Sleep apnea in men is associated with altered lipid metabolism, glucose tolerance, insulin sensitivity, and body fat percentage

Abstract

Purpose Obstructive sleep apnea (OSA) is associated with obesity and risk for type 2 diabetes. In this community-based study, we thoroughly investigated fatty acid metabolism, incretin response, glucose tolerance, insulin secretion and insulin sensitivity, and autonomic nerve activity in men with or without OSA. Methods Fifteen men without diabetes but with signs of severe OSA, defined as apnea–hypopnea index (AHI) >30, and 15 age- and BMI-matched men without OSA (AHI < 5) were recruited from a community-based cohort. Assessments included clinical and anthropometric measurements, a 2-h oral glucose tolerance test (OGTT), and autonomic nerve activity using heart rate variability (HRV). Results Men with OSA had higher body fat % than BMI-matched men without OSA (p = 0.046) and it was associated with markers of insulin resistance. The area under the curve for nonesterified fatty acids (NEFA) during OGTT was higher in men with OSA (p = 0.021) and fasting NEFA levels were numerically higher (p = 0.097). The plasma glucose at fasting and during OGTT was higher in men with OSA (p < 0.001). Incretin response was similar between groups. Fasting and OGTT-derived indices indicated impaired insulin sensitivity in men with OSA. Compared with men without OSA, Matsuda index (p = 0.068) and Gutt index (p < 0.01) were lower in men with OSA. The HRV measures did not differ between groups. Conclusions Our study suggests that fatty acid handling, glucose tolerance, and insulin sensitivity are impaired in men with severe OSA. This might partly be explained by the increased body fat percentage.

New insights into diabetes mellitus and its complications: a narrative review

“…OSA is characterized by recurrent partial (hypopnea) or complete (apnea) upper airway obstruction, leading to hypoxia, recurrent arousal from sleep, and desaturationreoxygenation sequences (43). Data from previous research suggest OSA is associated with many metabolic abnormalities, including impaired fatty acid handling, glucose tolerance, and insulin sensitivity, atherogenesis, and high blood pressure, through the effects of sleep fragmentation, intermittent hypoxia, sympathetic overactivity, and adipose tissue inflammation (43,44). Also, many studies have confirmed that OSA is an independent risk factor for CVD (45).…”

Plasma Free Fatty Acid Concentration as a Modifiable Risk Factor for Metabolic Disease

“…Higher fasting plasma FFA is also associated with elevated risk for all-cause mortality [ 43 , 44 ] and death from CVD [ 43 , 44 ]. In addition to obesity and its associated FFA levels, it is known that various aspects of the metabolic syndrome (IR and vascular health indicators) are detrimentally impacted by factors such as sleep deprivation [ 49 , 50 , 51 , 52 ], sleep apnea [ 49 , 53 , 54 , 55 ], cigarette smoking [ 56 , 57 , 58 , 59 ], and physical inactivity [ 60 , 61 , 62 , 63 ]; as discussed below, each of these factors leads to elevated plasma FFA as well, and this impact on circulating FFA concentration may be a causal factor in the detrimental health impacts of these factors. When we take this information as a whole, it becomes apparent that plasma FFA concentration is a disease risk factor which is modifiable.…”

“…OSA increases risk for developing IR, other metabolic syndrome factors, and vascular disease [ 49 , 53 , 54 , 55 ]. The literature indicates that this type of sleep dysfunction also elevates plasma FFA concentration.…”

“…Furthermore, the severity of OSA in these men and women correlated with the magnitude of plasma FFA elevation [ 54 ]. In another cross-sectional study, comparing men with and without OSA, the OSA patients exhibited higher fasting glucose, a worsened glucose excursion during an OGTT, and less suppression of plasma FFA during the OGTT [ 55 ]. In conclusion, OSA is a common comorbidity of obesity which leads to worsened metabolic health, likely in part through effects upon plasma FFA concentration.…”

“…Adipose tissue IR is typically assessed by the degree of plasma FFA suppression during an OGTT or during a hyperinsulinemic euglycemic clamp. Indeed suppression of plasma FFA concentration by insulin is blunted in T2D [ 45 ], as well as in other instances of IR such as sleep deprivation [ 110 ] and following cigarette smoking [ 58 , 113 ]; furthermore, weight loss via gastric bypass surgery [ 94 ] and treatment of sleep apnea [ 55 ] each enhance the ability to suppress plasma FFA concentration during an OGTT. Activation of the sympathetic nervous system can also impose challenges upon metabolic health, as β-adrenergic signaling in adipose tissue enhances lipolysis and thus accelerates the release of FFA into circulation.…”