The Effect of Lactation on Insulin Sensitivity and Lipolysis in Women

NCT ID: NCT04146909

Last Updated: 2024-02-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-17
• Study Completion Date: 2022-11-28

Brief Summary

This purpose of this study is to investigate whether lactation improves insulin sensitivity and increases lipolysis in women.

Detailed Description

There are two aims that this research will address.

In Aim 1, the research question is "Does lactation improve insulin sensitivity and increase lipolysis in women?" In this Aim, researchers will assess whether lactation amongst women with a history of gestational diabetes mellitus (GDM) will improve whole body insulin sensitivity as well as increase whole body lipid turnover by using hyperinsulinemic-euglycemic clamps combined with [6,6-2H]-glucose and [2H5]-glycerol infusions. These stable, non-radiating isotopes have been used extensively and safely to study the mechanisms of insulin resistance amongst non-pregnant as well as pregnant humans; however, these techniques have not previously been applied to the study of insulin sensitivity during lactation. Therefore, the goals will be two-fold: 1) to determine whether lactation induces similar changes in insulin sensitivity in humans as in mice and 2) to pilot the feasibility of performing larger, more detailed metabolic studies in this population of women post-partum.

The second aim (Aim 2) will use a retrospective chart review of women with a history of GDM who had an oral glucose tolerance test (OGTT) 6-8 weeks post-partum as part of standard of care.

The focus of this protocol registration will be Aim 1.

Conditions

GDM; Lactation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Breast Feeding

This group will consist of women who exclusively or mostly breast-fed for at least 4-6 months (\< 6 ounces of formula/24 hours at 6-9 weeks of delivery)1 and who delivered within the past 18 months.

Group Type: ACTIVE_COMPARATOR

Hyperinsulinemic-euglycemic clamp

Intervention Type: DIAGNOSTIC_TEST

After an overnight fast and an equilibration period lasting 2 hours, the 2-step euglycemic-hyperinsulinemic clamp study will be performed. A primed-continuous infusion of regular insulin will be given at 8 mU/(m2 × min) during the first 2 hours, and increased to 40 mU/(m2 × min) for the subsequent 2 hours. Plasma glucose levels will be measured every 5 min, and a variable glucose infusion will be initiated to maintain levels at ∼90 mg/dl. Plasma samples will be drawn at baseline and throughout the infusion period for measurement of isotope enrichment, insulin, NEFA, glycerol turnover, and additional hormones which may be altered with lactation. Approximately 160 mL of blood will be drawn at this visit.

Formula Feeding

This group will consist of women who exclusively or mostly formula-fed (no breastfeeding or \< 3 weeks of breastfeeding)1 and who delivered within the past 18 months.

Group Type: ACTIVE_COMPARATOR

Hyperinsulinemic-euglycemic clamp

Intervention Type: DIAGNOSTIC_TEST

After an overnight fast and an equilibration period lasting 2 hours, the 2-step euglycemic-hyperinsulinemic clamp study will be performed. A primed-continuous infusion of regular insulin will be given at 8 mU/(m2 × min) during the first 2 hours, and increased to 40 mU/(m2 × min) for the subsequent 2 hours. Plasma glucose levels will be measured every 5 min, and a variable glucose infusion will be initiated to maintain levels at ∼90 mg/dl. Plasma samples will be drawn at baseline and throughout the infusion period for measurement of isotope enrichment, insulin, NEFA, glycerol turnover, and additional hormones which may be altered with lactation. Approximately 160 mL of blood will be drawn at this visit.

Interventions

Hyperinsulinemic-euglycemic clamp

After an overnight fast and an equilibration period lasting 2 hours, the 2-step euglycemic-hyperinsulinemic clamp study will be performed. A primed-continuous infusion of regular insulin will be given at 8 mU/(m2 × min) during the first 2 hours, and increased to 40 mU/(m2 × min) for the subsequent 2 hours. Plasma glucose levels will be measured every 5 min, and a variable glucose infusion will be initiated to maintain levels at ∼90 mg/dl. Plasma samples will be drawn at baseline and throughout the infusion period for measurement of isotope enrichment, insulin, NEFA, glycerol turnover, and additional hormones which may be altered with lactation. Approximately 160 mL of blood will be drawn at this visit.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• A history of GDM (as defined as the American Diabetes Association criteria)
• Delivered a singleton, live birth at ≥ 35 weeks gestation within the past 18 months
• HbA1C < 6.5% at time of screening
• Delivery within the past 18 months
• Breast Feed Group: exclusively or mostly breast-fed (< 6 ounces of formula/24 hours at 6-9 weeks of delivery) for at least 4-6 months

Exclusion Criteria

• Currently lactating or lactation within the past 1 month at the time of the screening visit
• Diagnosis of diabetes (T1D or T2D) prior to pregnancy
• Current use of any glucose-lowering agents
• Pregnancy related medical problems including preeclampsia
• Major congenital fetal anomalies
• Creatinine > 1.5mg/dL, Hematocrit < 35%, ALT and AST > 2.5X upper limit of normal
• Known psychiatric disorders, alcohol abuse, HIV, hepatitis, renal disease, hepatic disease, untreated heart disease, untreated thyroid disease, active systemic infection or malignancy
• Illicit drug use (by the participant's self-report)
• History of post-partum depression
• Use of weight loss supplements or dieting 6 months prior to study
• Corticosteroid or opiate use within 6 months of study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Renate Belfort De Aguiar, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistant Professor of Medicine (Endocrinology)

Locations

Yale University School of Medicine

New Haven, Connecticut, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1R21HD100751-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000025731

Identifier Type: -

Identifier Source: org_study_id