Relationship of Family History of Type 2 Diabetes, Hypoglycemia, and Autoantibodies to Weight Gain and Lipids With Intensive and Conventional Therapy in the Diabetes Control and Complications Trial

Relationship of Family History of Type 2 Diabetes, Hypoglycemia, and Autoantibodies to Weight Gain and Lipids With Intensive and Conventional Therapy in the Diabetes Control and Complications Trial Jonathan Q. Purnell 1 , Raj K. Dev 2 , Michael W. Steffes 3 , Patricia A. Cleary 4 , Jerry P. Palmer 2 , Irl B. Hirsch 2 , John E. Hokanson 5 and John D. Brunzell 2 1 Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health & Science University, Portland, Oregon 2 Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, Washington 3 University of Minnesota, Minneapolis, Minnesota 4 George Washington University, Rockville, Maryland 5 University of Colorado, Denver, Colorado Address correspondence and reprint requests to Jonathan Q. Purnell, MD, Oregon Health & Science University, Division of Endocrinology, Diabetes, and Clinical Nutrition, L607, 3181 SW Sam Jackson Park Rd., Portland, OR 97201. E-mail: purnellj{at}ohsu.edu Abstract Intensive therapy for type 1 diabetes results in greater weight gain than conventional therapy. Many factors may predispose to this greater weight gain, including improved glycemic control, genetic susceptibility to obesity, and hypoglycemia. To study this, relationships among family history of type 2 diabetes, frequency of severe hypoglycemia, β-cell autoantibodies, and weight gain were examined in 1,168 subjects aged ≥18 years at baseline randomized to intensive and conventional therapy groups in the Diabetes Control and Complications Trial. With intensive therapy, subjects with a family history of type 2 diabetes had greater central weight gain and dyslipidemia characterized by higher triglyceride levels and greater cholesterol in VLDLs and intermediate-density lipoproteins compared with subjects with no family history. Neither the frequency of severe hypoglycemia nor positivity to GAD65 and insulinoma-associated protein 2 antibodies was associated with increased weight gain with either intensive or conventional therapy. These data support the hypothesis that increased weight gain with intensive therapy might be explained, in part, by genetic traits. DCCT, Diabetes Control and Complications Trial IA-2, insulinoma-associated protein 2 IDL, intermediate-density lipoprotein WHR, waist-to-hip ratio Footnotes Accepted July 16, 2003. Received October 28, 2002. DIABETES