The Effect of Lactation on Insulin Sensitivity and Lipolysis in Women

Not Applicable

Terminated

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.

Recruitment & 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

Arm && Interventions

Group	Intervention	Description
Breast Feeding	Hyperinsulinemic-euglycemic clamp	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.
Formula Feeding	Hyperinsulinemic-euglycemic clamp	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.

Primary Outcome Measures

Name	Time	Method
Whole Body Lipid Turnover Rates	4 hours	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.
Whole Body Insulin Sensitivity Measured by the Glucose Infusion Rate	2 hours and 4 hours	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.
Endogenous Glucose Production	4 hours	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.

Secondary Outcome Measures

Name	Time	Method
Triglycerides	4 hours	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.
Plasma NEFA	4 hours	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.
Insulin Levels	4 hours	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.

Locations (1): Yale University School of Medicine
🇺🇸
New Haven, Connecticut, United States