Updates on Gestational Diabetes Screening

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We last talked on the podcast about gestational diabetes with Dr. Coustan very shortly after we began in December 2018. Those podcasts are so good, and feature the man himself who is co-credited with the “Carpenter-Coustan” criteria we all know…

But if you’ve been watching journals recently, you probably have seen a lot of interesting papers with respect to GDM screening. So today’s episode will be a bit of an update on part one of those past GDM podcasts! Treatment fortunately hasn’t changed much so we won’t update that part today.

By the way – ACOG PB 190 on Gestational Diabetes Mellitus is still an excellent read!

Physiology of Insulin Resistance in Pregnancy 

  • Progesterone effects on insulin resistance

    • Normally, insulin binds to insulin receptor → phosphorylation of beta-subunit of receptor and leads to phosphorylation of the insulin receptor substrate I (IRS-I) 

    • Progesterone reduces expression of IRS-1  

  • Human placental lactogen effects on insulin resistance

    • Both insulin-like and anti-insulin effects 

    • Generally decreases maternal insulin sensitivity

    • Decreases maternal glucose utilization

    • Increases lipolysis and free fatty acids

      • This allows for free fatty acids to become available for mother’s metabolism (do not cross placenta) so fetus gets glucose preferentially

  • On the fetal side, exposure to hyperglycemia:

    • Leads to increase in its own endogenous insulin production and production of insulin-like growth factor 1

      • These lead to increased growth, fat deposition, and risk for macrosomia.

Prevalence and classifications of diabetes 

  • Prevalence - hard to know b/c not everyone is tested

    • 2009: 7% of pregnancies were in people with diabetes.

      • 86% of these cases were GDM  

  • Classification: The White Classifications

    • Depending on where you are, you may still see these in use; they are also helpful in classifying pre-gestational diabetes.

    • Named for Dr. Priscilla White, who developed the schema in the 1950s and 1960s

      • Class A1: diet-controlled GDM

      • Class A2: medication-controlled GDM

      • Class B: onset at age 20 or older or with duration of less than 10 years

      • Class C: onset at age 10-19 or duration of 10–19 years

      • Class D: onset before age 10 or duration greater than 20 years

      • Class E: overt diabetes mellitus with calcified pelvic vessels

      • Class F: diabetic nephropathy 

      • Class H: ischemic heart disease

      • Class R: proliferative retinopathy

      • Class RF: retinopathy and nephropathy

      • Class T: prior kidney transplant

Complications of GDM - ie. Why do we care? 

  • Maternal complications

    • High risk of developing preeclampsia, undergoing C/S

    • Increased risk of developing type 2 diabetes later in life (up to 70% of patients with GDM develop T2DM within 22-28 years after pregnancy) 

  • Fetal complications

    • Increased risk of macrosomia, neonatal hypoglycemia, hyperbilirubinemia, shoulder dystocia and birth trauma 

    • Increased risk of stillbirth 

    • Fetal exposure to maternal diabetes may contribute to adult-onset obesity and diabetes in offspring 

Screening for GDM - The Basics 

  • Used to be medical history and past obstetric outcomes and family history → fails to get 50% of patients with GDM 

  • All pregnancies should be screened between 24-28 weeks of gestation, with one of two strategies:

    • Two Step:

      • 1973: O’Sullivan et al - described a 1 hr GTT with 50g of glucose  

        • Carpenter-Coustan criteria: positive if >/= 130 mg/dL, though some institutions use 140 mg/dL

      • If screened positive, should get a follow up test with 3hr GTT (100g)

        • Diagnose if 2 abnormal values 

          • However, even 1 elevated → increased risk of adverse perinatal outcomes compared to those without GDM or elevated values

      • Carpenter-Coustan: Fasting: 95, 1 hr: 180, 2 hr: 155, 3 hr: 140  

      • Alternative criteria (not in wide use): National Diabetes Data Group: 105, 190, 165, 145 

    • One-Step alternative screening: International Association for the Study of Diabetes in Pregnancy Group (IASDPG) method:

      • 75g 2hr test - just one test!

      • Fasting: 92 mg/dL, 1hr: 180 mg/dL , 2hr: 153 mg/dL 

      • If > 1 elevated = GDM

  • “Early GDM screening” to look for early gestational diabetes  should be considered in some patients with risk factors.

    • The best test to use for early screening is up for debate, however:

      • Some might consider A1c, but because of new red cell generation / faster turnover in pregnancy, may artificially lower the A1c

      • Some consider using an OGTT, but then it might be hard to convince patients to do it again if they screen negative.

      • Some might consider a trial of “glucose profiling” with a glucometer but not any rigorous testing done about this.

ACOG PB 190


Updates in the World of GDM Screening:

  • What’s better: two-step Carpenter-Coustan style, or one-step IASDPG style?

    • In the last year, two randomized trials (NEJM, AJOG) and a systematic review/meta analysis (Green) have been published to help answer this question. 

    • Because findings are similar, summarized from the meta-analysis:

      • Patients with one-step screening are more likely to be diagnosed with GDM (16.3% vs 8.3% in the meta-analysis)

      • Patient with one-step screening are more likely to be started on medications (7.1% vs 3.8%)

      • Patients undergoing one-step screening were more likely to have NICU admission (5.1% vs 4.5%)

      • Patients undergoing one-step screening were more likely to have babies experience hypoglycemia (9.3% vs 7.6%)

      • Rates of LGA  babies are similar between strategies (8.8% one step, 9.2% two step)

      • Rate of primary cesarean delivery was similar between groups (24.0% one step vs 24.7% two-step).

    • What can we conclude from this?

      • One-step testing seems to lead to increased resource utilization (more diagnoses, more folks on treatment, more NICU admissions)

      • One-step testing does not appear to differ from two-step testing for some maternal short-term outcomes (LGA, cesarean delivery rate) or fetal outcomes (did not cover above but shoulder dystocia, RDS, stillbirth, neonatal death were all similar between groups)

      • We don’t have any significant evidence about long-term outcomes for mother or fetus (i.e., later-in-life diabetes diagnoses, obesity rates in offspring, etc.)

        • An editorial about the meta-analysis makes the case that one-step testing might still be cost-effective if the increased resource utilization means fewer downstream consequences… remains to be seen and tough to study!

  • Early GDM screening: do we have anything new?

    • Since our last podcast, there have been two US-based RCTs about this (Roeder, Harper)

      • In the Roeder paper, patients with an A1c of > 5.7% or fasting glucose of > 92 were randomized to hyperglycemia therapy and nutritional counseling at the time of enrollment (early pregnancy) vs usual timing (3rd trimester)

        • The study was ended early due to poor enrollment, but:

          • Treatment in early pregnancy didn’t improve maternal or neonatal outcomes, including fat mass, weight percentile, macrosomia, or maternal weight gain.

          • Treatment also didn’t significantly reduce the diagnosis rate of GDM at a usual-timing screening test (14.2% early treatment vs 25.8% usual treatment, p=0.17)

      • In the Harper paper, obese patients (BMI > 30) were randomized to a traditional two-step test in early pregnancy (14-20 weeks) versus traditional timing.

        • Those who screened negative early were also re-tested at traditional timing.

        • Early screening did not reduce a composite perinatal outcome, nor did it seem to affect other important secondary outcomes.

      • What can we take away from these papers?

        • We still have a ways to go on proving the value of the “early GDM screen,” particularly of doing multiple glucose challenge tests.

  • Guidance before the 1st step of the two-step approach:

    • One common patient question is whether fasting or eating anything in particular might make one more likely to “screen in” on the 50g, 1h OGTT.

      • In the January 2023 Green Journal, a group at Stanford randomized patients to a 6-hour fast prior to the 1hr test, versus eating within 2hr of the OGTT.

      • The “fed” group actually had a lower rate of screening positive (13%) versus the “fasting” group (31%).

        • Ultimately, the incidence of GDM was also higher in this “fasting” group (12.4% vs 5.1%). 

      • The group theorizes this is due to a phenomenon previously called “starvation diabetes,” in which fasting leads to an increase in glucagon and decrease in insulin, thus making one transiently glucose intolerant; and then later, insulin kicks back in and returns you to a normal metabolic state. 

      • This study only had about 100 individuals per arm of the trial, so hard to draw conclusions about neonatal/obstetrical outcomes, but none different in what they were able to assess.

    • What can we take away?

      • Hard to know totally, but probably don’t encourage fasting prior to the 1hr OGTT!