Cross-Sectional and Longitudinal Studies of "Pre-Diabetes" in the Pima Indians

Obesity Clinical Trial

Official title:

Cross-Sectional and Longitudinal Studies of 'Pre-Diabetes'

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00340132
• Other study ID #: 9999820136
• Secondary ID: OH82-DK-0136
• Status: Completed
• Start date: January 1, 1983

Study information

• Verified date: April 18, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Insulin resistance and a defect in early insulin secretion are risk factors for the development of type 2 diabetes mellitus. A recent longitudinal analysis which tracked the development of diabetes demonstrated that both insulin action and early insulin secretion deteriorate as individuals progress from normal to impaired glucose tolerance and then to diabetes. These results suggest that both inherent (apparent in normal glucose tolerant subjects who progress to diabetes and likely to have a genetic basis) and acquired (evident as individuals progress from NGT to IGT to diabetes and possibly environmental in origin) defects in insulin action and secretion contribute to the pathogenesis of type 2 diabetes. To identify the genetic and environmental determinants of diabetes we are continuing to determine: (1) if there are genes that segregate with metabolic risk factors for diabetes which might therefore be genetic markers for type 2 diabetes and (2) the mechanisms mediating genetic and environmental determinants of insulin resistance and impaired insulin secretion.

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Volunteers for this study will be admitted to the clinical research ward where they will undergo several tests to determine body composition, oral and intravenous glucose tolerance and in vivo insulin action. In addition, in selected subjects, adipose and/or skeletal muscle tissue will be obtained by percutaneous biopsy for in vitro studies of gene expression and insulin action in these tissues. A transformed lymphocyte cell line will be established for each subject as a permanent source of DNA for genetic studies. Genetic markers for type 2 diabetes and insulin resistance will be sought by typing each individual at positional and functional candidate loci in the hopes of finding an association between these loci and obesity, insulin secretion, insulin resistance and/or type 2 diabetes.

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Description:

Insulin resistance and a defect in early insulin secretion are risk factors for the development of type 2 diabetes mellitus. A recent longitudinal analysis which tracked the development of diabetes demonstrated that both insulin action and early insulin secretion deteriorate as individuals progress from normal to impaired glucose tolerance and then to diabetes. These results suggest that both inherent (apparent in normal glucose tolerant subjects who progress to diabetes and likely to have a genetic basis) and acquired (evident as individuals progress from NGT to IGT to diabetes and possibly environmental in origin) defects in insulin action and secretion contribute to the pathogenesis of type 2 diabetes. To identify the genetic and environmental determinants of diabetes we are continuing to determine: (1) if there are genes that segregate with metabolic risk factors for diabetes which might therefore be genetic markers for type 2 diabetes and (2) the mechanisms mediating genetic and environmental determinants of insulin resistance and impaired insulin secretion.

Volunteers for this study will be admitted to the clinical research ward where they will undergo several tests to determine body composition, oral and intravenous glucose tolerance and in vivo insulin action. In addition, in selected subjects, adipose and/or skeletal muscle tissue will be obtained by percutaneous biopsy for in vitro studies of gene expression and insulin action in these tissues. A transformed lymphocyte cell line will be established for each subject as a permanent source of DNA for genetic studies. Genetic markers for type 2 diabetes and insulin resistance will be sought by typing each individual at positional and functional candidate loci in the hopes of finding an association between these loci and obesity, insulin secretion, insulin resistance and/or type 2 diabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1759
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

• INCLUSION CRITERIA:

Subjects from all racial and ethnic backgrounds will be invited to participate if they are:

• Ages: 18-55 years old (up to 2200 participants)

• Gender: male or female

EXCLUSION CRITERIA:

Subjects will be excluded who are:

• Taking medication for a chronic illness.

• Have any acute or chronic diseases or conditions not specifically mentioned that in the opinion of the provider may interfere with the study or decrease safety for participation will be considered exclusionary.

• Women who currently pregnant or breastfeeding.

• Positive for drug and/or nicotine use.

All medications and alcohol consumption are to be stopped for two weeks prior to admission. A urine drug-screening test for drugs such as narcotics, marijuana, and barbiturates will be performed on everyone to exclude from the study people whose urine show active or recent drug use. A positive drug test could confound the results of the study in an unpredictable manner. The results of this test will become a part of the patient s medical records and may be released if requested (please see page 6 of the consent for details regarding medical records release).

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Insulin Resistance
• Obesity
• Overweight
• Prediabetic State
• Weight Gain

Locations

Country	Name	City	State
United States	NIDDK, Phoenix	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glucose tolerance via oral glucose tolerance test (OGTT)	Measured via OGTT after ingestion of 75 grams of glucose over 2 minutes	Baseline, and after 180 minutes on day 4
Primary	Glucose tolerance via intravenous glucose tolerance test (IVGTT)	Measured via IVGTT after administration of a glucose bolus (25 g as a 50% solution injected over 3 minutes)	Baseline and after 10 minutes on day 5
Primary	Basal endogenous glucose production	Assessed using deuterium (D-6,6 2H) glucose as a tracer, infused as a 10 mL bolus followed by 0.150 mL/min for a total of 350 minutes	Baseline, and after 100 minutes on day 10
Primary	24-hour metabolic rate	Assessed from the rates of caloric expenditure and substrate utilization while in the human respiratory chamber for 24 hours	Baseline and after 23.5 hours on day 7