Leptin, an adipocyte-secreted hormone, regulates energy homeostasis as well as reproductive, neuroendocrine, immune and metabolic functions. Subjects with decreased amounts of fat in their adipose tissue, i.e., lipoatrophy, have low leptin levels. In the context of open-label, uncontrolled studies leptin administration, in physiological replacement doses, has been shown to have metabolically salutary effects in the rare patients with the syndrome of congenital lipodystrophy accompanied by leptin deficiency. Much more patients with lipodystrophy suffer from lipodystrophy and the metabolic syndrome associated with the use of highly active antiretroviral therapy. In this so called highly active antiretroviral therapy (HAART)-associated lipodystrophy and metabolic syndrome, patients demonstrate fat maldistribution with dyslipidemia, insulin resistance, and other metabolic complications. Leptin administration has been shown to decrease central fat mass and to improve fasting insulin/glucose levels and insulin sensitivity in human immunodeficiency virus-infected hypoleptinemic patients with HAART induced lipodystrophy and the metabolic syndrome. By contrast, the results of leptin treatment in leptin replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. In this review, we present the emerging clinical applications and potential therapeutic uses of leptin in humans with lipodystrophy and the metabolic syndrome.
Adipose Tissue ; Antiretroviral Therapy, Highly Active ; Diabetes Mellitus ; Dyslipidemias ; Fasting ; Glucose Intolerance ; HIV ; Homeostasis ; Humans ; Insulin Resistance ; Leptin ; Lipodystrophy ; Therapeutic Uses

The purpose of this study was to investigate the stage of glucose intolerance in which persons showed a maximum obesity in Korea. A total of 4,479 participants, who were involved in the 2005 Korean National Health and Nutrition Examination Survey, was examined. The participants were divided into 5 groups by fasting plasma glucose (FPG); normal fasting glucose (NFG)1, FPG < 90 mg/dL; NFG2, FPG 90-99 mg/dL; impaired fasting glucose (IFG)1, FPG 100-109 mg/dL; IFG2, FPG 110-125 mg/dL; and diabetes mellitus, FPG > or = 126 mg/dL or with anti-diabetes drugs. In those with FPG < 110 mg/dL, body mass index (BMI) and waist circumference (WC) were increased with increase of FPG (BMI in men; NFG1, 23.3 +/- 0.1; NFG2, 24.4 +/- 0.1; IFG1, 25.0 +/- 0.2 kg/m2, in women; NFG1, 23.0 +/- 0.1; NFG2, 24.0 +/- 0.1; IFG1, 24.8 +/- 0.2 kg/m2, WC in men; NFG1, 82.1 +/- 0.3; NFG2, 85.3 +/- 0.3; IFG1, 86.7 +/- 0.5 cm, in women; NFG1, 77.1 +/- 0.2; NFG2, 79.4 +/- 0.3; IFG1, 81.8 +/- 0.6 cm). In IFG2 and diabetes range, there was no more increase of BMI and WC with increase of FPG in each sex. The data suggest that degree of obesity increases with an increase of FPG in range of FPG < 100 mg/dL, peaked in FPG of 100-109 mg/dL, and then plateaus in higher FPG range in general Korean population.
Adult ; Blood Glucose/analysis ; *Body Mass Index ; Diabetes Mellitus, Type 2/drug therapy ; Female ; *Glucose Intolerance ; Humans ; Hypoglycemic Agents/therapeutic use ; Male ; Middle Aged ; *Nutrition Surveys ; Obesity/epidemiology ; Republic of Korea/epidemiology ; *Waist Circumference

Introduction of tacrolimus has been accepted as one of the major advance in the management of rejection following solid organ transplantation. This open-label, multi-center study is designed to confirm the efficacy of tacrolimus in primary kidney transplantation. A total of 64 renal transplant recipients were recruited from 4 medical centers, and received dual drug therapy consists of tacrolimus and low-dose corticosteroids after kidney transplantation. Tacrolimus was started 2 days prior to the transplantation with the dosage of 0.2 mg/kg/day. Daily dose of tacrolimus was modulated to maintain the trough blood level between 15 ng/ml and 20 ng/ml for the first 3 months and between 10 ng/ml and 15 ng/ml for the next 3 months after the transplantation. Steroid pulse therapy with methylprednisolone was used as a first line modality of acute rejection treatment. Steroid resistant rejection was treated with anti- lymphocyte agents. Post-transplant diabetes mellitus was defined as the cases when patients who had no history of glucose intolerance need the use of oral hypoglycemics and/or insulin for 30 days or longer to control their hyperglycemia after transplantation. There were 51 live donor and 13 cadaveric donor transplantations. Live donor transplantation consisted with 33 related (10 HLA identical, 23 HLA haplo- identical) and 18 unrelated pairs. Mean age of the patients was 39.4 9.6 (range; 22-58). There were 36 male and 28 female patients. There were 21 acute rejection episodes in 17 patients (26.6%) during the first 6 months after transplantation. Six patients were treated with anti-lymphocyte agents, and 4 patients showed complete response but 2 episodes (9.5%) showed partial rescue. Six-month patient and graft survivals were 100% and 98.4%, respectively. A total of 18 patients (28.1%) experienced glucose intolerance during the study period. Tacrolimus showed satisfactory efficacy in primary kidney transplantation. Long-term follow up is needed for further evaluation of efficacy and safety.
Adrenal Cortex Hormones ; Cadaver ; Diabetes Mellitus ; Drug Therapy ; Female ; Follow-Up Studies ; Glucose Intolerance ; Graft Survival ; Humans ; Hyperglycemia ; Hypoglycemic Agents ; Insulin ; Kidney Transplantation ; Kidney* ; Lymphocytes ; Male ; Methylprednisolone ; Organ Transplantation ; Prospective Studies* ; Tacrolimus* ; Tissue Donors ; Transplantation ; Transplants