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Cardiac Autonomic Nervous Dysfunction in Diabetic Patients With a Mitochondrial DNA Mutation

Assessment by heart rate variability

¹ First Department of Internal Medicine, National Defense Medical College, Saitama, Japan
² Division of Internal Medicine, Tokyo Saiseikai Central Hospital, Tokyo, Japan
³ Division of Laboratory Medicine, Tokyo Saiseikai Central Hospital, Tokyo, Japan

OBJECTIVE—To elucidate the degree and characteristics of cardiac autonomic nervous dysfunction in diabetic patients associated with a mitochondrial DNA mutation at base pair 3243.

RESEARCH DESIGN AND METHODS—We investigated heart rate variability using 24-h Holter monitoring in 10 diabetic patients with the mutation compared with 55 ordinary diabetic patients and 45 nondiabetic control subjects.

RESULTS—Age and sex were similar in the three groups. Between patients with the mutation and ordinary diabetic patients, the duration of diabetes and blood glycemic levels were not different. In the time domain analysis of heart rate variability, patients with the mutation and ordinary diabetic patients had significantly smaller SDNN index and pNN50 than control subjects. Compared with ordinary diabetic patients, patients with the mutation had smaller SDNN index (P < 0.02), but rMSSD and pNN50 were not different. In the frequency domain analysis, total, low frequency (LF), and high frequency (HF) spectra were significantly smaller in patients with the mutation and ordinary diabetic patients than in control subjects. Compared with ordinary diabetic patients, patients with the mutation had smaller total and LF spectra (P < 0.02). However, HF spectra were not significantly different. Notably, the LF/HF spectra ratio was lower in patients with the mutation than in ordinary diabetic patients and control subjects (P < 0.05), but this ratio was similar in ordinary diabetic patients and control subjects.

CONCLUSIONS—Our results suggest that diabetic patients with the mitochondrial DNA mutation have more severely impaired cardiac autonomic nervous function with sympathovagal imbalance, as compared with ordinary diabetic patients.

Abbreviations: bp, base pair • DM-Mt3243 • diabetes associated with the 3243-bp mutation • HF, high frequency • HRV, heart rate variability • LF, low frequency • LVH, left ventricular hypertrophy • MELAS, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes • MIBG, metaiodobenzylguanidine • PN, peripheral neuropathy • pNN50, the proportion of adjacent R-R intervals varying by >50 ms • SDANN, the SD of 5-min mean R-R intervals • SDNN, SD of all R-R intervals • RMSSD, the root-mean-square difference of successive R-R intervals

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