J Korean Diabetes Assoc.  2006 May;30(3):226-235. 10.4093/jkda.2006.30.3.226.

Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus

• Ko SH
• Kwon HS
• Lee JM
• Kim SR
• Cho JH
• Yoo KD
• Park YM
• Lee WC
• Song KH
• Yoon KH
• Cha BY
• Son HY
• Ahn YB

• KMID: 2177618
• DOI: http://doi.org/10.4093/jkda.2006.30.3.226

Abstract

BACKGROUND: Diabetic autonomic neuropathy has a significant negative impact on survival and quality of life in type 2 diabetic patients. Especially cardiovascular autonomic neuropathy (CAN) is clinically important, because of its correlation to cardiovascular death. Therefore, we investigated the prevalence of CAN in Korean type 2 diabetic patients.
METHODS
1798 type 2 diabetic patients, 727 males and 1071 females, visited Diabetes Clinic at St. Vincent Hospital, Korea, were included from January 2001 to December 2005. Clinical evaluation, laboratory test and assessment of diabetic complication were completed. Standard test for CAN were performed: 1) heart rate variability (HRV) during deep breathing (E/I ratio) 2) Valsalva maneuver 3) 30:15 ratio 4) blood pressure response to standing. CAN score was determined according to the results of the test as following: 0 = normal, 1 = abnormal.
RESULTS
Mean age and diabetic duration of patients were 56.7 +/- 10.9, and 9.4 +/- 7.5 years. Normal and abnormal CAN were detected in 815 (45.3%) and 983 (54.7%) of the patients, respectively. Abnormal E/I, valsalva, and 30:15 ratio were found in 333 (18.5%), 717 (39.9%), and 546 (30.4%) patients, respectively. Age, diabetic duration, postprandial hyperglycemia, HbA1c, C-reactive protein, and microalbumuria levels were significantly different between normal and abnormal CAN groups. 49 (6.0%) patients of normal and 100 (10.2%) patients of abnormal CAN group showed previous attack of stroke (P = 0.004). In addition, diabetic foot was more frequent in patients with CAN (normal vs. abnormal, 14 (1.7%) vs. 73 (7.4%), P < 0.05).
CONCLUSION
CAN is frequently found in Korean type 2 diabetic patients. It was associated with diabetic duration, uncontrolled diabetes, increased albumin excretion rate, presence of retinopathy, postprandial hyperglycemia.

Keyword

Autonomic function test; Cardiovascular autonomic neuropathy (CAN); Diabetic complication; Type 2 diabetes mellitus

MeSH Terms

Blood Pressure
C-Reactive Protein
Diabetes Complications
Diabetes Mellitus, Type 2*
Diabetic Foot
Diabetic Neuropathies
Female
Heart Rate
Humans
Hyperglycemia
Korea
Male
Prevalence
Quality of Life
Respiration
Stroke
Valsalva Maneuver
C-Reactive Protein

Figure

• 

  Fig. 1 The prevalence of diabetic complication in type 2 diabetic patients according to total score of cardiovascular autonomic function test. In the patients with proliferative diabetic retinopathy (A) and overt proteinuria (B), total score of autonomic function test was high.

Reference

1. Choi KM, Lee J, Kim DR, Kim SK, Shin DH, Kim NH, Park IB, Choi DS, Baik SH. Comparison of ADA and WHO criteria for the diagnosis of diabetes in elderly Koreans. Diabet Med. 2002. 19:853–857.

2. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and without prior myocardial infarction. N Engl J Med. 1998. 339:229–234.

3. Wheeler SG, Ahroni JH, Boyko EJ. Prospective study of autonomic neuropathy as a predictor of mortality in patients with diabetes. Diabetes Res Clin Pract. 2002. 58(2):131–138.

4. Turner RC. The U.K. Prospective Diabetes Study. A review. Diabetes Care. 1998. 21:Suppl 3. C35–C38.

5. Turner RC, Holman RR. Lessons from UK prospective diabetes study. Diabetes Res Clin Pract. 1995. 28:Suppl. S151–S157.

6. Coppini DV, Bowtell PA, Weng C, Young PJ, Sonksen PH. Showing neuropathy is related to increased mortality in diabetic patients - a survival analysis using an accelerated failure time model. J Clin Epidemiol. 2000. 53(5):519–523.

7. Gerritsen J, Dekker JM, TenVoorde BJ, Kostense PJ, Heine RJ, Bouter LM, Heethaar RM, Stehouwer CD. Impaired autonomic function is associated with increased mortality, especially in subjects with diabetes, hypertension, or a history of cardiovascular disease. Diabetes Care. 2001. 24:1793–1798.

8. The Diabetes Control and Complications Trial Research Group. The effect of intensive diabetes therapy on the development and progression of neuropathy. The Diabetes Control and Complications Trial Research Group. Ann Intern Med. 1995. 122(8):561–568.

9. Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care. 2003. 26(5):1553–1579.

10. Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, Malik RA, Maser RE, Sosenko JM, Ziegler D. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005. 28(4):956–962.

11. Fisher BM, Frier BM. Usefulness of cardiovascular tests of autonomic function in asymptomatic diabetic patients. Diabetes Res Clin Prac. 1989. 6:157–160.

12. Kennedy WR, Navarro X, Sutherland DE. Neuropathy profile of diabetic patients in a pancreas transplantation program. Neurology. 1995. 45(4):773–780.

13. Hulper B, Willms B. Investigations of autonomic diabetic neuropathy of the cardiovascular system. Horm Metab Res Suppl. 1980. 9:77–80.

14. O'Brien IA, McFadden JP, Corrall RJ. The influence of autonomic neuropathy on mortality in insulin-dependent diabetes. Q J Med. 1991. 79(290):495–502.

15. Valensi P, Paries J, Attali JR, French Group. Cardiac autonomic neuropathy in diabetic patients: influence of diabetes duration, obesity, and microangiopathic complications - the French multicenter study. Metabolism. 2003. 52(7):815–820.

16. Gottsater A, Ryden-Ahlgren A, Szelag B, Hedblad B, Persson J, Berglund G, Wroblewski M, Sundkvist G. Cardiovascular autonomic neuropathy associated with carotid atherosclerosis in type 2 diabetic patients. Diabet Med. 2003. 20(6):495–499.

17. Ziegler D, Laux G, Dannehl K, Spuler M, Muhlen H, Mayer P, Gries FA. Assessment of cardiovascular autonomic function: age-related normal ranges and reproducibility of spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses. Diabet Med. 1992. 9(2):166–175.

18. Hilsted J, Parving HH, Christensen NJ, Benn J, Galbo H. Hemodynamics in diabetic orthostatic hypotension. J Clin Invest. 1981. 68(6):1427–1434.

19. Bazett HC. An analysis of the time relationships of electrocardiograms. Heart. 1920. 7:353–357.

20. Kearney EM, Mount JN, Watts GF, Slavin BM, Kind PR. Simple immunoturbidimetric method for determ ining urinary albumin at low concentrations using Cobas-Biocentrifugal analyser. J Clin Pathol. 1987. 40(4):465–468.

21. Kempler P, Varadi A, Tamas GY. Autonomic neuropathy in newly diagnosed diabetes mellitus. Diabetes Care. 1993. 16:848–849.

22. Valensi P, Sachs RN, Harfouche B, Lormeau B, Paries J, Cosson E, Paycha F, Leutenegger M, Attali JR. Predictive value of cardiac autonomic neuropathy in diabetic patients with or without silent myocardial ischemia. Diabetes Care. 2001. 24(2):339–343.

23. Ziegler D. Diabetic cardiovascular autonomic neuropathy: prognosis, diagnosis and treatment. Diabetes Metab Rev. 1994. 10(4):339–383.

24. Toyry JP, Niskanen LK, Lansimies EA, Partanen KP, Uusitupa MI. Autonomic neuropathy predicts the development of stroke in patients with non-insulin-dependent diabetes mellitus. Stroke. 1996. 27(8):1316–1318.

25. Lawrence GP, Home PD, Murray A. Repeatability of measurements and sources of variability in tests of cardiovascular autonomic function. Br Heart J. 1992. 68:205–211.

29. Krolewski AS, Berzilay J, Warram JH, Martin BC, Pfeifer M, Rand LI. Risk of early-onset proliferative retinopathy in IDDM is closely related to cardiovascular autonomic neuropathy. Diabetes. 1992. 41(4):430–437.

30. Clark CV. Autonomic neuropathy in proliferative diabetic retinopathy. Eye. 1987. 1:496–499.

31. Ferrari-Dileo G, Davis EB, Anderson DR. Angiotensin binding sites in bovine and human retinal blood vessels. Invest Opthalmol Vis Sci. 1987. 28:1747–1751.

32. Jakobsen J, Christiansen JS, Kristoffersen I, Christensen CK, Hermansen K, Schmitz A, Mogensen CE. Autonomic and somatosensory nerve function after 2 years of continuous subcutaneous insulin infuction in type 1 diabetes. Diabetes. 1988. 37(4):452–455.

33. Tesfaye S, Chaturvedi N, Eaton SE, Ward JD, Manes C, Ionescu-Tirgoviste C, Witte DR, Fuller JH. EURODIAB Prospective Complications Study Group. Vascular risk factors and diabetic neuropathy. N Engl J Med. 2005. 352(4):341–350.