{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T20:45:51Z","timestamp":1770410751664,"version":"3.49.0"},"reference-count":31,"publisher":"American Diabetes Association","issue":"1","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,1,1]]},"abstract":"<jats:p>OBJECTIVE\u2014To investigate whether leptin-induced improvements in glycemic control, hyperlipidemia, and insulin sensitivity in hypoleptinemic patients with generalized lipodystrophies are accompanied by reduction in intrahepatic and intramyocellular lipid (IMCL) accumulation.<\/jats:p><jats:p>RESEARCH DESIGN AND METHODS\u2014We examined the effects 8\u201310 months of subcutaneous leptin replacement therapy on insulin sensitivity, IMCL, and intrahepatic lipid content in two patients with acquired generalized lipodystrophy and one patient with congenital generalized lipodystrophy. All patients had extreme lack of body fat, low plasma leptin levels, and elevated serum triglycerides, but only two had diabetes. Insulin sensitivity was measured by a high-dose (0.2 IU\/kg) insulin tolerance test, as well as by hyperinsulinemic-euglycemic glucose clamp studies in two patients. IMCL and intrahepatic lipid content were measured by 1H magnetic resonance spectroscopy. All measurements were obtained before and during 2\u201310 months of leptin therapy.<\/jats:p><jats:p>RESULTS\u2014Glycemic control and lipoprotein levels markedly improved with leptin therapy in the two diabetic patients, and a slight improvement in lipoprotein levels was seen in the nondiabetic patients. Insulin stimulated glucose uptake during 60\u2013120 min of the euglycemic clamp studies, and the rate of glucose disappearance during the insulin tolerance test nearly doubled with leptin therapy. As compared with the baseline period, after 8\u201310 months of leptin therapy, the mean intrahepatic lipid content was reduced by \u223c80% and the IMCL content was reduced by \u223c42%.<\/jats:p><jats:p>CONCLUSIONS\u2014Reduction in IMCL and intrahepatic lipid content may partly explain leptin-induced improvement in insulin sensitivity in patients with generalized lipodystrophy.<\/jats:p>","DOI":"10.2337\/diacare.26.1.30","type":"journal-article","created":{"date-parts":[[2007,3,5]],"date-time":"2007-03-05T22:51:27Z","timestamp":1173135087000},"page":"30-35","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":102,"title":["Effect of Leptin Replacement on Intrahepatic and Intramyocellular Lipid Content in Patients With Generalized Lipodystrophy"],"prefix":"10.2337","volume":"26","author":[{"given":"Vinaya","family":"Simha","sequence":"first","affiliation":[{"name":"Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas"},{"name":"Center for Human Nutrition, Unviersity of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidia S.","family":"Szczepaniak","sequence":"additional","affiliation":[{"name":"Division of Hypertension, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony J.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Amgen, Inc., Thousand Oaks, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex M.","family":"DePaoli","sequence":"additional","affiliation":[{"name":"Amgen, Inc., Thousand Oaks, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhimanyu","family":"Garg","sequence":"additional","affiliation":[{"name":"Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas"},{"name":"Center for Human Nutrition, Unviersity of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031215065323000_R1","doi-asserted-by":"crossref","unstructured":"Garg A: Lipodystrophies. 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