Study of Pregnancy Regulation of Insulin and Glucose

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
Study of Pregnancy Regulation of Insulin and Glucose

Conditions
-----------------
Gestational Diabetes Mellitus

Intervention / Treatment
-----------------
* Other: Oral glucose tolerance test


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 44 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pregnant Women<br>Pregnant women with history of GDM or at risk for diabetes mellitus will enter study during first trimester (4-14 weeks) and receive an oral glucose tolerance test (OGTT) at baseline, mid-pregnancy, and at delivery. | Other: Oral glucose tolerance test<br>* 75 gram oral glucose tolerance test (fasting) at: Visit 1 (pregnant [4-14 weeks gestation] and nonpregnant women); Visit 2 (pregnant subjects only at 24-28 weeks gestation); Visit 3 (pregnant subjects only at 6-12 weeks postpartum)<br>* Other names: OGTT;|
| Nonpregnant Women<br>Nonpregnant women with a history of GDM will undergo an OGTT at baseline. | Other: Oral glucose tolerance test<br>* 75 gram oral glucose tolerance test (fasting) at: Visit 1 (pregnant [4-14 weeks gestation] and nonpregnant women); Visit 2 (pregnant subjects only at 24-28 weeks gestation); Visit 3 (pregnant subjects only at 6-12 weeks postpartum)<br>* Other names: OGTT;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin secretory response | Insulin secretory response to a glucose load (insulinogenic index), adjusted for differences in insulin resistance, in pregnant women in the 1st trimester will be compared to the insulin secretory response in non-pregnant women | 1st trimester (gestational weeks 4-14) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin secretory response | Insulin secretory response to a glucose load (insulinogenic index), adjusted for differences in insulin resistance, in pregnant women at 24-28 weeks gestation will be compared to the insulin secretory response in non-pregnant women | Mid-pregnancy (gestational weeks 24-28) | 
| Change in insulin secretory response | Change in insulin secretory response to a glucose load (insulinogenic index) between 1st trimester and 24 to 28 weeks gestation, adjusted for changes in insulin resistance, in pregnant women who do and do not develop GDM | 1st trimester to 24-28 weeks gestation | 
| Change in insulin secretory response | Change in insulin secretory response to a glucose load (insulinogenic index) between 1st trimester and postpartum, adjusted for changes in insulin resistance, in pregnant women who do and do not develop GDM | 1st trimester to postpartum (up to 12 weeks post-partum or up to 50 weeks after the first trimester visit, whichever comes first) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pregnancy, Insulin sensitivity, Insulin secretion, Placental proteins