Sleep-disordered breathing early in pregnancy linked to insulin resistance
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Sleep disordered breathing is associated with an increase in insulin resistance but not insulin secretion during early pregnancy among women with overweight and obesity, according to a study published in Sleep.
“We decided to conduct this study to better understand the association between maternal sleep disordered breathing (SDB) and glucose metabolism in early pregnancy,” author Laura Sanapo, MD, MSHS, RDMS, a research scientist with the Miriam Hospital, Women’s Medicine Collaborative in Providence, Rhode Island, told Healio.
Women often experience snoring and obstructive sleep apnea (OSA) during pregnancy, Sanapo said. SDB also is underdiagnosed, although it affects up to 70% of high-risk pregnancies, she continued, especially those complicated by maternal obesity, and it is more common than other obstetric complications such as diabetes and hypertension.
Previous research has demonstrated that women with SDB during pregnancy have a higher risk for developing diabetes in late gestation than women without SDB after controlling for obesity and other confounding factors, according to Sanapo.
Yet whether women with SDB at the beginning of gestation start pregnancy with glucose abnormalities that precede the onset of diabetes such as reduced insulin sensitivity was unknown, Sanapo added.
What the study showed
The cross-sectional study was based on the baseline characteristics of 192 women with singleton pregnancies and risk factors for OSA such as a BMI equal to or greater than 27 kg/m2 and snoring three or more days per week.
The researchers conducted home sleep apnea testing (HSAT) at 11 weeks of gestation and homeostatic model assessments (HOMA) at 15 weeks.
HSAT found 61 participants (32%) with OSA based on respiratory-event index (REI) values of five events or more per hour. These participants were older, had a higher BMI and were more likely to be multipara than those not diagnosed with OSA.
Virtually all the respiratory events were obstructive, and both groups saw minimal sleep hypoxemia. The median REI was categorized as mild (fewer than 15 events per hour), though 10 women had REI values of more than 15 events per hour.
HOMA, designed to yield an estimate of insulin resistance, sensitivity and B cell function (HOMA %B), measured fasting glucose and c-peptide. Venipuncture following an 8-hour fast provided morning blood.
Participants who were diagnosed with OSA exhibited higher glucose and c-peptide values and had a higher degree of insulin resistance (HOMA-IR) than the participants who were not diagnosed with OSA, the researchers said.
For each 10-unit increase in REI, there was a 0.3-unit increase in HOMA-IR and a 4-unit increase in fasting glucose levels. However, there was no significant association between REI and HOMA %B.
The researchers also found an association between HOMA-IR and oxygen desaturation index (ODI), but they did not find an association between ODI and HOMA %B.
Further, 20 participants (32.8%) in the OSA group and 22 (16.8%) in the non-OSA group had fasting glucose levels of 95 mg/dL or higher. REI and ODI both were associated with fasting glucose levels after adjusting for the same covariates (B = .22; P = .012 and B = .27; P = .003, respectively).
“Among a group of women without pregestational diabetes, those who are diagnosed with SDB at the beginning of pregnancy have lower sensitivity to insulin and higher fasting glucose levels compared to pregnant women without SDB,” Sanapo said.
The researchers controlled for several factors that may contribute to abnormal glucose markers in pregnancy such as maternal BMI, age, race, ethnicity and number of previous pregnancies.
Why the findings are important
Sanapo said these results were important for four reasons.
First, a reduced sensitivity to insulin usually precedes the development of diabetes. Second, the study showed this association between SDB and reduced insulin sensitivity very early in pregnancy, approximately 10 weeks before typical screenings for gestational diabetes in the general pregnant population.
Third, Sanapo noted that the normal range of insulin resistance in pregnancy is very narrow, so even mild changes related to maternal SDB can lead to abnormal values. Finally, SDB is a modifiable risk factor that can be treated by non-pharmacological interventions that are safe in pregnancy.
“Therefore, women with overweight and obesity may benefit from SDB screening before conception or early pregnancy to improve glucose metabolic outcome and decrease the risk of developing diabetes in pregnancy,” Sanapo said.
These women then may benefit from tailored interventions to improve pregnancy outcomes such as early gestational diabetes screenings and SDB therapy, though weight loss or exercise programs are not usually advised in pregnancy, Sanapo said.
“Hence, the ideal time to actually screen and intervene would be in reproductive-age women considering pregnancy,” she said.
The researchers now aim to better understand the mechanistic processes that connect these disorders to identify therapeutic targets. They also seek to establish whether screenings should be universal or for select groups of high-risk pregnancies, or if screenings should occur before conception.
Further, the researchers aim to evaluate whether SDB treatment can prevent the development of gestational diabetes or other adverse perinatal outcomes.
“SDB represents a common morbidity in high-risk pregnancies and is associated with many disorders that are directly linked or considered an important contributor to maternal mortality,” Sanapo said. “Research in this field is needed and may greatly impact maternal health.”
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For more information:
Laura Sanapo, MD, MSHS, RDMS, can be reached at laura_sanapo@brown.edu.