This purpose of this study is to investigate whether lactation improves insulin sensitivity and increases lipolysis in women.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
7
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.
Yale University School of Medicine
New Haven, Connecticut, United States
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.
Time frame: 2 hours and 4 hours
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.
Time frame: 4 hours
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.
Time frame: 4 hours
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.
Time frame: 4 hours
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.
Time frame: 4 hours
Insulin Levels
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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.
Time frame: 4 hours