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Published in: Diabetologia 1/2005

01-01-2005 | Article

Risk factors for cardiac autonomic neuropathy in type 1 diabetes mellitus

Authors: D. R. Witte, S. Tesfaye, N. Chaturvedi, S. E. M. Eaton, P. Kempler, J. H. Fuller, EURODIAB Prospective Complications Study Group

Published in: Diabetologia | Issue 1/2005

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Abstract

Aims/hypothesis

Cardiac autonomic neuropathy (CAN) is associated with increased morbidity and mortality in type 1 diabetes. Apart from glycaemic control, risk factors for CAN have not been extensively studied.

Methods

As part of the EURODIAB Prospective Complications Study, CAN—defined as either a loss of heart rate variability or postural hypotension on standing—was assessed at baseline and follow-up (7.3±0.6 years from baseline) in patients with type 1 diabetes.

Results

Follow-up measurements were available for 956 participants without CAN at baseline (age at baseline 31.3±8.9 years, duration of diabetes 13.5±8.3 years). During follow-up, 163 (17%) subjects developed CAN, yielding an incidence of 23.4 per 1,000 person-years. Blood pressure, weight, the presence of cardiovascular disease, albuminuria, distal symmetrical polyneuropathy (DSP) and retinopathy at baseline were associated with the incidence of CAN after adjustment for sex, duration of diabetes and HbA1c. In a multivariate regression model, baseline factors associated with an increased risk of developing CAN were age [odds ratio (OR)=1.3 per decade, 95% CI 1.1–1.7], HbA1c (OR=1.2 per percentage point, 95% CI 1.1–1.4), systolic blood pressure (OR=1.1 per 10 mmHg, 95% CI 1.0–1.3), feeling faint on standing (OR=2.0, 95% CI 1.2–3.2), DSP (OR=1.9, 95% CI 1.2–3.0) and retinopathy (OR=1.7, 95% CI 1.1–2.6).

Conclusion/interpretation

This study confirms the importance of exposure to hyperglycaemia as a risk factor for CAN. A small set of variables, including HbA1c, hypertension, DSP and retinopathy, predict the risk of CAN. Clinical trials are needed to address the impact of intensive antihypertensive treatment on CAN in type 1 diabetes.
Literature
1.
go back to reference The Diabetes Control and Complications Trial Research Group (1995) The effect of intensive diabetes therapy on the development and progression of neuropathy. Ann Intern Med 122:561–568 The Diabetes Control and Complications Trial Research Group (1995) The effect of intensive diabetes therapy on the development and progression of neuropathy. Ann Intern Med 122:561–568
2.
go back to reference Kempler P, Tesfaye S, Chaturvedi N et al (2002) Autonomic neuropathy is associated with increased cardiovascular risk factors: the EURODIAB IDDM Complications Study. Diabet Med 19:900–909PubMed Kempler P, Tesfaye S, Chaturvedi N et al (2002) Autonomic neuropathy is associated with increased cardiovascular risk factors: the EURODIAB IDDM Complications Study. Diabet Med 19:900–909PubMed
3.
go back to reference Valensi P, Sachs RN, Harfouche B et al (2001) Predictive value of cardiac autonomic neuropathy in diabetic patients with or without silent myocardial ischemia. Diabetes Care 24:339–343 Valensi P, Sachs RN, Harfouche B et al (2001) Predictive value of cardiac autonomic neuropathy in diabetic patients with or without silent myocardial ischemia. Diabetes Care 24:339–343
4.
go back to reference Maser RE, Mitchell BD, Vinik AI, Freeman R (2003) The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis. Diabetes Care 26:1895–1901PubMed Maser RE, Mitchell BD, Vinik AI, Freeman R (2003) The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis. Diabetes Care 26:1895–1901PubMed
5.
go back to reference Vinik AI, Maser RE, Mitchell BD, Freeman R (2003) Diabetic autonomic neuropathy. Diabetes Care 26:1553–1579PubMed Vinik AI, Maser RE, Mitchell BD, Freeman R (2003) Diabetic autonomic neuropathy. Diabetes Care 26:1553–1579PubMed
6.
go back to reference Whang W, Bigger JT Jr (2003) Comparison of the prognostic value of RR-interval variability after acute myocardial infarction in patients with versus those without diabetes mellitus. Am J Cardiol 92:247–251 Whang W, Bigger JT Jr (2003) Comparison of the prognostic value of RR-interval variability after acute myocardial infarction in patients with versus those without diabetes mellitus. Am J Cardiol 92:247–251
7.
go back to reference Pfeifer M (1999) Cardiovascular assessment. In: Dyck PJ, Thomas PK (eds) Diabetic neuropathy. Saunders, Philadelphia, pp 171–183 Pfeifer M (1999) Cardiovascular assessment. In: Dyck PJ, Thomas PK (eds) Diabetic neuropathy. Saunders, Philadelphia, pp 171–183
8.
go back to reference Ewing DJ, Boland O, Neilson JM, Cho CG, Clarke BF (1991) Autonomic neuropathy, QT interval lengthening, and unexpected deaths in male diabetic patients. Diabetologia 34:182–185PubMed Ewing DJ, Boland O, Neilson JM, Cho CG, Clarke BF (1991) Autonomic neuropathy, QT interval lengthening, and unexpected deaths in male diabetic patients. Diabetologia 34:182–185PubMed
9.
go back to reference Veglio M, Borra M, Stevens LK, Fuller JH, Perin PC (1999) The relation between QTc interval prolongation and diabetic complications. The EURODIAB IDDM Complication Study Group. Diabetologia 42:68–75CrossRefPubMed Veglio M, Borra M, Stevens LK, Fuller JH, Perin PC (1999) The relation between QTc interval prolongation and diabetic complications. The EURODIAB IDDM Complication Study Group. Diabetologia 42:68–75CrossRefPubMed
10.
go back to reference Orchard TJ, Lloyd CE, Maser RE, Kuller LH (1996) Why does diabetic autonomic neuropathy predict IDDM mortality? An analysis from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Res Clin Pract 34 [Suppl]:S165–S171 Orchard TJ, Lloyd CE, Maser RE, Kuller LH (1996) Why does diabetic autonomic neuropathy predict IDDM mortality? An analysis from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Res Clin Pract 34 [Suppl]:S165–S171
11.
go back to reference Cameron NE, Eaton SE, Cotter MA, Tesfaye S (2001) Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia 44:1973–1988 Cameron NE, Eaton SE, Cotter MA, Tesfaye S (2001) Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia 44:1973–1988
12.
go back to reference Vinik AI (1999) Diabetic neuropathy: pathogenesis and therapy. Am J Med 107:17S–26S Vinik AI (1999) Diabetic neuropathy: pathogenesis and therapy. Am J Med 107:17S–26S
13.
go back to reference Stella P, Ellis D, Maser RE, Orchard TJ (2000) Cardiovascular autonomic neuropathy (expiration and inspiration ratio) in type 1 diabetes. Incidence and predictors. J Diabetes Complications 14:1–6 Stella P, Ellis D, Maser RE, Orchard TJ (2000) Cardiovascular autonomic neuropathy (expiration and inspiration ratio) in type 1 diabetes. Incidence and predictors. J Diabetes Complications 14:1–6
14.
go back to reference Riihimaa PH, Suominen K, Knip M, Tapanainen P, Tolonen U (2002) Cardiovascular autonomic reactivity is decreased in adolescents with type 1 diabetes. Diabet Med 19:932–938 Riihimaa PH, Suominen K, Knip M, Tapanainen P, Tolonen U (2002) Cardiovascular autonomic reactivity is decreased in adolescents with type 1 diabetes. Diabet Med 19:932–938
15.
go back to reference The EURODIAB Prospective Complications Study Group (1994) Microvascular and acute complications in IDDM patients. Diabetologia 37:278–285CrossRefPubMed The EURODIAB Prospective Complications Study Group (1994) Microvascular and acute complications in IDDM patients. Diabetologia 37:278–285CrossRefPubMed
16.
go back to reference Siedel J, Hagele EO, Ziegenhorn J, Wahlefeld AW (1983) Reagent for the enzymatic determination of serum total cholesterol with improved lipolytic efficiency. Clin Chem 29:1075–1080 Siedel J, Hagele EO, Ziegenhorn J, Wahlefeld AW (1983) Reagent for the enzymatic determination of serum total cholesterol with improved lipolytic efficiency. Clin Chem 29:1075–1080
17.
go back to reference Bucolo G, David H (1973) Quantitative determination of serum triglycerides by the use of enzymes. Clin Chem 19:476–482PubMed Bucolo G, David H (1973) Quantitative determination of serum triglycerides by the use of enzymes. Clin Chem 19:476–482PubMed
18.
go back to reference Warnick GR, Albers JJ (1978) A comprehensive evaluation of the heparin-manganese precipitation procedure for estimating high density lipoprotein cholesterol. J Lipid Res 19:65–76 Warnick GR, Albers JJ (1978) A comprehensive evaluation of the heparin-manganese precipitation procedure for estimating high density lipoprotein cholesterol. J Lipid Res 19:65–76
19.
go back to reference Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502PubMed Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502PubMed
20.
go back to reference John WG, Gray MR, Bates DL, Beacham JL (1993) Enzyme immunoassay—a new technique for estimating hemoglobin A1c. Clin Chem 39:663–666PubMed John WG, Gray MR, Bates DL, Beacham JL (1993) Enzyme immunoassay—a new technique for estimating hemoglobin A1c. Clin Chem 39:663–666PubMed
21.
go back to reference Greaves M, Malia RG, Goodfellow K et al (1997) Fibrinogen and von Willebrand factor in IDDM: relationships to lipid vascular risk factors, blood pressure, glycaemic control and urinary albumin excretion rate: the EURODIAB IDDM Complications Study. Diabetologia 40:698–705 Greaves M, Malia RG, Goodfellow K et al (1997) Fibrinogen and von Willebrand factor in IDDM: relationships to lipid vascular risk factors, blood pressure, glycaemic control and urinary albumin excretion rate: the EURODIAB IDDM Complications Study. Diabetologia 40:698–705
22.
go back to reference Rossi E, Mondonico P, Lombardi A, Preda L (1988) Method for the determination of functional (clottable) fibrinogen by the new family of ACL coagulometers. Thromb Res 52:453–468 Rossi E, Mondonico P, Lombardi A, Preda L (1988) Method for the determination of functional (clottable) fibrinogen by the new family of ACL coagulometers. Thromb Res 52:453–468
23.
go back to reference Short PE, Williams CE, Picken AM, Hill FG (1982) Factor VIII related antigen: an improved enzyme immunoassay. Med Lab Sci 39:351–355 Short PE, Williams CE, Picken AM, Hill FG (1982) Factor VIII related antigen: an improved enzyme immunoassay. Med Lab Sci 39:351–355
24.
go back to reference Ford I, Malik RA, Newrick PG, Preston FE, Ward JD, Greaves M (1992) Relationships between haemostatic factors and capillary morphology in human diabetic neuropathy. Thromb Haemost 68:628–633 Ford I, Malik RA, Newrick PG, Preston FE, Ward JD, Greaves M (1992) Relationships between haemostatic factors and capillary morphology in human diabetic neuropathy. Thromb Haemost 68:628–633
25.
go back to reference Kearney EM, Mount JN, Watts GF, Slavin BM, Kind PR (1987) Simple immunoturbidimetric method for determining urinary albumin at low concentrations using Cobas-Bio centrifugal analyser. J Clin Pathol 40:465–468 Kearney EM, Mount JN, Watts GF, Slavin BM, Kind PR (1987) Simple immunoturbidimetric method for determining urinary albumin at low concentrations using Cobas-Bio centrifugal analyser. J Clin Pathol 40:465–468
26.
go back to reference Aldington SJ, Kohner EM, Meuer S, Klein R, Sjolie AK (1995) Methodology for retinal photography and assessment of diabetic retinopathy: the EURODIAB IDDM Complications Study. Diabetologia 38:437–444CrossRefPubMed Aldington SJ, Kohner EM, Meuer S, Klein R, Sjolie AK (1995) Methodology for retinal photography and assessment of diabetic retinopathy: the EURODIAB IDDM Complications Study. Diabetologia 38:437–444CrossRefPubMed
27.
go back to reference Koivisto VA, Stevens LK, Mattock M et al (1996) Cardiovascular disease and its risk factors in IDDM in Europe. EURODIAB IDDM Complications Study Group. Diabetes Care 19:689–697 Koivisto VA, Stevens LK, Mattock M et al (1996) Cardiovascular disease and its risk factors in IDDM in Europe. EURODIAB IDDM Complications Study Group. Diabetes Care 19:689–697
28.
go back to reference Forrest KY, Maser RE, Pambianco G, Becker DJ, Orchard TJ (1997) Hypertension as a risk factor for diabetic neuropathy: a prospective study. Diabetes 46:665–670 Forrest KY, Maser RE, Pambianco G, Becker DJ, Orchard TJ (1997) Hypertension as a risk factor for diabetic neuropathy: a prospective study. Diabetes 46:665–670
29.
go back to reference Young MJ, Boulton AJ, MacLeod AF, Williams DR, Sonksen PH (1993) A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia 36:150–154PubMed Young MJ, Boulton AJ, MacLeod AF, Williams DR, Sonksen PH (1993) A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia 36:150–154PubMed
30.
go back to reference Wiles PG, Pearce SM, Rice PJ, Mitchell JM (1991) Vibration perception threshold: influence of age, height, sex, and smoking, and calculation of accurate centile values. Diabet Med 8:157–161 Wiles PG, Pearce SM, Rice PJ, Mitchell JM (1991) Vibration perception threshold: influence of age, height, sex, and smoking, and calculation of accurate centile values. Diabet Med 8:157–161
31.
go back to reference The Consensus Committee of the American Autonomic Society and the American Academy of Neurology (1996) Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. Neurology 46:1470 The Consensus Committee of the American Autonomic Society and the American Academy of Neurology (1996) Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. Neurology 46:1470
32.
go back to reference Kempler P, Tesfaye S, Chaturvedi N et al (2001) Blood pressure response to standing in the diagnosis of autonomic neuropathy: the EURODIAB IDDM Complications Study. Arch Physiol Biochem 109:215–222 Kempler P, Tesfaye S, Chaturvedi N et al (2001) Blood pressure response to standing in the diagnosis of autonomic neuropathy: the EURODIAB IDDM Complications Study. Arch Physiol Biochem 109:215–222
33.
go back to reference Mankovsky BN, Piolot R, Mankovsky OL, Ziegler D (2003) Impairment of cerebral autoregulation in diabetic patients with cardiovascular autonomic neuropathy and orthostatic hypotension. Diabet Med 20:119–126 Mankovsky BN, Piolot R, Mankovsky OL, Ziegler D (2003) Impairment of cerebral autoregulation in diabetic patients with cardiovascular autonomic neuropathy and orthostatic hypotension. Diabet Med 20:119–126
34.
go back to reference Meijer JW, Bosma E, Lefrandt JD et al (2003) Clinical diagnosis of diabetic polyneuropathy with the diabetic neuropathy symptom and diabetic neuropathy examination scores. Diabetes Care 26:697–701 Meijer JW, Bosma E, Lefrandt JD et al (2003) Clinical diagnosis of diabetic polyneuropathy with the diabetic neuropathy symptom and diabetic neuropathy examination scores. Diabetes Care 26:697–701
35.
go back to reference Spitzer A, Lang E, Birklein F, Claus D, Neundorfer B (1997) Cardiac autonomic involvement and peripheral nerve function in patients with diabetic neuropathy. Funct Neurology 12:115–122 Spitzer A, Lang E, Birklein F, Claus D, Neundorfer B (1997) Cardiac autonomic involvement and peripheral nerve function in patients with diabetic neuropathy. Funct Neurology 12:115–122
36.
go back to reference Meinhold JA, Maslowska-Wessel E, Bender R, Sawicki PT (2001) Low prevalence of cardiac autonomic neuropathy in type 1 diabetic patients without nephropathy. Diabet Med 18:607–613 Meinhold JA, Maslowska-Wessel E, Bender R, Sawicki PT (2001) Low prevalence of cardiac autonomic neuropathy in type 1 diabetic patients without nephropathy. Diabet Med 18:607–613
37.
go back to reference Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O (2003) Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 348:383–393CrossRefPubMed Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O (2003) Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 348:383–393CrossRefPubMed
Metadata
Title
Risk factors for cardiac autonomic neuropathy in type 1 diabetes mellitus
Authors
D. R. Witte
S. Tesfaye
N. Chaturvedi
S. E. M. Eaton
P. Kempler
J. H. Fuller
EURODIAB Prospective Complications Study Group
Publication date
01-01-2005
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 1/2005
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-004-1617-y

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