American Diabetes Association (ADA) 72nd Scientific Sessions: Page 3 of 3

August 16, 2012

Insulin Glargine has Neutral Effect on Cardiovascular Outcomes and Cancers

After more than 6 years of follow-up, a large, international, randomized trial found that daily injections of insulin glargine in patients with type 2 diabetes, or with a high risk of the disease, had a neutral effect on cancer, serious cardiovascular outcomes, and death compared with standard care. The drug also reduced the progression of diabetes.

Hertzel Gerstein, MD, the study’s principal investigator and a professor of medicine at McMaster University in Ontario, Canada, said that the researchers found no new side effects with insulin glargine. Common side effects of the medication are hypoglycemia and weight gain, both of which were cited in this study.

Results were presented during a symposium at the ADA meeting. The findings were simultaneously published online in the New England Journal of Medicine (N Engl J Med. 2012;367[4]:319-328). Gerstein said that the academic steering committee first analyzed the data and then shared the findings with Sanofi, the drug’s manufacturer. “It is very unlikely that the drug is either causing harm or benefit in these individuals,” Gerstein said. “There is a very clear neutral effect, which is important for patients to know.”

The ORIGIN (Outcome Reduction with an Initial Glargine Intervention) trial had two main objectives for high cardiovascular risk patients: (1) determining if administering insulin glargine once daily and adjusting the dose to target a normal fasting glucose level (≤95 mg/dL) reduces cardiovascular outcomes more than standard care; and (2) determining if adding omega-3 fatty acids to the regimen reduces cardiovascular death.

The trial included 12,537 patients who had new or recently diagnosed diabetes or impaired fasting glucose/impaired glucose tolerance plus additional risk factors for cardiovascular disease. They were recruited from 573 sites in 40 countries, representing every continent with the exception of Antarctica. Mean age was 63.5 years, and 35% of patients were women. Of the patients, 82% had prior diabetes for a mean of 5.4 years and 6% had new diabetes detected when they were randomized.

The rates of the composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes in the two groups were similar: 2.94 per 100 person-years in the insulin glargine group compared with 2.85 per 100 person-years in the standard care group (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.94-1.11; P=.63). There was also no statistically significant difference in the rates of those three events plus revascularization or hospitalization for heart failure: 5.52 per 100 person-years compared with 5.28 per 100 person-years (HR, 1.04; 95% CI, 0.97-1.11; P=.27). In addition, there was no difference in mortality (HR, 0.98; 95% CI, 0.90-1.08; P=.70) or cancer (HR, 1.00; 95% CI, 0.88-1.13; P=.97).

The authors also noted side effects associated with the drug. In the insulin glargine group, 57% of patients had at least one episode of hypoglycemia compared with 25% in the standard group (P<.001). In addition, 6% of patients in the insulin glargine group had at least one episode of severe hypoglycemia compared with 2% in the standard group (P<.001). The insulin glargine group gained a median of 3.5 pounds during the trial compared with a loss of 1 pound for the standard group (P<.001).

Omega-3 Fatty Acids Analysis

Jackie Bosch, MSc, McMaster University, presented the analysis of the same patient population who received a 1-g capsule of omega-3 fatty acids or placebo on a daily basis for more than 6 years. She said that adding the omega-3 fatty acids did not reduce cardiovascular outcomes in people with disglycemia and other cardiovascular risk factors.

The study found that compared with placebo, omega-3 fatty acids had a neutral effect on cardiovascular death and other serious outcomes, but they lowered triglyceride levels. Patients who took omega-3 fatty acids tolerated them well, and 88% adhered to the treatment until the study’s completion.

Of the patients taking omega-3 fatty acids, 9.1% died from a cardiovascular cause compared with 9.3% of patients in the placebo group (HR, 0.98; 95% CI, 0.87-1.10; P=.72). The results were similar for the composite of myocardial infarction, stroke, and cardiovascular death: 16.5% in the omega-3 fatty acids group and 16.3% in the placebo group (HR, 1.01; 95% CI, 0.93-1.10; P=.81).—Tim Casey

The study was funded by Sanofi.


Dual Screening for IFG and Elevated HbA1c May More Accurately Predict Diabetes in Older Adults

Impaired fasting glucose (IFG) is defined by the American Academy of Family Physicians as glucose levels of 100 mg/dL to 125 mg/dL in fasting patients; these levels are above normal, but below the level that is diagnostic for diabetes. Therefore, persons with IFG are an important target group for the primary prevention of diabetes. Similarly, a high level of hemoglobin A1c (HbA1c), a biomarker of cumulative glycemic exposure, is suspected to predict type 2 diabetes and other cardiovascular diseases.

During a poster session at the ADA meeting, Kasia J. Lipska, MD, Section of Endocrinology, Yale University School of Medicine, New Haven, CT, and colleagues set out to determine which measure—IFG or elevated HbA1c—is more strongly associated with incident diabetes in older adults. The results of their study demonstrated that older adults with IFG or elevated HbA1c are at similarly increased risk—about seven times more likely—of developing diabetes over 7 years compared with those with normal glucose metabolism. Additionally, older adults with both IFG and high HbA1c are at a markedly increased risk—about 20 times more likely—of developing diabetes.

At year 1, data was taken from the Health, Aging, and Body Composition Study for 3075 well-functioning adults without diabetes. Baseline values of IFG and HbA1c were measured at year 4, using modern methods, which narrowed the cohort down to 1790 participants without diabetes (mean age, 76.5±2.9 years; 46.5% men; 67.1% white). Participants were divided into the following groups: normal IFG (defined as 100 mg/dL-125 mg/dL) and elevated HbA1c (defined as 5.7%-6.4%), per current definitions from the ADA; normal glycemic function (fasting plasma glucose [FPG] <100 mg/dL and HbA1c <5.7%); IFG only; elevated HbA1c only; and combined IFG and elevated HbA1c.

An FPG test can determine whether a patient has IFG. The test requires a person to fast overnight and measure blood glucose the following morning. A normal FPG is <100 mg/dL, whereas persons suspected of prediabetes have an FPG level between 100 mg/dL and 125 mg/dL. Patients with diabetes have an FPG level of >126 mg/dL.

Among the 1790 participants, 7.9% (n=141) developed diabetes over the 7-year follow-up period. A diagnosis of diabetes was based on annual self-report, use of antihyperglycemic medicines, or any FPG ≥126 mg/dL. Logistic regression analyses were adjusted for age, sex, and race.

Lipska and colleagues determined that IFG and elevated HbA1c levels similarly increase the likelihood of developing diabetes mellitus over 7 years by more than 8-fold compared with normal glycemic parameters. Furthermore, the authors concluded, “Combined use of the FPG and HbA1c for screening purposes identifies a group of older adults at very high risk for future diabetes.”

Despite these results, the authors acknowledged several limitations of the study. The analyses did not take into account death or loss to follow-up; however, sensitivity analyses excluding those individuals yielded similar results. Additionally, a relatively small number of diabetes diagnoses (n=141) precluded systematic subgroup analyses. The authors also noted that cost-effectiveness of this dual screening strategy should be an area of future study.—Allison Musante



Knowledge of Age-Related Complications in Type 1 Diabetes Patients Could Lead to Improved Treatment

There is a lack of understanding of the characteristics of older adults with type 1 diabetes and the complications that they experience with age. Heightened awareness of the efficacy and safety of current approaches to treatment and serious acute complications of type 1 diabetes could yield better approaches to treatment in individuals as they age, explained Ruth S. Weinstock, MD, PhD, Division of Endocrinology, Diabetes, and Metabolism, Upstate University Hospital, Syracuse, NY, and colleagues during an ADA poster session.

The researchers presented a data analysis gleaned from the T1D Exchange Clinic Registry. The analysis included 5546 participants between the ages of 31 and 93 years who had type 1 diabetes for 1 year or longer, from 39 endocrinology centers across the United States. The participants included 639 adults aged ≥65 years, 1907 adults aged 50 to 65 years, and 3000 adults aged 31 to 50 years. Information regarding participants’ complications, medications, body mass index, and hemoglobin A1c (HbA1c) levels was gleaned from medical records; use of insulin pumps and sensors were reported by participants in a questionnaire and then confirmed by medical records. The prevalence of complications was assessed by age and diabetes duration.

Among the study’s key findings was that the presence of macrovascular complications increased with greater disease duration and age. Coronary artery disease or myocardial infarction was present in 26% of adults aged ≥65 years and in 12% of adults aged 50 to 65 years. The majority of adults ≥65 years were also taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (72%), statins (73%), and aspirin (79%). These patients had a mean HbA1c level of 7.4%, and only 8% used continuous glucose

In all age groups, the presence of severe hypoglycemia increased significantly with longer durations of type 1 diabetes. In adults aged ≥65 years, severe hypoglycemia was present in 21% of patients ≥40 years, in 16% of those with the disease for 20 to 40 years, and in 7% of those with type 1 diabetes for <20 years. At least one severe episode of hypoglycemia resulting in seizure or coma in the previous 12 months was recorded in 16% of adults aged ≥65 years.

Diabetic peripheral neuropathy, a microvascular complication of diabetes, was most commonly reported in adults aged ≥65 years with the disease for ≥40 years (43%), followed by adults aged 50 to 65 years with type 1 diabetes for ≥40 years (30%).

Despite the high prevalence of diabetic retinopathy, the researchers found that a significant proportion of adults with type 1 diabetes had not been treated for diabetic retinopathy in either eye. Adults aged ≥65 years with type 1 diabetes for ≥40 years were most likely to have been treated for retinopathy (54%) compared with 32% of adults aged ≥65 years with the disease for 20 to 40 years.

The authors concluded that a large proportion of adults with type 1 diabetes do not have clinically significant renal disease or macrovascular disease, despite decades of living with the disease; however, “better approaches are needed to prevent severe hypoglycemia and chronic diabetes-related microvascular and macrovascular complications in adults with type 1 diabetes.”—Allison Musante

The T1D Exchange Clinic Registry and Statistical Resource Center are supported by the Leona M. and Harry B. Helmsley Charitable Trust.