Obesity Epidemiology

162 EPIDEMIOLOGIC STUDIES OF CONSEQUENCES OF OBESITYabdominal obesity. 127 The majority of women with PCOS have various components ofthe metabolic syndrome and insulin resistance. 128,129 In cross-sectional analyses, metabolicsyndrome was highly prevalent in women with PCOS, even at the relatively young age ofapproximately 30 years. 130 Thus, the term “syndrome XX” has been used to refer to PCOS,with the implication that it is a “female-specific form of the metabolic syndrome.” 131Cross-sectional data suggest increased rates of atherosclerosis and CHD among womenwith PCOS. 132 In prospective studies, highly irregular menstrual cycles, a common featureof PCOS, have been associated with incident type 2 diabetes 133 and CVD. 132Insulin resistance is thought to play an important role in the development of PCOS.Among women with PCOS, insulin-mediated glucose disposal is significantly reduced,and the degree of insulin resistance is similar to that in patients with type 2 diabetes. 134The reduction in insulin sensitivity is also evident among nonobese women with PCOS,suggesting that defective insulin action in PCOS is not completely caused by obesity.In addition to insulin resistance, both obese and nonobese women with PCOS have significantlydecreased beta-cell function. 135 The fundamental causes of insulin resistancein PCOS are not completely understood, but abdominal obesity, hyperandrogenism, andgenetic defects all appear to play a role in its development. 128Sleep ApneaSleep apnea is a common clinical manifestation of the metabolic syndrome and insulinresistance. 136 Obstructive sleep apnea (OSA), defined as a lack of airflow despite continuedrespiratory efforts, is strongly correlated with age, obesity, weight gain, male gender,and smoking. 137 Heavy snoring is a cardinal symptom of sleep apnea, and epidemiologicdata have indicated a strong association between obesity and regular snoring. 138There is growing evidence that sleep apnea is independently associated with insulin resistance.In a cross-sectional study, Ip et al. 139 found that those with OSA (defined as an apneahypopneaindex or AHI of ≥ 5) had significantly higher levels of fasting serum insulin(P = .001) and homeostasis model assessment of insulin resistance (HOMA-IR) (P < .001).This association was seen in obese as well as nonobese subjects. Similarly, Punjabi et al. 140found an association between sleep-disordered breathing and increased risk of impaired glucosetolerance (odds ratio, 2.15; 95% CI: 1.05 to 4.38) after adjusting for BMI and percentagebody fat. There was a dose-response relationship between the severity of oxygen desaturationand the impairment in glucose tolerance. A positive association between sleep-disorderedbreathing with glucose intolerance and insulin resistance was also found among communitydwellingsubjects (n = 2,656) in the Sleep Heart Health Study. 141The cross-sectional nature of these analyses makes it difficult to know whether sleepapnea is the cause or consequence of insulin resistance. However, increasing evidencesuggests that sleep disorders (e.g., reduced sleep hours) may increase risk of weight gainand obesity (see Chapter 16). Also, prospective studies have found that sleep apnea orregular snoring significantly predict future risk of hypertension, 142 type 2 diabetes, 143,144and CVD in healthy individuals. 145,146Sleep apnea has been associated with increased concentrations of proinflammatorycytokines (e.g., IL-6 and TNF-α) that are thought to mediate the relationship betweensleep apnea and CVD. 136 It has also been associated with other cardiovascular risk factors,for example, vascular endothelial dysfunction, increased oxidative stress, inflammation,and increased platelet aggregation. 147 Because of the close relationship betweensleep disorders and metabolic and cardiovascular risk factors, the term Syndrome Z hasbeen used to describe the addition of sleep apnea to the cluster of risk factors in themetabolic syndrome. 148