Maternal Glucose and Fatty Acid Kinetics and Infant Birth Weight in Obese Women With Type 2 Diabetes

W. Todd Cade; Rachel A. Tinius; Dominic N. Reeds; Bruce W. Patterson; Alison G. Cahill

Disclosures

Diabetes. 2016;65(4):893-901. 

In This Article

Abstract and Introduction

Abstract

The objectives of this study were 1) to describe maternal glucose and lipid kinetics and 2) to examine the relationships with infant birth weight in obese women with pregestational type 2 diabetes during late pregnancy. Using stable isotope tracer methodology and mass spectrometry, maternal glucose and lipid kinetic rates during the basal condition were compared in three groups: lean women without diabetes (Lean, n = 25), obese women without diabetes (OB, n = 26), and obese women with pregestational type 2 diabetes (OB+DM, n = 28; total n = 79). Glucose and lipid kinetics during hyperinsulinemia were also measured in a subset of participants (n = 56). Relationships between maternal glucose and lipid kinetics during both conditions and infant birth weight were examined. Maternal endogenous glucose production (EGP) rate was higher in OB+DM than OB and Lean during hyperinsulinemia. Maternal insulin value at 50% palmitate R a suppression (IC50) for palmitate suppression with insulinemia was higher in OB+DM than OB and Lean. Maternal EGP per unit insulin and plasma free fatty acid concentration during hyperinsulinemia most strongly predicted infant birth weight. Our findings suggest maternal fatty acid and glucose kinetics are altered during late pregnancy and might suggest a mechanism for higher birth weight in obese women with pregestational diabetes.

Introduction

Pregnancy complicated by pregestational diabetes is associated with a host of adverse neonatal outcomes, including preterm birth, congenital malformations, increased birth weight, and neonatal hypoglycemia.[1,2] Higher birth weight in infants born to women with diabetes contributes to elevated rates of birth injury and cesarean delivery, as well as higher risk for future obesity, diabetes, and cardiovascular disease.[3–6] Maternal substrate metabolism during pregnancy plays a key role in fetal growth[7] and thus may be an important target for interventions aimed to modulate the deleterious effect of diabetes on infant birth weight.

Traditionally, higher birth weight in infants born to women with diabetes has been thought to be caused primarily by maternal hyperglycemia. Thus, current treatment in diabetic pregnancy focuses on achieving as close to maternal normoglycemia as possible.[8] However, some past and more recent data suggest that maternal glycemia is a poor predictor of infant birth weight[9,10] and that markers of maternal lipid metabolism during pregnancy might contribute to and possibly be a better predictor of infant birth weight and adiposity.[11–19] Previous studies demonstrating associations between indices of maternal glucose and lipid metabolism and infant birth weight have focused only on clinical measures of maternal metabolism, including fasting plasma glucose,[9,16,17,20] HbA1c,[15] oral glucose tolerance testing,[9,11,16,18,19] and plasma concentrations of free fatty acid (FFA),[15] triglyceride,[11–15,20] and cholesterol.[20] Although clinical measures are easily collected and some are part of routine clinical care, these measures have not elucidated the pathologic abnormalities that lead to pregnancy-associated risks. Therefore, identification of the pathophysiologic mechanisms during both the fasting and hyperinsulinemic states that drive alterations in glucose and lipid metabolism in women with type 2 diabetes during pregnancy is needed.

Thus, the primary objective of the study was to compare maternal glucose and fatty acid kinetics during late pregnancy in obese women with diabetes to obese women without diabetes and lean, healthy control subjects. The secondary objective of the study was to examine the relationships between maternal glucose and fatty acid kinetics and infant birth weight. We hypothesized that glucose and fatty acid kinetics during basal and hyperinsulinemic conditions are abnormal in obese women with diabetes and would be better predictors of infant birth weight than clinical markers of glucose and lipid metabolism.

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