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C-peptide, islet autoantibodies may predict severe hypoglycemia risk
During intensification of type 2 diabetes treatment, the risk for severe hypoglycemia may be predicted by the biomarkers C-peptide and islet autoantibodies, according to recent study findings.
Lisa S. Chow, MD, of the department of medicine at the University of Minnesota, and colleagues evaluated patients from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial who were assigned to intensive treatment for type 2 diabetes.
Lisa S. Chow
Presence of severe hypoglycemia and failure to achieve HbA1c levels of less than 6% before the ACCORD transition or death were defined as cases (n = 326), and controls were defined as those without severe hypoglycemia who achieved an HbA1c level less than 6% (n = 1,075).
Higher HbA1c levels and longer duration of diabetes were found among cases compared with controls. Similarly, cases had a higher frequency of insulin deficiency (17%) compared with controls (1%) and a higher percentage of insulin use (cases, 89% vs. 24%, controls). Fasting glucose levels were comparable between the groups; however, cases had higher rates of positive islet autoantibodies for glutamic acid decarboxylase (GAD), tyrosine phosphatase-related islet antigen 2 (IA2), insulin autoantibodies and zinc transporter 8 (ZnT8).
There were 63 participants with insulin deficiency, but they were taking insulin and were classified as positive for islet autoantibodies to insulin. After excluding insulin autoantibodies, GAD was the most common positive islet autoantibody (44.4% in participants with insulin deficiency; 6.7% in those without insulin sufficiency).
After adjustment for age, BMI, diabetes duration and exclusion of those who died during the study, severe hypoglycemia along with an inability to achieve an HbA1c level of less than 6% was linked to insulin deficiency (adjusted OR = 23.2; 95% CI, 9-59.5), positive insulin autoantibody status or baseline insulin use (adjusted OR = 3.8; 95% CI, 2.7-5.3), GAD autoantibodies (adjusted OR = 3.9; 95% CI, 2.5-6), IA2 autoantibodies (adjusted OR = 16.7; 95% CI, 3.9-71.6) and ZnT8 autoantibodies (adjusted OR = 3.9; 95% CI, 1.2-12.4).
Mark L. Evans
“In the ACCORD study, baseline measures of C-peptide and islet autoantibodies are associated with [severe hypoglycemia] during intensification of type 2 diabetes treatment,” the researchers wrote. “Since a major goal of type 2 diabetes treatment is to minimize patient risk of microvascular complications without increasing the therapy burden, these blood biomarkers may prove useful in the individualization of type 2 diabetes treatment.”
In an accompanying editorial, Sankalpa Neupane, MBBS, MRCP, and Mark L. Evans, MD, FRCP, both of the University of Cambridge, wrote that the study brings to question whether biomarkers would help clinicians identify patients at lower or greater risk for treatment-induced hypoglycemia.
“Individualizing treatment regimens is of course already the stock trade of clinical teams,” they wrote. “For example, the choice of therapy and glycemic targets will probably be different in an 85-year-old with type 2 diabetes compared with a 40-year-old patient. All of this emphasizes that type 2 diabetes is a mixed bag and that clinical management should be individualized — an important point that can easily be lost with generic type 2 diabetes clinical guidelines.” – by Amber Cox
Disclosure: Chow, Neupane and Evans report no relevant financial disclosures. Study medications, equipment or supplies were provided by Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca, Bayer HealthCare, Closer Healthcare, GlaxoSmithKline, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis and Schering-Plough.