Study of Growth Hormone Inhibition Using Pegvisomant in Severe Insulin Resistance

* INCLUSION CRITERIA: To be eligible to participate in this study, an individual must meet all the following criteria: * Either * Known pathogenic variant in the insulin receptor gene, either dominant negative or recessive, OR * Clinical diagnosis of partial lipodystrophy based on reduction in adipose tissue outside the normal range in selected adipose depots (including, at a minimum, the gluteofemoral depot) with preservation of adipose tissue in other depots. * Male or female, aged 18-70 years. * Completed linear growth and puberty. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: * Use of niacin or other drugs that directly affect lipolysis within 8 weeks prior to enrollment. * Patients taking anticoagulants (blood thinning medications). * Use of non-steroidal anti-inflammatory medications (e.g., aspirin, ibuprofen) 2 weeks prior to the biopsy date (in patients who choose to undergo biopsy). * Changes in medications for diabetes or dyslipidemia within 2 weeks prior to enrollment. * Pregnancy or lactation. * For females of reproductive potential: inability or unwillingness to use contraception during study participation and for an additional 1 month after the end of pegvisomant administration. * For males of reproductive potential: inability or unwillingness to use condoms or other methods to ensure effective contraception with partner during the study and for an additional 1 month after the end of pegvisomant administration. * Known allergic reactions pegvisomant or any of its components. * Clinically significant liver disease, evidenced by any of the following: * ALT or AST \>3 times the upper limit of normal at screening. * Current known liver disease other than steatohepatitis (e.g., autoimmune or viral hepatitis). * History of cirrhosis * Triglycerides \>1500 mg/dL (non-fasting) or \>1000 mg/dL (fasting) at screening. * In subjects with partial lipodystrophy only, Hemoglobin A1c \>10% at screening. * Any other medical condition or medication that, in the judgement of the investigator, will increase risk to the subject or impede the measurement of study outcomes. * Inability of subject to understand or the unwillingness to sign a written informed consent document.