Cross-Sectional and Longitudinal Studies of "Pre-Diabetes" in the Pima Indians
Condition: Weight Gain; Overweight; Insulin Resistance; Obesity; Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Overweight; Diabetes Mellitus, Type 2; Insulin Resistance; Prediabetic State; Weight Gain
Study type: Observational

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.

      <TAB>

      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.
    

Detailed 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.

      <TAB>

      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Community sample from eligible participants from greater Phoenix metropolitan area@@@@@@
      
Keywords: Insulin Sensitivity; Insulin Secretion; Glucose Tolerance; Adipose Tissue; Preadipocytes; Natural History