Type 1 Diabetes Associated with Acquired Generalized Lipodystrophy and Insulin Resistance: The Effect of Long-Term Leptin Therapy

Abstract

Acquired generalized lipodystrophy (AGL) is marked by severe insulin resistance and hypertriglyceridemia. Rarely, AGL and type 1 diabetes (T1D) coexist. Our objective was to describe the response to leptin therapy in patients with coexisting AGL and T1D and to document the autoimmune diseases associated with AGL. We conducted an open-label prospective study at the Clinical Research Center of the National Institutes of Health. Participants included 50 patients with generalized or partial lipodystrophy (acquired or congenital); two patients had both AGL and T1D. Patients were treated with 12 months of recombinant human leptin administration to achieve high-normal serum concentrations. Two patients had both AGL and T1D. The first was diagnosed with T1D at age 8 yr. Beginning at age 11 yr, he developed generalized lipodystrophy, elevated transaminases, and poor glycemic control [hemoglobin A 1c (HbA 1c) 10.7%] despite markedly increased insulin requirements (3.3-5 U/kg.d). Further evaluation revealed hypoleptinemia and hypertriglyceridemia. At age 15 yr, leptin therapy was initiated, and after 1 yr, his insulin requirements fell to 1 U/kg.d, his glycemic control improved (HbA 1c 8.4%), and both his triglycerides and transaminases normalized. The second patient developed concurrent AGL and T1D at age 6 yr. Despite insulin doses of up to 32 U/kg.d, she developed poor glycemic control (HbA 1c 10.6%), hypertriglyceridemia (2984 mg/dl), elevated transaminases, and nonalcoholic steatohepatitis. At age 13 yr, leptin therapy was started, and after 1 yr, her glycemic control improved (HbA 1c 7.3%) and her insulin requirements decreased (17 U/kg.d). Her triglycerides remained elevated but were improved (441 mg/dl). Long-term recombinant leptin therapy is effective in treating the insulin resistance of patients with the unusual combination of T1D and AGL.