Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy.

Abstract

BACKGROUND:

Lack of leptin is implicated in insulin resistance and other metabolic abnormalities in generalized lipodystrophy; however, the efficacy, safety, and underlying mechanisms of leptin-replacement therapy in patients with generalized lipodystrophy remain unclear.

METHODS:

Seven Japanese patients with generalized lipodystrophy, two acquired and five congenital type, were treated with the physiological replacement dose of recombinant leptin during an initial 4-month hospitalization followed by outpatient follow-up for up to 36 months.

RESULTS:

The leptin-replacement therapy with the twice-daily injection dramatically improved fasting glucose (mean +/- SE, 172 +/- 20 to 120 +/- 12 mg/dl, P < 0.05) and triglyceride levels (mean +/- SE, 700 +/- 272 to 260 +/- 98 mg/dl, P < 0.05) within 1 wk. The leptin-replacement therapy reduced insulin resistance evaluated by euglycemic clamp method and augmented insulin secretion at glucose tolerance test with different responses between acquired and congenital types. Improvement of the fatty liver was also observed. The efficacy and safety of the once-daily injection were comparable to those of the twice-daily injection. The leptin-replacement therapy ameliorated macro- and microalbuminuria and showed no deterioration of neuropathy and retinopathy of these patients. The leptin-replacement therapy is beneficial to diabetic complications and lipodystrophic ones. Two patients developed antileptin antibodies but not neutralizing antibodies. The therapy was well tolerated, and its effects were maintained for up to 36 months without any notable adverse effects such as hypoglycemia, high blood pressure, or reduction of bone mineral density.

CONCLUSIONS:

The present study demonstrates the efficacy and safety of the long-term leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy.

• Authors: Ken Ebihara, Toru Kusakabe, Masakazu Hirata, Hiroaki Masuzaki, Fumiko Miyanaga, Nozomi Kobayashi, Tomohiro Tanaka, Hideki Chusho, Takashi Miyazawa, Tatsuya Hayashi, Kiminori Hosoda, Yoshihiro Ogawa, Alex M DePaoli, Masanori Fukushima, Kazuwa Nakao
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 92 Issue 2 Pg. 532-41 (Feb 2007) ISSN: 0021-972X [Print] United States
• PMID: 17118991 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Leptin
• Triglycerides

Topics

• Adolescent
• Adult
• Albuminuria (complications, drug therapy)
• Blood Glucose (drug effects)
• Child
• Diabetes Complications (complications, drug therapy)
• Fatty Liver (drug therapy)
• Female
• Follow-Up Studies
• Glucose Clamp Technique
• Glucose Tolerance Test
• Hormone Replacement Therapy (methods)
• Humans
• Hyperinsulinism
• Injections, Subcutaneous
• Insulin Resistance
• Leptin (administration & dosage, adverse effects)
• Lipodystrophy (complications, drug therapy)
• Male
• Time Factors
• Treatment Outcome
• Triglycerides (blood)