Genetics of Beta Cell Failure in Mexican Americans

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.

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.