Genetic studies on insulin and diabetes

Natural History of Disorders of Insulin Resistance

This study is trying to understand how genetics affects insulin resistance and diabetes by comparing people with these conditions to healthy individuals.

Quick facts

• Study type: Observational
• Enrollment: 1200 (estimated)
• Ages: 6 Months to 120 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT00001987 on ClinicalTrials.gov

What this trial studies

This study focuses on understanding the genetic factors contributing to insulin resistance and diabetes mellitus by comparing patients with these conditions to healthy individuals. Researchers will collect blood, plasma, DNA, and RNA samples to investigate how insulin functions and its attachment to cells. The study aims to explore the pathophysiology of insulin resistance, its relationship to cardiovascular disease, and the natural history of insulin resistance disorders. Additionally, it will assess the genetic causes of insulin resistance and the response to FDA-approved therapies.

Who should consider this trial

Good fit: Ideal candidates include patients with severe insulin resistance, specific genetic mutations related to insulin function, or healthy individuals without insulin resistance.

Not a fit: Patients without any form of insulin resistance or related disorders may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and treatment options for patients with insulin resistance and diabetes.

How similar studies have performed: Other studies have shown success in understanding insulin resistance through genetic approaches, making this a promising area of research.

Eligibility criteria

* 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

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Rebecca J Brown, M.D. — National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Study coordinator: Megan S Startzell, R.N.

Conditions Diabetes Mellitus; Severe Insulin Resistance; Type B Insulin Resistance; Natural History