Genetic Studies of Insulin and Diabetes

June 2, 2026 updated by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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 diabetes, dyslipidemia, cardiovascular disease, liver disease, kidney disease, reproductive function, bone disease, and other organ dysfunction, (2) To study the molecular genetics underlying various causes of insulin resistance and diabetes mellitus, (3) To understand the natural history of insulin resistance disorders, including their response to FDA approved therapies, and (4) To conduct ex vivo studies of the physiology and pathophysiology underlying disorders of insulin resistance, and possible treatments for these disorders, using cells and tissues collected in this study.

Endpoints:

Primary Endpoint: Genetic causes of insulin resistance

Secondary Endpoints: Diabetes control (hemoglobin A1c) and complications (rates of micro- and macrovascular disease)

Study Type

Observational

Enrollment (Estimated)

1200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Subjects with severe insulin resistance disorders.

Description

  • INCLUSION CRITERIA:

Three categories of subjects will be included in this study:

  • Patients with evidence for insulin resistance or a disorder associated with severe insulin resistance, including:

    • Patients with various syndromes of lipodystrophy
    • Patients with known or suspected mutations on the insulin receptor gene
    • Patients with known or suspected autoantibodies to the insulin receptor
    • Patients with other severe forms of insulin resistance
  • Family members of patients, above
  • Healthy control subjects without insulin resistance

Inclusion criteria for each group of subjects are given below:

  • 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)

EXCLUSION CRITERIA:

  • Patients with evidence for insulin resistance or a disorder associated with severe insulin resistance

    --none

  • Family members of patients, above

    --Pregnant at the time of enrollment

  • Healthy control subjects Cohort 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.
    • Recent (past 2 months) use of drugs or supplements that alter glucose or lipid metabolism (e.g. niacin, fish oil, red yeast rice)
    • History of diabetes or abnormal glucose tolerance
    • 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
    • Pregnant or lactating

  • Healthy control subjects Cohort 2. Subjects from Cohort 1 may NOT be included in Cohort 2 if they have any of the following ADDITIONAL exclusion criteria.

    • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Healthy Volunteers
Device: HR-pQCT scan
HR-pQCT is a non-invasive, low-dose three-dimensional imaging method used to evaluate volumetric bone mineral density and bone microarchitecture of peripheral skeletal sites, including distal radius and distal tibia. HR-pQCT has an ability to differentiate between cortical and trabecular bone compartments providing density and structure parameters.
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.
Device: HR-pQCT scan
HR-pQCT is a non-invasive, low-dose three-dimensional imaging method used to evaluate volumetric bone mineral density and bone microarchitecture of peripheral skeletal sites, including distal radius and distal tibia. HR-pQCT has an ability to differentiate between cortical and trabecular bone compartments providing density and structure parameters.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genetics of insulin resistance
Time Frame: End of Study
To discover the cause of the insulin resistance to better assist with treatment for it.
End of Study
Diabetes control
Time Frame: every 6-12 months
To help prevent additional health issues associated with poor glucose and insulin levels.
every 6-12 months
Pathophysiology of insulin resistance and its relationship to cardiovascular disease.
Time Frame: End of study
To understand the pathophysiology of insulin resistance and its relationship to cardiovascular disease.
End of study
Obtain tissue samples for ex vivo studies.
Time Frame: End of study
To understand physiology and pathophysiology of insulin resistance and develop possible treatments.
End of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 1976

Study Registration Dates

First Submitted

January 28, 2000

First Submitted That Met QC Criteria

January 28, 2000

First Posted (Estimated)

January 31, 2000

Study Record Updates

Last Update Posted (Actual)

June 3, 2026

Last Update Submitted That Met QC Criteria

June 2, 2026

Last Verified

May 28, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 760006
  • 76-DK-0006

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Subject level data will be shared upon request after appropriate collaboration agreements are in place.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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