Paradigm Shifts in the Management of Diabetes in Pregnancy: The Importance of Type 2 Diabetes and Early Hyperglycemia in Pregnancy

Abstract

For over 50 years, the diagnosis of gestational diabetes mellitus (GDM) has been based upon an oral glucose tolerance test at 24-28 weeks' gestation. This is the time during pregnancy when insulin resistance is increasing and hyperglycemia develops among those with insufficient insulin secretory capacity to maintain euglycemia. The Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study and the two major randomized controlled trials of treating GDM are based upon recruitment of women at this time during pregnancy. Meanwhile, the increasing prevalence of type 2 diabetes in pregnancy, with its significant risk of adverse pregnancy outcomes, has led to a need to identify undiagnosed diabetes as near to conception as possible. Screening for undiagnosed diabetes early in pregnancy also identifies women with hyperglycemia less than overt diabetes, yet at increased risk of adverse pregnancy outcomes. Such women are more insulin resistant-with higher blood pressure, triglycerides, perinatal mortality, and neonatal hypoglycemia with a greater need for insulin treatment-than those with GDM diagnosed at 24-28 weeks' gestation. Currently, there is uncertainty over how to diagnose GDM early in pregnancy and the benefits and harms from using the current management regimen. Randomized controlled trials testing the criteria for, and treatment of, GDM early in pregnancy are urgently needed to address this existing equipoise. In the meantime, the importance of early or "prevalent GDM" (i.e., mild hyperglycemia present from early [before] pregnancy) warrants interim criteria and thresholds for medication, which may differ from those in use for GDM diagnosed at 24-28 weeks' gestation.For over 50 years, the diagnosis of gestational diabetes mellitus (GDM) has been based upon an oral glucose tolerance test (OGTT) at 24-28 weeks' gestation (1). This time in gestation is when insulin resistance is increasing with the development of hyperglycemia among those with insufficient insulin secretory capacity to maintain euglycemia (2). In Freinkel's iconic Banting Lecture in 1980, building upon the Pederson hypothesis (3, 4), hyperglycemia was described as causing short-and long-term harm to the growing fetus through "fuel-mediated teratogenesis" (5). Different time-dependent impacts of hyperglycemia on the fetus, shown in Fig. 1,

High prevalence and significant ethnic differences in actionable HbA1C after gestational diabetes mellitus in women living in Norway

“…Whether adding FPG to HbA 1c identifies more women at risk for high glucose levels in subsequent pregnancies, and thereby adverse pregnancy outcomes [33][34][35], are not answered by our study and deserve further studies. In clinical practice, we support the use of HbA 1c testing for women post-GDM.…”

Applying a Women’s Health Lens to Endocrine and Metabolic Disorders

“…[ 2 ] The prevalence of prediabetes in young women of India is alarming with conversion to overt diabetes as they age. [ 3 ] Women of reproductive age with preexisting type 1 or type 2 diabetes are at unacceptably high risk for pregnancy-related complications, pregnancy losses, preterm births or delivering babies with serious birth defects. [ 4 ]…”

“…The pressing issue now facing the endocrine and Ob Gyn community is to address hyperglycemia in early pregnancy or prevalent GDM. [ 3 ]…”

Early diabetes treatment is associated with improved outcomes in pregnant women with a first antenatal HbA1c of 41–46 mmol/mol

“…1 However, there is no consensus around the early management of women who have either a 75 g oral glucose tolerance test (OGTT) or HbA1c result consistent with a diagnosis of gestational diabetes mellitus (GDM) or underlying hyperglycaemia/prediabetes, respectively, but below the threshold used to define overt diabetes. 2 In New Zealand since 2011, outside pregnancy, HbA1c has been used instead of a 75 g OGTT to diagnose prediabetes or diabetes. Therefore, at that time, at our hospital, (National Women's Health at Auckland City Hospital) we also changed to measuring DOI: 10.1111/ajo.13476…”

“…There is consensus that women should be screened in early pregnancy to identify those with previously unrecognised or overt diabetes, so that treatment can be initiated early 1 . However, there is no consensus around the early management of women who have either a 75 g oral glucose tolerance test (OGTT) or HbA1c result consistent with a diagnosis of gestational diabetes mellitus (GDM) or underlying hyperglycaemia/prediabetes, respectively, but below the threshold used to define overt diabetes 2 …”