Among Metabolic Factors, Significance of Fasting and Postprandial Increases in Acyl and Desacyl Ghrelin and the Acyl/Desacyl Ratio in Obstructive Sleep Apnea before and after Treatment

Abstract

Study Objectives: There are reports suggesting that obstructive sleep apnea (OSA) may itself cause weight gain. However, recent reports showed increases in body mass index (BMI) following continuous positive airway pressure (CPAP) treatments. When considering weight changes, changes in humoral factors that have signifi cant effects on appetite such as acyl (AG) and desacyl ghrelin (DAG), leptin, insulin, and glucose and their interactions, examples of which are AG/DAG and AG/insulin, are important. The aim of this study was to test the hypothesis that some appetite-related factors had a specifi c profi le before and after CPAP treatment. Methods: Metabolic parameters were measured crosssectionally while fasting and 30, 60, 90, and 120 min following breakfast in no or mild OSA (apnea-hypopnea index < 15, n = 15) and moderate-to-severe OSA (apnea-hypopnea index ≥ 15, n = 39) participants in a single institute. There were no differences in age, sex, BMI, or visceral fat accumulation between the two groups. Twenty-one patients with moderate-to-severe OSA who received CPAP treatment also prospectively underwent the same testing following 3 months of CPAP treatment. Results: Although fasting and postprandial glucose, insulin, and leptin levels did not differ between no or mild OSA and moderateto-severe OSA participants, AG and DAG, including AG/DAG and AG/insulin, under fasting and postprandial conditions were signifi cantly increased in the moderate-to-severe OSA patients (p < 0.01). After 3 months of CPAP treatment in 21 of the moderate-to-severe OSA participants, AG/DAG did not change signifi cantly, but other ghrelin-related parameters including AG/ insulin signifi cantly decreased compared with values before treatment but remained higher than in no or mild OSA. 1,2 Obesity is considered a major risk factor for OSA, and reports suggest that OSA may itself cause weight gain.3-5 When considering weight changes, humoral factors such as ghrelin, leptin, insulin, and glucose, which have signifi cant effects on appetite, are important. 6-8Most data on the associations between OSA and some humoral factors have been acquired in the fasting state.9-12 However, it is important to investigate not only fasting data but postprandial data because these humoral secretions are signifi cantly affected by food intake. [13][14][15] Ghrelin exists in 3 forms: acyl ghrelin (AG), desacyl ghrelin (DAG), and the fragmented form. Recent data showed that interactions between AG and DAG as well as between AG and insulin are important in the energy balance and insulin resistance in patients with conditions such as obesity, BRIEF SUMMARYCurrent Knowledge/Study Rationale: It is said that there is a reciprocal interaction between obesity and obstructive sleep apnea (OSA). A few studies have shown that the treatment of OSA with continuous positive airway pressure (CPAP) is associated with a signifi cant reduction in body mass index (BMI), while other studies have found a signifi cant increase in BMI following CPAP treatment. It is important to ...

Effects of continuous positive airway pressure on energy intake in obstructive sleep apnea: A pilot sham-controlled study

“…This may further suggest that CPAP affects EI by targeting the homeostatic as opposed to hedonic regulation of EI. Indeed, CPAP may alter EI by normalizing levels of hunger/satiety hormones, as was reported after CPAP use for ghrelin [4,5,11,23] and leptin [2,5,6,24–29]. Based on reports of increased activation in brain regions involved in motivation and reward in response to food stimuli after sleep restriction [30], future investigations should extend beyond homeostatic/hormonal mechanisms to explore if and how CPAP treatment affects the hedonic and/or cognitive controls of food intake, using functional magnetic resonance imaging.…”

“…A hormonal profile that would predispose to high EI appears to exist in OSA patients, who have increased leptin [2–10], suggestive of leptin resistance, and increased ghrelin [4,5,10,11], relative to controls. Increased liking for high-fat foods [12] and preference for calorie-rich foods high in fat and carbohydrate [13] were observed in association with OSA severity.…”

Effects of continuous positive airway pressure on energy balance regulation: a systematic review

“…Several within-patient studies have investigated the effects of CPAP on leptin levels by comparing baseline to post-treatment values, with 12 reporting significant reductions in leptin after treatment [7, 9, 10, 32, 33, 50–56] and six reporting no change [17, 18, 48, 57–59]. In most cases, leptin was sampled in the morning after an overnight fast [7, 9, 10, 17, 18, 32, 33, 48, 50–52, 55–59], and in one case, which did report post-treatment reductions, it was sampled throughout the night [53]. The duration of treatment from baseline to follow-up ranged from 1 day to 6 months, and does not seem to contribute to disparate findings.…”

“…Four of these reported a significant reduction in ghrelin levels after treatment duration of 2 days [9], 1 month [18], 3 months [17] and 6 months [58]. In the study with the 1-month follow-up, despite significantly reduced levels at the end-point, ghrelin levels were not changed at a proximal follow-up after 3–4 days of treatment [18].…”

“…There is some evidence for a dysregulation of hunger/satiety-regulating hormones in OSA, with increased leptin levels, suggestive of leptin resistance [7–16], and increased ghrelin [9, 17–19] relative to controls. OSA is associated with a hormonal profile that may encourage low satiety ( via leptin resistance) and high hunger ( via ghrelin) and therefore excessive energy intake.…”