OSA and Insulin Resistance
Subjects with OSA may have multiple factors that promote insulin resistance and glucose intolerance. Central obesity itself leads to insulin resistance via increased lipolysis and fatty acid availability.
There is a variety of methods for the evaluation of glucose metabolism and different ones have been used in OSA studies. Despite negative results in earlier reports, there is growing evidence, from cross-sectional studies, of a positive and independent association between OSA and insulin resistance/glucose intolerance/diabetes.[69,70,71,72] The increase in insulin resistance attributable to OSA was observed not only in the overweight or obese, but also in the nonobese.[34,70] Nevertheless, it should be acknowledged that adiposity is an important factor towards adverse glucose metabolism in OSA, probably more so than sleep-disordered breathing alone. Whether there is indeed any additive, synergistic or redundant effect of the two conditions on glucose homeostasis awaits further research. In contrast to the positive association on cross-sectional analysis, a longitudinal study of 1300 subjects in the Wisconsin Sleep Cohort did not find any independent relationship between OSA and incident diabetes at 4-year follow-up, despite a higher prevalence of diabetes in OSA subjects independent of other risk factors at baseline.
Interventional data regarding glucose metabolism in OSA have shown conflicting results. Most studies were observational and comprised a small sample size. Using the hyperinsulinemic euglycemic clamp method, considered the ‘gold standard’ for evaluation of insulin sensitivity, CPAP was found to improve insulin sensitivity after 2 days as well as 3 months of treatment, respectively, and the improvement was greater in nonobese patients with a BMI of less than 30 compared with those with a higher BMI. It was subsequently demonstrated that the improvement of insulin sensitivity was maintained at 3 years in these nonobese subjects whose weight remained constant. A case-controlled study reported that sleepy, but not non-sleepy, OSA subjects had elevated insulin resistance indicated by the homeostasis model assessment index for insulin resistance (HOMA-IR), and that 3 months of CPAP treatment reduced HOMA-IR in sleepy but not in non-sleepy OSA subjects with similar AHI levels. Recently, using the intravenous glucose-tolerance test, nondiabetic OSA men were shown to have impaired insulin sensitivity as well as impaired insulin secretion.
Data from randomized, controlled trials are limited. A study of diabetic men with OSA showed no change in insulin sensitivity, measured using the hyperinsulinemic euglycemic clamp method, during 3 months of CPAP treatment compared with sham CPAP, and similarly, a crossover study of nondiabetic OSA men found no change in HOMA-IR during 6 weeks of CPAP treatment. By contrast, we found an improvement in glucose disposal after exogenous insulin, using the short insulin-tolerance test, in response to therapeutic CPAP compared with sham CPAP for 1 week.
Expert Rev Resp Med. 2009;3(2):177-186. © 2009 Expert Reviews Ltd.
Cite this: Obstructive Sleep Apnea and the Metabolic Syndrome - Medscape - Apr 01, 2009.