The Arg Variant in Insulin Receptor Substrate-1 Is Associated With an Increased Risk of Secondary Failure to Sulfonylurea in Patients With Type 2 Diabetes

RESEARCH DESIGN AND METHODS — A total of 477 unrelated Caucasian type 2 diabetic patients were recruited according to the following criteria: onset of diabetes after age 35 years, absence of ketonuria at diagnosis, and anti-GAD antibody. Type 2 diabetes was diagnosed according to the American Diabetes Association criteria. Patients with secondary sulfonylurea failure were defined as those requiring insulin due to uncontrolled hyperglycemia (fasting plasma glucose 300 mg/dl) despite sulfonylurea-metformin combined therapy, appropriate diet, and absence of any conditions causing hyperglycemia.