Pathophysiology Clinical Trial
Official title:
Ethnic Dependence of the Metabolic Defects in Prediabetic Individuals: Kuwaiti Arabs Versus Indians
Insulin resistance and beta cell dysfunction are the major core defects responsible for the
development of type 2 diabetes (T2DM). Although insulin resistance is the early metabolic
defect detected in subjects destined to develop T2DM, it is the beta cell failure which is
responsible for the development of hyperglycemia.
Longitudinal and cross-sectional studies have demonstrated that, initially, the compensatory
hyperinsulinemia is sufficient to offset the insulin resistance and maintain normal glucose
tolerance. However, when the beta cell fails to adequately compensate for the insulin
resistance, glucose homeostasis deteriorates. Initially, this is manifest as impaired glucose
tolerance (IGT) and later as overt diabetes. It follows that the level of beta cell failure
at which hyperglycemia becomes evident depends upon the prevailing level of insulin
resistance. A more severe insulin resistance results in development of overt hyperglycemia at
lower level of beta cell failure. The investigators previously have shown that the severity
of insulin resistance varies amongst different ethnic groups (Arabs versus Indians). Thus,
the level of beta cell failure at which overt hyperglycemia becomes evident amongst each
ethnic group also varies. Thus, individuals/ethnic groups with more severe insulin
resistance, overt hyperglycemia becomes evident at lower level of beta cell dysfunction.
Conversely, severe beta cell dysfunction is required for evert hyperglycemia to develop in
individuals/ethnicities with less severe insulin resistance.
In the present study, the investigators aim to quantitate beta cell function with the gold
standard technique (i.e. hyperglycemic clamp) in Arab and Indian non-diabetic individuals and
relate the level of beta cell function to the prevailing level of insulin resistance measured
as the glucose infusion rate divided by the mean plasma insulin concentration during the
clamp.
Status | Recruiting |
Enrollment | 120 |
Est. completion date | December 31, 2021 |
Est. primary completion date | July 15, 2021 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 21 Years to 65 Years |
Eligibility |
Inclusion Criteria: 1. age 21-65 years 2. BMI=18-45 kg/m2 3. NGT (FPG<100 mg/dl and 2-hour PG <140 mg/dl) or IGT (FPG < 125 mg/dl, and 2-hour PG=140-199 mg/dl) according to the ADA criteria. 4. Good general health as determined by physical exam, medical history, blood chemistries, CBC, TSH, T4, lipid profile. 5. Stable body weight (± 3 lbs) over the preceding three months 6. Not participate in an excessively heavy exercise program. Exclusion Criteria: Subjects with - Haematocrit < 34.0 - Diabetes, Thyroid disorders, Cardiovascular Diseases, Cancer, Bronchial Asthma and any autoimmune disease. - Subjects who receive medications which affect glucose tolerance, e.g. Steroids - Subjects who participate in excessively heavy exercise programs, e.g. Athletes |
Country | Name | City | State |
---|---|---|---|
Kuwait | Dasman Diabetes Institute | Kuwait |
Lead Sponsor | Collaborator |
---|---|
Dasman Diabetes Institute |
Kuwait,
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* Note: There are 15 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Insulin Resistance | Insulin Resistance measured as total glucose disposal TGD with the Insulin Clamp | 15 months | |
Primary | Insulin Secretion | First phase and second phase insulin secretion measured with the hyperglycemic clamp | 15 months | |
Primary | Beta Cell function | Beta cell function for the first phase and second phase measured as ?C-Pep/(1/TGD) | 15 months | |
Primary | Comparison of genetic markers | Genetic markers that correlate with the metabolic phenotype measured using GWAS | 15 months | |
Primary | GLP1 Action | GLP1 Action measured as increase in C-peptide during the hyperglycemic clamp caused by exenatide infusion | 15 months |
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