Bethesda, Maryland 20892

  • Severe Insulin Resistance

Purpose:

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.


Study summary:

Study Description: Insulin is the key hormone responsible for regulating the level of glucose in plasma. In several disease states (e.g., obesity, type 2 diabetes, and acromegaly), the target cells are resistant to insulin action. Insulin resistance leads to metabolic complications including diabetes, dyslipidemia, cardiovascular disease, non-alcoholic fatty liver disease, and reproductive dysfunction. The intramural research program of the NIDDK has a long history of studying patients with rare disorders of extreme insulin resistance. We use what is learned from these rare patients both to develop therapeutics for rare diseases, and to apply what is learned to understand more common forms of insulin resistance. Objectives: Primary Objectives: (1) To understand the pathophysiology of insulin resistance and its relationship to cardiovascular disease, (2) To study the molecular genetics underlying various causes of insulin resistance and diabetes mellitus, and (3) To understand the natural history of insulin resistance disorders, including their response to FDA approved therapies. Endpoints: Primary Endpoint: Genetic causes of insulin resistance Secondary Endpoints: Diabetes control (hemoglobin A1c) and complications (rates of micro- and macrovascular disease)


Criteria:

- INCLUSION CRITERIA: Three categories of subjects will be included in this study: 1. Patients with evidence for insulin resistance or a disorder associated with severe insulin resistance, including: 1. Patients with various syndromes of lipodystrophy 2. Patients with known or suspected mutations on the insulin receptor gene 3. Patients with known or suspected autoantibodies to the insulin receptor 4. Patients with other severe forms of insulin resistance 2. Family members of patients, above 3. Healthy control subjects without insulin resistance Inclusion criteria for each group of subjects are given below: 1. Patients with evidence for severe insulin resistance or a disorder associated with severe insulin resistance must meet all of the following criteria: a. Suspected severe insulin resistance, or a disorder associated with severe insulin resistance, as evidenced by one or more of the following: i. Hyperinsulinemia (i.e. fasting insulin >30microunits/mL) ii. High insulin requirement (> 2 units per kg per day or > 200 units total per day) iii. Phenotypic features suggesting a defect in glucose/lipid metabolism: - Acanthosis nigricans - Lipodystrophy/abnormal fat distribution - Xanthomata - Fatty liver iv. Known or suspected mutations of the insulin receptor gene v. Known or suspected autoantibodies to the insulin receptor b. Age >= 6 months c. Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document. 2. Family members of patients, above (either affected or unaffected) must meet all of the following criteria 1. Biological relatives of patients in category (1) in whom a genetic cause of insulin resistance is known or suspected. 2. Age >= 6 months 3. Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document. 3. Healthy control subjects without insulin resistance must meet all of the following criteria 1. In good general health with no known active medical conditions as evidenced by medical history 2. Age >= 12 years 3. Fasting glucose <100 mg/dL 4. HbA1c <5.7% 5. Fasting triglycerides <150 mg/dL 6. Fasting insulin <20 mcU/mL 7. BMI <27 kg/m^2 or <90th %ile for age/sex (whichever is lower) 8. Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: 1. Patients with evidence for insulin resistance or a disorder associated with severe insulin resistance a. none 2. Family members of patients, above a. Pregnant or lactating at the time of enrollment 3. Healthy control subjects without insulin resistance 1. Current use of prescription or non-prescription medication. Certain exceptions are permitted, including topical medications, vitamins, and hormonal contraceptives. Other medications may be permitted at the discretion of the investigators. 2. Recent (past 2 months) use of drugs or supplements that alter glucose or lipid metabolism (e.g. niacin, fish oil, red yeast rice) 3. History of diabetes or abnormal glucose tolerance 4. Psychiatric or cognitive disorder that will, in the opinion of the investigators, limit the subject's ability to provide informed consent/assent, or to comply with study procedures 5. Pregnant or lactating 6. Abnormal screening labs, including the following: - ALT or AST more than 1.5 times the upper limit of normal - Glycosuria - Clinically significant anemia - Low eGFR (<60 mL/min/1.73m^2) - Any other abnormality that, in the opinion of the investigator, will increase risk to the subject from participation, or interfere with interpretation of study data


NCT ID:

NCT00001987


Primary Contact:

Principal Investigator
Rebecca J Brown, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Megan S Startzell, R.N.
Phone: (301) 402-6371
Email: megan.startzell@nih.gov


Backup Contact:

Email: brownrebecca@mail.nih.gov
Rebecca J Brown, M.D.
Phone: (301) 594-0609


Location Contact:

Bethesda, Maryland 20892
United States



There is no listed contact information for this specific location.

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 27, 2022

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