Cross-Sectional and Longitudinal Studies of "Pre-Diabetes" in the Pima Indians
| Status: | Recruiting |
|---|---|
| Conditions: | Endocrine, Diabetes |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 55 |
| Updated: | 9/27/2018 |
| Start Date: | August 18, 1982 |
| Contact: | Jonathan Krakoff, M.D. |
| Email: | jkrakoff@mail.nih.gov |
| Phone: | (602) 200-5217 |
Cross-Sectional and Longitudinal Studies of "Pre-Diabetes"
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.
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.
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.
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.
- INCLUSION CRITERIA:
Volunteers from all racial and ethnic backgrounds will be invited to participate if they
are:
Ages: 18 - 55 years old
Gender: male or female.
- Each subject who volunteers will be assigned to the clinical research ward physician
who made the initial contact and he/she will be responsible for completion of all
tests (see below) and compilation of data. This physician will consult with the
subject's personal physician or other health care personnel involved with the patient
in Sacaton. This includes sending a carefully written discharge summary to appropriate
health care workers at the time of discharge.
- 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).
EXCLUSION CRITERIA:
Subjects will be excluded who are on chronic medications for problems such as seizure
disorders.
Exclusions for occasional medications will be at the discretion of the interviewing
physician.
Women who are currently pregnant or breastfeeding will be excluded from the study.
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