Short-term Effects of Leptin in People With Lipodystrophy

* INCLUSION CRITERIA: * Age 14-70 years (children under age 18 will only be enrolled in the leptin-naive arm of the study * Clinically-significant lipodystrophy as defined in protocol 02-DK-0022 (Long Term Efficacy of Leptin Replacement in the Treatment of Lipodystrophy). Relevant inclusion criteria for enrollment in protocol 02-DK-0022 are (summarized): * Lipodystrophy identified by the study physician during physical examination as an absence of fat outside the range of normal * Circulating leptin levels \< 12.0 ng/mL in females and \< 8.0 ng/mL in males * Presence of at least one of the following metabolic abnormalities: 1. Diabetes as defined by the 2007 American Diabetes Association criteria 2. Fasting insulin \>30 microU/mL 3. Fasting hypertriglyceridemia \>200 mg/dL * Co-enrolled in protocol 02-DK-0022 and either: * Leptin naive, with plans to initiate leptin treatment during the current study. For the purpose of this study, leptin naive will be defined as having received no exogenous leptin in the 4 months prior to study participation. Thus, subjects who previously received leptin therapy, discontinued, and wish to restart are eligible. Or --Leptin treated, meaning the subject has taken a stable dose of exogenous leptin for a minimum of 4 months (adults over age 18, only) EXCLUSION CRITERIA: In leptin treated subjects only, the following exclusion criteria apply: * Poorly controlled diabetes at study entry (hemoglobin A1c greater than or equal to 9%) * Poorly controlled hypertriglyceridemia at study entry (serum triglycerides \> 800 mg/dL) * Extreme hypertriglyceridemia prior to leptin (triglycerides greater than 2000 mg/dL at initiation of leptin treatment) * History of chronic or recurrent acute pancreatitis (\> 1 episode), or a single episode of pancreatitis while receiving leptin treatment * Lipase greater than the upper limit of normal (491 units/L) at study entry In all subjects (leptin treated and leptin naive), the following exclusion criteria apply: * Known HIV infection or HIV-associated lipodystrophy * History of diabetic ketoacidosis * Active inflammatory disease (e.g. dermatomyositis) * Change in diabetes or lipid-lowering medications within the past 6 weeks * Estimated glomerular filtration rate \< 30 mL/minute * Current or recent (past 2 weeks) use of systemic glucocorticoids * Inadequately controlled hypothyroidism (TSH \< 0.4 or \>4 mcIU/L) or change in thyroid medication in the past 8 weeks. * Pregnancy or breast-feeding * Psychiatric disorder impeding competence or compliance * Any medical condition or medication that will increase risk to the subject (e.g. ischemic heart disease, decompensated liver disease) or that will interfere with interpretation of study data (e.g. Cushing s syndrome).