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Summary

Perinatal outcomes: infants born to women with diabetes are at increased risk for admission to the neonatal intensive care unit (NICU), neonatal hypoglycemia, hyperbilirubinemia, and respiratory distress syndrome (RDS); mounting evidence suggests that risks for obesity, hypertension, and type 2 diabetes (T2D) are also increased; these risks may apply to infants born to mothers with prediabetes as well

Epidemiology: ≈33% of Americans are prediabetic; among women of reproductive age, the rate of prediabetes now exceeds 25%; additionally, undiagnosed diabetes has increased by ≈50% in this age group

Prediabetes: risk factors include overweight, obesity, age, sedentary lifestyles, unhealthy diets, and genetic predisposition; individuals with prediabetes are at increased risk for cardiovascular disease, cardiovascular events, and all-cause mortality compared with those who are euglycemic; the prevalence of retinopathy in prediabetic individuals ranges from 8% to 10%; the prevalence of nephropathy is ≈10%; prediabetes increases the risk for preeclampsia

Diagnosis of prediabetes: defined as hemoglobin A_1c (HbA_1c) of 5.7% to 6.4%; HbA_1c >6.4% is diagnostic of T2D; patients in early pregnancy have increased red blood cell turnover, which reduces HbA_1c; fasting plasma glucose of 100 to 125 mg/dL or 75-g oral glucose tolerance test (OGTT) of 140 to 199 mg/dL also indicates prediabetes

Screening: the American Diabetes Society (2022) recommends testing for prediabetes and diabetes in all individuals who are overweight or possess ≥1 risk factors, ie, first-degree relative with diabetes, high-risk ethnicity (Black, Latinx, Native American, Asian American and Pacific Islander), history of cardiovascular disease, hypertension, hyperlipidemia, polycystic ovary syndrome, or severe obesity, or signs of insulin resistance; the American Diabetes Association (ADA) recommends screening for prediabetes or diabetes at least every 3 yr for women with a history of gestational diabetes mellitus (GDM) and for all women ≥35 yr of age

Prevention: the ADA recommends metformin therapy to prevent T2D in adults who have known prediabetes with body mass index of >35, fasting glucose of 110 mg/dL, or HbA_1C≥6%; metformin therapy should be considered for women with prediabetes and history of GDM; lifestyle changes are recommended

Diagnosis of GDM: insulin resistance that begins during pregnancy occurs at ≈16 wk of gestation; the American College of Obstetricians and Gynecologists (ACOG) prefers use of a two-step diagnostic approach; initial screening for GDM is performed using a 1-hr OGTT between 24 and 28 wk; the threshold for glucose tolerance is institution and prevalence specific; patients whose 1-hr OGTT is abnormal undergo a 100-g 3-hr test; per ACOG, treatment is indicated if glucose levels are above the threshold at 2 time intervals during the 3-hr test (can also be considered with one elevated value); the clinician should individualize recommendations based on the patient’s risk profile

Early screening for GDM: no single test has been proven better than the others; the ADA recommends universal screening at <15 wk; ACOG prefers a risk-based approach; patients whose early screening is negative are screened again with 1-hr OGTT at 24 to 28 wk; those with a positive 1-hr screen but a negative 3-hr OGTT are screened again at 24 to 28 wk with the 3-hr test only

Pathophysiology of GDM: sensitivity to insulin decreases with increasing body weight; simultaneously, insulin secretion decreases; in women with abnormal screening, the pancreas is unable to keep pace with beta cell secretion and/or some beta cell mass has been lost

Evidence on early GDM: Simmons et al (2023) — randomized women with GDM to receive early vs deferred or no treatment; used a composite neonatal outcome (ie, preterm birth, birth trauma, large-for-gestational-age [LGA] babies, RDS, phototherapy for hyperbilirubinemia, still birth, neonatal death, or shoulder dystocia), pregnancy-related hypertensive disorders, and neonatal lean body mass; a statistically significant decrease was seen in the composite outcome with treatment (≈20%); the number needed to treat was ≈18; no difference was observed between groups in terms of rate of preeclampsia or cesarean delivery, maternal weight gain, or mean birth weight; subgroup analysis revealed greater benefit in patients who were positive for high glycemic range; women with low glycemic range had higher rates of small-for-gestational age (SGA) babies; findings suggest that these groups represent 2 different types of early diabetes

Adverse perinatal outcomes (prediabetes vs euglycemia vs GDM): early studies found no difference at HbA_1c levels ≤5.7%; Mane et al (2016) — found increased rates of congenital anomalies, preeclampsia, shoulder dystocia, death, and macrosomia when a threshold HbA_1c of ≥5.9% was used to define GDM; Relph et al (2021) — found similar rates of microvascular complications in women with prediabetes and those with T2D at initiation of prenatal care; patients with T2D had higher rates of nephropathy, required higher doses of metformin, and were more likely to require multiple injections of insulin per day; no difference was seen in rates of preeclampsia, LGA, SGA, gestational age of delivery, preterm birth, cesarean section, or NICU admissions; children born to diabetic mothers had higher rates of macrosomia and neonatal jaundice; implications — although ACOG does not advocate treating prediabetes, the similarity of outcomes between women with prediabetes and those with T2D suggests it may be warranted; most women with prediabetes do not return to a euglycemic state after delivery (20% are diagnosed with T2D); Jamieson et al (2021) — showed similar maternal and fetal outcomes in women with prediabetes vs GDM (diagnosed at <20 wk), with the exception of higher rates of LGA among children born to mothers with GDM; caveat — observational studies may lack the power to detect small intergroup differences

Take-home points: an individualized treatment approach is warranted; careful postpartum follow-up is key; society guidelines may change in the next several years; mounting evidence suggests that pregnancy complications are markers for acceleration of maladaptive maternal physiology, particularly cardiovascular and metabolic; a “life-course approach” to women’s health care may improve pregnancy outcomes