Type 1 diabetes associated with acquired generalized lipodystrophy and insulin resistance: the effect of long-term leptin therapy

J Clin Endocrinol Metab. 2008 Jan;93(1):26-31. doi: 10.1210/jc.2007-1856. Epub 2007 Oct 16.


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 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).

Conclusions: Long-term recombinant leptin therapy is effective in treating the insulin resistance of patients with the unusual combination of T1D and AGL.

Publication types

  • Case Reports
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Fatal Outcome
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / complications
  • Hypertriglyceridemia / drug therapy
  • Insulin Resistance / physiology*
  • Leptin / blood
  • Leptin / therapeutic use*
  • Lipodystrophy / blood
  • Lipodystrophy / complications*
  • Lipodystrophy / drug therapy*
  • Male
  • Prospective Studies
  • Recombinant Proteins / blood
  • Recombinant Proteins / therapeutic use
  • Triglycerides / blood


  • Blood Glucose
  • Glycated Hemoglobin A
  • Leptin
  • Recombinant Proteins
  • Triglycerides
  • Aspartate Aminotransferases
  • Alanine Transaminase