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

@article{citeulike:2216580, abstract = {Context: Acquired generalized lipodystrophy (AGL) is marked by severe insulin resistance and hypertriglyceridemia. Rarely, AGL and type 1 diabetes (T1D) coexist. Objective: 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. Design and Setting: We conducted an open-label prospective study at the Clinical Research Center of the National Institutes of Health. Patients: Participants included 50 patients with generalized or partial lipodystrophy (acquired or congenital); two patients had both AGL and T1D. Intervention: Patients were treated with 12 months of recombinant human leptin administration to achieve high-normal serum concentrations. Results: 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 A1c (HbA1c) 10.7\%] despite markedly increased insulin requirements (3.35 U/kg{middle dot}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{middle dot}d, his glycemic control improved (HbA1c 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{middle dot}d, she developed poor glycemic control (HbA1c 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 (HbA1c 7.3\%) and her insulin requirements decreased (17 U/kg{middle dot}d). Her triglycerides remained elevated but were improved (441 mg/dl). Conclusions: Long-term recombinant leptin therapy is effective in treating the insulin resistance of patients with the unusual combination of T1D and AGL. 10.1210/jc.2007-1856}, author = {Park, Jean Y. and Chong, Angeline Y. and Cochran, Elaine K. and Kleiner, David E. and Haller, Michael J. and Schatz, Desmond A. and Gorden, Phillip }, citeulike-article-id = {2216580}, doi = {10.1210/jc.2007-1856}, journal = {J Clin Endocrinol Metab}, keywords = {diabetestype1, lipodystrophy, therapy}, month = {January}, number = {1}, pages = {26--31}, posted-at = {2008-01-10 23:09:36}, priority = {2}, title = {Type 1 Diabetes Associated with Acquired Generalized Lipodystrophy and Insulin Resistance: The Effect of Long-Term Leptin Therapy}, url = {http://dx.doi.org/10.1210/jc.2007-1856}, volume = {93}, year = {2008} }

TY - JOUR ID - citeulike:2216580 L3 - citeulike-article-id:2216580 TI - Type 1 Diabetes Associated with Acquired Generalized Lipodystrophy and Insulin Resistance: The Effect of Long-Term Leptin Therapy JF - J Clin Endocrinol Metab VL - 93 IS - 1 SP - 26 EP - 31 N2 - Context: Acquired generalized lipodystrophy (AGL) is marked by severe insulin resistance and hypertriglyceridemia. Rarely, AGL and type 1 diabetes (T1D) coexist. Objective: 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. Design and Setting: We conducted an open-label prospective study at the Clinical Research Center of the National Institutes of Health. Patients: Participants included 50 patients with generalized or partial lipodystrophy (acquired or congenital); two patients had both AGL and T1D. Intervention: Patients were treated with 12 months of recombinant human leptin administration to achieve high-normal serum concentrations. Results: 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 A1c (HbA1c) 10.7%] despite markedly increased insulin requirements (3.35 U/kg{middle dot}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{middle dot}d, his glycemic control improved (HbA1c 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{middle dot}d, she developed poor glycemic control (HbA1c 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 (HbA1c 7.3%) and her insulin requirements decreased (17 U/kg{middle dot}d). Her triglycerides remained elevated but were improved (441 mg/dl). Conclusions: Long-term recombinant leptin therapy is effective in treating the insulin resistance of patients with the unusual combination of T1D and AGL. 10.1210/jc.2007-1856 KW - diabetestype1 KW - lipodystrophy KW - therapy AU - Park, Jean AU - Chong, Angeline AU - Cochran, Elaine AU - Kleiner, David AU - Haller, Michael AU - Schatz, Desmond AU - Gorden, Phillip PY - 2008/01/01/ UR - http://dx.doi.org/10.1210/jc.2007-1856 ER -