35% compared with 12% for those in cohort 2, a statistically significant difference. Similarly, the life expectancy at birth for those in cohort 1 was estimated to be 53.4 years compared with 68.8 years for those in cohort 2, a difference of about 15 years (P less than .0001). This persisted regardless of sex or pubertal status at diagnosis of diabetes.

The life expectancy of cohort 2 is 3.6 years less than that estimated for a comparable cohort of the U.S. general population (72.4 years), Dr. Orchard said, while the life expectancy of cohort 1 is about 18 years less than that of a comparable cohort of the general population (71.5 years).

Reasons for the improvement in life expectancy between the two cohorts are multifactorial, he said, including the development of blood glucose self-monitoring and the use of the hemoglobin A_1c test, which was not available in cohort 1.

"It’s difficult to partition the exact reasons for the changes, but the major improvement in terms of complications has been in renal disease," Dr. Orchard said. "Cardiovascular disease is not improving in these patients as dramatically as renal disease."

Dr. Orchard disclosed that he is a consultant for AstraZeneca and Abbott Laboratories, received research support from VeraLight, and has inherited Bristol-Myers Squibb stock

SAN DIEGO – Life expectancy of patients with type 1 diabetes has improved dramatically since 1950, results from a long-term prospective study have shown.

According to the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study, life expectancy at birth for those diagnosed with type 1 diabetes during 1965-1980 was 68.8 years, or about 4 years less than that of a comparable cohort of the U.S. general population, while life expectancy for those diagnosed during 1950-1964 was 53.4 years, or about 18 years less than that of a comparable cohort of the general population.

"Individuals with childhood-onset diabetes do not represent a major insurance risk and should be minimally penalized, if at all, in terms of life insurance and other mortality-based decisions," Dr. Trevor J. Orchard said at the annual scientific sessions of the American Diabetes Association.

While numerous other studies have shown that mortality in type 1 diabetes has been decreasing in recent decades, "how this currently translates into improved life expectancy in the United States was not clear," said Dr. Orchard, professor of epidemiology, pediatrics, and medicine at the University of Pittsburgh.

The objective of the current study was to compare the life expectancy among two different cohorts of patients enrolled in the Pittsburgh EDC Study, which is a prospective study of childhood-onset type 1 diabetes. Of the 933 patients, 390 were diagnosed or seen within 1 year of diagnosis at Children’s Hospital of Pittsburgh during 1950-1964 (cohort 1), while 543 were diagnosed or seen within a year of diagnosis during 1965-1980 (cohort 2). Half of the participants were female, and their mean age at diagnosis was 8 years. All were followed through 2009.

To ascertain mortality, the researchers used death certificates and hospital, autopsy, and coroner reports. They used Kaplan-Meier curves and the log-rank statistic to determine differences in survival benefits between the cohorts, and constructed abridged life tables to calculate life expectancy.

Dr. Orchard reported that the 30-year mortality for patients in cohort 1 was 35% compared with 12% for those in cohort 2, a statistically significant difference. Similarly, the life expectancy at birth for those in cohort 1 was estimated to be 53.4 years compared with 68.8 years for those in cohort 2, a difference of about 15 years (P less than .0001). This persisted regardless of sex or pubertal status at diagnosis of diabetes.

The life expectancy of cohort 2 is 3.6 years less than that estimated for a comparable cohort of the U.S. general population (72.4 years), Dr. Orchard said, while the life expectancy of cohort 1 is about 18 years less than that of a comparable cohort of the general population (71.5 years).

Reasons for the improvement in life expectancy between the two cohorts are multifactorial, he said, including the development of blood glucose self-monitoring and the use of the hemoglobin A_1c test, which was not available in cohort 1.

"It’s difficult to partition the exact reasons for the changes, but the major improvement in terms of complications has been in renal disease," Dr. Orchard said. "Cardiovascular disease is not improving in these patients as dramatically as renal disease."

Dr. Orchard disclosed that he is a consultant for AstraZeneca and Abbott Laboratories, received research support from VeraLight, and has inherited Bristol-Myers Squibb stock

SAN DIEGO – Life expectancy of patients with type 1 diabetes has improved dramatically since 1950, results from a long-term prospective study have shown.

According to the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study, life expectancy at birth for those diagnosed with type 1 diabetes during 1965-1980 was 68.8 years, or about 4 years less than that of a comparable cohort of the U.S. general population, while life expectancy for those diagnosed during 1950-1964 was 53.4 years, or about 18 years less than that of a comparable cohort of the general population.

"Individuals with childhood-onset diabetes do not represent a major insurance risk and should be minimally penalized, if at all, in terms of life insurance and other mortality-based decisions," Dr. Trevor J. Orchard said at the annual scientific sessions of the American Diabetes Association.

While numerous other studies have shown that mortality in type 1 diabetes has been decreasing in recent decades, "how this currently translates into improved life expectancy in the United States was not clear," said Dr. Orchard, professor of epidemiology, pediatrics, and medicine at the University of Pittsburgh.

The objective of the current study was to compare the life expectancy among two different cohorts of patients enrolled in the Pittsburgh EDC Study, which is a prospective study of childhood-onset type 1 diabetes. Of the 933 patients, 390 were diagnosed or seen within 1 year of diagnosis at Children’s Hospital of Pittsburgh during 1950-1964 (cohort 1), while 543 were diagnosed or seen within a year of diagnosis during 1965-1980 (cohort 2). Half of the participants were female, and their mean age at diagnosis was 8 years. All were followed through 2009.

To ascertain mortality, the researchers used death certificates and hospital, autopsy, and coroner reports. They used Kaplan-Meier curves and the log-rank statistic to determine differences in survival benefits between the cohorts, and constructed abridged life tables to calculate life expectancy.

Dr. Orchard reported that the 30-year mortality for patients in cohort 1 was 35% compared with 12% for those in cohort 2, a statistically significant difference. Similarly, the life expectancy at birth for those in cohort 1 was estimated to be 53.4 years compared with 68.8 years for those in cohort 2, a difference of about 15 years (P less than .0001). This persisted regardless of sex or pubertal status at diagnosis of diabetes.

The life expectancy of cohort 2 is 3.6 years less than that estimated for a comparable cohort of the U.S. general population (72.4 years), Dr. Orchard said, while the life expectancy of cohort 1 is about 18 years less than that of a comparable cohort of the general population (71.5 years).

Reasons for the improvement in life expectancy between the two cohorts are multifactorial, he said, including the development of blood glucose self-monitoring and the use of the hemoglobin A_1c test, which was not available in cohort 1.

"It’s difficult to partition the exact reasons for the changes, but the major improvement in terms of complications has been in renal disease," Dr. Orchard said. "Cardiovascular disease is not improving in these patients as dramatically as renal disease."

Dr. Orchard disclosed that he is a consultant for AstraZeneca and Abbott Laboratories, received research support from VeraLight, and has inherited Bristol-Myers Squibb stock

SAN DIEGO – Life expectancy of patients with type 1 diabetes has improved dramatically since 1950, results from a long-term prospective study have shown.

According to the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study, life expectancy at birth for those diagnosed with type 1 diabetes during 1965-1980 was 68.8 years, or about 4 years less than that of a comparable cohort of the U.S. general population, while life expectancy for those diagnosed during 1950-1964 was 53.4 years, or about 18 years less than that of a comparable cohort of the general population.

"Individuals with childhood-onset diabetes do not represent a major insurance risk and should be minimally penalized, if at all, in terms of life insurance and other mortality-based decisions," Dr. Trevor J. Orchard said at the annual scientific sessions of the American Diabetes Association.

While numerous other studies have shown that mortality in type 1 diabetes has been decreasing in recent decades, "how this currently translates into improved life expectancy in the United States was not clear," said Dr. Orchard, professor of epidemiology, pediatrics, and medicine at the University of Pittsburgh.

The objective of the current study was to compare the life expectancy among two different cohorts of patients enrolled in the Pittsburgh EDC Study, which is a prospective study of childhood-onset type 1 diabetes. Of the 933 patients, 390 were diagnosed or seen within 1 year of diagnosis at Children’s Hospital of Pittsburgh during 1950-1964 (cohort 1), while 543 were diagnosed or seen within a year of diagnosis during 1965-1980 (cohort 2). Half of the participants were female, and their mean age at diagnosis was 8 years. All were followed through 2009.

To ascertain mortality, the researchers used death certificates and hospital, autopsy, and coroner reports. They used Kaplan-Meier curves and the log-rank statistic to determine differences in survival benefits between the cohorts, and constructed abridged life tables to calculate life expectancy.

Dr. Orchard reported that the 30-year mortality for patients in cohort 1 was 35% compared with 12% for those in cohort 2, a statistically significant difference. Similarly, the life expectancy at birth for those in cohort 1 was estimated to be 53.4 years compared with 68.8 years for those in cohort 2, a difference of about 15 years (P less than .0001). This persisted regardless of sex or pubertal status at diagnosis of diabetes.

The life expectancy of cohort 2 is 3.6 years less than that estimated for a comparable cohort of the U.S. general population (72.4 years), Dr. Orchard said, while the life expectancy of cohort 1 is about 18 years less than that of a comparable cohort of the general population (71.5 years).

Reasons for the improvement in life expectancy between the two cohorts are multifactorial, he said, including the development of blood glucose self-monitoring and the use of the hemoglobin A_1c test, which was not available in cohort 1.

"It’s difficult to partition the exact reasons for the changes, but the major improvement in terms of complications has been in renal disease," Dr. Orchard said. "Cardiovascular disease is not improving in these patients as dramatically as renal disease."

Dr. Orchard disclosed that he is a consultant for AstraZeneca and Abbott Laboratories, received research support from VeraLight, and has inherited Bristol-Myers Squibb stock

SAN DIEGO – Life expectancy of patients with type 1 diabetes has improved dramatically since 1950, results from a long-term prospective study have shown.

According to the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study, life expectancy at birth for those diagnosed with type 1 diabetes during 1965-1980 was 68.8 years, or about 4 years less than that of a comparable cohort of the U.S. general population, while life expectancy for those diagnosed during 1950-1964 was 53.4 years, or about 18 years less than that of a comparable cohort of the general population.

"Individuals with childhood-onset diabetes do not represent a major insurance risk and should be minimally penalized, if at all, in terms of life insurance and other mortality-based decisions," Dr. Trevor J. Orchard said at the annual scientific sessions of the American Diabetes Association.

While numerous other studies have shown that mortality in type 1 diabetes has been decreasing in recent decades, "how this currently translates into improved life expectancy in the United States was not clear," said Dr. Orchard, professor of epidemiology, pediatrics, and medicine at the University of Pittsburgh.

The objective of the current study was to compare the life expectancy among two different cohorts of patients enrolled in the Pittsburgh EDC Study, which is a prospective study of childhood-onset type 1 diabetes. Of the 933 patients, 390 were diagnosed or seen within 1 year of diagnosis at Children’s Hospital of Pittsburgh during 1950-1964 (cohort 1), while 543 were diagnosed or seen within a year of diagnosis during 1965-1980 (cohort 2). Half of the participants were female, and their mean age at diagnosis was 8 years. All were followed through 2009.

To ascertain mortality, the researchers used death certificates and hospital, autopsy, and coroner reports. They used Kaplan-Meier curves and the log-rank statistic to determine differences in survival benefits between the cohorts, and constructed abridged life tables to calculate life expectancy.

Dr. Orchard reported that the 30-year mortality for patients in cohort 1 was 35% compared with 12% for those in cohort 2, a statistically significant difference. Similarly, the life expectancy at birth for those in cohort 1 was estimated to be 53.4 years compared with 68.8 years for those in cohort 2, a difference of about 15 years (P less than .0001). This persisted regardless of sex or pubertal status at diagnosis of diabetes.

The life expectancy of cohort 2 is 3.6 years less than that estimated for a comparable cohort of the U.S. general population (72.4 years), Dr. Orchard said, while the life expectancy of cohort 1 is about 18 years less than that of a comparable cohort of the general population (71.5 years).

Reasons for the improvement in life expectancy between the two cohorts are multifactorial, he said, including the development of blood glucose self-monitoring and the use of the hemoglobin A_1c test, which was not available in cohort 1.

"It’s difficult to partition the exact reasons for the changes, but the major improvement in terms of complications has been in renal disease," Dr. Orchard said. "Cardiovascular disease is not improving in these patients as dramatically as renal disease."

Dr. Orchard disclosed that he is a consultant for AstraZeneca and Abbott Laboratories, received research support from VeraLight, and has inherited Bristol-Myers Squibb stock

SAN DIEGO – Several potential approaches are being attempted to slow the autoimmune progression of type 1 diabetes in newly diagnosed patients, with varying degrees of success.

The studies, funded by government agencies, biotechnology companies, and pharmaceutical manufacturers, are in various phases. "We’re testing things in new-onset type 1 diabetes to see whether or not they modify the course of the disease, and to gain insights as to which ones are safe enough to take into prevention studies. ... The field is in a state of flux at the moment," Dr. Jay S. Skyler said in an interview.

Dr. Skyler chairs the National Institutes of Health–funded Type 1 Diabetes TrialNet study group, which sponsored two of the trials that were presented at the annual scientific sessions of the American Diabetes Association and simultaneously published in the Lancet on June 28.

One of those studies, in which new-onset type 1 patients were treated with the antigen glutamic acid decarboxylase (GAD), produced negative results. A total of 145 patients aged 3-45 years who had been diagnosed within the prior 100 days were randomized to either three injections of 20 mcg of GAD formulated with aluminum hydroxide (GAD-alum), two injections of GAD-alum plus one of alum alone, or three injections of alum alone.

At 1 year, the 2-hour area under the curve (AUC) of C-peptide, adjusted for age, sex, and baseline C-peptide value, was 0.412 nmol/L in the GAD-alum group, 0.382 nmol/L in the GAD-alum plus alum group, and 0.413 in the alum-only group. Those differences were not significant (Lancet 2011 June 27 [doi:10.1016/S0140-6736[11]60895-7]).

Importantly, however, there were no adverse events. "What we’ve learned is that some of [the agents being tested] don’t work in new onset diabetes, but they are safe. So, they might work earlier in the disease process for prevention. Whether we need a combination of things to really arrest the disease process is another open question," said Dr. Skyler, professor of medicine, pediatrics, and psychology at the University of Miami.

The other TrialNet study involved abatacept (Bristol Myers Squibb’s Orencia), which modulates T-cell costimulation and prevents full T-cell activation. Orencia is currently on the U.S. market for treating adult rheumatoid arthritis and juvenile idiopathic arthritis. In the study, 112 patients were randomized to treatment with either abatacept (77 patients) or placebo (35 patients) intravenous infusions on days 1, 14, 28, and monthly for a total of 27 infusions over 2 years (Lancet 2011 June 28 [doi:10.1016/S0140-6736[11]60886-6]).

Here, there was a significant difference between groups, with the AUC for C-peptide 59% higher with abatacept than placebo at 2 years, and the estimated delay in C-peptide reduction of 9.6 months. However, despite continued administration of abatacept over 24 months, the decrease in beta-cell function with abatacept was parallel to that with placebo after 6 months of treatment, suggesting that T-cell activation lessens with time, said Dr. Tihamer Orban of Joslin Diabetes Center, Boston.

Two additional drugs under study, teplizumab and otelixizumab, are both anti-CD3 monoclonal antibodies that bind to the surface of T-cells and modulate their action. Two studies of teplizumab were presented. In one phase II study called AbATE (anti-cd3 mAb), 52 type 1 patients aged 8-30 years were given two intravenous courses of the drug 1 year apart, while 25 patients received placebo infusions.

There was a significant retention of C-peptide with teplizumab compared with controls. The teplizumab group had a 45% decrease in beta-cell function over 2 years, compared with a 77% reduction in the untreated group, said Dr. Stephen E. Gitelman, professor of clinical pediatrics at the University of California, San Francisco.

The AbATE trial was sponsored by the Immune Tolerance Network, which is funded by the National Institutes of Health. Funding was also provided by the Juvenile Diabetes Research Foundation.

The other teplizumab trial, Protégé, was funded by MacroGenics. It was a 2-year, phase III, double-blind, placebo-controlled, multinational study, with the combined goal of reducing hemoglobin A_1c to less than 6.5% for those newly diagnosed with type 1 diabetes and reducing the amount of insulin needed to less than 0.5 units/kg per day.

The primary end point did not differ between the two groups, with 19.8% in the teplizumab group and 20.4% of placebo patients achieving the combined end point at 1 year, said Dr. Nicole Sherry, director of the Diabetes Center at Massachusetts General Hospital for Children in Boston (Lancet 2011 June 28 [doi:10.1016/S0140-6736[11]60931-8]).

However, 5% of the 513 study patients no longer required insulin at 1 year, compared with none of those who received placebo. Moreover, in a post hoc analysis, C-peptide was preserved or increased in 40% of those who received the 14-day regimen of the drug, compared with just 28% of the placebo group. Children were more likely than were adults to retain C-peptide function, as were patients treated within 6 weeks of diagnosis. Adverse events were similar between the two groups, she noted.

A phase III study of the anti-CD3 drug oteliximab in 240 newly diagnosed type 1 diabetes patients also produced negative findings. The dose – one-sixteenth of that used in previous trials – had been chosen to reduce adverse events seen previously, particularly Epstein-Barr virus activation. The low dose was not effective in preserving C-peptide. This study, dubbed DEFEND, was funded by Tolerx, with support from the Juvenile Diabetes Research Foundation.

"This is clearly an important pathway. Further studies will try to increase that dosage to duplicate the previous efficacy with fewer side effects," said Dr. Peter Gottlieb, professor of medicine and pediatrics at the University of Colorado, Denver.

Another compound under study, DiaPep277, was developed with the goal of preventing beta-cell destruction. Created by the removal of 24 of 500 amino acids from a "heat shock" protein involved in beta-cell destruction via T-cell activation, DiaPep277 had been shown to change destructive T cells into cytokine-secreting protective T-cells in mouse models of type 1 diabetes.

In one phase II study, injections of DiaPep277 in 100 newly diagnosed patients with type 1 diabetes preserved beta-cell insulin secretion for up to 2 years following diagnosis, said Dr. Itamar Raz, professor of medicine and director of the Hadassah Diabetic Center in Jerusalem, Hadassah Hebrew University Hospital.

DiaPep277 is currently in two phase III trials in which beta-cell function, insulin use, and glucose control are being monitored as key outcomes in more than 450 patients per trial. Results for one of the studies are expected by early next year, Dr. Raz said.

Dr. Skyler is an advisory panel and/or board member for a long list of companies that make diabetes-related products. He holds stock in and/or is a shareholder of Amylin Pharmaceuticals, Circulat Biotech, Dexcom, Ideal Life, Inspire Pharmaceuticals, Moerae Matrix, and Tandem Diabetes Care.

Dr. Gitelman and Dr. Sherry stated that they have no disclosures. Dr. Orban serves on the data safety monitoring board for Osiris Therapeutics and is a founding member of Orban Biotechs LLC. Dr. Gottlieb receives research funding from Tolerx, GlaxoSmithKline, MacroGenics, and Diamyd. He has consulted for Eli Lilly, Sanofi-Aventis, and Genentech.

Dr. Raz is a board member of, serves on the advisory panel for, is on the speakers bureau, or is a consultant for AstraZeneca LP, Bristol-Myers Squibb, Novo-Nordisk Pharma Ltd., Roche Pharmaceuticals, and Andromeda.

SAN DIEGO – Several potential approaches are being attempted to slow the autoimmune progression of type 1 diabetes in newly diagnosed patients, with varying degrees of success.

The studies, funded by government agencies, biotechnology companies, and pharmaceutical manufacturers, are in various phases. "We’re testing things in new-onset type 1 diabetes to see whether or not they modify the course of the disease, and to gain insights as to which ones are safe enough to take into prevention studies. ... The field is in a state of flux at the moment," Dr. Jay S. Skyler said in an interview.

Dr. Skyler chairs the National Institutes of Health–funded Type 1 Diabetes TrialNet study group, which sponsored two of the trials that were presented at the annual scientific sessions of the American Diabetes Association and simultaneously published in the Lancet on June 28.

One of those studies, in which new-onset type 1 patients were treated with the antigen glutamic acid decarboxylase (GAD), produced negative results. A total of 145 patients aged 3-45 years who had been diagnosed within the prior 100 days were randomized to either three injections of 20 mcg of GAD formulated with aluminum hydroxide (GAD-alum), two injections of GAD-alum plus one of alum alone, or three injections of alum alone.

At 1 year, the 2-hour area under the curve (AUC) of C-peptide, adjusted for age, sex, and baseline C-peptide value, was 0.412 nmol/L in the GAD-alum group, 0.382 nmol/L in the GAD-alum plus alum group, and 0.413 in the alum-only group. Those differences were not significant (Lancet 2011 June 27 [doi:10.1016/S0140-6736[11]60895-7]).

Importantly, however, there were no adverse events. "What we’ve learned is that some of [the agents being tested] don’t work in new onset diabetes, but they are safe. So, they might work earlier in the disease process for prevention. Whether we need a combination of things to really arrest the disease process is another open question," said Dr. Skyler, professor of medicine, pediatrics, and psychology at the University of Miami.

The other TrialNet study involved abatacept (Bristol Myers Squibb’s Orencia), which modulates T-cell costimulation and prevents full T-cell activation. Orencia is currently on the U.S. market for treating adult rheumatoid arthritis and juvenile idiopathic arthritis. In the study, 112 patients were randomized to treatment with either abatacept (77 patients) or placebo (35 patients) intravenous infusions on days 1, 14, 28, and monthly for a total of 27 infusions over 2 years (Lancet 2011 June 28 [doi:10.1016/S0140-6736[11]60886-6]).

Here, there was a significant difference between groups, with the AUC for C-peptide 59% higher with abatacept than placebo at 2 years, and the estimated delay in C-peptide reduction of 9.6 months. However, despite continued administration of abatacept over 24 months, the decrease in beta-cell function with abatacept was parallel to that with placebo after 6 months of treatment, suggesting that T-cell activation lessens with time, said Dr. Tihamer Orban of Joslin Diabetes Center, Boston.

Two additional drugs under study, teplizumab and otelixizumab, are both anti-CD3 monoclonal antibodies that bind to the surface of T-cells and modulate their action. Two studies of teplizumab were presented. In one phase II study called AbATE (anti-cd3 mAb), 52 type 1 patients aged 8-30 years were given two intravenous courses of the drug 1 year apart, while 25 patients received placebo infusions.

There was a significant retention of C-peptide with teplizumab compared with controls. The teplizumab group had a 45% decrease in beta-cell function over 2 years, compared with a 77% reduction in the untreated group, said Dr. Stephen E. Gitelman, professor of clinical pediatrics at the University of California, San Francisco.

The AbATE trial was sponsored by the Immune Tolerance Network, which is funded by the National Institutes of Health. Funding was also provided by the Juvenile Diabetes Research Foundation.

The other teplizumab trial, Protégé, was funded by MacroGenics. It was a 2-year, phase III, double-blind, placebo-controlled, multinational study, with the combined goal of reducing hemoglobin A_1c to less than 6.5% for those newly diagnosed with type 1 diabetes and reducing the amount of insulin needed to less than 0.5 units/kg per day.

The primary end point did not differ between the two groups, with 19.8% in the teplizumab group and 20.4% of placebo patients achieving the combined end point at 1 year, said Dr. Nicole Sherry, director of the Diabetes Center at Massachusetts General Hospital for Children in Boston (Lancet 2011 June 28 [doi:10.1016/S0140-6736[11]60931-8]).

However, 5% of the 513 study patients no longer required insulin at 1 year, compared with none of those who received placebo. Moreover, in a post hoc analysis, C-peptide was preserved or increased in 40% of those who received the 14-day regimen of the drug, compared with just 28% of the placebo group. Children were more likely than were adults to retain C-peptide function, as were patients treated within 6 weeks of diagnosis. Adverse events were similar between the two groups, she noted.

A phase III study of the anti-CD3 drug oteliximab in 240 newly diagnosed type 1 diabetes patients also produced negative findings. The dose – one-sixteenth of that used in previous trials – had been chosen to reduce adverse events seen previously, particularly Epstein-Barr virus activation. The low dose was not effective in preserving C-peptide. This study, dubbed DEFEND, was funded by Tolerx, with support from the Juvenile Diabetes Research Foundation.

"This is clearly an important pathway. Further studies will try to increase that dosage to duplicate the previous efficacy with fewer side effects," said Dr. Peter Gottlieb, professor of medicine and pediatrics at the University of Colorado, Denver.

Another compound under study, DiaPep277, was developed with the goal of preventing beta-cell destruction. Created by the removal of 24 of 500 amino acids from a "heat shock" protein involved in beta-cell destruction via T-cell activation, DiaPep277 had been shown to change destructive T cells into cytokine-secreting protective T-cells in mouse models of type 1 diabetes.

In one phase II study, injections of DiaPep277 in 100 newly diagnosed patients with type 1 diabetes preserved beta-cell insulin secretion for up to 2 years following diagnosis, said Dr. Itamar Raz, professor of medicine and director of the Hadassah Diabetic Center in Jerusalem, Hadassah Hebrew University Hospital.

DiaPep277 is currently in two phase III trials in which beta-cell function, insulin use, and glucose control are being monitored as key outcomes in more than 450 patients per trial. Results for one of the studies are expected by early next year, Dr. Raz said.

Dr. Skyler is an advisory panel and/or board member for a long list of companies that make diabetes-related products. He holds stock in and/or is a shareholder of Amylin Pharmaceuticals, Circulat Biotech, Dexcom, Ideal Life, Inspire Pharmaceuticals, Moerae Matrix, and Tandem Diabetes Care.

Dr. Gitelman and Dr. Sherry stated that they have no disclosures. Dr. Orban serves on the data safety monitoring board for Osiris Therapeutics and is a founding member of Orban Biotechs LLC. Dr. Gottlieb receives research funding from Tolerx, GlaxoSmithKline, MacroGenics, and Diamyd. He has consulted for Eli Lilly, Sanofi-Aventis, and Genentech.

Dr. Raz is a board member of, serves on the advisory panel for, is on the speakers bureau, or is a consultant for AstraZeneca LP, Bristol-Myers Squibb, Novo-Nordisk Pharma Ltd., Roche Pharmaceuticals, and Andromeda.

SAN DIEGO – Several potential approaches are being attempted to slow the autoimmune progression of type 1 diabetes in newly diagnosed patients, with varying degrees of success.

The studies, funded by government agencies, biotechnology companies, and pharmaceutical manufacturers, are in various phases. "We’re testing things in new-onset type 1 diabetes to see whether or not they modify the course of the disease, and to gain insights as to which ones are safe enough to take into prevention studies. ... The field is in a state of flux at the moment," Dr. Jay S. Skyler said in an interview.

Dr. Skyler chairs the National Institutes of Health–funded Type 1 Diabetes TrialNet study group, which sponsored two of the trials that were presented at the annual scientific sessions of the American Diabetes Association and simultaneously published in the Lancet on June 28.

One of those studies, in which new-onset type 1 patients were treated with the antigen glutamic acid decarboxylase (GAD), produced negative results. A total of 145 patients aged 3-45 years who had been diagnosed within the prior 100 days were randomized to either three injections of 20 mcg of GAD formulated with aluminum hydroxide (GAD-alum), two injections of GAD-alum plus one of alum alone, or three injections of alum alone.

At 1 year, the 2-hour area under the curve (AUC) of C-peptide, adjusted for age, sex, and baseline C-peptide value, was 0.412 nmol/L in the GAD-alum group, 0.382 nmol/L in the GAD-alum plus alum group, and 0.413 in the alum-only group. Those differences were not significant (Lancet 2011 June 27 [doi:10.1016/S0140-6736[11]60895-7]).

Importantly, however, there were no adverse events. "What we’ve learned is that some of [the agents being tested] don’t work in new onset diabetes, but they are safe. So, they might work earlier in the disease process for prevention. Whether we need a combination of things to really arrest the disease process is another open question," said Dr. Skyler, professor of medicine, pediatrics, and psychology at the University of Miami.

The other TrialNet study involved abatacept (Bristol Myers Squibb’s Orencia), which modulates T-cell costimulation and prevents full T-cell activation. Orencia is currently on the U.S. market for treating adult rheumatoid arthritis and juvenile idiopathic arthritis. In the study, 112 patients were randomized to treatment with either abatacept (77 patients) or placebo (35 patients) intravenous infusions on days 1, 14, 28, and monthly for a total of 27 infusions over 2 years (Lancet 2011 June 28 [doi:10.1016/S0140-6736[11]60886-6]).

Here, there was a significant difference between groups, with the AUC for C-peptide 59% higher with abatacept than placebo at 2 years, and the estimated delay in C-peptide reduction of 9.6 months. However, despite continued administration of abatacept over 24 months, the decrease in beta-cell function with abatacept was parallel to that with placebo after 6 months of treatment, suggesting that T-cell activation lessens with time, said Dr. Tihamer Orban of Joslin Diabetes Center, Boston.

Two additional drugs under study, teplizumab and otelixizumab, are both anti-CD3 monoclonal antibodies that bind to the surface of T-cells and modulate their action. Two studies of teplizumab were presented. In one phase II study called AbATE (anti-cd3 mAb), 52 type 1 patients aged 8-30 years were given two intravenous courses of the drug 1 year apart, while 25 patients received placebo infusions.

There was a significant retention of C-peptide with teplizumab compared with controls. The teplizumab group had a 45% decrease in beta-cell function over 2 years, compared with a 77% reduction in the untreated group, said Dr. Stephen E. Gitelman, professor of clinical pediatrics at the University of California, San Francisco.

The AbATE trial was sponsored by the Immune Tolerance Network, which is funded by the National Institutes of Health. Funding was also provided by the Juvenile Diabetes Research Foundation.

The other teplizumab trial, Protégé, was funded by MacroGenics. It was a 2-year, phase III, double-blind, placebo-controlled, multinational study, with the combined goal of reducing hemoglobin A_1c to less than 6.5% for those newly diagnosed with type 1 diabetes and reducing the amount of insulin needed to less than 0.5 units/kg per day.

The primary end point did not differ between the two groups, with 19.8% in the teplizumab group and 20.4% of placebo patients achieving the combined end point at 1 year, said Dr. Nicole Sherry, director of the Diabetes Center at Massachusetts General Hospital for Children in Boston (Lancet 2011 June 28 [doi:10.1016/S0140-6736[11]60931-8]).

However, 5% of the 513 study patients no longer required insulin at 1 year, compared with none of those who received placebo. Moreover, in a post hoc analysis, C-peptide was preserved or increased in 40% of those who received the 14-day regimen of the drug, compared with just 28% of the placebo group. Children were more likely than were adults to retain C-peptide function, as were patients treated within 6 weeks of diagnosis. Adverse events were similar between the two groups, she noted.

A phase III study of the anti-CD3 drug oteliximab in 240 newly diagnosed type 1 diabetes patients also produced negative findings. The dose – one-sixteenth of that used in previous trials – had been chosen to reduce adverse events seen previously, particularly Epstein-Barr virus activation. The low dose was not effective in preserving C-peptide. This study, dubbed DEFEND, was funded by Tolerx, with support from the Juvenile Diabetes Research Foundation.

"This is clearly an important pathway. Further studies will try to increase that dosage to duplicate the previous efficacy with fewer side effects," said Dr. Peter Gottlieb, professor of medicine and pediatrics at the University of Colorado, Denver.

Another compound under study, DiaPep277, was developed with the goal of preventing beta-cell destruction. Created by the removal of 24 of 500 amino acids from a "heat shock" protein involved in beta-cell destruction via T-cell activation, DiaPep277 had been shown to change destructive T cells into cytokine-secreting protective T-cells in mouse models of type 1 diabetes.

In one phase II study, injections of DiaPep277 in 100 newly diagnosed patients with type 1 diabetes preserved beta-cell insulin secretion for up to 2 years following diagnosis, said Dr. Itamar Raz, professor of medicine and director of the Hadassah Diabetic Center in Jerusalem, Hadassah Hebrew University Hospital.

DiaPep277 is currently in two phase III trials in which beta-cell function, insulin use, and glucose control are being monitored as key outcomes in more than 450 patients per trial. Results for one of the studies are expected by early next year, Dr. Raz said.

Dr. Skyler is an advisory panel and/or board member for a long list of companies that make diabetes-related products. He holds stock in and/or is a shareholder of Amylin Pharmaceuticals, Circulat Biotech, Dexcom, Ideal Life, Inspire Pharmaceuticals, Moerae Matrix, and Tandem Diabetes Care.

Dr. Gitelman and Dr. Sherry stated that they have no disclosures. Dr. Orban serves on the data safety monitoring board for Osiris Therapeutics and is a founding member of Orban Biotechs LLC. Dr. Gottlieb receives research funding from Tolerx, GlaxoSmithKline, MacroGenics, and Diamyd. He has consulted for Eli Lilly, Sanofi-Aventis, and Genentech.

Dr. Raz is a board member of, serves on the advisory panel for, is on the speakers bureau, or is a consultant for AstraZeneca LP, Bristol-Myers Squibb, Novo-Nordisk Pharma Ltd., Roche Pharmaceuticals, and Andromeda.

SAN DIEGO – Several potential approaches are being attempted to slow the autoimmune progression of type 1 diabetes in newly diagnosed patients, with varying degrees of success.

The studies, funded by government agencies, biotechnology companies, and pharmaceutical manufacturers, are in various phases. "We’re testing things in new-onset type 1 diabetes to see whether or not they modify the course of the disease, and to gain insights as to which ones are safe enough to take into prevention studies. ... The field is in a state of flux at the moment," Dr. Jay S. Skyler said in an interview.

Dr. Skyler chairs the National Institutes of Health–funded Type 1 Diabetes TrialNet study group, which sponsored two of the trials that were presented at the annual scientific sessions of the American Diabetes Association and simultaneously published in the Lancet on June 28.

One of those studies, in which new-onset type 1 patients were treated with the antigen glutamic acid decarboxylase (GAD), produced negative results. A total of 145 patients aged 3-45 years who had been diagnosed within the prior 100 days were randomized to either three injections of 20 mcg of GAD formulated with aluminum hydroxide (GAD-alum), two injections of GAD-alum plus one of alum alone, or three injections of alum alone.

At 1 year, the 2-hour area under the curve (AUC) of C-peptide, adjusted for age, sex, and baseline C-peptide value, was 0.412 nmol/L in the GAD-alum group, 0.382 nmol/L in the GAD-alum plus alum group, and 0.413 in the alum-only group. Those differences were not significant (Lancet 2011 June 27 [doi:10.1016/S0140-6736[11]60895-7]).

Importantly, however, there were no adverse events. "What we’ve learned is that some of [the agents being tested] don’t work in new onset diabetes, but they are safe. So, they might work earlier in the disease process for prevention. Whether we need a combination of things to really arrest the disease process is another open question," said Dr. Skyler, professor of medicine, pediatrics, and psychology at the University of Miami.

The other TrialNet study involved abatacept (Bristol Myers Squibb’s Orencia), which modulates T-cell costimulation and prevents full T-cell activation. Orencia is currently on the U.S. market for treating adult rheumatoid arthritis and juvenile idiopathic arthritis. In the study, 112 patients were randomized to treatment with either abatacept (77 patients) or placebo (35 patients) intravenous infusions on days 1, 14, 28, and monthly for a total of 27 infusions over 2 years (Lancet 2011 June 28 [doi:10.1016/S0140-6736[11]60886-6]).

Here, there was a significant difference between groups, with the AUC for C-peptide 59% higher with abatacept than placebo at 2 years, and the estimated delay in C-peptide reduction of 9.6 months. However, despite continued administration of abatacept over 24 months, the decrease in beta-cell function with abatacept was parallel to that with placebo after 6 months of treatment, suggesting that T-cell activation lessens with time, said Dr. Tihamer Orban of Joslin Diabetes Center, Boston.

Two additional drugs under study, teplizumab and otelixizumab, are both anti-CD3 monoclonal antibodies that bind to the surface of T-cells and modulate their action. Two studies of teplizumab were presented. In one phase II study called AbATE (anti-cd3 mAb), 52 type 1 patients aged 8-30 years were given two intravenous courses of the drug 1 year apart, while 25 patients received placebo infusions.

There was a significant retention of C-peptide with teplizumab compared with controls. The teplizumab group had a 45% decrease in beta-cell function over 2 years, compared with a 77% reduction in the untreated group, said Dr. Stephen E. Gitelman, professor of clinical pediatrics at the University of California, San Francisco.

The AbATE trial was sponsored by the Immune Tolerance Network, which is funded by the National Institutes of Health. Funding was also provided by the Juvenile Diabetes Research Foundation.

The other teplizumab trial, Protégé, was funded by MacroGenics. It was a 2-year, phase III, double-blind, placebo-controlled, multinational study, with the combined goal of reducing hemoglobin A_1c to less than 6.5% for those newly diagnosed with type 1 diabetes and reducing the amount of insulin needed to less than 0.5 units/kg per day.

The primary end point did not differ between the two groups, with 19.8% in the teplizumab group and 20.4% of placebo patients achieving the combined end point at 1 year, said Dr. Nicole Sherry, director of the Diabetes Center at Massachusetts General Hospital for Children in Boston (Lancet 2011 June 28 [doi:10.1016/S0140-6736[11]60931-8]).

However, 5% of the 513 study patients no longer required insulin at 1 year, compared with none of those who received placebo. Moreover, in a post hoc analysis, C-peptide was preserved or increased in 40% of those who received the 14-day regimen of the drug, compared with just 28% of the placebo group. Children were more likely than were adults to retain C-peptide function, as were patients treated within 6 weeks of diagnosis. Adverse events were similar between the two groups, she noted.

A phase III study of the anti-CD3 drug oteliximab in 240 newly diagnosed type 1 diabetes patients also produced negative findings. The dose – one-sixteenth of that used in previous trials – had been chosen to reduce adverse events seen previously, particularly Epstein-Barr virus activation. The low dose was not effective in preserving C-peptide. This study, dubbed DEFEND, was funded by Tolerx, with support from the Juvenile Diabetes Research Foundation.

"This is clearly an important pathway. Further studies will try to increase that dosage to duplicate the previous efficacy with fewer side effects," said Dr. Peter Gottlieb, professor of medicine and pediatrics at the University of Colorado, Denver.

Another compound under study, DiaPep277, was developed with the goal of preventing beta-cell destruction. Created by the removal of 24 of 500 amino acids from a "heat shock" protein involved in beta-cell destruction via T-cell activation, DiaPep277 had been shown to change destructive T cells into cytokine-secreting protective T-cells in mouse models of type 1 diabetes.

In one phase II study, injections of DiaPep277 in 100 newly diagnosed patients with type 1 diabetes preserved beta-cell insulin secretion for up to 2 years following diagnosis, said Dr. Itamar Raz, professor of medicine and director of the Hadassah Diabetic Center in Jerusalem, Hadassah Hebrew University Hospital.

DiaPep277 is currently in two phase III trials in which beta-cell function, insulin use, and glucose control are being monitored as key outcomes in more than 450 patients per trial. Results for one of the studies are expected by early next year, Dr. Raz said.

Dr. Skyler is an advisory panel and/or board member for a long list of companies that make diabetes-related products. He holds stock in and/or is a shareholder of Amylin Pharmaceuticals, Circulat Biotech, Dexcom, Ideal Life, Inspire Pharmaceuticals, Moerae Matrix, and Tandem Diabetes Care.

Dr. Gitelman and Dr. Sherry stated that they have no disclosures. Dr. Orban serves on the data safety monitoring board for Osiris Therapeutics and is a founding member of Orban Biotechs LLC. Dr. Gottlieb receives research funding from Tolerx, GlaxoSmithKline, MacroGenics, and Diamyd. He has consulted for Eli Lilly, Sanofi-Aventis, and Genentech.

Dr. Raz is a board member of, serves on the advisory panel for, is on the speakers bureau, or is a consultant for AstraZeneca LP, Bristol-Myers Squibb, Novo-Nordisk Pharma Ltd., Roche Pharmaceuticals, and Andromeda.

SAN DIEGO – Several potential approaches are being attempted to slow the autoimmune progression of type 1 diabetes in newly diagnosed patients, with varying degrees of success.

The studies, funded by government agencies, biotechnology companies, and pharmaceutical manufacturers, are in various phases. "We’re testing things in new-onset type 1 diabetes to see whether or not they modify the course of the disease, and to gain insights as to which ones are safe enough to take into prevention studies. ... The field is in a state of flux at the moment," Dr. Jay S. Skyler said in an interview.

Dr. Skyler chairs the National Institutes of Health–funded Type 1 Diabetes TrialNet study group, which sponsored two of the trials that were presented at the annual scientific sessions of the American Diabetes Association and simultaneously published in the Lancet on June 28.

One of those studies, in which new-onset type 1 patients were treated with the antigen glutamic acid decarboxylase (GAD), produced negative results. A total of 145 patients aged 3-45 years who had been diagnosed within the prior 100 days were randomized to either three injections of 20 mcg of GAD formulated with aluminum hydroxide (GAD-alum), two injections of GAD-alum plus one of alum alone, or three injections of alum alone.

At 1 year, the 2-hour area under the curve (AUC) of C-peptide, adjusted for age, sex, and baseline C-peptide value, was 0.412 nmol/L in the GAD-alum group, 0.382 nmol/L in the GAD-alum plus alum group, and 0.413 in the alum-only group. Those differences were not significant (Lancet 2011 June 27 [doi:10.1016/S0140-6736[11]60895-7]).

Importantly, however, there were no adverse events. "What we’ve learned is that some of [the agents being tested] don’t work in new onset diabetes, but they are safe. So, they might work earlier in the disease process for prevention. Whether we need a combination of things to really arrest the disease process is another open question," said Dr. Skyler, professor of medicine, pediatrics, and psychology at the University of Miami.

The other TrialNet study involved abatacept (Bristol Myers Squibb’s Orencia), which modulates T-cell costimulation and prevents full T-cell activation. Orencia is currently on the U.S. market for treating adult rheumatoid arthritis and juvenile idiopathic arthritis. In the study, 112 patients were randomized to treatment with either abatacept (77 patients) or placebo (35 patients) intravenous infusions on days 1, 14, 28, and monthly for a total of 27 infusions over 2 years (Lancet 2011 June 28 [doi:10.1016/S0140-6736[11]60886-6]).

Here, there was a significant difference between groups, with the AUC for C-peptide 59% higher with abatacept than placebo at 2 years, and the estimated delay in C-peptide reduction of 9.6 months. However, despite continued administration of abatacept over 24 months, the decrease in beta-cell function with abatacept was parallel to that with placebo after 6 months of treatment, suggesting that T-cell activation lessens with time, said Dr. Tihamer Orban of Joslin Diabetes Center, Boston.

Two additional drugs under study, teplizumab and otelixizumab, are both anti-CD3 monoclonal antibodies that bind to the surface of T-cells and modulate their action. Two studies of teplizumab were presented. In one phase II study called AbATE (anti-cd3 mAb), 52 type 1 patients aged 8-30 years were given two intravenous courses of the drug 1 year apart, while 25 patients received placebo infusions.

There was a significant retention of C-peptide with teplizumab compared with controls. The teplizumab group had a 45% decrease in beta-cell function over 2 years, compared with a 77% reduction in the untreated group, said Dr. Stephen E. Gitelman, professor of clinical pediatrics at the University of California, San Francisco.

The AbATE trial was sponsored by the Immune Tolerance Network, which is funded by the National Institutes of Health. Funding was also provided by the Juvenile Diabetes Research Foundation.

The other teplizumab trial, Protégé, was funded by MacroGenics. It was a 2-year, phase III, double-blind, placebo-controlled, multinational study, with the combined goal of reducing hemoglobin A_1c to less than 6.5% for those newly diagnosed with type 1 diabetes and reducing the amount of insulin needed to less than 0.5 units/kg per day.

The primary end point did not differ between the two groups, with 19.8% in the teplizumab group and 20.4% of placebo patients achieving the combined end point at 1 year, said Dr. Nicole Sherry, director of the Diabetes Center at Massachusetts General Hospital for Children in Boston (Lancet 2011 June 28 [doi:10.1016/S0140-6736[11]60931-8]).

However, 5% of the 513 study patients no longer required insulin at 1 year, compared with none of those who received placebo. Moreover, in a post hoc analysis, C-peptide was preserved or increased in 40% of those who received the 14-day regimen of the drug, compared with just 28% of the placebo group. Children were more likely than were adults to retain C-peptide function, as were patients treated within 6 weeks of diagnosis. Adverse events were similar between the two groups, she noted.

A phase III study of the anti-CD3 drug oteliximab in 240 newly diagnosed type 1 diabetes patients also produced negative findings. The dose – one-sixteenth of that used in previous trials – had been chosen to reduce adverse events seen previously, particularly Epstein-Barr virus activation. The low dose was not effective in preserving C-peptide. This study, dubbed DEFEND, was funded by Tolerx, with support from the Juvenile Diabetes Research Foundation.

"This is clearly an important pathway. Further studies will try to increase that dosage to duplicate the previous efficacy with fewer side effects," said Dr. Peter Gottlieb, professor of medicine and pediatrics at the University of Colorado, Denver.

Another compound under study, DiaPep277, was developed with the goal of preventing beta-cell destruction. Created by the removal of 24 of 500 amino acids from a "heat shock" protein involved in beta-cell destruction via T-cell activation, DiaPep277 had been shown to change destructive T cells into cytokine-secreting protective T-cells in mouse models of type 1 diabetes.

In one phase II study, injections of DiaPep277 in 100 newly diagnosed patients with type 1 diabetes preserved beta-cell insulin secretion for up to 2 years following diagnosis, said Dr. Itamar Raz, professor of medicine and director of the Hadassah Diabetic Center in Jerusalem, Hadassah Hebrew University Hospital.

DiaPep277 is currently in two phase III trials in which beta-cell function, insulin use, and glucose control are being monitored as key outcomes in more than 450 patients per trial. Results for one of the studies are expected by early next year, Dr. Raz said.

Dr. Skyler is an advisory panel and/or board member for a long list of companies that make diabetes-related products. He holds stock in and/or is a shareholder of Amylin Pharmaceuticals, Circulat Biotech, Dexcom, Ideal Life, Inspire Pharmaceuticals, Moerae Matrix, and Tandem Diabetes Care.

Dr. Gitelman and Dr. Sherry stated that they have no disclosures. Dr. Orban serves on the data safety monitoring board for Osiris Therapeutics and is a founding member of Orban Biotechs LLC. Dr. Gottlieb receives research funding from Tolerx, GlaxoSmithKline, MacroGenics, and Diamyd. He has consulted for Eli Lilly, Sanofi-Aventis, and Genentech.

Dr. Raz is a board member of, serves on the advisory panel for, is on the speakers bureau, or is a consultant for AstraZeneca LP, Bristol-Myers Squibb, Novo-Nordisk Pharma Ltd., Roche Pharmaceuticals, and Andromeda.

SAN DIEGO – Several potential approaches are being attempted to slow the autoimmune progression of type 1 diabetes in newly diagnosed patients, with varying degrees of success.

The studies, funded by government agencies, biotechnology companies, and pharmaceutical manufacturers, are in various phases. "We’re testing things in new-onset type 1 diabetes to see whether or not they modify the course of the disease, and to gain insights as to which ones are safe enough to take into prevention studies. ... The field is in a state of flux at the moment," Dr. Jay S. Skyler said in an interview.

Dr. Skyler chairs the National Institutes of Health–funded Type 1 Diabetes TrialNet study group, which sponsored two of the trials that were presented at the annual scientific sessions of the American Diabetes Association and simultaneously published in the Lancet on June 28.

One of those studies, in which new-onset type 1 patients were treated with the antigen glutamic acid decarboxylase (GAD), produced negative results. A total of 145 patients aged 3-45 years who had been diagnosed within the prior 100 days were randomized to either three injections of 20 mcg of GAD formulated with aluminum hydroxide (GAD-alum), two injections of GAD-alum plus one of alum alone, or three injections of alum alone.

At 1 year, the 2-hour area under the curve (AUC) of C-peptide, adjusted for age, sex, and baseline C-peptide value, was 0.412 nmol/L in the GAD-alum group, 0.382 nmol/L in the GAD-alum plus alum group, and 0.413 in the alum-only group. Those differences were not significant (Lancet 2011 June 27 [doi:10.1016/S0140-6736[11]60895-7]).

Importantly, however, there were no adverse events. "What we’ve learned is that some of [the agents being tested] don’t work in new onset diabetes, but they are safe. So, they might work earlier in the disease process for prevention. Whether we need a combination of things to really arrest the disease process is another open question," said Dr. Skyler, professor of medicine, pediatrics, and psychology at the University of Miami.

The other TrialNet study involved abatacept (Bristol Myers Squibb’s Orencia), which modulates T-cell costimulation and prevents full T-cell activation. Orencia is currently on the U.S. market for treating adult rheumatoid arthritis and juvenile idiopathic arthritis. In the study, 112 patients were randomized to treatment with either abatacept (77 patients) or placebo (35 patients) intravenous infusions on days 1, 14, 28, and monthly for a total of 27 infusions over 2 years (Lancet 2011 June 28 [doi:10.1016/S0140-6736[11]60886-6]).

Here, there was a significant difference between groups, with the AUC for C-peptide 59% higher with abatacept than placebo at 2 years, and the estimated delay in C-peptide reduction of 9.6 months. However, despite continued administration of abatacept over 24 months, the decrease in beta-cell function with abatacept was parallel to that with placebo after 6 months of treatment, suggesting that T-cell activation lessens with time, said Dr. Tihamer Orban of Joslin Diabetes Center, Boston.

Two additional drugs under study, teplizumab and otelixizumab, are both anti-CD3 monoclonal antibodies that bind to the surface of T-cells and modulate their action. Two studies of teplizumab were presented. In one phase II study called AbATE (anti-cd3 mAb), 52 type 1 patients aged 8-30 years were given two intravenous courses of the drug 1 year apart, while 25 patients received placebo infusions.

There was a significant retention of C-peptide with teplizumab compared with controls. The teplizumab group had a 45% decrease in beta-cell function over 2 years, compared with a 77% reduction in the untreated group, said Dr. Stephen E. Gitelman, professor of clinical pediatrics at the University of California, San Francisco.

The AbATE trial was sponsored by the Immune Tolerance Network, which is funded by the National Institutes of Health. Funding was also provided by the Juvenile Diabetes Research Foundation.

The other teplizumab trial, Protégé, was funded by MacroGenics. It was a 2-year, phase III, double-blind, placebo-controlled, multinational study, with the combined goal of reducing hemoglobin A_1c to less than 6.5% for those newly diagnosed with type 1 diabetes and reducing the amount of insulin needed to less than 0.5 units/kg per day.

The primary end point did not differ between the two groups, with 19.8% in the teplizumab group and 20.4% of placebo patients achieving the combined end point at 1 year, said Dr. Nicole Sherry, director of the Diabetes Center at Massachusetts General Hospital for Children in Boston (Lancet 2011 June 28 [doi:10.1016/S0140-6736[11]60931-8]).

However, 5% of the 513 study patients no longer required insulin at 1 year, compared with none of those who received placebo. Moreover, in a post hoc analysis, C-peptide was preserved or increased in 40% of those who received the 14-day regimen of the drug, compared with just 28% of the placebo group. Children were more likely than were adults to retain C-peptide function, as were patients treated within 6 weeks of diagnosis. Adverse events were similar between the two groups, she noted.

A phase III study of the anti-CD3 drug oteliximab in 240 newly diagnosed type 1 diabetes patients also produced negative findings. The dose – one-sixteenth of that used in previous trials – had been chosen to reduce adverse events seen previously, particularly Epstein-Barr virus activation. The low dose was not effective in preserving C-peptide. This study, dubbed DEFEND, was funded by Tolerx, with support from the Juvenile Diabetes Research Foundation.

"This is clearly an important pathway. Further studies will try to increase that dosage to duplicate the previous efficacy with fewer side effects," said Dr. Peter Gottlieb, professor of medicine and pediatrics at the University of Colorado, Denver.

Another compound under study, DiaPep277, was developed with the goal of preventing beta-cell destruction. Created by the removal of 24 of 500 amino acids from a "heat shock" protein involved in beta-cell destruction via T-cell activation, DiaPep277 had been shown to change destructive T cells into cytokine-secreting protective T-cells in mouse models of type 1 diabetes.

In one phase II study, injections of DiaPep277 in 100 newly diagnosed patients with type 1 diabetes preserved beta-cell insulin secretion for up to 2 years following diagnosis, said Dr. Itamar Raz, professor of medicine and director of the Hadassah Diabetic Center in Jerusalem, Hadassah Hebrew University Hospital.

DiaPep277 is currently in two phase III trials in which beta-cell function, insulin use, and glucose control are being monitored as key outcomes in more than 450 patients per trial. Results for one of the studies are expected by early next year, Dr. Raz said.

Dr. Skyler is an advisory panel and/or board member for a long list of companies that make diabetes-related products. He holds stock in and/or is a shareholder of Amylin Pharmaceuticals, Circulat Biotech, Dexcom, Ideal Life, Inspire Pharmaceuticals, Moerae Matrix, and Tandem Diabetes Care.

Dr. Gitelman and Dr. Sherry stated that they have no disclosures. Dr. Orban serves on the data safety monitoring board for Osiris Therapeutics and is a founding member of Orban Biotechs LLC. Dr. Gottlieb receives research funding from Tolerx, GlaxoSmithKline, MacroGenics, and Diamyd. He has consulted for Eli Lilly, Sanofi-Aventis, and Genentech.

Dr. Raz is a board member of, serves on the advisory panel for, is on the speakers bureau, or is a consultant for AstraZeneca LP, Bristol-Myers Squibb, Novo-Nordisk Pharma Ltd., Roche Pharmaceuticals, and Andromeda.

SAN DIEGO – Girls with type 1 diabetes had significantly increased mean hemoglobin A_1c levels, body mass index, LDL cholesterol, and C-reactive protein, compared with boys who have the disease, results from a single-center study demonstrated.

The finding suggests that adolescence "may be a critical period for CVD prevention in girls with type 1 diabetes," Talia L. Brown said at the annual scientific sessions of the American Diabetes Association. "Future studies should investigate factors contributing to these gender differences."

Adults with type 1 diabetes are known to have a higher risk of cardiovascular disease compared with nondiabetic adults, said Ms. Brown, a graduate student who is a research assistant at the Barbara Davis Center for Childhood Diabetes, Aurora, Colo.

"There is a greater relative increase in women, where women with type 1 diabetes have four times the CVD risk as nondiabetic women," Ms. Brown said. "Meanwhile, men with type 1 diabetes have two times greater CVD risk than nondiabetic men. It is uncertain when these gender differences begin."

To find out, she and her associates compared the CVD risk profile of 302 adolescents with type 1 diabetes with 100 nondiabetic adolescents and evaluated gender differences between the groups. The adolescents’ mean age was 15 years. Tanner stage was assessed by a physician or self report at the visit. Measures included fasting lipids, assays for HbA_1c and C-reactive protein, diastolic and systolic blood pressure, and body mass index z score. The researchers used questionnaires to assess physical activity and average insulin dose, and multivariate linear regression to examine each CVD risk factor.

Ms. Brown reported that physical activity was equivalent among the study participants (a mean of about 2 hours per day), and insulin dose was similar between boys and girls (a mean of 1.1 vs. 1.2 units/kg, respectively).

Compared with boys with type 1 diabetes, girls with the disease had significantly increased mean hemoglobin A_1c (9.1% vs. 8.7%, respectively), BMI z score (0.72 vs. 0.49), LDL cholesterol (95 mg/dL vs. 82 mg/dL), and CRP (0.86 mg/dL vs. 0.15 mg/dL). Boys with type 1 had higher levels of systolic blood pressure, compared with girls with the disease – 115 mm Hg vs. 111 mm Hg, respectively. But girls with type 1 had higher levels of systolic blood pressure, compared with nondiabetic girls (111 mm Hg vs. 106 mm Hg, respectively).

"Girls with diabetes had higher LDL levels than both boys with type 1 diabetes and girls without diabetes," Ms. Brown added. "CRP was ninefold higher in girls with type 1 diabetes than in both girls without diabetes and boys with type 1 diabetes."

After adjustment for HbA_1c and BMI z score, a significant increase in CRP and LDL in girls with type 1 diabetes remained. The researchers also found a significant interaction between gender and diabetes, "causing type 1 diabetes to have a more detrimental effect in girls than in boys with regard to LDL cholesterol and systolic blood pressure," Ms. Brown said.

Increased HbA_1c and body mass index "are likely to contribute to the increased blood pressure, inflammation, and cholesterol that we observed in girls with type 1 diabetes," she said. "These findings are somewhat unexpected, because generally there can be an inverse relationship between glycemic control and weight. Increased HbA_1c and obesity are likely to translate into worse CVD outcomes for females, and raises concern for the long-term effects in CVD health."

When asked to speculate why HbA_1c and body mass index were increased in girls with type 1, Ms. Brown said that girls generally "have a hard time controlling both [factors], so it’s hard to know what’s contributing to this."

Prevention efforts such as maintaining a healthy diet, getting adequate physical exercise, and controlling blood pressure and cholesterol levels "may improve this problem," she said.

The study was funded by the Juvenile Diabetes Research Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, and Children’s Hospital Colorado Clinical Translational Research Center.

Ms. Brown said that she had no relevant financial conflicts to disclose.

SAN DIEGO – Girls with type 1 diabetes had significantly increased mean hemoglobin A_1c levels, body mass index, LDL cholesterol, and C-reactive protein, compared with boys who have the disease, results from a single-center study demonstrated.

The finding suggests that adolescence "may be a critical period for CVD prevention in girls with type 1 diabetes," Talia L. Brown said at the annual scientific sessions of the American Diabetes Association. "Future studies should investigate factors contributing to these gender differences."

Adults with type 1 diabetes are known to have a higher risk of cardiovascular disease compared with nondiabetic adults, said Ms. Brown, a graduate student who is a research assistant at the Barbara Davis Center for Childhood Diabetes, Aurora, Colo.

"There is a greater relative increase in women, where women with type 1 diabetes have four times the CVD risk as nondiabetic women," Ms. Brown said. "Meanwhile, men with type 1 diabetes have two times greater CVD risk than nondiabetic men. It is uncertain when these gender differences begin."

To find out, she and her associates compared the CVD risk profile of 302 adolescents with type 1 diabetes with 100 nondiabetic adolescents and evaluated gender differences between the groups. The adolescents’ mean age was 15 years. Tanner stage was assessed by a physician or self report at the visit. Measures included fasting lipids, assays for HbA_1c and C-reactive protein, diastolic and systolic blood pressure, and body mass index z score. The researchers used questionnaires to assess physical activity and average insulin dose, and multivariate linear regression to examine each CVD risk factor.

Ms. Brown reported that physical activity was equivalent among the study participants (a mean of about 2 hours per day), and insulin dose was similar between boys and girls (a mean of 1.1 vs. 1.2 units/kg, respectively).

Compared with boys with type 1 diabetes, girls with the disease had significantly increased mean hemoglobin A_1c (9.1% vs. 8.7%, respectively), BMI z score (0.72 vs. 0.49), LDL cholesterol (95 mg/dL vs. 82 mg/dL), and CRP (0.86 mg/dL vs. 0.15 mg/dL). Boys with type 1 had higher levels of systolic blood pressure, compared with girls with the disease – 115 mm Hg vs. 111 mm Hg, respectively. But girls with type 1 had higher levels of systolic blood pressure, compared with nondiabetic girls (111 mm Hg vs. 106 mm Hg, respectively).

"Girls with diabetes had higher LDL levels than both boys with type 1 diabetes and girls without diabetes," Ms. Brown added. "CRP was ninefold higher in girls with type 1 diabetes than in both girls without diabetes and boys with type 1 diabetes."

After adjustment for HbA_1c and BMI z score, a significant increase in CRP and LDL in girls with type 1 diabetes remained. The researchers also found a significant interaction between gender and diabetes, "causing type 1 diabetes to have a more detrimental effect in girls than in boys with regard to LDL cholesterol and systolic blood pressure," Ms. Brown said.

Increased HbA_1c and body mass index "are likely to contribute to the increased blood pressure, inflammation, and cholesterol that we observed in girls with type 1 diabetes," she said. "These findings are somewhat unexpected, because generally there can be an inverse relationship between glycemic control and weight. Increased HbA_1c and obesity are likely to translate into worse CVD outcomes for females, and raises concern for the long-term effects in CVD health."

When asked to speculate why HbA_1c and body mass index were increased in girls with type 1, Ms. Brown said that girls generally "have a hard time controlling both [factors], so it’s hard to know what’s contributing to this."

Prevention efforts such as maintaining a healthy diet, getting adequate physical exercise, and controlling blood pressure and cholesterol levels "may improve this problem," she said.

The study was funded by the Juvenile Diabetes Research Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, and Children’s Hospital Colorado Clinical Translational Research Center.

Ms. Brown said that she had no relevant financial conflicts to disclose.

SAN DIEGO – Girls with type 1 diabetes had significantly increased mean hemoglobin A_1c levels, body mass index, LDL cholesterol, and C-reactive protein, compared with boys who have the disease, results from a single-center study demonstrated.

The finding suggests that adolescence "may be a critical period for CVD prevention in girls with type 1 diabetes," Talia L. Brown said at the annual scientific sessions of the American Diabetes Association. "Future studies should investigate factors contributing to these gender differences."

Adults with type 1 diabetes are known to have a higher risk of cardiovascular disease compared with nondiabetic adults, said Ms. Brown, a graduate student who is a research assistant at the Barbara Davis Center for Childhood Diabetes, Aurora, Colo.

"There is a greater relative increase in women, where women with type 1 diabetes have four times the CVD risk as nondiabetic women," Ms. Brown said. "Meanwhile, men with type 1 diabetes have two times greater CVD risk than nondiabetic men. It is uncertain when these gender differences begin."

To find out, she and her associates compared the CVD risk profile of 302 adolescents with type 1 diabetes with 100 nondiabetic adolescents and evaluated gender differences between the groups. The adolescents’ mean age was 15 years. Tanner stage was assessed by a physician or self report at the visit. Measures included fasting lipids, assays for HbA_1c and C-reactive protein, diastolic and systolic blood pressure, and body mass index z score. The researchers used questionnaires to assess physical activity and average insulin dose, and multivariate linear regression to examine each CVD risk factor.

Ms. Brown reported that physical activity was equivalent among the study participants (a mean of about 2 hours per day), and insulin dose was similar between boys and girls (a mean of 1.1 vs. 1.2 units/kg, respectively).

Compared with boys with type 1 diabetes, girls with the disease had significantly increased mean hemoglobin A_1c (9.1% vs. 8.7%, respectively), BMI z score (0.72 vs. 0.49), LDL cholesterol (95 mg/dL vs. 82 mg/dL), and CRP (0.86 mg/dL vs. 0.15 mg/dL). Boys with type 1 had higher levels of systolic blood pressure, compared with girls with the disease – 115 mm Hg vs. 111 mm Hg, respectively. But girls with type 1 had higher levels of systolic blood pressure, compared with nondiabetic girls (111 mm Hg vs. 106 mm Hg, respectively).

"Girls with diabetes had higher LDL levels than both boys with type 1 diabetes and girls without diabetes," Ms. Brown added. "CRP was ninefold higher in girls with type 1 diabetes than in both girls without diabetes and boys with type 1 diabetes."

After adjustment for HbA_1c and BMI z score, a significant increase in CRP and LDL in girls with type 1 diabetes remained. The researchers also found a significant interaction between gender and diabetes, "causing type 1 diabetes to have a more detrimental effect in girls than in boys with regard to LDL cholesterol and systolic blood pressure," Ms. Brown said.

Increased HbA_1c and body mass index "are likely to contribute to the increased blood pressure, inflammation, and cholesterol that we observed in girls with type 1 diabetes," she said. "These findings are somewhat unexpected, because generally there can be an inverse relationship between glycemic control and weight. Increased HbA_1c and obesity are likely to translate into worse CVD outcomes for females, and raises concern for the long-term effects in CVD health."

When asked to speculate why HbA_1c and body mass index were increased in girls with type 1, Ms. Brown said that girls generally "have a hard time controlling both [factors], so it’s hard to know what’s contributing to this."

Prevention efforts such as maintaining a healthy diet, getting adequate physical exercise, and controlling blood pressure and cholesterol levels "may improve this problem," she said.

The study was funded by the Juvenile Diabetes Research Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, and Children’s Hospital Colorado Clinical Translational Research Center.

Ms. Brown said that she had no relevant financial conflicts to disclose.

SAN DIEGO – Girls with type 1 diabetes had significantly increased mean hemoglobin A_1c levels, body mass index, LDL cholesterol, and C-reactive protein, compared with boys who have the disease, results from a single-center study demonstrated.

The finding suggests that adolescence "may be a critical period for CVD prevention in girls with type 1 diabetes," Talia L. Brown said at the annual scientific sessions of the American Diabetes Association. "Future studies should investigate factors contributing to these gender differences."

Adults with type 1 diabetes are known to have a higher risk of cardiovascular disease compared with nondiabetic adults, said Ms. Brown, a graduate student who is a research assistant at the Barbara Davis Center for Childhood Diabetes, Aurora, Colo.

"There is a greater relative increase in women, where women with type 1 diabetes have four times the CVD risk as nondiabetic women," Ms. Brown said. "Meanwhile, men with type 1 diabetes have two times greater CVD risk than nondiabetic men. It is uncertain when these gender differences begin."

To find out, she and her associates compared the CVD risk profile of 302 adolescents with type 1 diabetes with 100 nondiabetic adolescents and evaluated gender differences between the groups. The adolescents’ mean age was 15 years. Tanner stage was assessed by a physician or self report at the visit. Measures included fasting lipids, assays for HbA_1c and C-reactive protein, diastolic and systolic blood pressure, and body mass index z score. The researchers used questionnaires to assess physical activity and average insulin dose, and multivariate linear regression to examine each CVD risk factor.

Ms. Brown reported that physical activity was equivalent among the study participants (a mean of about 2 hours per day), and insulin dose was similar between boys and girls (a mean of 1.1 vs. 1.2 units/kg, respectively).

Compared with boys with type 1 diabetes, girls with the disease had significantly increased mean hemoglobin A_1c (9.1% vs. 8.7%, respectively), BMI z score (0.72 vs. 0.49), LDL cholesterol (95 mg/dL vs. 82 mg/dL), and CRP (0.86 mg/dL vs. 0.15 mg/dL). Boys with type 1 had higher levels of systolic blood pressure, compared with girls with the disease – 115 mm Hg vs. 111 mm Hg, respectively. But girls with type 1 had higher levels of systolic blood pressure, compared with nondiabetic girls (111 mm Hg vs. 106 mm Hg, respectively).

"Girls with diabetes had higher LDL levels than both boys with type 1 diabetes and girls without diabetes," Ms. Brown added. "CRP was ninefold higher in girls with type 1 diabetes than in both girls without diabetes and boys with type 1 diabetes."

After adjustment for HbA_1c and BMI z score, a significant increase in CRP and LDL in girls with type 1 diabetes remained. The researchers also found a significant interaction between gender and diabetes, "causing type 1 diabetes to have a more detrimental effect in girls than in boys with regard to LDL cholesterol and systolic blood pressure," Ms. Brown said.

Increased HbA_1c and body mass index "are likely to contribute to the increased blood pressure, inflammation, and cholesterol that we observed in girls with type 1 diabetes," she said. "These findings are somewhat unexpected, because generally there can be an inverse relationship between glycemic control and weight. Increased HbA_1c and obesity are likely to translate into worse CVD outcomes for females, and raises concern for the long-term effects in CVD health."

When asked to speculate why HbA_1c and body mass index were increased in girls with type 1, Ms. Brown said that girls generally "have a hard time controlling both [factors], so it’s hard to know what’s contributing to this."

Prevention efforts such as maintaining a healthy diet, getting adequate physical exercise, and controlling blood pressure and cholesterol levels "may improve this problem," she said.

The study was funded by the Juvenile Diabetes Research Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, and Children’s Hospital Colorado Clinical Translational Research Center.

Ms. Brown said that she had no relevant financial conflicts to disclose.

SAN DIEGO – Girls with type 1 diabetes had significantly increased mean hemoglobin A_1c levels, body mass index, LDL cholesterol, and C-reactive protein, compared with boys who have the disease, results from a single-center study demonstrated.

The finding suggests that adolescence "may be a critical period for CVD prevention in girls with type 1 diabetes," Talia L. Brown said at the annual scientific sessions of the American Diabetes Association. "Future studies should investigate factors contributing to these gender differences."

Adults with type 1 diabetes are known to have a higher risk of cardiovascular disease compared with nondiabetic adults, said Ms. Brown, a graduate student who is a research assistant at the Barbara Davis Center for Childhood Diabetes, Aurora, Colo.

"There is a greater relative increase in women, where women with type 1 diabetes have four times the CVD risk as nondiabetic women," Ms. Brown said. "Meanwhile, men with type 1 diabetes have two times greater CVD risk than nondiabetic men. It is uncertain when these gender differences begin."

To find out, she and her associates compared the CVD risk profile of 302 adolescents with type 1 diabetes with 100 nondiabetic adolescents and evaluated gender differences between the groups. The adolescents’ mean age was 15 years. Tanner stage was assessed by a physician or self report at the visit. Measures included fasting lipids, assays for HbA_1c and C-reactive protein, diastolic and systolic blood pressure, and body mass index z score. The researchers used questionnaires to assess physical activity and average insulin dose, and multivariate linear regression to examine each CVD risk factor.

Ms. Brown reported that physical activity was equivalent among the study participants (a mean of about 2 hours per day), and insulin dose was similar between boys and girls (a mean of 1.1 vs. 1.2 units/kg, respectively).

Compared with boys with type 1 diabetes, girls with the disease had significantly increased mean hemoglobin A_1c (9.1% vs. 8.7%, respectively), BMI z score (0.72 vs. 0.49), LDL cholesterol (95 mg/dL vs. 82 mg/dL), and CRP (0.86 mg/dL vs. 0.15 mg/dL). Boys with type 1 had higher levels of systolic blood pressure, compared with girls with the disease – 115 mm Hg vs. 111 mm Hg, respectively. But girls with type 1 had higher levels of systolic blood pressure, compared with nondiabetic girls (111 mm Hg vs. 106 mm Hg, respectively).

"Girls with diabetes had higher LDL levels than both boys with type 1 diabetes and girls without diabetes," Ms. Brown added. "CRP was ninefold higher in girls with type 1 diabetes than in both girls without diabetes and boys with type 1 diabetes."

After adjustment for HbA_1c and BMI z score, a significant increase in CRP and LDL in girls with type 1 diabetes remained. The researchers also found a significant interaction between gender and diabetes, "causing type 1 diabetes to have a more detrimental effect in girls than in boys with regard to LDL cholesterol and systolic blood pressure," Ms. Brown said.

Increased HbA_1c and body mass index "are likely to contribute to the increased blood pressure, inflammation, and cholesterol that we observed in girls with type 1 diabetes," she said. "These findings are somewhat unexpected, because generally there can be an inverse relationship between glycemic control and weight. Increased HbA_1c and obesity are likely to translate into worse CVD outcomes for females, and raises concern for the long-term effects in CVD health."

When asked to speculate why HbA_1c and body mass index were increased in girls with type 1, Ms. Brown said that girls generally "have a hard time controlling both [factors], so it’s hard to know what’s contributing to this."

Prevention efforts such as maintaining a healthy diet, getting adequate physical exercise, and controlling blood pressure and cholesterol levels "may improve this problem," she said.

The study was funded by the Juvenile Diabetes Research Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, and Children’s Hospital Colorado Clinical Translational Research Center.

Ms. Brown said that she had no relevant financial conflicts to disclose.

SAN DIEGO – Girls with type 1 diabetes had significantly increased mean hemoglobin A_1c levels, body mass index, LDL cholesterol, and C-reactive protein, compared with boys who have the disease, results from a single-center study demonstrated.

The finding suggests that adolescence "may be a critical period for CVD prevention in girls with type 1 diabetes," Talia L. Brown said at the annual scientific sessions of the American Diabetes Association. "Future studies should investigate factors contributing to these gender differences."

Adults with type 1 diabetes are known to have a higher risk of cardiovascular disease compared with nondiabetic adults, said Ms. Brown, a graduate student who is a research assistant at the Barbara Davis Center for Childhood Diabetes, Aurora, Colo.

"There is a greater relative increase in women, where women with type 1 diabetes have four times the CVD risk as nondiabetic women," Ms. Brown said. "Meanwhile, men with type 1 diabetes have two times greater CVD risk than nondiabetic men. It is uncertain when these gender differences begin."

To find out, she and her associates compared the CVD risk profile of 302 adolescents with type 1 diabetes with 100 nondiabetic adolescents and evaluated gender differences between the groups. The adolescents’ mean age was 15 years. Tanner stage was assessed by a physician or self report at the visit. Measures included fasting lipids, assays for HbA_1c and C-reactive protein, diastolic and systolic blood pressure, and body mass index z score. The researchers used questionnaires to assess physical activity and average insulin dose, and multivariate linear regression to examine each CVD risk factor.

Ms. Brown reported that physical activity was equivalent among the study participants (a mean of about 2 hours per day), and insulin dose was similar between boys and girls (a mean of 1.1 vs. 1.2 units/kg, respectively).

Compared with boys with type 1 diabetes, girls with the disease had significantly increased mean hemoglobin A_1c (9.1% vs. 8.7%, respectively), BMI z score (0.72 vs. 0.49), LDL cholesterol (95 mg/dL vs. 82 mg/dL), and CRP (0.86 mg/dL vs. 0.15 mg/dL). Boys with type 1 had higher levels of systolic blood pressure, compared with girls with the disease – 115 mm Hg vs. 111 mm Hg, respectively. But girls with type 1 had higher levels of systolic blood pressure, compared with nondiabetic girls (111 mm Hg vs. 106 mm Hg, respectively).

"Girls with diabetes had higher LDL levels than both boys with type 1 diabetes and girls without diabetes," Ms. Brown added. "CRP was ninefold higher in girls with type 1 diabetes than in both girls without diabetes and boys with type 1 diabetes."

After adjustment for HbA_1c and BMI z score, a significant increase in CRP and LDL in girls with type 1 diabetes remained. The researchers also found a significant interaction between gender and diabetes, "causing type 1 diabetes to have a more detrimental effect in girls than in boys with regard to LDL cholesterol and systolic blood pressure," Ms. Brown said.

Increased HbA_1c and body mass index "are likely to contribute to the increased blood pressure, inflammation, and cholesterol that we observed in girls with type 1 diabetes," she said. "These findings are somewhat unexpected, because generally there can be an inverse relationship between glycemic control and weight. Increased HbA_1c and obesity are likely to translate into worse CVD outcomes for females, and raises concern for the long-term effects in CVD health."

When asked to speculate why HbA_1c and body mass index were increased in girls with type 1, Ms. Brown said that girls generally "have a hard time controlling both [factors], so it’s hard to know what’s contributing to this."

Prevention efforts such as maintaining a healthy diet, getting adequate physical exercise, and controlling blood pressure and cholesterol levels "may improve this problem," she said.

The study was funded by the Juvenile Diabetes Research Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, and Children’s Hospital Colorado Clinical Translational Research Center.

Ms. Brown said that she had no relevant financial conflicts to disclose.