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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #114: Diabetes and Sleep Apnea Part 4

Feb 27, 2018

OSA and glucose metabolism

OSA and dysglycemia have similar risk factors (namely obesity) and hence it is not surprising that these conditions co-exist. However, not all obese patients have both conditions and many patients have one and not the other. Hence, understanding this association and the mechanisms that underpin this relationship is important to understand the pathogenesis of OSA and T2DM. There are many studies that have examined the association between snoring, as a surrogate marker of OSA, and different aspects of glucose metabolism [32]; here, however, we will mainly focus on studies that validated the presence and severity of OSA using more accurate methods.

OSA and prediabetes

OSA has been associated with components of the metabolic syndrome and with IR independent of obesity [33]. Some studies reported that abnormal glycemia could occur in as many as 79% of patients with OSA [34]. In a cross-sectional analysis in a subset of the Sleep Heart Health Study, relative to those with RDI < 5, individuals with mild and moderate to severe OSA had adjusted OR of 1.27 (95% CI 0.98–1.64) and 1.46 (95% CI 1.09 –1.97), respectively for fasting glucose intolerance [35]. Sleep-related hypoxemia was also associated with glucose intolerance independently of age, gender, BMI, and waist circumference [35]. In another study that included 150 men not known to have diabetes, anAHI ≥5 was associated with an increased risk of IGT or DM (based on OGTT) (OR: 2.15; 95% CI 1.05–4.38) following adjustment for BMI and body fat (as measured by hydrodensitometry) [36]. For each 4% decrease in oxygen saturation, the OR of worsening glucose tolerance was 1.99 (95% CI 1.11–3.56) after adjusting for percent body fat, BMI, and AHI [36]. Similarly, in a cross-sectional analysis of 2588 participants (aged 52–96 years; 46% men), the OSA group (RDI ≥10) had higher adjusted OR of 1.3 (95% CI 1.1–1.6) for IFG (impaired fasting glucose), 1.2 (1.0–1.4) for IGT, 1.4 (1.1–2.7) for IFG plus IGT, and 1.7  (1.1–2.7) for occult diabetes compared to those without OSA [37]. In overweight/obese individuals, FPG and the 2-h OGTT glucose values were significantly higher in patients with vs. without OSA while there was no such difference in normal-weight subjects [37]. In the same study, the prevalence of abnormal glycemia was significantly higher in normal (679 subjects) and overweight/obese (1909 subjects) individuals with OSA compared to those without (no OSA vs. OSA: 17.6% vs. 25.5%, p=0.03 and 36.9% vs. 43%, p=0.02 for IFG; 5.1% vs. 9.3%, p=0.06 and 13.6% vs. 17.3%, p=0.05 for combined IFG and IGT; 5.7% vs. 9.3%, p=0.09 and 9.3% vs. 13.2%, p=0.01 for normal and overweight/obese subjects, respectively] [37]. More recently, the higher AHI and lower nocturnal hypoxemia were shown to be associated with higher HbA1c in patients without diabetes despite adjustment for a wide range of confounders in a cross-sectional study [38].

OSA and insulin resistance

Several studies examined the association between OSA and IR (Table 22.1). The majority of these studies were conducted in white Caucasians, but some included patients of other racial groups and ethnicities. The major difficulty in examining the association between OSA and IR is teasing out the impact of OSA from that of obesity. Most studies showed an association between OSA and IR, but some did not (Table 22.1). Studies that did not show such a relationship included fewer participants and potentially were underpowered.

Interestingly, a small recent study suggests that excessive daytime sleepiness may be, in part, responsible for the IR in patients with OSA [39]. Barcelo et al. studied 44 patients with OSA (22 with and 22 without excessive daytime sleepiness) matched for age, BMI and AHI, and 23 healthy controls [39]. Patients with excessive daytime sleepiness (assessed by the Epworth Sleepiness Scale and the Multiple Sleep Latency Test) had higher HOMA-IR compared with OSA patients without excessive daytime sleepiness or healthy controls [39]. The difference in HOMA-IR between OSA patients without excessive daytime sleepiness and healthy controls was not significant [39]. Glucose levels were significantly higher in patients with OSA and excessive daytime sleepiness compared to those with OSA without excessive daytime sleepiness and healthy controls [39]. In support for the association between excessive daytime sleepiness and IR, CPAP treatment in the same study reduced the HOMA-IR and increased IGF-1 levels in patients with excessive daytime sleepiness, but did not modify any of these variables in patients without excessive daytime sleepiness [39]. This impact of excessive daytime sleepiness may explain in part some of the variation in the association between OSA and IR observed in cross-sectional studies. Recent studies tried to exclude the impact of obesity on IR by examining healthy lean men and found that OSA was associated with IR despite the lack of obesity (Table 22.1) [40,41].

Unlike previous cross-sectional studies, OSA, AHI, ODI, and minimal oxygen saturations were independently associated with IR development over an 11-year follow-up period after adjustment for age, baseline BMI, hypertension, BMI change over follow-up, and CPAP treatment [42].

In the light of the association between OSA and IR, there was a wide interest in the impact of CPAP treatment on IR. Unfortunately the impact of CPAP on IR is not clear. While some studies showed that CPAP treatment lowered IR [69,70], others did not [45,49,71–73]. CPAP treatment varied in these studies from 1 night to 3 years. The lack of a positive effect of CPAP on IR may be the result of several methodological limitations such as the lack of a control group, short duration of CPAP treatment, and small sample sizes. However, it is possible that the impact of long-standing OSA on IR is irreversible. Two recent meta-analyses showed that CPAP treatment was associated with a reduction in HOMA-IR [74,75], although this benefit may occur only in those using CPAP >4h per night [76]. An in-depth review on the impact of CPAP on glucose metabolism can be found in [77].

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