The Effect of Lactation on Insulin Sensitivity and Lipolysis in Women

Lactation Clinical Trial

Official title:

The Effect of Lactation on Insulin Sensitivity and Lipolysis in Women

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04146909
• Other study ID #: 2000025731
• Secondary ID: 1R21HD100751-01
• Status: Terminated
• Phase: N/A
• Start date: November 17, 2020
• Est. completion date: November 28, 2022

Study information

• Verified date: February 2024
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: November 28, 2022
• Est. primary completion date: November 28, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• GDM
• Insulin Resistance
• Lactation

Intervention

Diagnostic Test:
• 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.

Locations

Country	Name	City	State
United States	Yale University School of Medicine	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Whole Body Insulin Sensitivity Measured by the Glucose Infusion Rate	The glucose infusion rate is determined by the amount of 20% dextrose given during the hyperinsulinemic-euglycemic clamp study, necessary to keep blood glucose levels at the target range (90-100 mg/dL). Higher rates of infused dextrose indicates greater sensitivity to infused insulin during the hyperinsulinemic-euglycemic clamp. Women with gestational diabetes are expected to be insulin resistant.	2 hours and 4 hours
Primary	Endogenous Glucose Production	Determined with [6,6-2H] Glucose tracer given during the hyperinsulinemic-euglycemic clamp study. Lower values of endogenous glucose production indicates greater hepatic insulin sensitivity.	4 hours
Primary	Whole Body Lipid Turnover Rates	Determined with [2H5] Glycerol tracer given during the hyperinsulinemic-euglycemic clamp study. Tracer levels in the plasma determinates how the body uses fat in the blood during the hyperinsulinemic-euglycemic clamp study.	4 hours
Secondary	Plasma NEFA	Measurement of non-esterified fatty acids levels in the plasma at fasting and during the hyperinsulinemic-euglycemic clamp study. NEFA levels in the plasma are higher in individuals less sensitive to the effects of insulin.	4 hours
Secondary	Triglycerides	Measurement of triglycerides levels in the plasma at fasting and during the hyperinsulinemic-euglycemic clamp study. Triglycerides levels in the plasma are higher in individuals less sensitive to the effects of insulin and with type 2 diabetes.	4 hours
Secondary	Insulin Levels	Measurement of insulin levels in the plasma at fasting and during the hyperinsulinemic-euglycemic clamp study. Insulin levels in the plasma are higher in insulin resistant individuals.	4 hours