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Published in: Cardiovascular Diabetology 1/2015

Open Access 01-12-2015 | Original investigation

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

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

Published in: Cardiovascular Diabetology | Issue 1/2015

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Abstract

Background

It 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.

Methods

This 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.

Results

In 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.

Conclusions

Hyperleptinemia may be involved in cardiac autonomic dysfunction in patients with type 2 diabetes and visceral obesity.
Literature
1.
go back to reference Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766–81. doi:10.1016/S0140-6736(14)60460-8.CrossRefPubMed Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766–81. doi:10.​1016/​S0140-6736(14)60460-8.CrossRefPubMed
2.
go back to reference Nakamura T, Tokunaga K, Shimomura I, Nishida M, Yoshida S, Kotani K, et al. Contribution of visceral fat accumulation to the development of coronary artery disease in non-obese men. Atherosclerosis. 1994;107(2):239–46.CrossRefPubMed Nakamura T, Tokunaga K, Shimomura I, Nishida M, Yoshida S, Kotani K, et al. Contribution of visceral fat accumulation to the development of coronary artery disease in non-obese men. Atherosclerosis. 1994;107(2):239–46.CrossRefPubMed
3.
go back to reference Okauchi Y, Nishizawa H, Funahashi T, Ogawa T, Noguchi M, Ryo M, et al. Reduction of visceral fat is associated with decrease in the number of metabolic risk factors in Japanese men. Diabetes Care. 2007;30(9):2392–4. doi:10.2337/dc07-0218.CrossRefPubMed Okauchi Y, Nishizawa H, Funahashi T, Ogawa T, Noguchi M, Ryo M, et al. Reduction of visceral fat is associated with decrease in the number of metabolic risk factors in Japanese men. Diabetes Care. 2007;30(9):2392–4. doi:10.​2337/​dc07-0218.CrossRefPubMed
5.
go back to reference Tsuji H, Larson MG, Venditti FJ Jr, Manders ES, Evans JC, Feldman CL, et al. Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation. 1996;94(11):2850–5.CrossRefPubMed Tsuji H, Larson MG, Venditti FJ Jr, Manders ES, Evans JC, Feldman CL, et al. Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation. 1996;94(11):2850–5.CrossRefPubMed
6.
go back to reference Liao D, Cai J, Rosamond WD, Barnes RW, Hutchinson RG, Whitsel EA, et al. Cardiac autonomic function and incident coronary heart disease: a population-based case-cohort study. The ARIC Study. Atherosclerosis Risk in Communities Study. Am J Epidemiol. 1997;145(8):696–706.CrossRefPubMed Liao D, Cai J, Rosamond WD, Barnes RW, Hutchinson RG, Whitsel EA, et al. Cardiac autonomic function and incident coronary heart disease: a population-based case-cohort study. The ARIC Study. Atherosclerosis Risk in Communities Study. Am J Epidemiol. 1997;145(8):696–706.CrossRefPubMed
7.
9.
go back to reference Schwartz MW, Prigeon RL, Kahn SE, Nicolson M, Moore J, Morawiecki A, et al. Evidence that plasma leptin and insulin levels are associated with body adiposity via different mechanisms. Diabetes Care. 1997;20(9):1476–81.CrossRefPubMed Schwartz MW, Prigeon RL, Kahn SE, Nicolson M, Moore J, Morawiecki A, et al. Evidence that plasma leptin and insulin levels are associated with body adiposity via different mechanisms. Diabetes Care. 1997;20(9):1476–81.CrossRefPubMed
11.
go back to reference Nishimura R, Sano H, Matsudaira T, Morimoto A, Miyashita Y, Shirasawa T, et al. Changes in body mass index, leptin and adiponectin in Japanese children during a three-year follow-up period: a population-based cohort study. Cardiovasc Diabetol. 2009;8:30. doi:10.1186/1475-2840-8-30.PubMedCentralCrossRefPubMed Nishimura R, Sano H, Matsudaira T, Morimoto A, Miyashita Y, Shirasawa T, et al. Changes in body mass index, leptin and adiponectin in Japanese children during a three-year follow-up period: a population-based cohort study. Cardiovasc Diabetol. 2009;8:30. doi:10.​1186/​1475-2840-8-30.PubMedCentralCrossRefPubMed
13.
go back to reference Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task force of the European society of cardiology and the North American society of pacing and electrophysiology. Eur Heart J. 1996;17(3):354–81.CrossRef Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task force of the European society of cardiology and the North American society of pacing and electrophysiology. Eur Heart J. 1996;17(3):354–81.CrossRef
14.
go back to reference Katz A, Liberty IF, Porath A, Ovsyshcher I, Prystowsky EN. A simple bedside test of 1-minute heart rate variability during deep breathing as a prognostic index after myocardial infarction. Am Heart J. 1999;138(1 Pt 1):32–8.CrossRefPubMed Katz A, Liberty IF, Porath A, Ovsyshcher I, Prystowsky EN. A simple bedside test of 1-minute heart rate variability during deep breathing as a prognostic index after myocardial infarction. Am Heart J. 1999;138(1 Pt 1):32–8.CrossRefPubMed
15.
go back to reference Valensi P, Sachs RN, Harfouche B, Lormeau B, Paries J, Cosson E, et al. Predictive value of cardiac autonomic neuropathy in diabetic patients with or without silent myocardial ischemia. Diabetes Care. 2001;24(2):339–43.CrossRefPubMed Valensi P, Sachs RN, Harfouche B, Lormeau B, Paries J, Cosson E, et al. Predictive value of cardiac autonomic neuropathy in diabetic patients with or without silent myocardial ischemia. Diabetes Care. 2001;24(2):339–43.CrossRefPubMed
16.
go back to reference Maser RE, Mitchell BD, Vinik AI, Freeman R. The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis. Diabetes Care. 2003;26(6):1895–901.CrossRefPubMed Maser RE, Mitchell BD, Vinik AI, Freeman R. The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis. Diabetes Care. 2003;26(6):1895–901.CrossRefPubMed
18.
go back to reference Veglio M, Borra M, Stevens LK, Fuller JH, Perin PC. The relation between QTc interval prolongation and diabetic complications. The EURODIAB IDDM Complication Study Group. Diabetologia. 1999;42(1):68–75.CrossRefPubMed Veglio M, Borra M, Stevens LK, Fuller JH, Perin PC. The relation between QTc interval prolongation and diabetic complications. The EURODIAB IDDM Complication Study Group. Diabetologia. 1999;42(1):68–75.CrossRefPubMed
19.
go back to reference Karjalainen JJ, Kiviniemi AM, Hautala AJ, Piira OP, Lepojarvi ES, Peltola MA, et al. Determinants and prognostic value of cardiovascular autonomic function in coronary artery disease patients with and without type 2 diabetes. Diabetes Care. 2014;37(1):286–94. doi:10.2337/dc13-1072.CrossRefPubMed Karjalainen JJ, Kiviniemi AM, Hautala AJ, Piira OP, Lepojarvi ES, Peltola MA, et al. Determinants and prognostic value of cardiovascular autonomic function in coronary artery disease patients with and without type 2 diabetes. Diabetes Care. 2014;37(1):286–94. doi:10.​2337/​dc13-1072.CrossRefPubMed
22.
24.
go back to reference Kadoya M, Koyama H, Kanzaki A, Kurajoh M, Hatayama M, Shiraishi J, et al. Plasma brain-derived neurotrophic factor and reverse dipping pattern of nocturnal blood pressure in patients with cardiovascular risk factors. PLoS One. 2014;9(8):e105977.PubMedCentralCrossRefPubMed Kadoya M, Koyama H, Kanzaki A, Kurajoh M, Hatayama M, Shiraishi J, et al. Plasma brain-derived neurotrophic factor and reverse dipping pattern of nocturnal blood pressure in patients with cardiovascular risk factors. PLoS One. 2014;9(8):e105977.PubMedCentralCrossRefPubMed
26.
go back to reference Sugisawa N, Tokunaga M, Tanizawa Y, Bando E, Kawamura T, Terashima M. Intra-abdominal infectious complications following gastrectomy in patients with excessive visceral fat. Gastric Cancer. 2012;15(2):206–12. doi:10.1007/s10120-011-0099-0.CrossRefPubMed Sugisawa N, Tokunaga M, Tanizawa Y, Bando E, Kawamura T, Terashima M. Intra-abdominal infectious complications following gastrectomy in patients with excessive visceral fat. Gastric Cancer. 2012;15(2):206–12. doi:10.​1007/​s10120-011-0099-0.CrossRefPubMed
28.
go back to reference Vinagre I, Sanchez-Quesada JL, Sanchez-Hernandez J, Santos D, Ordonez-Llanos J, De Leiva A, et al. Inflammatory biomarkers in type 2 diabetic patients: effect of glycemic control and impact of LDL subfraction phenotype. Cardiovasc Diabetol. 2014;13:34. doi:10.1186/1475-2840-13-34.PubMedCentralCrossRefPubMed Vinagre I, Sanchez-Quesada JL, Sanchez-Hernandez J, Santos D, Ordonez-Llanos J, De Leiva A, et al. Inflammatory biomarkers in type 2 diabetic patients: effect of glycemic control and impact of LDL subfraction phenotype. Cardiovasc Diabetol. 2014;13:34. doi:10.​1186/​1475-2840-13-34.PubMedCentralCrossRefPubMed
29.
go back to reference Soliman AT, Omar M, Assem HM, Nasr IS, Rizk MM, El Matary W, et al. Serum leptin concentrations in children with type 1 diabetes mellitus: relationship to body mass index, insulin dose, and glycemic control. Metabolism. 2002;51(3):292–6.CrossRefPubMed Soliman AT, Omar M, Assem HM, Nasr IS, Rizk MM, El Matary W, et al. Serum leptin concentrations in children with type 1 diabetes mellitus: relationship to body mass index, insulin dose, and glycemic control. Metabolism. 2002;51(3):292–6.CrossRefPubMed
31.
go back to reference Garcia-Serrano S, Gutierrez-Repiso C, Gonzalo M, Garcia-Arnes J, Valdes S, Soriguer F, et al. C-peptide modifies leptin and visfatin secretion in human adipose tissue. Obesity (Silver Spring). 2015;23(8):1607–15. doi:10.1002/oby.21137.CrossRefPubMed Garcia-Serrano S, Gutierrez-Repiso C, Gonzalo M, Garcia-Arnes J, Valdes S, Soriguer F, et al. C-peptide modifies leptin and visfatin secretion in human adipose tissue. Obesity (Silver Spring). 2015;23(8):1607–15. doi:10.​1002/​oby.​21137.CrossRefPubMed
32.
go back to reference Paolisso G, Manzella D, Montano N, Gambardella A, Varricchio M. Plasma leptin concentrations and cardiac autonomic nervous system in healthy subjects with different body weights. J Clin Endocrinol Metab. 2000;85(5):1810–4. doi:10.1210/jcem.85.5.6511.CrossRefPubMed Paolisso G, Manzella D, Montano N, Gambardella A, Varricchio M. Plasma leptin concentrations and cardiac autonomic nervous system in healthy subjects with different body weights. J Clin Endocrinol Metab. 2000;85(5):1810–4. doi:10.​1210/​jcem.​85.​5.​6511.CrossRefPubMed
33.
35.
go back to reference Piestrzeniewicz K, Luczak K, Lelonek M, Wranicz JK, Goch JH. Obesity and heart rate variability in men with myocardial infarction. Cardiol J. 2008;15(1):43–9.PubMed Piestrzeniewicz K, Luczak K, Lelonek M, Wranicz JK, Goch JH. Obesity and heart rate variability in men with myocardial infarction. Cardiol J. 2008;15(1):43–9.PubMed
37.
go back to reference Cowley MA, Smart JL, Rubinstein M, Cerdan MG, Diano S, Horvath TL, et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature. 2001;411(6836):480–4. doi:10.1038/35078085.CrossRefPubMed Cowley MA, Smart JL, Rubinstein M, Cerdan MG, Diano S, Horvath TL, et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature. 2001;411(6836):480–4. doi:10.​1038/​35078085.CrossRefPubMed
39.
go back to reference Lee DK, Jeong JH, Chun SK, Chua S Jr, Jo YH. Interplay between glucose and leptin signalling determines the strength of GABAergic synapses at POMC neurons. Nat Commun. 2015;6:6618. doi:10.1038/ncomms7618.CrossRefPubMed Lee DK, Jeong JH, Chun SK, Chua S Jr, Jo YH. Interplay between glucose and leptin signalling determines the strength of GABAergic synapses at POMC neurons. Nat Commun. 2015;6:6618. doi:10.​1038/​ncomms7618.CrossRefPubMed
41.
42.
go back to reference Ziegler D, Voss A, Rathmann W, Strom A, Perz S, Roden M, et al. Increased prevalence of cardiac autonomic dysfunction at different degrees of glucose intolerance in the general population: the KORA S4 survey. Diabetologia. 2015;58(5):1118–28. doi:10.1007/s00125-015-3534-7.CrossRefPubMed Ziegler D, Voss A, Rathmann W, Strom A, Perz S, Roden M, et al. Increased prevalence of cardiac autonomic dysfunction at different degrees of glucose intolerance in the general population: the KORA S4 survey. Diabetologia. 2015;58(5):1118–28. doi:10.​1007/​s00125-015-3534-7.CrossRefPubMed
43.
go back to reference Huikuri HV, Ylitalo A, Pikkujamsa SM, Ikaheimo MJ, Airaksinen KE, Rantala AO, et al. Heart rate variability in systemic hypertension. Am J Cardiol. 1996;77(12):1073–7.CrossRefPubMed Huikuri HV, Ylitalo A, Pikkujamsa SM, Ikaheimo MJ, Airaksinen KE, Rantala AO, et al. Heart rate variability in systemic hypertension. Am J Cardiol. 1996;77(12):1073–7.CrossRefPubMed
44.
go back to reference Mylonopoulou M, Tentolouris N, Antonopoulos S, Mikros S, Katsaros K, Melidonis A, et al. Heart rate variability in advanced chronic kidney disease with or without diabetes: midterm effects of the initiation of chronic haemodialysis therapy. Nephrol Dial Transplant. 2010;25(11):3749–54. doi:10.1093/ndt/gfq226.CrossRefPubMed Mylonopoulou M, Tentolouris N, Antonopoulos S, Mikros S, Katsaros K, Melidonis A, et al. Heart rate variability in advanced chronic kidney disease with or without diabetes: midterm effects of the initiation of chronic haemodialysis therapy. Nephrol Dial Transplant. 2010;25(11):3749–54. doi:10.​1093/​ndt/​gfq226.CrossRefPubMed
46.
go back to reference Ryan C, Hollenberg M, Harvey DB, Gwynn R. Impaired parasympathetic responses in patients after myocardial infarction. Am J Cardiol. 1976;37(7):1013–8.CrossRefPubMed Ryan C, Hollenberg M, Harvey DB, Gwynn R. Impaired parasympathetic responses in patients after myocardial infarction. Am J Cardiol. 1976;37(7):1013–8.CrossRefPubMed
Metadata
Title
Plasma leptin level is associated with cardiac autonomic dysfunction in patients with type 2 diabetes: HSCAA study
Authors
Masafumi Kurajoh
Hidenori Koyama
Manabu Kadoya
Mariko Naka
Akio Miyoshi
Akinori Kanzaki
Miki Kakutani-Hatayama
Hirokazu Okazaki
Takuhito Shoji
Yuji Moriwaki
Tetsuya Yamamoto
Masanori Emoto
Masaaki Inaba
Mitsuyoshi Namba
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2015
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-015-0280-6

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