TY - JOUR
T1 - Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy
AU - Ebihara, Ken
AU - Kusakabe, Toru
AU - Hirata, Masakazu
AU - Masuzaki, Hiroaki
AU - Miyanaga, Fumiko
AU - Kobayashi, Nozomi
AU - Tanaka, Tomohiro
AU - Chusho, Hideki
AU - Miyazawa, Takashi
AU - Hayashi, Tatsuya
AU - Hosoda, Kiminori
AU - Ogawa, Yoshihiro
AU - DePaoli, Alex M.
AU - Fukushima, Masanori
AU - Nakao, Kazuwa
N1 - Funding Information:
This work was supported by grants from the Japanese Ministry of Education, Science, Sports, and Culture; the Japanese Ministry of Health, Welfare, and Labor; the Japan Medical Association; Japan Research Foundation for Clinical Pharmacology; the Fujisawa Foundation; the Takeda Science Foundation; and The Study Grant for Japan Insulin Study Group.
PY - 2007/2
Y1 - 2007/2
N2 - 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.
AB - 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.
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U2 - 10.1210/jc.2006-1546
DO - 10.1210/jc.2006-1546
M3 - Article
C2 - 17118991
AN - SCOPUS:33846950833
VL - 92
SP - 532
EP - 541
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 2
ER -