Skip to content
naulon

No retraction, correction or concern found when last checked on Oct 30, 2026.

Autonomic imbalance: prophet of doom or scope for hope?

A. I. Vinik, R. E. Maser, D. Ziegler

Diabetic Medicine · 2011 · Review

doi:10.1111/j.1464-5491.2010.03184.x

Abstract

Diabet. Med. 28, 643–651 (2011) It has long been recognized that cardiac autonomic neuropathy increases morbidity and mortality in diabetes and may have greater predictive power than traditional risk factors for cardiovascular events. Significant morbidity and mortality can now be attributable to autonomic imbalance between the sympathetic and parasympathetic nervous system regulation of cardiovascular function. New and emerging syndromes include orthostatic tachycardia, orthostatic bradycardia and an inability to use heart rate as a guide to exercise intensity because of the resting tachycardia. Recent studies have shown that autonomic imbalance may be a predictor of risk of sudden death with intensification of glycaemic control. This review examines an association of autonomic dysregulation and the role of inflammatory cytokines and adipocytokines that promote cardiovascular risk. In addition, conditions of autonomic imbalance associated with cardiovascular risk are discussed. Potential treatment for restoration of autonomic balance is outlined.

Shown for reading. Its publisher allows quoting it, not republishing it.

References 80

  1. 1.

    Vinik AI, Ziegler D. Diabetic cardiovascular autonomic neuropathy. Circulation. 2007;115:387-397.

    Not in our library10.1161/circulationaha.106.634949

  2. 2.

    Ondicova K, Mravec B. Multilevel interactions between the sympathetic and parasympathetic nervous systems: a mini-review. Endocr Regul. 2010;44:69-75.

    Not in our library10.4149/endo_2010_02_69

  3. 3.

    Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care. 2003;26:1553-1579.

    Not in our library10.2337/diacare.26.5.1553

  4. 4.

    Diabetes Control, Complications Trial. The effect of intensive diabetes therapy on measures of autonomic nervous system function in the Diabetes Control and Complications Trial (DCCT). Diabetologia. 1998;41:416-423.

    Not in our library10.1007/s001250050924

  5. 5.

    Kennedy WR, Navarro X, Sutherland DE. Neuropathy profile of diabetic patients in a pancreas transplantation program. Neurology. 1995;45:773-780.

    Not in our library10.1212/wnl.45.4.773

  6. 6.

    Ziegler D, Gries FA, Muhlen H, Rathmann W, Spuler M, Lessmann F. Prevalence and clinical correlates of cardiovascular autonomic and peripheral diabetic neuropathy in patients attending diabetes centers. The Diacan Multicenter Study Group. Diabetes Metab. 1993;19:143-151.

    Not in our library

  7. 7.

    Wu JS, Yang YC, Lin TS, Huang YH, Chen JJ, Lu FH, et al. Epidemiological evidence of altered cardiac autonomic function in subjects with impaired glucose tolerance but not isolated impaired fasting glucose. J Clin Endocrinol Metab. 2007;92:3885-3889.

    Not in our library10.1210/jc.2006-2175

  8. 8.

    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;26:1895-1901.

    Not in our library10.2337/diacare.26.6.1895

  9. 9.

    Beijers HJ, Ferreira I, Bravenboer B, Dekker JM, Nijpels G, Heine RJ, et al. Microalbuminuria and cardiovascular autonomic dysfunction are independently associated with cardiovascular mortality: evidence for distinct pathways: the Hoorn Study. Diabetes Care. 2009;32:1698-1703.

    Not in our library10.2337/dc08-1544

  10. 10.

    Ziegler D, Zentai CP, Perz S, Rathmann W, Haastert B, Doring A, et al. Prediction of mortality using measures of cardiac autonomic dysfunction in the diabetic and non-diabetic population: the MONICA/KORA Augsburg Cohort Study. Diabetes Care. 2008;31:556-561.

    Not in our library10.2337/dc07-1615

  11. 11.

    Orchard TJ, Lloyd CE, Maser RE, Kuller LH. Why does diabetic autonomic neuropathy predict IDDM mortality? An analysis from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Res Clin Pract. 1996;34:S165-S171.

    Not in our library10.1016/s0168-8227(96)90025-x

  12. 12.

    Pop-Busui R, Low PA, Waberski BH, Martin CL, Albers JW, Feldman EL, et al. Effects of prior intensive insulin therapy on cardiac autonomic nervous system function in type 1 diabetes mellitus: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study (DCCT/EDIC). Circulation. 2009;119:2886-2893.

    Not in our library10.1161/circulationaha.108.837369

  13. 13.

    White NH, Cleary PA, Dahms W, Goldstein D, Malone J, Tamborlane WV. Beneficial effects of intensive therapy of diabetes during adolescence: outcomes after the conclusion of the Diabetes Control and Complications Trial (DCCT). J Pediatr. 2001;139:804-812.

    Not in our library10.1067/mpd.2001.118887

  14. 14.

    Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348:383-393.

    Not in our library10.1056/nejmoa021778

  15. 15.

    Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358:580-591.

    Not in our library10.1056/nejmoa0706245

  16. 16.

    Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129-139.

    Not in our library10.1056/nejmoa0808431

  17. 17.

    LeRoith D, Fonseca V, Vinik A. Metabolic memory in diabetes—focus on insulin. Diabetes Metab Res Rev. 2005;21:85-90.

    Not in our library10.1002/dmrr.530

  18. 18.

    Casellini CM, Barlow PM, Rice AL, Casey M, Simmons K, Pittenger G, et al. A 6-month, randomized, double-masked, placebo-controlled study evaluating the effects of the protein kinase C-β inhibitor ruboxistaurin on skin microvascular blood flow and other measures of diabetic peripheral neuropathy. Diabetes Care. 2007;30:896-902.

    Not in our library10.2337/dc06-1699

  19. 19.

    Ceriello A, Esposito K, Ihnat M, Thorpe J, Giugliano D. Long-term glycemic control influences the long-lasting effect of hyperglycemia on endothelial function in type 1 diabetes. J Clin Endocrinol Metab. 2009;94:2751-2756.

    Not in our library10.1210/jc.2009-0762

  20. 20.

    Cumbie BC, Hermayer KL. Current concepts in targeted therapies for the pathophysiology of diabetic microvascular complications. Vasc Health Risk Manag. 2007;3:823-832.

    Not in our library

  21. 21.

    Witte DR, Tesfaye S, Chaturvedi N, Eaton SE, Kempler P, Fuller JH. Risk factors for cardiac autonomic neuropathy in type 1 diabetes mellitus. Diabetologia. 2005;48:164-171.

    Not in our library10.1007/s00125-004-1617-y

  22. 22.

    Stella P, Ellis D, Maser RE, Orchard TJ. Cardiovascular autonomic neuropathy (expiration and inspiration ratio) in type 1 diabetes. Incidence and predictors. J Diabetes Complications. 2000;14:1-6.

    Not in our library10.1016/s1056-8727(00)00054-4

  23. 23.

    Kles KA, Vinik AI. Pathophysiology and treatment of diabetic peripheral neuropathy: the case for diabetic neurovascular function as an essential component. Curr Diabetes Rev. 2006;2:131-145.

    Not in our library10.2174/157339906776818569

  24. 24.

    Lampert R, Bremner JD, Su S, Miller A, Lee F, Cheema F, et al. Decreased heart rate variability is associated with higher levels of inflammation in middle-aged men. Am Heart J. 2008;156:759-757.

    Not in our library10.1016/j.ahj.2008.07.009

  25. 25.

    Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000;405:458-462.

    Not in our library10.1038/35013070

  26. 26.

    Mohamed-Ali V, Flower L, Sethi J, Hotamisligil G, Gray R, Humphries SE, et al. β-Adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies. J Clin Endocrinol Metab. 2001;86:5864-5869.

    Not in our library10.1210/jcem.86.12.8104

  27. 27.

    Soszynski D, Kozak W, Conn CA, Rudolph K, Kluger MJ. β-Adrenoceptor antagonists suppress elevation in body temperature and increase in plasma IL-6 in rats exposed to open field. Neuroendocrinology. 1996;63:459-467.

    Not in our library10.1159/000127072

  28. 28.

    Herder C, Lankisch M, Ziegler D, Rathmann W, Koenig W, Illig T, et al. Subclinical inflammation and diabetic polyneuropathy: MONICA/KORA Survey F3 (Augsburg, Germany). Diabetes Care. 2009;32:680-682.

    Not in our library10.2337/dc08-2011

  29. 29.

    Carlyle M, Jones OB, Kuo JJ, Hall JE. Chronic cardiovascular and renal actions of leptin: role of adrenergic activity. Hypertension. 2002;39:496-501.

    Not in our library10.1161/hy0202.104398

  30. 30.

    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;85:1810-1814.

    Not in our library10.1210/jcem.85.5.6511

  31. 31.

    Murialdo G, Casu M, Falchero M, Brugnolo A, Patrone V, Cerro PF, et al. Alterations in the autonomic control of heart rate variability in patients with anorexia or bulimia nervosa: correlations between sympathovagal activity, clinical features, and leptin levels. J Endocrinol Invest. 2007;30:356-362.

    Not in our library10.1007/bf03346310

  32. 32.

    Rosenbaum M, Goldsmith R, Bloomfield D, Magnano A, Weimer L, Heymsfield S, et al. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Invest. 2005;115:3579-3586.

    Not in our library10.1172/jci25977

  33. 33.

    da Costa Goncalves AC, Tank J, Diedrich A, Hilzendeger A, Plehm R, Bader M, et al. Diabetic hypertensive leptin receptor-deficient db/db mice develop cardioregulatory autonomic dysfunction. Hypertension. 2009;53:387-392.

    Not in our library10.1161/hypertensionaha.108.124776

  34. 34.

    Imai J, Katagiri H, Yamada T, Ishigaki Y, Ogihara T, Uno K, et al. Cold exposure suppresses serum adiponectin levels through sympathetic nerve activation in mice. Obesity (Silver Spring). 2006;14:1132-1141.

    Not in our library10.1038/oby.2006.130

  35. 35.

    Wakabayashi S, Aso Y. Adiponectin concentrations in sera from patients with type 2 diabetes are negatively associated with sympathovagal balance as evaluated by power spectral analysis of heart rate variation. Diabetes Care. 2004;27:2392-2397.

    Not in our library10.2337/diacare.27.10.2392

  36. 36.

    Hoyda TD, Samson WK, Ferguson AV. Adiponectin depolarizes parvocellular paraventricular nucleus neurons controlling neuroendocrine and autonomic function. Endocrinology. 2009;150:832-840.

    Not in our library10.1210/en.2008-1179

  37. 37.

    Hoyda TD, Smith PM, Ferguson AV. Adiponectin acts in the nucleus of the solitary tract to decrease blood pressure by modulating the excitability of neuropeptide Y neurons. Brain Res. 2009;1256:76-84.

    Not in our library10.1016/j.brainres.2008.12.012

  38. 38.

    Tanida M, Shen J, Horii Y, Matsuda M, Kihara S, Funahashi T, et al. Effects of adiponectin on the renal sympathetic nerve activity and blood pressure in rats. Exp Biol Med (Maywood). 2007;232:390-397.

    Not in our library

  39. 39.

    Kreier F, Fliers E, Voshol PJ, Van Eden CG, Havekes LM, Kalsbeek A, et al. Selective parasympathetic innervation of subcutaneous and intra-abdominal fat—functional implications. J Clin Invest. 2002;110:1243-1250.

    Not in our library10.1172/jci15736

  40. 40.

    Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007;87:315-424.

    Not in our library10.1152/physrev.00029.2006

All 80 references

Cited by papers we hold 3

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.