Effective Treatment of Sleep Apnea in Prediabetes to Reduce Cardiometabolic Risk

The investigators overall goal is therefore to conduct over the next 2 years a "proof of concept" study to fill this major gap of knowledge and to rigorously test the hypothesis that effective continuous positive airway pressure (CPAP) treatment of Obstructive Sleep Apnea (OPA) with all night optimum compliance can improve glucose metabolism in prediabetes and reduce cardiometabolic risk. The investigators propose to study overweight or obese adults who have prediabetes and OSA at baseline and after randomization to either: (i) 2 weeks of effective CPAP treatment ("CPAP group") or (ii) 2 weeks of oral administration of a placebo tablet 30min before bedtime ("placebo group"). Both groups will spend each of the 14 nights in the laboratory with 8-hour bedtimes. In the CPAP group, optimum CPAP compliance during the entire night will be ensured by continuous supervision by a registered PSG technician. In all participants, the investigators will perform at baseline and at the end of the intervention, an intravenous glucose tolerance test (ivGTT) to assess insulin sensitivity (SI), insulin secretion (i.e. acute insulin response to glucose,AIRg) and the disposition index (DI; a validated marker of diabetes risk) as well as an oral glucose tolerance test (OGTT) to translate ivGTT findings into end points commonly used in clinical practice. The findings from the ivGTT will allow for the dissection of the respective roles of improvements in SI and AIRg on diabetes risk. Blood pressure (BP) will be recorded continuously over 24 hours and cardiac sympathetic activity will be assessed by heart rate variability of ambulatory EKG recordings. For all cardiometabolic measures, post-intervention changes from baseline will be compared between the CPAP and placebo groups. The investigators specific aims are: 1) to test the hypothesis that effective CPAP treatment of OSA in prediabetics reduces diabetes risk, as assessed by the DI; 2) to test the hypothesis that CPAP treatment of OSA in prediabetics enhances the nocturnal dipping of BP and reduces daytime BP. The investigators will also use state-of-the-art quantitative PSG analysis to identify potential biomarkers that may predict the cardiometabolic response to CPAP. Secondary outcomes will be plasma levels of catecholamines, free fatty acids, leptin and C-reactive protein, and GLP-1. The investigators will also collect daily data on weight, caloric intake, and energy expenditure.