Horm Metab Res 2022; 54(05): 308-315
DOI: 10.1055/a-1775-8251
Original Article: Endocrine Care

Cardiac Autonomic Neuropathy in Patients with Newly Diagnosed Carbohydrate Disturbances

Antoaneta Gateva
1   Department of Internal Medicine, Medical University, Sofia, Bulgaria
,
Zdravko Kamenov
1   Department of Internal Medicine, Medical University, Sofia, Bulgaria
› Author Affiliations
Funding Information This study received financial support from The Bulgarian National Science Fund (BNSF) (Research grant KП-06-H23/11/18.12.2018).

Abstract

Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus that can predispose patients to higher risk for cardiovascular death. The aim of the present study was to evaluate the presence of cardiac autonomic neuropathy and sudomotor dysfunction in patients with newly diagnosed carbohydrate disturbances (prediabetes or diabetes) and to assess their relationship to metabolic disturbances and cardiovascular risk. In the present study, we included 160 patients −78 with obesity without carbohydrate disturbances, 52 with prediabetes, and 30 with newly diagnosed diabetes. CAN was diagnosed using cardiovascular reflex tests and sudomotor function was evaluated by SUDOSCAN. Cardiovascular risk was calculated using SCORE and FRMINGHAM risk scores. The prevalence of cardiac autonomic neuropathy was significantly higher in patients with newly diagnosed diabetes. Independently of their glycemic status, the patients who had blood glucose on the 60th-minute of OGTT>8.5 mmol/l had significantly higher prevalence of cardiac autonomic neuropathy (30.2% vs 15.6%, р=0.044). Patients with high cardiovascular risk according to FRAMINGHAM and SCORE had worse heart rate variability scores. Autonomic neuropathy risk assessed by SUDOSCAN was a good predictor for the presence of CAN. In conclusion, CAN has a higher prevalence on patients with newly diagnosed diabetes compared to prediabetic and normoglycemic subjects, while the patients with blood glucose>8.5 mmol/l on the 60th-minute of OGTT have higher prevalence of CAN independently of their glycemic status. SUDOSCAN testing can be used to assess the risk of CAN and to select patients that should undergo further testing.



Publication History

Received: 23 September 2021

Accepted after revision: 07 February 2022

Article published online:
24 March 2022

© 2022. Thieme. All rights reserved.

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  • References

  • 1 Vinik AI, Maser RE, Mitchell BD. et al. Diabetic autonomic neuropathy. Diabetes Care 2013; 26: 1553-1579
  • 2 Ziegler D, Voss A, Rathmann W. 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: 1118-1128
  • 3 Vinik AI, Casellini C, Parson HK. et al. Cardiac autonomic neuropathy in diabetes: a predictor of cardiometabolic events. Front Neurosci 2018; 12: 591
  • 4 Pop-Busui R. Cardiac autonomic neuropathy in diabetes: a clinical perspective. Diabetes Care 2010; 33: 434-441
  • 5 Benichou T, Pereira B, Mermillod M. et al. Heart rate variability in type 2 diabetes mellitus: a systematic review and meta-analysis. PLoS One 2018; 13: e0195166
  • 6 Serhiyenko VA, Serhiyenko A. Cardiac autonomic neuropathy: risk factors, diagnosis and treatment. World J Diabetes 2018; 9: 1-24
  • 7 Schroeder EB, Chambless LE, Liao D. et al. Diabetes, glucose, insulin, and heart rate variability: the Atherosclerosis Risk in Communities (ARIC) study. Diabetes Care 2005; 28: 668-674
  • 8 Williams SM, Eleftheriadou A, Alam U. et al. Cardiac autonomic neuropathy in obesity, the metabolic syndrome and prediabetes: a narrative review. Diabetes Ther 2019; 10: 1995-2021
  • 9 Ziegler D, Rathmann W, Dickhaus T. et al. Prevalenceof polyneuropathy in pre-diabetes and diabetes is associatedwith abdominal obesity and macroangiopathy: theMONICA/KORA Augsburg Surveys S2 and S3. Diabetes Care 2008; 31: 464-469
  • 10 Beijers HJ, Ferreira I, Bravenboer B. 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
  • 11 Dimova R, Tankova T, Guergueltcheva V. et al. Risk factors for autonomic and somatic nerve dysfunction in different stages of glucose tolerance. J Diabetes Complicat 2017; 31: 537-543
  • 12 Tesfaye S, Boulton AJ, Dyck PJ. et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 2010; 33: 2285-2293
  • 13 Ge X, Pan SM, Zeng F. et al. A simple Chinese risk score model for screening cardiovascular autonomic neuropathy. PLoS One 2014; 9: e89623
  • 14 Matthews DR, Hosker JP, Rudenski AS. et al. Homeostasis model assessment: insulin resistance and b cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
  • 15 Arancibia C, Galgani J, Valderas JP. et al. Evaluation of serum insulin levels after an oral glucose load for the diagnosis of insulin resistance. Rev Med Chil 2014; 142: 1106-1112
  • 16 Ascaso JF, Pardo S, Real JT. et al. Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care 2003; 26: 3320-3325
  • 17 Ascaso JF, Romero P, Real JT. et al. Insulin resistance quantification by fasting insulid plasma values and HOMA index in non diabetic population. Med Clin (Barc) 2001; 117: 530-533
  • 18 Alberti K, Eckel R, Grundy S. et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640-1645
  • 19 Krieger SM, Reimann M, Haase R. et al. Sudomotor testing of diabetes polyneuropathy. Front Neurol 2018; 9: 803
  • 20 Ewing D, Martyn C, Young R. et al. The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care 1985; 8: 491-498
  • 21 Bellavere F, Bosello G, Fedele D. et al. Diagnosis and management of diabetic autonomic neuropathy. Br Med J (Clin Res Ed) 1983; 287: 61
  • 22 Spallone V, Ziegler D, Freeman R. et al. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev 2011; 27: 639-653
  • 23 Holle R, Happich M, Lowel H. et al. KORA – a research platform for population based health research. Gesundheitswesen 2005; 67: S19-S25
  • 24 Dimova R, Tankova T, Kirilov G. et al. Endothelial and autonomic dysfunction at early stages of glucose intolerance and in metabolic syndrome. Horm Metab Res 2020; 52: 39-48
  • 25 Putz Z, Tabák A, Tóth N. et al. Noninvasive evaluation of neural impairment in subjects with impaired glucose tolerance. Diabetes Care 2009; 32: 181-183
  • 26 Gerritsen J, Dekker JM, TenVoorde BJ. et al. Glucose tolerance and other determinants of cardiovascular autonomic function: the Hoorn Study. Diabetologia 2000; 43: 561-570
  • 27 Perciaccante A, Fiorentini A, Paris A. et al. Circadian rhythm of the autonomic nervous system in insulin resistant subjects with normoglycemia, impaired fasting glycemia, impaired glucose tolerance, type 2 diabetes mellitus. BMC Cardiovasc Disord 2006; 6: 19
  • 28 Wu JS, Wu JS, Yang YC. 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
  • 29 Diakakis GF, Parthenakis FI, Patrianakos AP. et al. Myocardial sympathetic innervation in patients with impaired glucose tolerance: relationship to subclinical inflammation. Cardiovasc Pathol 2008; 17: 172-177
  • 30 Elming MB, Hornum M, Feldt-Rasmussen B. et al. Cardiac autonomic neuropathy in patients with uraemia is not related to pre-diabetes. Dan Med Bull 2011; 58: A4244
  • 31 Wu J, Yang Y, Lu F. et al. Populationbased study on the prevalence and risk factors of orthostatic hypotension in subjects with pre-diabetes and diabetes. Diabetes Care 2009; 32: 69-74
  • 32 Stein PK, Barzilay JI, Domitrovich PP. et al. The relationship of heart rate and heart rate variability to non-diabetic fasting glucose levels and the metabolic syndrome: the Cardiovascular Health Study. Diabet Med 2007; 24: 855-863
  • 33 Russo B, Menduni M, Borboni P. et al. Autonomic nervous system in obesity and insulin-resistance - the complex interplay between leptin and central nervous system. Int J Mol Sci 2021; 22: 5187
  • 34 Eleftheriadou A, Williams S, Nevitt S. et al. The prevalence of cardiac autonomic neuropathy in prediabetes: a systematic review. Diabetologia 2021; 64: 288-303
  • 35 Laitinen T, Lindström J, Eriksson J. et al. Cardiovascular autonomic dysfunction is associated with central obesity in persons with impaired glucose tolerance. Diabet Med 2011; 28: 699-704
  • 36 Putz Z, Nemeth N, Istenes I. et al. Autonomic dysfunction and circadian blood pressure variations in people with impaired glucose tolerance. Diabet Med 2013; 30: 358-362
  • 37 Callaghan BC, Reynolds E, Banerjee M. et al. Central obesity is associated with neuropathy in the severely obese. Mayo Clin Proc 2020; 95: 1342-1353
  • 38 Ziegler D. Diabetic peripheral and autonomic neuropathy, In: Textbook of Diabetes. Holt R, Cockra C, Flyvbjerg A et al. (eds) New York: Wiley; 2017
  • 39 Ziegler D, Zentai C, Perz S. et al. Selective contribution of diabetes and other cardiovascular risk factors to cardiac autonomic dysfunction in the general population. Exp Clin Endocrinol Diabetes 2006; 114: 153-159
  • 40 Dinh W, Füth R, Lankisch M. et al. Cardiovascular autonomic neuropathy contributes to left ventricular diastolic dysfunction in subjects with type 2 diabetes and impaired glucose tolerance undergoing coronary angiography. Diabet Med 2011; 28: 311-318
  • 41 Balbinot LF, Canani LH, Robinson CC. et al. Plantar thermography is useful in the early diagnosis of diabetic neuropathy. Clinics (Sao Paulo) 2012; 67: 1419-1425
  • 42 Kamel J, Vogrin S, Knight-Sadler R. et al. Combining cutaneous silent periods with quantitative sudomotor axon reflex testing in the assessment of diabetic small fiber neuropathy. Clin Neurophysiol 2014; 126: 1047-1053
  • 43 Williams S, Eleftheriadou A, Alam U. et al. Cardiac autonomic neuropathy in obesity, the metabolic syndrome and prediabetes: a narrative review. Diabetes Ther 2019; 10: 1995-2021
  • 44 Watkins LL, Surwit RS, Grossman P. et al. Is there a glycemic threshold for impaired autonomic control?. Diabetes Care 2000; 23: 826-830
  • 45 Saito I, Maruyama K, Eguchi E. et al. Low heart rate variability and sympathetic dominance modifies the association between insulin resistance and metabolic syndrome – the Toon Health Study. Circ J 2017; 81: 1447-1453
  • 46 Greco C, Spallone V. Obstructive sleep apnoea syndrome and diabetes. Fortuitous association or interaction?. Curr Diabetes Rev 2015; 12: 129-155
  • 47 Thorp AA, Schlaich MP. Relevance of sympathetic nervous system activation in obesity and metabolic syndrome. J Diabetes Res 2015; 341583
  • 48 Svensson MK, Lindmark S, Wiklund U. et al. Alterations in heart rate variability during everyday life are linked to insulin resistance. A role of dominating sympathetic over parasympathetic nerve activity?. Cardiovasc Diabetol 2016; 15: 91
  • 49 Sumner CJ, Sheth S, Griffin JW. et al. The spectrum of neuropathy in diabetes and impaired glucose tolerance. Neurology 2003; 60: 108-111
  • 50 Smith AG, Russell J, Feldman EL. et al. Lifestyle intervention for prediabetic neuropathy. Diabetes Care 2006; 29: 1294-1299
  • 51 Low PA. Evaluation of sudomotor function. Clin Neurophysiol 2004; 115: 1506-1513
  • 52 Low LA, Sandroni P, Fealey RD. et al. Detection of small-fiber neuropathy by sudomotor testing. Muscle Nerve 2006; 34: 57-61
  • 53 Jaradeh SS, Prieto TE. Evaluation of the autonomic nervous system. Phys Med Rehabil Clin N Am 2003; 14: 287-305
  • 54 Mayaudon H, Miloche PO, Bauduceau B. A new simple method for assessing sudomotor function: relevance in type 2 diabetes. Diabetes Metab 2010; 36: 450-454
  • 55 Yuan T, Li J, Fu Y. et al. A cardiac risk score based on sudomotor function to evaluate cardiovascular autonomic neuropathy in asymptomatic Chinese patients with diabetes mellitus. PLoS One 2018; 13: e0204804
  • 56 Smith AG, Lessard M, Reyna S. et al. The diagnostic utility of Sudoscan for distal symmetric peripheral neuropathy. J Diabetes Complicat 2014; 28: 511-516
  • 57 Gatev T, Gateva A, Assyov Y. et al. The role of Sudoscan feet asymmetry in the diabetic foot. Prim Care Diabetes 2020; 14: 47-52
  • 58 Casellini C, Parson H, Richardson M. et al. Sudoscan, a noninvasive tool for detecting diabetic small fiber neuropathy and autonomic dysfunction. Diabetes Technol Ther 2013; 15: 948-953
  • 59 Carbajal-Ramírez A, Hernández-Domínguez J, Molina-Ayala M. et al. Early identification of peripheral neuropathy based on sudomotor dysfunction in Mexican patients with type 2 diabetes. BMC Neurol 2019; 19: 109
  • 60 Grandinetti A, Chow DC, Sletten DM. et al. Impaired glucose tolerance is associated with postganglionic sudomotor impairment. Clin Auton Res 2007; 17: 231-233
  • 61 Gabriel R, Calvet JH, Vilier A. et al. Prevalence of neuropathy in prediabetes and healthy volunteers by quantitative assessment of sudomotor function. presented at International Diabetes Federation 2017 Congress; P-0909
  • 62 Yang Z, Xu B, Lu J. et al. Autonomic test by EZSCAN in the screening for prediabetes and diabetes. PLoS One 2013; 8: e56480
  • 63 Müller G, Parfentyeva E, Olschewsky J. et al. Assessment of small fiber neuropathy to predict future risk of type 2 diabetes. Prim Care Diabetes 2013; 7: 269-273
  • 64 Zeng Q, Dong SY, Wang ML. et al. Association of EZSCAN values with arterial stiffness in individuals without diabetes or cardiovascular disease. PLoS One 2014; 9: e90854