Using sleep duration and snoring information, provided in early pregnancy, we were able to detect associations between sleep characteristics and maternal plasma 1-hour glucose concentrations after a 50-gram oral glucose challenge screening test later in pregnancy. Curvilinear relations were observed across nocturnal sleep duration categories. Additionally, glucose concentrations were statistically significantly elevated among women who snored during pregnancy; and the relative risk of GDM among overweight women who snored, compared to their non-snoring and lean counterparts was 6.91 (95% CI 2.87-16.6). Collectively, the findings from this pilot study provides evidence consistent with the notion that glucose homeostasis in pregnancy is sensitive to maternal habitual short sleep duration and snoring during pregnancy. To our knowledge, this is the first examination of the relation between plasma glucose concentrations, GDM risk and sleep parameters (i.e., snoring and habitual sleep duration) during pregnancy.
A large literature primarily focused on men and non-pregnant women suggest that sleep loss adversely affects glucose metabolism and increases the risk of type 2 diabetes [4
]. In their cross sectional study of 740 Canadians (323 men and 417 women), Chaput et al noted that short sleep duration (<7 hours) was associated with prevalent type 2 diabetes (OR = 1.58; 95% CI 1.13-2.31) [33
]. Ayas et al, in their study of 70,026 US nurses, followed for 10 years, reported that individuals who slept ≤ 5 hours per night had a significantly higher risk of symptomatic incident diabetes (OR = 1.34; 95% CI 1.04-1.72) [4
]. Analysis of data from the Massachusetts Male Aging Study revealed that short sleep duration at baseline (≤5 or 6 hours per night) was associated with elevated risk of developing incident type 2 diabetes after adjustment for covariates, including age, hypertension, smoking, self-rated health, waist circumference, education, total testosterone and cortisol [11
]. Further, Gangwisch et al, in their analysis of data from the first National Health and Nutrition Examination Survey (NHANES I) noted that individuals reporting ≤ 5 hours of sleep (OR = 1.47; 95% CI 1.03-2.09) and those reporting sleeping ≥ 9 hours (OR = 1.52; 95% CI 1.06-2.18) had increased risks of developing diabetes as compared to those reporting 7 hours of sleep [34
]. Our findings of elevated risks of incident GDM among women reporting both long and short sleep durations in early pregnancy are consistent with these earlier reports from men and non pregnant women.
Our observations of impaired post-load glucose tolerance and increased risk of GDM among women who snore during pregnancy are also consistent with a growing body of epidemiological evidence that documents markers of the severity of obstructive sleep apnea (OSA) and increased risk of type 2 diabetes in diverse populations of men and non-pregnant women from various geographic regions [32
]. In a cross-sectional study of elderly Danish men and women, investigators noted that self-reported snoring was associated with abnormal glucose tolerance test results after control for confounding factors [36
]. These findings were subsequently corroborated and extended by others, including, Al-Delaimy et al [32
] who reported that self-reported regular snoring was independently associated with a 2-fold increased risk (RR = 2.03; 95% CI 1.71-2.40) of developing type 2 diabetes over a 10-year follow-up period. Lindberg et al [37
], in their cross sectional study of 6,799 Swedish women, for instance, reported that self-reported snoring and excessive daytime sleepiness was an independent risk factor for type 2 diabetes (OR = 1.82; 95% CI 0.97-3.43). In a population-based Swedish study of 2,668 men followed for 10-years, investigators reported that the multivariable adjusted relative risk for incident type 2 diabetes was highest for obese snorers (OR = 7.0; 95% CI 2.9-16.9) than for lean non-snorers [38
]. In our study we found that the adjusted relative risk of GDM was highest among overweight mothers who snored during pregnancy (OR = 6.91; 95% CI 2.87-16.3) when compared with lean mothers who did not snore. In summary, available data support the notion that habitual snoring may be a risk factor for abnormal glucose metabolism. Our finding extends this literature by adding preliminary evidence that links snoring with pregnancy-related impaired glucose tolerance and GDM.
Our present pilot study has several important strengths. First, our determination of maternal sleep duration and snoring was based on reports made early during pregnancy, so reporting was not conditional on pregnancy outcomes or on signs and symptoms of GDM. Our results suggest that habitual short/long sleep duration and snoring precede the clinical diagnosis of GDM. Second, the high follow-up rate (>95%) minimized possible selection bias. However, several limitations merit discussion and consideration. Maternal habitual sleep duration and snoring was obtained from self-report, and thus are likely susceptible to misclassification. Reported sleep duration is known to be only moderately correlated with wrist actigraph-measured sleep duration (ρ = 0.47), and reports are generally longer by approximately 34 minutes for each hour of objectively measured sleep [39
]. The use of self-reported snoring as a tool to detect sleep disordered breathing is well established. Investigators have shown that self-reported snoring correlates well with objective findings from nocturnal polysomnography, especially in frequent snorers [40
]. Snoring that is infrequent or non-habitual has not been shown to be a useful screen for sleep disordered breathing in large epidemiologic studies [41
]. It was therefore necessary to distinguish frequent snorers from infrequent snorers in our study. Our pilot study was also limited by the relatively small sample of GDM cases (n = 68) and the imprecision of relative risk estimates which were reflected by their wide 95% confidence intervals. A total of 251 study subjects had a post-50 gram 1-hour glucose concentration ≥ 140 mg/dl and thus required the follow-up diagnostic 100-gram oral glucose tolerance test (OGTT). Although qualitative results (i.e., normal/abnormal blood glucose concentrations) for the diagnostic test were available for all 251 subjects, specific glucose concentrations for each time point (i.e., fasting; 1-hour; 2-hour; and 3-hour post glucose load) were unavailable for approximately 44% of subjects. Lastly, the generalizability of our study may be limited, as our cohort was primarily comprised of Non-Hispanic White and well-educated women.
The pathophysiological mechanisms underlying these consistently observed associations of short sleep duration, sleep-related breathing disorders, including snoring, with altered glucose metabolism and diabetes are likely to be multifactorial [2
]. Notably, high sympathetic nervous system activity, intermittent hypoxemia, dysregulation of the HPA axis, endothelial dysfunction and alterations in cytokine and adipokine synthesis and release have all been proposed mechanisms for these consistently observed epidemiological observations. Sympathetic hyperactivity can alter glucose homeostasis and induce insulin resistance by increasing glycogen breakdown and gluconeogenesis. Recently, investigators reported that mild sleep restriction induces marked reduction in basal glucagon concentrations [19
]. Furthermore, individuals with sleep disorders may be predisposed to insulin resistance and glucose intolerance due to sleep-related dysregulation of the HPA axis with consequent elevations in serum cortisol [16
]. In a community dwelling sample of 2,751 middle aged men and women, Kumari et al reported that short sleep duration and increased sleep disturbance are independently associated with diurnal slope in cortisol secretion [45
Alternatively, cyclical hypoxemia with re-oxygenation, similar to repeated ischemia-reperfusion damage, may promote the formation of reactive oxygen species that may then elicit the release of pro-inflammatory cytokines including interleukin-6 and tumor necrosis factor-α [46
]. Investigators have shown that both acute total and short-term partial sleep loss results in elevated C-reactive protein (CRP) concentrations [48
]. Notably, investigators have reported that short sleep duration and other parameters of sleep disturbance during mid and late pregnancy are associated with increased systematic inflammation and higher stimulated levels of IL-6 [49
]; and we have previously reported that early pregnancy CRP concentrations are predictive of incident GDM [51
]. Collectively, these data suggest that sleep disturbances may augment pro-inflammatory responses that may then contribute to altered glucose metabolism. Causal biological mechanisms for the observed positive, though statistically in-significant association between long sleep duration and GDM are not clear. Some investigators, documenting similar positive association between long sleep duration and type 2 diabetes mellitus speculate that the association may be due in part to residual confounding by undiagnosed health conditions, co-morbid depression, unemployment, or poor general health [1
]. Despite unclear mechanisms, the positive relationship between later pregnancy hyperglycemia and GDM risk were evident among women who reported short/long sleep duration and snoring in our cohort. The risks were particularly elevated among overweight women with these sleep disorders.