Study of Pregnancy Regulation of Insulin and Glucose (SPRING)

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.

Study Overview

• Status: Completed
• Conditions: Gestational Diabetes Mellitus
• Intervention / Treatment: Other: Oral glucose tolerance test

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 Type: Observational
• Enrollment (Actual): 234

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 44 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pregnant Women; 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; 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); Other Names: OGTT
Nonpregnant Women; Nonpregnant women with a history of GDM will undergo an OGTT at baseline.	Other: Oral glucose tolerance test; 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); 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)

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Ravi I Thadhani, MD, MPH, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: February 17, 2016
• First Submitted That Met QC Criteria: May 4, 2016
• First Posted (Estimate): May 5, 2016

Study Record Updates

• Last Update Posted (Actual): May 10, 2022
• Last Update Submitted That Met QC Criteria: May 7, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Pregnancy; Insulin sensitivity; Insulin secretion; Placental proteins
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Pregnancy Complications; Diabetes, Gestational
• Other Study ID Numbers: 2015P002447

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED