It is unknown whether beta cell dysfunction and insulin resistance in Gestational Diabetes Mellitus (GDM) is representative of a chronic maternal defect, unmasked by pregnancy, or whether it is the result of an imbalance of a placental hormones. Undiscovered placental factors which vary between pregnancies likely contribute to the pathogenesis of GDM. To elucidate the pathophysiology underlying GDM, the investigators will attempt to discover these factors and characterize pregnancy-associated changes in insulin secretion and sensitivity in women with and without GDM.

Gestational diabetes mellitus (GDM) complicates 3-7% of pregnancies in the United States and is associated with perinatal morbidity and a high risk of future maternal type 2 diabetes. Current prevention and treatment of GDM relies on techniques developed in the type 2 diabetes population, without regard to unique physiology in pregnancy. GDM occurs in the setting of profound pregnancy changes in glucose metabolism: late pregnancy is normally characterized by marked insulin resistance. In order to maintain normal glucose levels and avoid GDM, pancreatic beta cells must augment insulin secretion to compensate. Women with GDM have inadequate beta-cell compensation for pregnancy-induced insulin resistance, resulting in hyperglycemia. It is unknown whether beta cell dysfunction and insulin resistance in GDM is representative of a chronic maternal defect, unmasked by pregnancy, or whether it is the result of an imbalance of a placental hormones. Undiscovered placental factors which vary between pregnancies likely contribute to the pathogenesis of GDM. Discovery of these factors and elucidation of the pathophysiology underlying GDM will allow for the development better GDM-specific prevention and treatment strategies.

Inclusion Criteria:

• Women, age 18-44, non-pregnant OR in the 1st trimester of pregnancy (4-14 weeks gestation),

• Who had GDM in a previous pregnancy

• At risk for diabetes mellitus, as specified by the American Diabetes Association (ADA):

• BMI ≥ 25 kg/m2 (or BMI ≥ 23 kg/m2 if Asian-American) PLUS one or more of the following:

  • history of giving birth to a neonate weighing > 9 lbs
  • first-degree family member with diabetes mellitus
  • high-risk ethnic or racial group (African-American, Hispanic, Native American, Asian-American, or Pacific Islander)
  • polycystic ovary syndrome
  • hypertension, dyslipidemia if known (HDL<45 and/or triglyceride level >250), or cardiovascular disease
  • physical inactivity

Exclusion Criteria:

• Known pre-existing diabetes mellitus, based on patient report or medical record review
• A1C ≥ 6.5%, detected at study visit 1
• Use of medications known to affect glucose tolerance including corticosteroids, metformin, sulfonylureas, and others as determined by the investigators.

150 Pregnant Women with history of GDM or at risk for diabetes mellitus and 200 Nonpregnant Women with history of GDM