Vsevolod Y. Polotsky

This paper provides first evidence that carotid body denervation abolishes hypertension and improves fasting blood glucose levels and glucose tolerance in mice with diet-induced obesity. Furthermore, we have shown that this phenomenon is associated with increased liver glycogen content, whereas insulin sensitivity and enzymes of gluconeogenesis were not affected.

Background and Objective Obesity hypoventilation syndrome (OHS) causes hypercapnia which is often refractory to current therapies. We examine whether hypercapnia in OHS can be improved by a ketogenic dietary intervention. Methods We conducted a single‐arm crossover clinical trial to examine the impact of a ketogenic diet on CO 2 levels in patients with OHS. Patients were instructed to adhere to 1 week of regular diet, 2 weeks of ketogenic diet, followed by 1 week of regular diet in an ambulatory setting. Adherence was assessed with capillary ketone levels and continuous glucose monitors. At weekly visits, we measured blood gases, calorimetry, body composition, metabolic profiles, and sleep studies. Outcomes were assessed with linear mixed models. Results A total of 20 subjects completed the study. Blood ketones increased from 0.14 ± 0.08 during regular diet to 1.99 ± 1.11 mmol/L ( p < 0.001) after 2 weeks of ketogenic diet. Ketogenic diet decreased venous CO 2 by 3.0 mm Hg ( p = 0.008), bicarbonate by 1.8 mmol/L ( p = 0.001), and weight by 3.4 kg (p < 0.001) . Sleep apnoea severity and nocturnal oxygen levels significantly improved. Ketogenic diet lowered respiratory quotient, fat mass, body water, glucose, insulin, triglycerides, leptin, and insulin‐like growth factor 1. Rebound hypercapnia was observed after resuming regular diet. CO 2 lowering was dependent on baseline hypercapnia, and associated with circulating ketone levels and respiratory quotient. The ketogenic diet was well tolerated. Conclusion This study demonstrates for the first time that a ketogenic diet may be useful for control of hypercapnia and sleep apnoea in patients with obesity hypoventilation syndrome.

Our diet-induced obesity (DIO) model reproduces sleep features of human obesity, including sleep fragmentation, increased apnea frequency, and larger breathing variability. DIO induces sleep fragmentation independently of apnea severity. Sleep fragmentation in DIO mice is mainly attributed to non-respiratory arousals. Increased breathing variability during sleep did not account for the higher arousal frequency in DIO. Our results provide a rationale to examine sleep in patients with obesity even when they are adequately treated for sleep-disordered breathing.