Role of free fatty acids on cardiac autonomic nervous system in noninsulin-dependent diabetic patients: Effects of metabolic control

Decreased heart rate variability (HRV) is a risk factor for cardiovascular mortality. Elevated plasma free fatty acid (FFA) levels decrease HRV in hea lthy subjects. Thus, we investigated the effect of changes in plasma FFA le vels on HRV, in non-insulin-dependent diabetes (NIDDM) patients. Thirty NID DM patients free from diabetic neuropathy volunteered for a study made by t wo phases. In study A, changes in HRV along a 10% lipid emulsion infusion heparin (n = 15) or saline infusion (control study; n = 15) were investiga ted. In study B, all patients (n = 30) underwent further determination of H RV after 3 months of improved metabolic control achieved by intensified ins ulin treatment. In study A, lipid emulsion infusion increased plasma FFA (P < 0.001) and catecholamine concentrations (P < 0.005), mean arterial blood pressure (P ( 0.005), low frequency/high frequency (LF/HF) ratio (P < 0.00 1). Delta plasma FFA levels correlated with delta LF/HF ratio (r = 0.57; P < 0.02). Along with saline infusion, metabolic and cardiovascular parameter s remained unchanged throughout the test. In study B, improved metabolic co ntrol lowered fasting plasma glucose (P < 0.005), FFA (P < 0.001), norepine phrine (P < 0.02), epinephrine (P < 0.04), and glycosylated hemoglobin leve ls (P < 0.001), mean arterial blood pressure(P < 0.05), and LF/HF ratio (P < 0.001). Again percent decline in plasma FFA correlated with the percent c hange in LF/HF ratio (r = 0.72; P < 0.001). In a multivariate analysis, per cent changes in LF/HF ratio were associated with percent changes in plasma FFA independently of gender and percent changes in body mass index, waist/h ip ratio, plasma norepinephrine, epinephrine, glycosylated hemoglobin, and daily insulin therapy. Our study demonstrates that changes in plasma FFA le vels may have a parallel effect on cardiac sympathetic/ parasympathetic ner vous system balance in NIDDM patients.