TITLE

Insulin Resistance and Generalized Lipodystrophy Associated with Type 1 Diabetes: The Response to Leptin Therapy

AUTHOR(S)
Park, Jean Y.; Cochran, Elaine K.; Haller, Michael J.; Schatz, Desmond A.; Gorden, Phillip
PUB. DATE
June 2007
SOURCE
Diabetes;Jun2007 Supplement 1, Vol. 56, pA165
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Acquired generalized lipodystrophy (AGL) presents a major therapeutic challenge due to severe insulin resistance and hypertriglyceridemia. Several studies have demonstrated the dramatic clinical improvement seen with the administration of recombinant leptin for generalized lipodystrophy. Rarely, AGL and autoimmune type 1 diabetes (T1D) co-exist. We describe the response to recombinant leptin therapy in 2 patients with co-existing AGL and T1D. The first patient is a Caucasian male who was diagnosed with T1D at age 8 years. At age 13.5 years, he developed generalized lipodystrophy, elevated transaminases (ALT 221 U/L, AST 107 U/L) and markedly increased insulin requirements (250-350 U/day). Further evaluation revealed hypoleptinemia (2.2 ng/mL), hypertriglyceridemia (679 mg/dL) and poor glycemic control despite the high doses of insulin (HbA1c 10.1%). At age 15 years, leptin therapy was initiated. Following 1 year of leptin therapy, insulin requirements decreased to 50 U/day, glycemic control improved (HbA1c 8.4%), and both triglycerides (86 mg/dL) and transaminases (ALT 19 U/L, AST 19 U/L) normalized. The second patient, a Caucasian female, developed concurrent generalized lipodystrophy and T1D at age 6 years. Despite an increase in insulin requirements to 1000 U/day she had poor glycemic control (HbA1c 10.6%). Triglycerides were over 5000 mg/dL and fell to 2984 mg/dL with the addition of fenofibrate and pioglitazone. She had elevated transaminases (ALT 79 U/L, and AST 85 U/L) and evidence of non-alcoholic steatohepatitis on liver biopsy. At age 13 years, leptin therapy was initiated. By 1 year, her triglycerides decreased to 441 mg/dL, glycemic control improved (HbA1c 7.3%), and insulin requirements decreased by almost half (550 U/day). In conclusion, long-term recombinant leptin therapy is effective in treating the extreme insulin resistance seen in patients with the unusual combination of T1D and AGL.
ACCESSION #
25820934

 

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