Normalizing Metabolism in Diabetic Pregnancy: Is It Time to Target Lipids?

Abstract

Outcomes in pregnancies complicated by preexisting diabetes (type 1 and type 2) and gestational diabetes mellitus have improved, but there is still excess morbidity compared with normal pregnancy. Management strategies appropriately focus on maternal glycemia, which demonstrably improves pregnancy outcomes for mother and infant. However, we may be reaching the boundaries of obtainable glycemic control for many women. It has been acknowledged that maternal lipids are important in pregnancies complicated by diabetes. Elevated maternal lipids are associated with preeclampsia, preterm delivery, and large-forgestational-age infants. Despite this understanding, assessment of management strategies targeting maternal lipids has been neglected to date. Consideration needs to be given to whether normalizing maternal lipids would further improve pregnancy outcomes. This review examines the dyslipidemia associated with pregnancy complicated by diabetes, reviews possible therapies, and considers whether it is time to start actively managing this aspect of maternal metabolism.Although rates of adverse outcomes in pregnancies complicated by preexisting diabetes (type 1 and type 2) and gestational diabetes mellitus (GDM) have improved, there is still excess maternal and fetal morbidity compared with normal pregnancy. Current management strategies focus on maternal glycemic control, which demonstrably improves pregnancy outcomes for mother and infant. Truly "normal" glucose levels in pregnancy appear lower than previously thought (1) and achieving currently recommended glucose targets in pregnancy carries a risk of hypoglycemia (2). The challenges in reaching glycemic targets before and after conception raise the question of whether other aspects of maternal metabolism could potentially be addressed to provide benefit to mother and infant.Multiple maternal metabolic, hormonal, and inflammatory factors other than maternal glucose are associated with maternal and fetal outcomes and are altered in pregnancies complicated by prepregnancy diabetes and GDM. These include maternal amino acids, glycerol, ketones, and lipids (3). Lipid management in diabetes is acknowledged as a key therapeutic target in the nonpregnant setting. However, it has not been accorded the same attention in pregnancy. Abnormal maternal lipids in pregnancy have been associated with preeclampsia (4,5), preterm delivery (6), and large-forgestational-age (LGA) infants (7). This review examines the dyslipidemia associated with pregnancy complicated by diabetes, reviews possible therapies, and considers whether there is sufficient evidence to start actively managing lipids in pregnancy. LIPID METABOLISM IN PREGNANCYMaternal metabolism is designed to provide adequate nutrition for fetal growth, in the form of glucose, ketones, lipids, and other fuels. In early pregnancy, maternal

Maternal Lipids May Predict Fetal Growth in Type 2 Diabetes Mellitus and Gestational Diabetes Mellitus Pregnancies

“…The rising levels of estrogen with the progression of pregnancy reflects the changes in lipoproteins [9]. On the other hand, dyslipidemia increases with the insulin resistance found in obesity, GDM and preexisting diabetes, as it has been extensively researched in the studies of Kitajima et al [10], Knopp et al [14] and Gobi et al [15].…”

“…More, but not all studies have reported the same lipid profiles in wellcontrolled DM1 as in normal pregnancies, high triglyceride and low HDL-C are found in DM1 women with metabolic syndrome in pregnancy, and those diabetic women who develop preeclampsia have high LDL-C and cholesterol levels. In pregnant GDM women frequent founding are the elevated triglycerides while in DM2 pregnancies the lipid profiles are between those observed in DM1 and GDM [9,10]. Hence, we decided to explore lipids in DM2 and GDM pregnancies because the latter is a form of type 2 diabetes and they share the same underlying pathophysiology (insulin resistance and beta cell dysfunction).…”

“…There are no recommendations for clinic management of lipids in pregnancy complicated by diabetes. Studies show lipid changes in the first, second and third trimester both in normal [8] as well as in diabetic pregnancies [9]. There is an association between insulin resistance and serum lipid levels in pregnancy, as adaptive mechanism allowing fetal grown.…”

A study of visceral adiposity index as a diagnostic index in gestational diabetes mellitus in a tertiary care centre

“…[13][14][15][16] Dyslipidemia as the cause of insulin resistance in GDM is still debated as questioned by Helen et al Though HDL levels were statistically insignificant in cases, an increasing trend towards the controls was observed which may be clinically significant. This lack of statistical significance can be substantiated based on the physiological drop in HDL levels in controls as shown in a population based study by Raghuram Pusukuru et al [17][18] Linear correlation analysis revealed a strong linear relation between OGCT and VAI (p <0.0001). VAI was significantly higher in cases compared to controls in parallel with increase in TGL, BMI, waist circumference and decrease in HDL in cases.…”

Early Postpartum Lipid Profile in Women with and Without Gestational Diabetes Mellitus: Results of a Prospective Cohort Study

“…Despite these findings, postpartum screening for lipid abnormalities and other cardiovascular risk factors has been neglected in women with gestational diabetes (13). In addition, few studies focused on early postpartum lipids profile, particularly in women with GDM.…”