Role of Free Fatty Acids in the Alteration of Cardiovascular Autonomic Activity and Its Postprandial Changes in Obese Patients with Glucose Intolerance

Abstract

Rationale: Depressed cardiac vagal activity and elevated sympathetic activity have been reported in prediabetic obese patients. In healthy individuals, insulin was shown to acutely induce such changes, and free fatty acids (FFA) to enhance sympathetic activity. This study aimed to examine the relations between glycemia, insulinemia and plasma FFA with cardio-vascular autonomic activity in obese patients with glucose intolerance. Patients and Methods: We included 24 obese patients (BMI 36.6±5.0 kg/m²) with glucose intolerance, normal blood pressure, and no cardio-vascular events. Cardiac vagal (HFnu-HR) and sympathetic (LFnu-HR) activity, and sympatho-vagal balance (LF/HF-HR) were measured by spectral analysis of heart rate variations during 6 minutes of controlled breathing rate (12 cycles/minute) (Task Force Monitor®). These measurements were performed at fasting and after a standardised breakfast including 75g of carbohydrates. The changes (∆) between fasting and 2 hours after breakfast were calculated. Results: At fasting, age correlated positively with LFnu-HR (p=0.02) and negatively with HFnu-HR (p=0.02). There was no significant correlation between autonomic indexes and glycemia and insulinemia. At fasting, FFA correlated positively with LFnu-HR and LF/HF-HR and negatively with HFnu-HR (p<0.04 and <0.02, respectively); and positively with nitrotyrosine (p=0.02). The correlations of FFA with spectral indexes were not altered after age adjustment, but were no more significant after adjustment for nitrotyrosine. Post-prandially, ∆FFA correlated positively with ∆LFnu-HR and ∆LF/HFnu-HR and negatively with ∆HFnu-HR (p<0.04 to <0.02). Conclusion: In prediabetic obese patients, FFA (lipotoxicity) play an important role both at fasting and post-prandially in sympathetic activation and vagal depression, probably by increasing oxidative stress. These effects could increase the arrhythmogenic risk. Disclosure A. Rezki: None. M. Fysekidis: None. C. Sabrina: None. I. Banu: None. E. Cosson: Consultant; Self; Lilly France. Board Member; Self; Novartis France. Consultant; Self; Roche Diagnostics France. Board Member; Self; Ascensia Diabetes Care. Consultant; Self; Bezins France. Board Member; Self; MSD France. P. Valensi: None.