Role of Free Fatty Acids on Cardiac Autonomic Nervous System in Noninsulin-Dependent Diabetic Patients: Effects of Metabolic Control
Daniela Manzella,
Michelangela Barbieri,
Maria Rosaria Rizzo,
Emilia Ragno,
Nicola Passariello,
Antonio Gambardella,
Raffaele Marfella,
Dario Giugliano and
Giuseppe Paolisso
Department of Geriatric Medicine and Metabolic Diseases, II
University of Naples, Naples, Italy 1–80138
Address all correspondence and requests for reprints to: Giuseppe Paolisso, M.D., Department of Geriatric Medicine and Metabolic Diseases, IV Internal Medicine, Piazza Miraglia 2, I-80138 Napoli, Italy. E-mail: gpaoliss{at}tin.it
Abstract
Decreased heart rate variability (HRV) is a risk factor for
cardiovascularmortality. Elevated plasma free fatty acid (FFA) levels
decreaseHRV in healthy subjects. Thus, we investigated the effect of
changesin plasma FFA levels on HRV, in non–insulin-dependentdiabetes
(NIDDM) patients. Thirty NIDDM patients free from diabeticneuropathy
volunteered for a study made by two phases. In studyA, changes in HRV
along a 10% lipid emulsion infusion + heparin(n = 15) or saline
infusion (control study; n = 15) were investigated.In study B,
all patients (n = 30) underwent further determinationof HRV after
3 months of improved metabolic control achievedby intensified insulin
treatment. In study A, lipid emulsioninfusion increased plasma FFA
(P < 0.001) and catecholamineconcentrations
(P < 0.005), mean arterial blood pressure
(P< 0.005), low frequency/high frequency (LF/HF)
ratio (P <0.001). Delta plasma FFA levels
correlated with delta LF/HFratio (r = 0.57; P
< 0.02). Along with saline infusion, metabolicand cardiovascular
parameters remained unchanged throughoutthe test. In study B, improved
metabolic control lowered fastingplasma glucose (P
< 0.005), FFA (P < 0.001), norepinephrine
(P< 0.02), epinephrine (P <
0.04), and glycosylated hemoglobinlevels (P <
0.001), mean arterial blood pressure(P < 0.05),
andLF/HF ratio (P < 0.001). Again percent decline
in plasmaFFA correlated with the percent change in LF/HF ratio (r
= 0.72;P < 0.001). In a multivariate analysis,
percent changes inLF/HF ratio were associated with percent changes in
plasma FFAindependently of gender and percent changes in body mass
index,waist/hip ratio, plasma norepinephrine, epinephrine,
glycosylatedhemoglobin, and daily insulin therapy. Our study
demonstratesthat changes in plasma FFA levels may have a parallel
effecton cardiac sympathetic/parasympathetic nervous system balancein
NIDDM patients.
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