Genetics of Beta Cell Failure in Mexican Americans

Study Overview
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Brief Summary
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This is a family based genotype-phenotype study designed to assess genetic and environmental influences on obesity, insulin resistance and beta cell function in the context of gestational diabetes.

Detailed Description
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Mexican American women with prior gestational diabetes and their first degree relatives and Mexican American women with prior normal glucose tolerance in pregnancy are studied with detailed phenotyping consisting of oral and intravenous glucose tolerance tests, body composition studies, diet and physical activity assessments, and circulating biomarkers potentially related to obesity, insulin resistance, pancreatic beta cell function, gestational diabetes and type 2 diabetes. Spouses of the gestational diabetic and control probands are studied with oral glucose tolerance tests. Offspring of the gestational and control probands have fasting glucose determinations. All participants provide DNA for genetics testing. A subset of the gestational diabetic probands and their first degree relatives return 3-5 years after baseline testing for repeat phenotyping.

Official Title
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Genetics of Beta Cell Failure in Mexican Americans

Conditions
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Gestational Diabetes, Diabetes Type 2, Insulin Resistance, Beta Cell Function, Genetics, Nutrition, Physical Activity, Adipokines, Obesity, Air Pollution

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Probands with Prior Gestational Diabetes Mellitus (GDM PROBANDS) Mexican American (parents and at least 3/4 four grandparents age >18 years GDM in singleton pregnancy in prior 5 years impaired glucose levels or sum of five OGTT glucose values >625 mg/dl on 75 gram oral glucose tolerance test Fasting plasma glucose <126 mg/dl At least two adult siblings of cousin not known to have diabetes and available for phenotyping; . Siblings and Cousins of GDM Probands Full sibling or first cousin of GDM proband Age >18 yrs Fasting plasma glucose <126 mg/dl. Parents, Uncles and Aunts of GDM Probands Full blooded parent, uncle or aunt of GDM proband Control Proband Mexican American as defined for GDM probands One glucose challenge test result <120 mg/dl at >24 weeks gestation No diabetes in first degree relative Frequency matched to GDM probands by distributions of age, BMI and parity. Spouse of GDM or Control Proband Spouse of GDM proband Age >18 At least one child with proband able to provide DNA Child of Proband Child of GDM or control proband and spouse who provided DNA EXCLUSION CRITERIA PROBANDS (GDM OR CONTROL): Chronic medical illness or medication known to alter glucose/insulin metabolism Current pregnancy or breastfeeding Ilicit drug or alcohol abuse, Inability or unwillingness to give informed consent. SIBLINGS AND COUSINS OF PROBANDS: Chronic medical illness or medication known to affect glucose/insulin metabolism Current pregnancy or breastfeeding, Ilicit drug or alcohol abuse Inability or unwillingness to give informed consent. PARENTS OF PROBANDS Inability or unwillingness to give informed consent. SPOUSE OF GDM or CONTROL PROBAND Inability or unwillingness to give informed consent. CHILD OF GDM or CONTROL PROBAND Lack of parent consent or child assent.

Ages Eligible for Study
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Minimum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pancreatic Beta Cell Compensation for Insulin Resistance | Disposition index from intravenous glucose tolerance test | Single time point for primary cohort, repeated 4.5 years later in subset | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Senstivity | Si from computer modeled intravenous glucose tolerance test | Single time point for primary cohort, repeated 4.5 years later in subset | 
| Acute Insulin Release | Incremental area under insulin curve during first 10 minutes intravenous glucose tolerance test | Single time point for primary cohort, repeated 4.5 years later in subset | 
| Glucose tolerance | normal, impaired or diabetic glucose level determined using American Diabetes Associate criteria applied to glucose levels from a 2-hour, 75 gram oral glucose tolerance test | Single time point for primary cohort, repeated 4.5 years later in subset | 
| Diabetes type 2 | Fasting glucose >125 mg/dl and/or 2-hour glucose on 75 gram oral glucose tolerance test >199 mg/dl | Single time point for primary cohort, repeated 4.5 years later in subset | 
| Dietary Intake | Measured by semi-quantitative Harvard Food Frequency Questionnaire | Single time point for primary cohort, repeated 4.5 years later in subset | 
| Physical Activity | Measured by Multi-ethnic Cohort Physical Activity Questionnaire | Single time point for primary cohort, repeated 4.5 years later in subset | 
| Body Fat | Percent body fat measured by dual photon X-ray absorptiometry | Single time point for primary cohort, repeated 4.5 years later in subset | 
| Circulating adipokine levels | Fasting levels of approximately 20 adipocytokines | Single time point for primary cohort, repeated 4.5 years later in subset |