Alterations in Glucose Disposal in Sleep-disordered Breathing

Abstract

Rationale: It is well established that sleep-disordered breathing (SDB) is independently associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. However, data on whether SDB alters in vivo kinetics of glucose and insulin are lacking.

Objectives: The primary goal of this study was to use the frequently sampled intravenous glucose tolerance test (FSIVGTT) in subjects with and without SDB to model the in vivo kinetics of glucose and insulin. Minimal model analysis of the FSIVGTT data was used to derive parameters of insulin sensitivity, glucose effectiveness (a measure of the ability of glucose to mediate its own disposal), and pancreatic beta-cell function.

Results: A total of 118 nondiabetic subjects underwent polysomnography, the FSIVGTT, and body composition measurements including determination of percent body fat. Compared with normal subjects (apnea-hypopnea index < 5 events/h), those with mild, moderate, and severe SDB displayed a 26.7, 36.5 and 43.7% reduction in insulin sensitivity, respectively, independent of age, sex, race, and percent body fat. The disposition index, an integrated measure of pancreatic beta-cell function, was also reduced in patients with moderate to severe SDB. The decrease in insulin sensitivity and the disposition index were correlated with the average degree of oxyhemoglobin desaturation. In contrast, glucose effectiveness was negatively correlated with the frequency of respiratory event-related arousals.

Conclusions: The results of this study suggest that, independent of adiposity, SDB is associated with impairments in insulin sensitivity, glucose effectiveness, and pancreatic beta-cell function. Collectively, these defects may increase the risk of glucose intolerance and type 2 diabetes mellitus in SDB.

Figure 1.

Glucose and insulin profiles from the frequently sampled intravenous glucose tolerance test in subjects with and without sleep-disordered breathing. Values are average concentrations of glucose (left) and insulin (right) versus time.

Figure 2.

Adjusted values of insulin sensitivity (A: average S_I and 95% confidence intervals), the disposition index (B: average DI and 95% confidence intervals), glucose effectiveness (C: median S_G and 95% confidence intervals), and glucose effectiveness at zero insulin (D: median GEZI and 95% confidence interval). Values adjusted for age, sex, race, and percent body fat.

Figure 3.

Adjusted average values of insulin sensitivity (S_I) as a function of average oxyhemoglobin desaturation (ΔSa_O2) during sleep. Displayed are measured S_I values (squares) and the fitted regression values (dark line with 95% confidence bands) adjusted for age, sex, race, and percent body fat.