Natural History of Disorders of Insulin Resistance
The study will allow researchers to obtain blood, plasma, DNA, and RNA for genetic studies of insulin. There will be a focus on the causes of insulin resistance and diabetes mellitus. Insulin is a hormone found in the body that controls the level of sugar in the blood. Insulin resistance refers to conditions like diabetes when insulin does not work properly. In this study researchers would like to compare patients with diabetes and other forms of insulin resistance to normal individuals. The study will investigate how insulin attaches to cells. Researchers will take 4 to 6 ounces (100-150 ml) of blood from adult patients and may request up to 12 ounces (one unit) of blood if necessary. Skin samples may be taken for a biopsy if further genetic testing is necessary. In addition some patients may be asked not to eat for up to 72 hours prior to testing.
• Patients with evidence for severe insulin resistance or a disorder associated with severe insulin resistance must meet all of the following criteria:
‣ Suspected severe insulin resistance, or a disorder associated with severe insulin resistance, as evidenced by one or more of the following:
⁃ Hyperinsulinemia (i.e. fasting insulin \>30microU/mL)
⁃ High insulin requirement (\> 2 units per kg per day or \> 200 units total per day)
⁃ Phenotypic features suggesting a defect in glucose/lipid metabolism:
• Acanthosis nigricans
∙ Lipodystrophy/abnormal fat distribution
∙ Xanthomata
∙ Fatty liver
⁃ Known or suspected mutations of the insulin receptor gene
⁃ Known or suspected autoantibodies to the insulin receptor
⁃ Age \>= 6 months
⁃ Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.
• Family members of patients, above (either affected or unaffected) must meet all of the following criteria:
‣ Biological relatives of patients in category (1) in whom a genetic cause of insulin resistance is known or suspected.
⁃ Age \>= 6 months
⁃ Ability of subject (and/or legal guardian, for minor subjects) to understand and the willingness to sign a written informed assent/consent document.
• Healthy control subjects Cohort 1 must meet all of the following criteria.
‣ Ability of subject (and/or legal guardian, for minor subjects) to understand and the willingness to sign a written informed assent/consent document.
⁃ In good general health with no known active medical conditions as evidenced by medical history
⁃ Age \>= 12 years
• Healthy control subjects Cohort 2. Subjects from Cohort 1 may be included in Cohort 2 if they meet the following ADDITIONAL inclusion criteria.
‣ Fasting glucose \<100 mg/dL
⁃ HbA1c \<5.7%
⁃ Fasting triglycerides \<150 mg/dL
⁃ Fasting insulin \<30 mcU/mL
⁃ BMI \<27 kg/m\^2 or \<90th percentile for age/sex (whichever is lower)