Management of Prediabetes in Pregnancy

Educational Objectives

The goal of this program is to improve perinatal outcomes through appropriate monitoring and treatment of hyperglycemia during pregnancy and postpartum. After hearing and assimilating this program, the clinician will be better able to:

1. Screen pregnant women for prediabetes, gestational diabetes, and type 2 diabetes mellitus.
2. Assess the potential benefits of treating women who are diagnosed with prediabetes during pregnancy.

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

Readings

American Diabetes Association Professional Practice Committee. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S17-S38. doi:10.2337/dc22-S002; Blonde L, Umpierrez GE, Reddy SS, et al. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update [published correction appears in Endocr Pract. 2023 Jan;29(1):80-81]. Endocr Pract. 2022;28(10):923-1049. doi:10.1016/j.eprac.2022.08.002; Jamieson EL, Spry EP, Kirke AB, et al. Prediabetes and pregnancy: Early pregnancy HbA1c identifies Australian Aboriginal women with high-risk of gestational diabetes mellitus and adverse perinatal outcomes. Diabetes Res Clin Pract. 2021;176:108868. doi:10.1016/j.diabres.2021.108868; Relph S, Patel T, Delaney L, et al. Adverse pregnancy outcomes in women with diabetes-related microvascular disease and risks of disease progression in pregnancy: A systematic review and meta-analysis. PLoS Med. 2021;18(11):e1003856. Published 2021 Nov 22. doi:10.1371/journal.pmed.1003856; Simmons D, Immanuel J, Hague WM, et al. Treatment of gestational diabetes mellitus diagnosed early in pregnancy. N Engl J Med. 2023;388(23):2132-2144. doi:10.1056/NEJMoa2214956.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Gomez was recorded at the USC Jorge H. Mestman Endocrine in Pregnancy and Women's Health Symposium 2024, held February 24, 2022, in Los Angeles, CA and online, and presented by the Keck School of Medicine of the University of Southern California. For information about upcoming CME activities from this presenter, please visit Keckusc.cloud-cme.com. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

OB710902

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.