Adipokines, Air Pollution, Beta Cell Function, Diabetes Type 2, Genetics, Gestational Diabetes, Insulin Resistance, Nutrition, Obesity, Physical Activity
Conditions
Brief summary
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
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.
Interventions
None listed
Sponsors
Kaiser Permanente
University of Southern California
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
8 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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; . 2. Siblings and Cousins of GDM Probands * Full sibling or first cousin of GDM proband * Age \>18 yrs * Fasting plasma glucose \<126 mg/dl. 3. Parents, Uncles and Aunts of GDM Probands * Full blooded parent, uncle or aunt of GDM proband 4. 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. 5. Spouse of GDM or Control Proband * Spouse of GDM proband * Age \>18 * At least one child with proband able to provide DNA 6. Child of Proband * Child of GDM or control proband and spouse who provided DNA
Exclusion criteria
1. 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. 2. 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. 3. PARENTS OF PROBANDS * Inability or unwillingness to give informed consent. 4. SPOUSE OF GDM or CONTROL PROBAND * Inability or unwillingness to give informed consent. 5. CHILD OF GDM or CONTROL PROBAND * Lack of parent consent or child assent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pancreatic Beta Cell Compensation for Insulin Resistance | Single time point for primary cohort, repeated 4.5 years later in subset | Disposition index from intravenous glucose tolerance test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Senstivity | Single time point for primary cohort, repeated 4.5 years later in subset | Si from computer modeled intravenous glucose tolerance test |
| Acute Insulin Release | Single time point for primary cohort, repeated 4.5 years later in subset | Incremental area under insulin curve during first 10 minutes intravenous glucose tolerance test |
| Glucose tolerance | Single time point for primary cohort, repeated 4.5 years later in subset | 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 |
| Diabetes type 2 | Single time point for primary cohort, repeated 4.5 years later in subset | Fasting glucose \>125 mg/dl and/or 2-hour glucose on 75 gram oral glucose tolerance test \>199 mg/dl |
| Dietary Intake | Single time point for primary cohort, repeated 4.5 years later in subset | Measured by semi-quantitative Harvard Food Frequency Questionnaire |
| Physical Activity | Single time point for primary cohort, repeated 4.5 years later in subset | Measured by Multi-ethnic Cohort Physical Activity Questionnaire |
| Body Fat | Single time point for primary cohort, repeated 4.5 years later in subset | Percent body fat measured by dual photon X-ray absorptiometry |
| Circulating adipokine levels | Single time point for primary cohort, repeated 4.5 years later in subset | Fasting levels of approximately 20 adipocytokines |
Outcome results
None listed