Study of Pregnancy Regulation of Insulin and Glucose

Completed

• Conditions: Gestational Diabetes Mellitus
• Interventions: Other: Oral glucose tolerance test

• Registration Number: NCT02763267
• Lead Sponsor: Massachusetts General Hospital

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.

Study Timeline

• Study Start: 2016-02
• Study First Submitted: 2016-02-17
• Study First Submitted QC: 2016-05-04
• Study First Posted: 2016-05-05
• Primary Completion: 2021-12
• Study Completion: 2021-12
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-07
• Last Update Posted: 2022-05-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 234

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Nonpregnant Women	Oral glucose tolerance test	Nonpregnant women with a history of GDM will undergo an OGTT at baseline.
Pregnant Women	Oral glucose tolerance test	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.

Primary Outcome Measures

Name	Time	Method
Insulin secretory response	1st trimester (gestational weeks 4-14)	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

Secondary Outcome Measures

Name	Time	Method
Insulin secretory response	Mid-pregnancy (gestational weeks 24-28)	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
Change in insulin secretory response	1st trimester to postpartum (up to 12 weeks post-partum or up to 50 weeks after the first trimester visit, whichever comes first)	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

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States