C-peptide and islet autoantibodies may serve as biomarkers to predict the risk of severe hypo’s during intensification of type 2 diabetes treatment….
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“Currently, there is no clear way to predict whether a patient with type 2 diabetes will have problems with hypoglycemia if we try to be more aggressive with blood sugar control. Now, there is the possibility that blood biomarkers may predict whether they might have an issue with this or not,” said lead study author, Lisa Chow, M.D., an endocrinologist and assistant professor at the University of Minnesota.
Using data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, University of Minnesota researchers designed a randomized, multi-center, double, 2×2 factorial study to examine the effects of glycemic control (intensive vs standard), blood pressure control and lipid control on cardiovascular morbidity and mortality in patients with clinically diagnosed type 2 diabetes. The study enrolled 10,251 participants with long standing type 2 diabetes and either diagnosed cardiovascular disease or at least two cardiovascular risk factors (in addition to diabetes) for intervention and subsequent follow-up. The study was re-analyzed using a nested case-control design to examine whether baseline insulin deficiency or the presence of islet autoantibodies was associated with severe hypoglycemia and an inability to achieve good glycemic control. Participants had had at least one episode of severe hypoglycemia during the ACCORD study and failed to achieve a target HbA1c level of <6.0% at any point during the follow-up period.
Compared with controls, cases had higher HbA1c levels, a longer duration of diabetes, a higher frequency of insulin deficiency (17% of cases vs 1% of controls), and a higher percentage of insulin use (89% of cases vs 24% of controls) at baseline. Cases had comparable fasting glucose levels to controls, but higher rates of positive islet antibodies. The quality of the optimal matching on the continuous age and BMI variables was excellent: 90.9% of age matches were within 5 years, with a median difference of 0.5 years. For BMI, 90.7% of matches were within 5 kg/m2, with a median difference of 1.21 kg/m2. The presence of one autoantibody compared with zero autoantibodies was associated with a significant increase in the odds of developing the adverse outcome (unadjusted OR 4.0 [95% CI 3.0, 5.3], p<0.0001; adjusted OR 3.3 [95% CI 2.4, 4.6], p<0.0001; fully adjusted and removing deaths, OR 3.4 [95% CI 2.4, 4.7], p<0.0001), although all participants on baseline insulin were considered positive for insulin. The presence of two or more autoantibodies compared with zero autoantibodies was associated with even higher odds of the adverse outcome (unadjusted OR 12.4 [95% CI 7.1, 21.6], p<0.0001; adjusted OR 9.2 [95% CI 5.2, 16.5], p<0.0001; fully adjusted and removing deaths, OR 9.9 [95% CI 5.4, 18.0], p<0.0001).
After analyzing patients from the ACCORD study, Chow found that the C-peptide and islet autoantibodies may serve as biomarkers to predict the risk of severe hypoglycemia during the intensification of type 2 diabetes treatment.
“Certainly this will have to be validated in larger, more comprehensive studies. However, these findings raise the possibility blood biomarkers may help individualize Type 2 diabetes treatment to maximize outcomes for a specific patient,” said Chow.
- Intensive treatment for patients with type 2 diabetes can increase risk for severe hypoglycemia.
- With long-standing type 2 diabetes and the presence of islet cell autoantibodies, patients with type 2 diabetes can develop insulin deficiency comparable to that of patients with type 1 diabetes, with similar hypoglycemia rate.
- This study demonstrates that blood biomarkers indicating insulin deficiency may predict the response of patients with type 2 diabetes to intensification of glycemic treatment.
University of Minnesota News Release. Chow L. Biomarkers related to severe hypoglycemia and lack of good glycemic control in ACCORD. Diabetologia, Clinical and Experimental Diabetes and Metabolism June 2015. 58:3512 DOI: 10.1007/s00125-015-3512-0.