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Genetic Studies of Insulin and Diabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00001987
Recruitment Status : Enrolling by invitation
First Posted : January 31, 2000
Last Update Posted : November 4, 2019
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )

Brief Summary:

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 or disease
Diabetes Mellitus Severe Insulin Resistance

Detailed Description:

Insulin is the key hormone responsible for regulating the level of glucose in plasma. In several disease states (e.g., obesity, non-insulin-dependent diabetes mellitus, and acromegaly), the target cells are resistant to insulin action. 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.

The purpose of this protocol is to threefold:

  1. To study the molecular genetics underlying various causes of insulin resistance and diabetes mellitus.
  2. To understand the natural history of insulin resistance disorders, including their response to FDA approved therapies. However, the treatment aspect of the protocol represents clinical care rather than prospective research.
  3. To educate fellows in the Inter-institute Endocrinology and Pediatric Endocrinology programs of the NIH about rare and common insulin resistant disorders.

Patients with 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 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

The frequency of visits and testing to be performed will vary due to the clinical heterogeneity of the patients studied as well as their worldwide geographic distribution, and will be adjusted on an individual basis. The total quantity of blood collected will be adjusted to remain within the approved NIH guidelines appropriate to the individual s age and size. The testing will include all or some of the following studies:

  • Fasting blood sampling (e.g. insulin, glucose, HbA1c, lipid profile, lipoprotein profile, IGF-1 level, leptin level)
  • Urine pregnancy test for applicable patients
  • adrenal hormones and growth hormone
  • Oral glucose tolerance test
  • Stable isotope tracer studies to measure glucose and lipid turnover
  • Hyperinsulinemic-euglycemic clamp studies to measure insulin sensitivity
  • Analysis of body composition (anthropometric measurements, DEXA, MRI)
  • Measurement of autoantibodies to the insulin receptor if Type B insulin resistance is suspected
  • Biopsy of skin for the establishment of fibroblast or induced pluripotential stem cell lines
  • Biopsies of subcutaneous adipose tissue and/or muscle for gene expression profiling
  • Biopsies of liver or kidney if clinically indicated in patients with lipodystrophy
  • Biopsies of thyroid tissue if clinically indicated

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Study Type : Observational
Actual Enrollment : 600 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Natural History of Disorders of Insulin Resistance
Actual Study Start Date : January 30, 1976

Resource links provided by the National Library of Medicine

Patients with severe insulin resistance
patients with severe insulin resistance manifesting with acanthosis nigricans, hyperinsulinemia, type A and B insulin resistance syndromes, and patients with lipodystrophy.

Primary Outcome Measures :
  1. Genetics of insulin resistance [ Time Frame: End of Study ]
    To discover the cause of the insulin resistance to better assist with treatment for it.

  2. Diabetes control [ Time Frame: every 6-12 months ]
    To help prevent additional health issues associated with poor glucose and insulin levels.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Subjects with severe insulin resistance disorders.@@@@@@

At least one of the following is required:

Hyperinsulinemia (i.e. greater than 30 microgramsU/mL).

Clinical presence of type 2 diabetes mellitus.

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;




Fatty liver

Family members of patients with known disease states of insulin action.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00001987

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: Rebecca J Brown, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Identifier: NCT00001987     History of Changes
Other Study ID Numbers: 760006
First Posted: January 31, 2000    Key Record Dates
Last Update Posted: November 4, 2019
Last Verified: October 29, 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ):
Diabetes Mellitus
Severe Insulin Resistance
Type B Insulin Resistance
Additional relevant MeSH terms:
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Diabetes Mellitus
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs