Biological sex-related differences in the postprandial triglyceride response to intermittent hypoxaemia in young adults: a randomized crossover trial.

Obstructive sleep apnoea is characterized by chronic intermittent hypoxaemia and is independently associated with an increased risk of metabolic comorbidities (e.g. type II diabetes and ischaemic heart disease). These comorbidities could be attributable to hypoxaemia-induced alterations in blood lipid profiles. However, it remains unclear whether intermittent hypoxaemia alters triglyceridaemia differently between biological sexes. Therefore, we used a randomized crossover design to examine whether 6 h of moderate intermittent hypoxaemia (15 hypoxaemic cycles/h, 85% oxyhaemoglobin saturation) alters plasma triglyceride levels differently between men and women after a high-fat meal. Relative to men, women displayed lower levels of total triglycerides, in addition to denser triglyceride-rich lipoprotein triglycerides (TRL-TG; mainly very low-density lipoprotein triglycerides and chylomicron remnant triglycerides) and buoyant TRL-TG (mainly chylomicron triglycerides) during normoxia (ambient air) and intermittent hypoxaemia (sex × time: all P ≤ 0.008). Intermittent hypoxaemia led to higher triglyceride levels (condition: all P ≤ 0.016); however, this effect was observed only in men (sex × condition: all P ≤ 0.002). Compared with normoxia, glucose levels were higher in men and lower in women during intermittent hypoxaemia (sex × condition: P < 0.001). The different postprandial responses between biological sexes occurred despite similar reductions in mean oxyhaemoglobin saturation and similar elevations in insulin levels, non-esterified fatty acid levels and mean heart rate (sex × condition: all P ≥ 0.185). These results support growing evidence showing that intermittent hypoxaemia impacts men and women differently, and they might help to explain biological sex-related discrepancies in the rate of certain comorbidities associated with intermittent hypoxaemia. KEY POINTS: Intermittent hypoxaemia is a key characteristic of obstructive sleep apnoea and alters lipid metabolism in multiple tissues, resulting in increased circulating triglyceride levels, an important risk factor for cardiometabolic diseases. Circulating triglyceride levels are regulated differently between biological sexes, with women typically displaying much lower fasting and postprandial triglyceride levels than men, partly explaining why women of all ages experience lower mortality rates from cardiometabolic diseases. In this study, healthy young men and women consumed a high-fat meal and were then exposed to 6 h of intermittent hypoxaemia or ambient air. We show that postprandial triglyceride levels are significantly lower in women compared with men and that intermittent hypoxaemia leads to higher postprandial triglyceride levels in men only. These results might help us to understand better why women living with obstructive sleep apnoea experience lower rates of cardiometabolic diseases (e.g. type II diabetes and ischaemic heart disease) than men living with obstructive sleep apnoea.

Changes in appetite during acute passive intermittent and continuous hypoxemia in postprandial and fasting states: A combined analysis of four laboratory-based randomized crossover trials.

Hypoxemia occurs during exposure to high altitude (continuous hypoxemia) or in the context of breathing disorders such as obstructive sleep apnea (OSA; intermittent hypoxemia). Growing evidence demonstrates that hypoxemia induces an anorexigenic effect on appetite; however, few studies have assessed hypoxemia-related reductions in appetite during acute passive exposures and during intermittent hypoxemia. This study thus pooled together four same-single-site randomized crossover trials using simulated models of high altitude (fraction of inspired oxygen = 0.1200, ∼5000 m) and moderate OSA (∼15 hypoxemic cycles per hour, ∼85 oxyhemoglobin saturation). Changes in appetite were evaluated during 6 h of passive normoxia and intermittent or continuous hypoxemia in postprandial or fasting states among healthy young adults (n = 40) and middle-aged individuals living with OSA (n = 7). Our results demonstrate that (1) acute passive intermittent hypoxemia leads to statistically significant, but likely not clinically significant reductions in appetite in the postprandial state, (2) the anorexigenic effect of acute passive hypoxemia on appetite is not consistent across hypoxemic methods and nutritional states, and (3) variations in individual factors may influence appetite responses during normoxia and hypoxemia. These findings indicate that the effect of acute passive hypoxemia on appetite is heterogeneous, particularly across different hypoxemic methods and nutritional states.

The effect of acute intermittent hypoxia on postprandial triglyceride levels in humans: a randomized crossover trial.

BACKGROUND: Obstructive sleep apnea (OSA), a sleep disorder frequently observed in individuals living with obesity, consists of repeated involuntary breathing obstructions during sleep, leading to intermittent hypoxia (IH). In humans, acute continuous hypoxia slightly increases plasma triglycerides (TG). However, no study yet compared the postprandial TG response of individuals with or without OSA under intermittent hypoxia. METHODS: Using a randomized crossover design, seven individuals diagnosed with moderate OSA and eight healthy individuals without OSA were given a meal after which they were exposed for 6 h to normoxia or intermittent hypoxia (e.g., 15 hypoxic events per hour). Blood lipid levels were measured hourly during each session. RESULTS: Peak postprandial TG concentrations tended to be 22% higher under IH irrespective of group (IH × time interaction, p = 0.068). This trend toward higher total plasma TG was attributable to increased levels of denser TG-rich lipoproteins such as very low-density lipoproteins (VLDL) and chylomicrons (CM) remnants. Irrespective of group, the postprandial TG concentrations in denser TG-rich lipoproteins was 20% higher under IH (IH × time interaction, p = 0.036), although IH had virtually no impact on denser TG-rich lipoprotein concentrations in the OSA group. CONCLUSION: Acute intermittent hypoxia tends to negatively affect postprandial TG levels in healthy individuals, which is attributable to an increase in denser TG-carrying lipoprotein levels such as VLDL and CM remnants. This altered postprandial TG response to acute intermittent hypoxia was not observed in individuals with OSA.

No impact of a high-fat meal coupled with intermittent hypoxemia on acute kidney injury biomarkers in adults with and without obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxemia, which is associated with progressive loss of kidney function, where postprandial fluctuations in renal physiology may further compromise oxygen supply and kidney function. Therefore, we measured biomarkers of acute kidney injury (AKI) following a high-fat meal with and without intermittent hypoxemia. Eighteen healthy young men (mean age [SD]: 22.7 years [3.1]) and seven middle-aged to older individuals with OSA (54.4 years [6.4]) consumed a high-fat meal during normoxia or intermittent hypoxemia (~15 hypoxic cycles per hour, ~85% oxyhemoglobin saturation) for 6 h. We observed no changes in estimated glomerular filtration rate and plasma concentrations of creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) at any measured time points. In both groups, plasma concentrations of interleukin-18 (IL-18) increased after 6 h during normoxia only (p = 0.033, ηp 2 = 0.122), and plasma concentrations of liver-type fatty acid-binding protein (L-FABP) transiently decreased after 3 h in both conditions (p = 0.008, ηp 2 = 0.152). These findings indicate that AKI biomarkers are not acutely elevated during the postprandial state with or without intermittent hypoxemia, suggesting that other mechanisms may play more important roles in the progression of kidney disease in OSA.