Plasma leptin level is associated with cardiac autonomic dysfunction in patients with type 2 diabetes: HSCAA study.

Masafumi Kurajoh,Manabu Kadoya,Mariko Naka,Hidenori Koyama,Mitsuyoshi Namba,Tetsuya Yamamoto,Masanori Emoto,Takuhito Shoji,Miki Kakutani-Hatayama,Akinori Kanzaki,Masaaki Inaba,Hirokazu Okazaki,Yuji Moriwaki,Akio Miyoshi

doi:10.1186/s12933-015-0280-6

Masafumi Kurajoh, Manabu Kadoya + Show 12 more

Open Access

https://doi.org/10.1186/s12933-015-0280-6

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Abstract

BackgroundIt has been shown that visceral fat accumulation is associated with autonomic dysfunction, though the precise mechanism remains unclear. A recent basic study found that leptin can directly modulate autonomic function through the dorsomedial hypothalamus in relation to obesity. Here, we investigated the mutual relationships among plasma leptin, visceral fat accumulation, and cardiac autonomic dysfunction in patients with type 2 diabetes.MethodsThis cross-sectional study included 100 diabetic patients, and 100 age- and gender-matched non-diabetic patients with cardiovascular risk factors. Plasma leptin and soluble leptin receptor levels, visceral fat area (VFA), and heart rate variability (HRV) were determined in addition to classical cardiovascular risk factors.ResultsIn the type 2 diabetic patients, VFA was significantly (p < 0.05) and inversely associated with HRV parameters (SDNN: r = −0.243; SDANN5: r = −0.238), while the plasma level of leptin, but not soluble leptin receptor, was also significantly (p < 0.05) and inversely associated with HRV parameters (SDNN: r = −0.243; SDANN5: r = −0.231). Multiple regression analysis showed that plasma leptin was significantly associated with SDNN and SDANN5 independent of other factors, including age, gender, presence of hypertension and dyslipidemia, duration of diabetes, HbA1c, and eGFR. Furthermore, the relationship of leptin with SDNN and SDANN5 (β = −0.279 and −0.254, respectively) remained significant (p < 0.05) after adjustment for VFA. In patients without diabetes, no significant associations were observed between leptin and any of the HRV parameters.ConclusionsHyperleptinemia may be involved in cardiac autonomic dysfunction in patients with type 2 diabetes and visceral obesity.

Highlights

It has been shown that visceral fat accumulation is associated with autonomic dysfunction, though the precise mechanism remains unclear
We examined the mutual relationships among plasma leptin, heart rate variability (HRV), and visceral fat volume in 100 patients with diabetes, as well as 100 age- and gender-matched non-diabetic patients with cardiovascular risk factors
Study design and participants This cross-sectional study included 100 patients with type 2 diabetes, and 100 age- and gender-matched patients without diabetes who participated in the Hyogo Sleep Cardio-Autonomic Atherosclerosis (HSCAA) Study, which was designed to examine the impacts of sleep, cardiac autonomic dysfunction, and subclinical atherosclerosis on cardiovascular events

Summary

Introduction

It has been shown that visceral fat accumulation is associated with autonomic dysfunction, though the precise mechanism remains unclear. A recent study clearly showed that hyperleptinemia, a result of obesity, directly modulated blood pressure and heart rate by acting on the dorsomedial hypothalamus expressing Ob-R in obese mice, probably via the sympathetic nervous system [12]. These basic findings led us to examine whether plasma leptin contributes to the pathophysiology of autonomic dysfunction in obesity in humans. We examined the mutual relationships among plasma leptin, HRV, and visceral fat volume in 100 patients with diabetes, as well as 100 age- and gender-matched non-diabetic patients with cardiovascular risk factors

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