Spotlight on genetic risk for diabetes

Recent studies looked at biomarkers to predict diabetes, characteristics of patients who developed type 1 diabetes during adulthood, and use of oral insulin to try to prevent type 1 diabetes.

People with increased genetic risk for diabetes were the focus of three recent studies.

In the first study, published by Diabetic Medicine on Nov. 13, researchers compared HbA1c, glycated albumin, and 1,5-anydroglucitol (1,5-AG) as methods for identifying glucose metabolism disturbances among first-degree relatives of people with diabetes. The study included 467 Chinese adults with normal weight and normal glucose tolerance: 208 who had a first-degree relative with diabetes and 259 who did not. Serum 1,5-AG levels were significantly lower in the first-degree relatives of those with diabetes (20.4 µg/mL vs. 23.8 µg/mL; P<0.001), while HbA1c and glycated albumin did not differ between groups. Compared to HbA1c, patients' 1,5-AG levels are more strongly correlated with intraday blood glucose excursions (with lower levels reflecting greater excursions). Logistic regression analysis showed an association between family history of diabetes and reduced serum 1,5-AG levels, leading the study authors to conclude that this could be a sensitive and convenient biomarker for monitoring early-stage glucose intolerance in a high-risk population with genetic susceptibility to diabetes. Larger population-based studies are needed to confirm the results, they cautioned.

The second study, published by The Lancet Diabetes & Endocrinology on Nov. 30, focused on people with a high genetic risk for type 1 diabetes. The study used the UK Biobank to identify white European patients who developed diabetes in the first six decades of life and found that 1,286 more cases of type 1 diabetes developed in the half of the population that was high risk according to the genetic score than in the low-risk half (almost a 10% increase). The study found that 42% of these diabetes diagnoses occurred between the ages of 31 and 60 years and that these patients had different clinical characteristics than patients in the Biobank database who were diagnosed with type 2 diabetes: lower body mass index (27.4 kg/m2 vs. 32.4 kg/m2), higher likelihood of using insulin within a year (89% vs. 6%), and higher risk of ketoacidosis (11% vs. 0.3%). The study authors concluded that genetic risk for type 1 diabetes leads to insulin-dependent diabetes presenting throughout the first six decades of life, which may be hard to differentiate in the background prevalence of type 2 diabetes. “Diagnosis of type 1 diabetes should be considered in any middle-aged patient with type 2 diabetes who does not show good glycaemic control on rapidly escalating therapy, especially if they are slim,” the authors said. An accompanying editorial noted that it's still uncertain how latent autoimmune diabetes of adults fits into this framework.

Finally, a trial published in the Nov. 21 JAMA provided oral insulin to relatives of patients with type 1 diabetes to try to prevent diabetes. The trial participants had at least two autoantibodies, including insulin autoantibodies, and normal glucose tolerance at baseline (median age at enrollment, 8.2 years). They were randomized to either 7.5 mg of oral insulin per day or placebo and followed for a median of 2.7 years. Overall, the oral insulin was not found to delay or prevent the development of type 1 diabetes, and the results do not support insulin as used in this study for diabetes prevention, the authors concluded. However, a prespecified subgroup analysis of patients whose first-phase insulin response was particularly low, the oral insulin appeared to delay the onset of diabetes. Future similar studies should consider this factor, as well as treatment adherence, genetic background, age at onset, and type of first-appearing diabetes-related autoantibody, the authors said.