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.

Condition
Diabetes Mellitus Insulin Resistance

The purpose of this protocol is to enable us to obtain adequate blood or tissue samples to study the molecular mechanisms underlying various causes of insulin resistance and diabetes mellitus. Patients with any evidence for insulin resistance will be eligible to participate in this study. We particularly focus our study on the following four groups of patients:

1. Patients with various syndromes of lipoatrophy, lipodystrophy

2. Patients with mutations on the insulin receptor gene

3. Patients with autoantibodies to the insulin receptor

4. Patients with severe forms of insulin resistance

In addition, patients displaying unusual phenotypic features (i.e. presence of acanthosis nigricans) in association with hyperinsulinemia (i.e. fasting insulin levels greater than 30 microgramsU/mL) or clinical diabetes mellitus may be eligible to be studied at NIH.

The work-up will include all or some of the following studies:

1. Routine biochemical profile

2. Fasting insulin, glucose, HbA1c, lipid profile, lipoprotein profile, IGF-1 level, leptin level

3. A panel of hormone levels: thyroid and sex hormones, pituitary hormones, adrenal hormones and growth hormone

4. Blood samples for genetic studies

5. Oral glucose tolerance test

6. Intravenous glucose tolerance test

7. In vitro insulin or IGF-1 binding

The total quantity of blood will be within the approved NIH guidelines appropriate to the individual's age and size. In addition, some subjects may undergo skin biopsy for the establishment of fibroblast cell lines. Mostly, patients with lipoatrophy and lipodystrophy may be asked to undergo a muscle and/or bone marrow biopsy to broaden the molecular studies. DEXA analysis and anthropometric measurements are performed when medically indicated during the diagnosis and evaluation to correlate markers of insulin resistance with parameters of whole body composition.

In a novel component of the study, we aim to study the biochemical and molecular changes that occur with standard therapies (such as high dose insulin, continuous insulain therapy, metformin, and TZD's) used for the treatment of insulin resistance and diabetes.

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION/EXCLUSION CRITERIA
At least one of the following is required:
Hyperinsulinemia (i.e. greater than 30 microgramsU/mL).
Clinical presence of diabetes.
Phenotypic features suggesting a defect in glucose/lipid metabolism:
Acanthosis nigricans;
Lipoatrophy/lipodystrophy;
Lipomatosis;
Xanthomata;
Fatty liver.
Family members of patients with known disease states of insulin action.

Maryland
      National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  760006; 76-DK-0006
Record last reviewed:  January 7, 2004
Last Updated:  January 7, 2004
Record first received:  January 28, 2000
ClinicalTrials.gov Identifier:  NCT00001987
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-11-08