Dysglycemia in Pregnancy and Maternal/Fetal Outcomes

Abstract

Maternal dysglycemia-including diabetes, impaired glucose tolerance, and impaired fasting glucose-affects one in six pregnancies worldwide and represents a significant health risk to the mother and the fetus. Maternal dysglycemia is an independent risk factor for perinatal mortality, major congenital anomalies, and miscarriages. Furthermore, it increases the longer-term risk of type 2 diabetes mellitus, metabolic syndrome, cardiovascular morbidity, malignancies, and ophthalmic, psychiatric, and renal diseases in the mother. The most commonly encountered form of maternal dysglycemia is gestational diabetes. Currently, international consensus does not exist for diagnostic criteria defining gestational diabetes at 24-28 weeks gestation, and potential diagnostic glucose thresholds earlier in gestation require further investigation. Likewise, recommendations regarding the timing and modality (e.g., lifestyle or pharmacological) of treatment vary greatly. Because a precise diagnosis determines the appropriate treatment and outcome of the pregnancy, it is imperative that a better definition of maternal dysglycemia and its treatment be achieved. This article will address some of the controversies related to diagnosing and managing maternal dysglycemia. In addition, the article will discuss the impact of maternal dysglycemia on complications experienced by the mother and infant, both at birth and in later life.

Hexokinase-2-Linked Glycolytic Overload and Unscheduled Glycolysis—Driver of Insulin Resistance and Development of Vascular Complications of Diabetes

“…There is evidence, therefore, that HK2-linked glycolytic overload occurs at the sites of vascular complications and early-stage embryo in diabetes and this likely contributes to hyperglycemia-linked pathogenesis developing therein in diabetes. Similar pathogenesis, of lower severity, is expected in prediabetes, consistent with the low risk and presence of vascular complications and embryo malformations in prediabetes [56,57]. Increased deposition of glycogen was a surprising mechanistic biomarker of HK2linked glycolytic overload [13].…”

Summary and Conclusion: Framing a New Research Agenda on Maternal Morbidities and Mortality in the United States

“…Despite significant progress in the past decades, several articles in this volume continue to find critical knowledge gaps in our understanding of the causes and prevention of a whole range of pregnancy complications, including hypertensive disorders of pregnancy, 14 peripartum cardiomyopathy, 14 gestational diabetes, 15 infectious diseases ranging from influenza to intra-amniotic infections, 16 and perinatal depression. 17 Reducing and ultimately eradicating maternal mortality will require us to get a lot better at preventing pregnancy complications.…”

“…Third, we need to get a lot better at tertiary prevention—preventing the serious and long-term sequelae of pregnancy complications. Silva et al 15 call attention to the “effects of maternal dysglycemia on mothers later in life and the transgenerational cycle of metabolic disease risk rooted in maternal dysglycemia.” Similarly, Varagic et al 14 observe that women's long-term cardiovascular health could be linked to adverse pregnancy outcomes. They review several large cohort studies and meta-analyses that found pregnancy complications—such as preeclampsia and other hypertensive disorders of pregnancy, gestational diabetes, preterm birth, pregnancy loss, and small for gestational age—to be associated with long-term risk for cardiovascular diseases in women.…”

“…Third, we need to get a lot better at tertiary preventionpreventing the serious and long-term sequelae of pregnancy complications. Silva et al 15 call attention to the ''effects of maternal dysglycemia on mothers later in life and the transgenerational cycle of metabolic disease risk rooted in maternal dysglycemia.'' Similarly, Varagic et al 14 observe that women's long-term cardiovascular health could be linked to adverse pregnancy outcomes.…”

Rural healthcare delivery and maternal and infant outcomes for diabetes in pregnancy: A systematic review

“…This disease burden extends past the perinatal period, with women who experienced GDM having a seven‐fold increased risk of developing type 2 diabetes mellitus, typically within 5–10 years of their diagnosis 8,9 . The risk of both short‐ and long‐term adverse outcomes can be minimised through the comprehensive management of DIP 10–14 . A reduction in adverse outcomes has been achieved in intervention studies with a focus on optimising glycaemic control through dietary advice, self‐monitoring of blood glucose levels and pharmacotherapy as required 12,13 .…”