Risk Factors for Diabetes in Familial Partial Lipodystrophy, Dunnigan Variety

Risk Factors for Diabetes in Familial Partial Lipodystrophy, Dunnigan Variety Wasim A. Haque , MD 1 , Elif Arioglu Oral , MD 2 , Kelly Dietz , MS 3 , Anne M. Bowcock , PHD 4 , Anil K. Agarwal , PHD 1 and Abhimanyu Garg , MD 1 1 Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 2 Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 3 National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 4 Division of Human Genetics, Department of Genetics and Pediatrics, Washington University School of Medicine, St. Louis, Missouri Abstract OBJECTIVES —Familial partial lipodystrophy, Dunnigan variety (FPLD), is an autosomal dominant disorder due to missense mutations in the lamin A/C ( LMNA) gene encoding nuclear lamina proteins. It is characterized by loss of subcutaneous fat from the extremities and trunk and accumulation of fat in the head and neck region beginning at puberty. Patients with FPLD are predisposed to metabolic complications of insulin resistance such as diabetes. We sought to identify risk factors for diabetes in patients with FPLD. RESEARCH DESIGN AND METHODS —A cross-sectional study comparing clinical, biochemical, and anthropometric variables and LMNA genotypes in FPLD patients with and without diabetes. RESULTS —We studied 52 women and 24 men with FPLD from 18 different families. Twenty-eight women (54%) but only four men (17%) had diabetes ( P < 0.001); therefore further comparisons were mostly limited to women. Compared with women without diabetes, those with diabetes had higher BMI (median values 23 vs. 24 kg/m 2 , respectively; P = 0.03), increased chin skinfold thickness (10 vs. 20 mm; P = 0.001), lower rates of nulliparity (60% vs. 28%; P = 0.04), and higher levels of fasting serum triglycerides (2.4 vs. 3.5 mmol/l; P < 0.001) but similar serum leptin levels (3.4 vs. 3.6 ng/ml; P = 0.9). The prevalence of diabetes was not related to age, menopausal status, family history of type 2 diabetes in unaffected relatives, or LMNA genotype. CONCLUSIONS —We conclude that increased adiposity as reflected by excess subcutaneous fat accumulation in the chin region and parity may predispose women with FPLD to develop diabetes. FPLD, familial partial lipodystrophy, Dunnigan variety Footnotes Address correspondence and