Adding CPAP to Gestational Diabetes Management: A Step Before Insulin?

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Gestational diabetes can have short- and long-term consequences for the health of the mother and the fetus. Mothers are more likely to experience preeclampsia during pregnancy and to develop cardiovascular disease.1 While dietary interventions may be enough to control blood sugars in some women, many with gestational diabetes must adapt to a complex and expensive exogenous insulin regimen. Emerging research suggests CPAP may be an effective, intermediate treatment for some women with gestational diabetes between nutritional interventions and pharmacological treatments. If CPAP may help pregnant women with sleep-disordered breathing and gestational diabetes control their blood glucose levels without pharmacological agents, then it would stand to reason that testing for sleep apnea would be a good first step with this patient population.

Gestational diabetes is increasingly common and potentially deadly

Gestational diabetes is a state of glucose intolerance that emerges during pregnancy. Unfortunately, gestational diabetes is common; the prevalence of gestational diabetes is around 15%, a rate that has been increasing over the past three decades.2 While most women with gestational diabetes return to a state of euglycemia within hours to days after delivery, maternal hyperglycemia is associated with preeclampsia, neonatal metabolic abnormalities and macrosomia, which lead to increased rates of cesarean section, birth injury, or perinatal mortality.3 Despite being a transient disease that will resolve on its own, maternal hyperglycemia requires tight control during the pregnancy for the health of the mother and the baby. 

Gestational diabetes is often treated on a two tier system

As with type 2 diabetes mellitus, the treatment of gestational diabetes begins with patient education and dietary management. Unless glucose levels are so high that they are unlikely to resolve with dietary interventions alone, women are prescribed nutritional therapy and exercise. For those who can adhere to the diet and exercise regimen, the approach does keep glucose levels under control and tends to avoid macrosomia, polyhydramnios or oligohydramnios and preeclampsia. As is also seen in type 2 diabetes, however, patients are not often able to adhere to a diet that will control blood glucose levels. In these cases, insulin or an antihyperglycemic drug are required.

The risks and burdens of pharmacologic therapy for gestational diabetes

Pregnant women with gestational diabetes who fail to achieve glucose control through diet and exercise are offered insulin, which is usually the first choice, or either metformin or glyburide.4 Each comes with risks and drawbacks. Patients must successfully administer the appropriate amount of insulin to avoid hypoglycemia, which requires point of care glucose monitoring, dosage calculations, and self-administered subcutaneous injections. Not surprisingly, insulin refusal or non-adherence is high, and quality of life suffers with insulin treatment.5 Oral medications are easier to self-administer, but come with potential risks to the fetus. The fetal drug levels of glyburide and metformin are 70 and 200 percent of the maternal levels, respectively. The long-term effects of this exposure, if any, are not known. Nevertheless, as many as one in four women fail to achieve glucose control with their oral diabetes medications alone.6 

The link between sleep-disordered breathing and gestational diabetes

Sleep-disordered breathing may occur in nearly 50% of pregnancies and, if present, triples the risk of gestational diabetes even after controlling for obesity.7,8 Likewise, sleep-disordered breathing during pregnancy increases nocturnal blood glucose levels.9 Certainly increased weight and decreased functional capacity during pregnancy contribute to sleep apnea, though pregnancy is also associated with upper airway narrowing, vascular and nasal congestion that appear to increase the risk of sleep apnea as well.10 Indeed, the prevalence and severity of sleep-disordered breathing during pregnancy argues for greater use of CPAP during pregnancy, but the argument is even more persuasive if CPAP could prevent or even treat gestational diabetes. 

CPAP significantly lowers nocturnal glucose levels in women with gestational diabetes

A research group at McGill University in Montreal, Canada published intriguing results at the 2020 American Thoracic Society International Conference.11 In the pilot randomized controlled trial, the researchers showed that in 45 pregnant women with sleep-disordered breathing and gestational diabetes, CPAP treatment (n = 22) significantly lowered nocturnal blood glucose levels compared to control (n = 23; adhesive nasal dilator strips) by 0.9 mmol/L or 16.2 mg/dl measured by continuous glucose monitoring. 

Should we try CPAP for gestational diabetes before pharmacological antihyperglycemic treatments?

It is important to keep in mind this is a pilot trial presented in abstract form. Also, mean CPAP adherence was only 3.3±2.4 hours per night (though that suggests better CPAP adherence may lead to more robust decreases in blood glucose levels). It will be interesting to see if follow-up studies confirm this finding. We know from previous work that CPAP is a safe and well-tolerated therapy in pregnant women with sleep-disordered breathing and improves maternal and fetal outcomes.12  What this work suggests is that CPAP may also help pregnant women with sleep-disordered breathing and gestational diabetes control their blood glucose levels without pharmacological agents. Future work could give women with gestational diabetes another treatment option in addition to diet and exercise but before starting metformin, glyburide, or insulin. 

At-home sleep apnea testing should be offered to pregnant women at risk for gestational diabetes

It is likely too onerous to expect pregnant women to have a formal sleep study in a sleep laboratory and then a second study to titrate CPAP levels, if sleep apnea is detected. Pregnant women with or at risk for gestational diabetes would seem like an ideal patient population to use at-home sleep apnea testing in lieu of polysomnography in a lab. Compliance with testing and titration would likely be higher with at-home sleep apnea testing and could also reduce healthcare costs. Given the potential benefits for blood sugar reduction and stabilization, it is reasonable for clinicians to offer testing for sleep apnea at home to all pregnant women at risk for gestational diabetes.

References

1. Tobias DK, Stuart JJ, Li S, et al. Association of History of Gestational Diabetes With Long-term Cardiovascular Disease Risk in a Large Prospective Cohort of US Women. JAMA Intern Med. 2017;177(12):1735-1742. 10.1001/jamainternmed.2017.2790

2. Halperin IJ, Feig DS. The role of lifestyle interventions in the prevention of gestational diabetes. Curr Diab Rep. 2014;14(1):452. 10.1007/s11892-013-0452-2

3. Buchanan TA, Xiang AH. Gestational diabetes mellitus. J Clin Invest. 2005;115(3):485-491. 10.1172/JCI24531

4. ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018;131(2):e49-e64. 10.1097/AOG.0000000000002501

5. Marchetti D, Carrozzino D, Fraticelli F, Fulcheri M, Vitacolonna E. Quality of Life in Women with Gestational Diabetes Mellitus: A Systematic Review. J Diabetes Res. 2017;2017:7058082. 10.1155/2017/7058082

6. Nachum Z, Zafran N, Salim R, et al. Glyburide Versus Metformin and Their Combination for the Treatment of Gestational Diabetes Mellitus: A Randomized Controlled Study. Diabetes Care. 2017;40(3):332-337. 10.2337/dc16-2307

7. Pamidi S, Meltzer SJ, Garfield N, et al. A Pilot Randomized-Controlled Trial on the Effect of CPAP Treatment on Glycemic Control in Gestational Diabetes: Study Design and Methods. Front Endocrinol (Lausanne). 2018;9(659):659. 10.3389/fendo.2018.00659

8. Pien GW, Pack AI, Jackson N, Maislin G, Macones GA, Schwab RJ. Risk factors for sleep-disordered breathing in pregnancy. Thorax. 2014;69(4):371-377. 10.1136/thoraxjnl-2012-202718

9. Newbold R, Benedetti A, Kimoff RJ, et al. Maternal Sleep-Disordered Breathing in Pregnancy and Increased Nocturnal Glucose Levels in Women with Gestational Diabetes Mellitus. Chest. 2021;159(1):356-365. 10.1016/j.chest.2020.07.014

10. Edwards N, Middleton PG, Blyton DM, Sullivan CE. Sleep disordered breathing and pregnancy. Thorax. 2002;57(6):555-558. 10.1136/thorax.57.6.555

11. Newbold R, Meltzer S, Benedetti A, et al. CPAP Treatment Reduces Nocturnal Glucose Levels in Gestational Diabetes: A Pilot Randomized-Controlled Trial (RCT). In: A97. SRN: NEW INSIGHTS INTO THE CARDIOMETABOLIC CONSEQUENCES OF INSUFFICIENT SLEEP.A2524-A2524.12. Izci Balserak B. Sleep disordered breathing in pregnancy. Breathe (Sheff). 2015;11(4):268-277. 10.1183/20734735.009215