NCT00001987

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,200

participants targeted

Target at P75+ for all trials

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 1976

Completed
24 years until next milestone

First Submitted

Initial submission to the registry

January 28, 2000

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 31, 2000

Completed
Last Updated

April 30, 2026

Status Verified

April 28, 2026

First QC Date

January 28, 2000

Last Update Submit

April 29, 2026

Conditions

Diabetes MellitusSevere Insulin Resistance

Keywords

Diabetes MellitusSevere Insulin ResistanceType B Insulin ResistanceNatural History

Outcome Measures

Primary Outcomes (4)

  • Diabetes control

    To help prevent additional health issues associated with poor glucose and insulin levels.

    every 6-12 months

  • Genetics of insulin resistance

    To discover the cause of the insulin resistance to better assist with treatment for it.

    End of Study

  • Pathophysiology of insulin resistance and its relationship to cardiovascular disease.

    To understand the pathophysiology of insulin resistance and its relationship to cardiovascular disease.

    End of study

  • Obtain tissue samples for ex vivo studies.

    To understand physiology and pathophysiology of insulin resistance and develop possible treatments.

    End of study

Study Arms (2)

Healthy Volunteers

Healthy Volunteers

Device: HR-pQCT scan

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

Interventions

HR-pQCT scanDEVICE

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.

Healthy VolunteersPatients with severe insulin resistance

Eligibility Criteria

Age6 Months - 120 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Subjects with severe insulin resistance disorders.

You may qualify if:

  • 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
  • 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
  • +19 more criteria

You may not qualify if:

  • 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
  • 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)
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (9)

  • Okawa MC, Tuska RM, Lightbourne M, Abel BS, Walter M, Dai Y, Cochran E, Brown RJ. Insulin Signaling Through the Insulin Receptor Increases Linear Growth Through Effects on Bone and the GH-IGF-1 Axis. J Clin Endocrinol Metab. 2023 Dec 21;109(1):e96-e106. doi: 10.1210/clinem/dgad491.

    PMID: 37595266DERIVED

  • Walzer D, Turcu AF, Jha S, Abel BS, Auchus RJ, Merke DP, Brown RJ. Excess 11-Oxygenated Androgens in Women With Severe Insulin Resistance Are Mediated by Adrenal Insulin Receptor Signaling. J Clin Endocrinol Metab. 2022 Aug 18;107(9):2626-2635. doi: 10.1210/clinem/dgac365.

    PMID: 35696182DERIVED

  • Okawa MC, Cochran E, Lightbourne M, Brown RJ. Long-Term Effects of Metreleptin in Rabson-Mendenhall Syndrome on Glycemia, Growth, and Kidney Function. J Clin Endocrinol Metab. 2022 Feb 17;107(3):e1032-e1046. doi: 10.1210/clinem/dgab782.

    PMID: 34718628DERIVED

  • Meral R, Malandrino N, Walter M, Neidert AH, Muniyappa R, Oral EA, Brown RJ. Endogenous Leptin Concentrations Poorly Predict Metreleptin Response in Patients With Partial Lipodystrophy. J Clin Endocrinol Metab. 2022 Mar 24;107(4):e1739-e1751. doi: 10.1210/clinem/dgab760.

    PMID: 34677608DERIVED

  • Nguyen ML, Sachdev V, Burklow TR, Li W, Startzell M, Auh S, Brown RJ. Leptin Attenuates Cardiac Hypertrophy in Patients With Generalized Lipodystrophy. J Clin Endocrinol Metab. 2021 Oct 21;106(11):e4327-e4339. doi: 10.1210/clinem/dgab499.

    PMID: 34223895DERIVED

  • Sekizkardes H, Chung ST, Chacko S, Haymond MW, Startzell M, Walter M, Walter PJ, Lightbourne M, Brown RJ. Free fatty acid processing diverges in human pathologic insulin resistance conditions. J Clin Invest. 2020 Jul 1;130(7):3592-3602. doi: 10.1172/JCI135431.

    PMID: 32191645DERIVED

  • Klubo-Gwiezdzinska J, Lange M, Cochran E, Semple RK, Gewert C, Brown RJ, Gorden P. Combined Immunosuppressive Therapy Induces Remission in Patients With Severe Type B Insulin Resistance: A Prospective Cohort Study. Diabetes Care. 2018 Nov;41(11):2353-2360. doi: 10.2337/dc18-0884. Epub 2018 Sep 10.

    PMID: 30201849DERIVED

  • Brown RJ, Joseph J, Cochran E, Gewert C, Semple R, Gorden P. Type B Insulin Resistance Masquerading as Ovarian Hyperthecosis. J Clin Endocrinol Metab. 2017 Jun 1;102(6):1789-1791. doi: 10.1210/jc.2016-3674.

    PMID: 27911591DERIVED

  • Kassai A, Muniyappa R, Levenson AE, Walter MF, Abel BS, Ring M, Taylor SI, Biddinger SB, Skarulis MC, Gorden P, Brown RJ. Effect of Leptin Administration on Circulating Apolipoprotein CIII levels in Patients With Lipodystrophy. J Clin Endocrinol Metab. 2016 Apr;101(4):1790-7. doi: 10.1210/jc.2015-3891. Epub 2016 Feb 22.

    PMID: 26900642DERIVED

Related Links

MeSH Terms

Conditions

Diabetes MellitusInsulin Resistance

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesHyperinsulinism

Study Officials

  • Rebecca J Brown, M.D.

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

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Megan S Startzell, R.N.

CONTACT

(301) 402-6371megan.startzell@nih.gov

Rebecca J Brown, M.D.

CONTACT

(301) 594-0609brownrebecca@mail.nih.gov

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 28, 2000

First Posted

January 31, 2000

Study Start

February 1, 1976

Last Updated

April 30, 2026

Record last verified: 2026-04-28

Data Sharing

IPD Sharing
Will not share

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

Locations

US(1)