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

2014-08-27 03:44:00 | BioPortfolio

Summary

The Pima Indians of Arizona have the highest prevalence and incidence of type 2 diabetes of any population in the world. Prospective analyses in this population have identified insulin resistance and a defect in early insulin secretion as risk factors for the development of the disease. A recent longitudinal analysis which tracked the development of diabetes in 17 Pima Indians 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 plan to study Pima Indian families 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.

Description

The Pima Indians of Arizona have the highest prevalence and incidence of type 2 diabetes of any population in the world (1). Prospective analyses in this population have identified insulin resistance and a defect in early insulin secretion as risk factors for the development of the disease (2). A recent longitudinal analysis which tracked the development of diabetes in 17 Pima Indians demonstrated that both insulin action and early insulin secretion deteriorate as individuals progress from normal to impaired glucose tolerance and then to diabetes (3). 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 plan to study Pima Indian families 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.

Study Design

N/A

Conditions

Diabetes

Location

NIDDK, Phoenix
Phoenix
Arizona
United States
85014

Status

Recruiting

Source

National Institutes of Health Clinical Center (CC)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:44:00-0400

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Medical and Biotech [MESH] Definitions

Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes (DIABETES MELLITUS; DIABETES INSIPIDUS).

The time period before the development of symptomatic diabetes. For example, certain risk factors can be observed in subjects who subsequently develop INSULIN RESISTANCE as in type 2 diabetes (DIABETES MELLITUS, TYPE 2).

A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.

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