Skip to main content
Log in

Could we predict asymptomatic cardiovascular autonomic neuropathy in type 1 diabetic patients attending out-patients clinics?

Lässt sich die kardiovaskuläre autonome Neuropathie bei symptomlosen Patienten mit Typ 1 Diabetes mellitus vorhersagen?

  • Original Article
  • Published:
Wiener klinische Wochenschrift Aims and scope Submit manuscript

Zusammenfassung

HINTERGRUND UND ZIELE: Die kardiovaskuläre autonome Neuropathie (KAN) ist bei Patienten mit Typ 1 Diabetes mellitus (DM1) mit einer erhöhten Morbidität und Mortalität verbunden. Diese Komplikation kann über lange Zeit ohne Symptome einhergehen. Ziel dieser Studie war es die Prävalenz, den Schweregrad und mögliche Vorhersageparameter der asymptomatischen KAN zu erfassen. PATIENTEN UND METHODEN: 107 Patienten mit DM1 (52 Männer, 55 Frauen, Alter 39,8 ± 12,4 Jahre [18–72]; Dauer des DM1: 16,6 ± 9,5 Jahre [0,5–43], Alter bei Manifestation 23,5 ± 12,8 Jahre [1–54], BMI 25,1 ± 3,2 [1,9–33,91]) wurden untersucht. Das Vorliegen einer KAN wurde mit Hilfe von Standard-Reflex-Testen (Ewing Batterie) erhoben und die Patienten wurden entsprechend den Ergebnissen in drei Gruppen eingeteilt: Gruppe 0 ohne KAN, Gruppe I mit erstgradiger KAN und Gruppe 2 mit zweitgradiger KAN. Wir erhoben außerdem die mit KAN am häufigsten einhergehenden chronischen Komplikationen des DM1, Episoden schwerer Hypoglykämie, zeitliche Parameter des DM1 (Patientenalter, Dauer des DM1, Alter bei Manifestation) und außerdem DM1-spezifische Parameter wie glykosyliertes Hb, BMI, kardiovaskuläre Erkrankungen und Blutdruck. Die Vorhersagbarkeit einer KAN wurde entsprechend den erhobenen Korrelationen beurteilt. ERGEBNISSE: Nur 50 der 107 der Patienten (46%) zeigten keine KAN. Bei 38 Patienten (36%) fanden wir eine erstgradige , bei 19 (18%) eine zweitgradige KAN. KAN korrelierte mehr mit der Dauer des DM1 (p < 0,001), als mit dem Alter der Patienten (p < 0,05). Es bestand eine grenzwertig signifikante Korrelation (p = 0,053) mit dem glykosylierten Hb. Weiters haben wir eine signifikant positive Korrelation zwischen KAN und dem Auftreten von chronischen Komplikationen (periphere Neuropathie: p < 0,001), Retinopathie: p < 0,001, Nephropathie: erhöhtes Kreatinin: p < 0,03, Albuminurie: p < 0,01) gefunden. Obwohl der Blutdruck bei allen Patienten im Normalbreich (124,2/74,5 ± 11,5/7,8 mmHg) lag, wurde eine positive Korrelation mit der KAN (p < 0,05) bestätigt. Zu den akuten Komplikationen des DM1 bestand keine Korrelation. SCHLUSSFOLGERUNGEN: Unsere Studie zeigt, dass die asymptomatische KAN bei Patienten mit DM1 sehr häufig ist. Mit Hilfe von multifaktorieller logistischer Regression konnten wir zeigen, dass bei gleichzeitigem Vorliegen von Albuminurie, peripherer Neuopathie und erhöhtem systolischem Blutdruck eine hohe Wahrscheinlichkeit für das zusätzliche Vorhandensein einer KAN besteht.

Summary

BACKGROUND AND AIMS: Diabetic cardiovascular autonomic neuropathy (CAN) is associated with increased morbidity and mortality. This complication may be asymptomatic for a long time. The aim of this study was to assess the prevalence, severity and predictors of asymptomatic CAN in patients with type 1 diabetes mellitus (DM1). PATIENTS AND METHODS: 107 patients with DM1 were enrolled: 52 men and 55 women aged 39.8 ± 12.4 years (18–72), duration of DM 16.6 ± 9.5 years (0.5–43), age at DM manifestation 23.5 ± 12.8 years (1–54) and BMI 25.1 ± 3.2 (18.9–33.91). CAN was assessed using standard cardiovascular reflex tests (Ewing battery) and the patients were divided into three groups according to the results: Group 0, without CAN; Group I, 1st degree CAN; Group II, 2nd degree CAN. We assessed the most frequent relationships between CAN and chronic complications, episodes of severe hypoglycemia, time-related parameters (age of patients, duration of diabetes, age at manifestation), glycosylated hemoglobin (HbA1c), BMI, cardiovascular diseases and blood pressure, and determined the predictability of CAN on the basis of these relationships. RESULTS: Only 50 of the 107 patients (46%) showed no CAN. We found 1st degree CAN in 38 patients (36%) and 2nd degree CAN in 19 (18%). CAN correlated more significantly with the duration of diabetes (p < 0.001) than with age (p < 0.05). The relationship between CAN and HbA1c was on the borderline of statistical significance (p = 0.053). We found a positive correlation between CAN and the presence of chronic complications [peripheral neuropathy (p < 0.001), retinopathy (p < 0.001), and some markers of nephropathy: creatinine (p < 0.03), albuminuria (p < 0.01)]. Although blood pressure was within the physiological range (124.2/74.5 ± 11.5/7.8 mmHg) in all patients, a positive correlation with CAN was confirmed (p < 0.05). No relationship with occurrence of severe hypoglycemia was found. CONCLUSIONS: According to our results, asymptomatic CAN is very frequent in patients with DM1. By using multifactorial logistic regression (step-wise) analysis we demonstrated that if albuminuria, peripheral neuropathy and elevated systolic BP are present simultaneously, there is a high probability that the patient also has CAN (84.9% of initial group correctly predicted, p < 0.001).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  • Maser RE, Lenhard MJ, DeCherney GS (2000) Cardiovascular autonomic neuropathy: the clinical significance of its determinations. The Endocrinologist 10: 27–33

    Google Scholar 

  • Ziegler D (1994) Diabetic cardiovascular autonomic neuropathy: prognosis, diagnosis and treatment. Diabetes/Metabolism Reviews 10: 339–383

    PubMed  CAS  Google Scholar 

  • Low PA, Benrud-Larson LM, Sletten DM, Opfer-Gehrkong TL, Weigand SD, O'Brien GA, Dyck PJ (2004) Autonomic symptoms and diabetic neuropathy. Diabetes Care 27: 2942–2947

    Article  PubMed  Google Scholar 

  • Ewing DJ, Martyn CN, Young RJ, Clarke BF (1985) The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care 8: 491–498

    Article  PubMed  CAS  Google Scholar 

  • Gautschy B, Weidmann P, Gnadiger MP (1986) Autonomic function tests as related to age and gender in normal man. Klin Wchschr 64: 499–505

    Article  CAS  Google Scholar 

  • Wieling W, Van Brederode JFM, De Rijk LG (1982) Reflex control in heart rate in normal subjects in relation to age: a data base for cardiac vagal neuropathy. Diabetologia 22: 163–166

    Article  PubMed  CAS  Google Scholar 

  • O'Brien IAD, O'Hare P, Corrall RJM (1986) Heart rate variability in healthy subjects: effects of age and the derivation of normal ranges for tests of autonomic function. Br Heart J 55: 348–354

    PubMed  Google Scholar 

  • Sallinger J, Vychodil R, Novotný J, Pumprla J, Opavský J, Stejskal P, et al (1995) Telemetric computer-aided system for non-invasive examination of heart rate variability, type VariaPulse TF3. Comput Cardiol IEEE Proc: 437–440

  • Dyck PJ (1988) Detection, characterisation and staging of polyneuropathy. Muscle Nerve 11: 21–32

    Article  PubMed  CAS  Google Scholar 

  • International Consensus on the Diabetic Foot (1999) International Working Group on the Diabetic Foot

  • Roithinger FX, Allinger S, Knoflach P, Punzengruber C, Pachinger O (1996) Short-term frequency and time domain analysis of heart rate variability in type 1 diabetic subjects. Wien Klin Wochenschr 108: 133–136

    PubMed  CAS  Google Scholar 

  • Chessa M, Butera G, Lanza GA, Bossone E, Delogu A, De Rosa G, et al (2002) Role of heart rate variability in the early diagnosis of diabetic autonomic neuropathy in children. Herz 27: 785–790

    Article  PubMed  Google Scholar 

  • Lluch A, Hernández JT, Real C, Morillas S, Tenés C, Sanchéz , et al (1998) Cardiovascular autonomic neuropathy in Type 1 diabetic patients with and without peripheral neuropathy. Diabetes Res Clin Pract 42: 35–40

    Article  PubMed  CAS  Google Scholar 

  • Lacigová S, Rušavý Z, Kárová R, Jankovec Z, Záhlava J (2000) The relation of cardiovascular and gastrointestinal neuropathy in diabetic patients. Cas Lek Ces 139: 79–83

    Google Scholar 

  • Valensi P, Paries J, Attali JR; French Group for Research and Study of Diabetic Neuropathy (2003) Cardiac autonomic neuropathy in diabetic patients: influence of diabetes duration, obesity, and microangiopathic complications – the French multicenter study. Metabolism 52: 815–820

    Article  PubMed  CAS  Google Scholar 

  • Keresztes K, Istenes I, Hermanyi Z, Vargha P, Barna I, Kempler P (2003) Risk factors of autonomic and sensory nerve dysfunction in patients with newly diagnosed type 1 diabetes. Diabetes Care 26: 2213–2214

    Article  PubMed  Google Scholar 

  • Ziegler D, Dannehl K, Volksw D, Muhlen H, Spuler M, Gries FA, et al (1992) Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis and standard tests of heart-rate variation in newly diagnosed IDDM patients. Diabetes Care 15: 908–911

    Article  PubMed  CAS  Google Scholar 

  • Witte DR, Tesfaye S, Chaturvedi N, Eaton SEM, Kempler P, Fuller JH; EURODIAB Prospective Complications Study Group (2005) Risk factors for cardiac autonomic neuropathy in type 1 diabetes mellitus. Diabetologia 48: 164–171

    Article  PubMed  CAS  Google Scholar 

  • Burger AJ, Weinrauch LA, D'Elia JA, Aronson D (1999) Effect of glycemic control on heart rate variability in type I diabetic patients with cardiac autonomic neuropathy. Am J Cardiol 84: 687–691

    Article  PubMed  CAS  Google Scholar 

  • The Diabetes Control and Complication Trial Research Group (1993) The effects of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329: 977–986

    Article  Google Scholar 

  • Weinrauch LA, Kennedy FJ, Burger A, Gleason RE, Keough J, D'Elia JA (1999) Prospective evaluation of autonomic dysfunction in aggressive management of diabetic microangiopathy. Am J Hypertens 12: 1135–1139

    Article  PubMed  CAS  Google Scholar 

  • Meyer C, Grossmann R, Mitrakou A, Mahler R, Veneman T, Gerich J, et al (1998) Effects of autonomic neuropathy on counterregulation and awareness of hypoglycemia in type 1 diabetic patients. Diabetes Care 21: 1960–1966

    Article  PubMed  CAS  Google Scholar 

  • Pontuch P, Vozár J, Potocký M, Krahulec B (1990) Relationship between neuropathy, retinopathy and autonomic neuropathy in patients with type 1 diabetes. J Diabetes Complications 4: 188–192

    Article  CAS  Google Scholar 

  • Tentolouris N, Grapsas E, Stambulis E, Papageorgious K, Katsilambros N (1999) Impact of body mass on autonomic function in persons with type 2 diabetes. Diabetes Res Clin Pract 46: 29–33

    Article  PubMed  CAS  Google Scholar 

  • Bergstrom B, Lilja B, Osterlin S, Sunkvist G (1990) Autonomic neuropathy in non-insulin dependent (type II) diabetes mellitus. Possible influence of obesity. J Intern Med 227: 57–63

    PubMed  CAS  Google Scholar 

  • Mehta S, Mathur D, Chaturvedi M, Verma K (2002) Incidence of cardiac autonomic neuropathy and its correlation with retinopathy, micro-albuminuria and glycated hemoglobin in non-insulin dependent diabetes mellitus. J Indian Med Assoc 100: 141–152

    PubMed  Google Scholar 

  • Kastenbauer T, Auinger M, Irsigler K (1994) Prevalence of cardiac autonomic neuropathies in uremia and diabetes mellitus. Wien Klin Wochenschr 106: 733–737

    PubMed  CAS  Google Scholar 

  • Valensi P, Huard LP, Giroux C, Attali J-R (1997) Factors involved in cardiac autonomic neuropathy in diabetic patients. J Diabetes Complications 11: 180–187

    Article  PubMed  CAS  Google Scholar 

  • Lobmann R, Kasten G, Kasten U, Lehnert H (2002) Association of increased plantar pressures with peripheral sensorimotor and peripheral autonomic neuropathy in Type 2 diabetic patients. Diabetes Nutr Metab 15: 165–138

    PubMed  CAS  Google Scholar 

  • Tentolouris N, Pagoni S, Tzonou A, Katsilambros N (2001) Peripheral neuropathy does not invariably coexist with autonomic neuropathy in diabetes mellitus. European J Int Med 12: 20–27

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Spallone V, Gambardella S, Maiello MR, Barini A, Frontuji S, Menzinger G (1994) Relationship between autonomic neuropathy, 24-h blood pressure profile, and nephropathy in normotensive IDDM patients. Diabetes Care 17: 578–584

    Article  PubMed  CAS  Google Scholar 

  • Poulen PL, Ebbehoj E, Hansen KW, Mogensen CE (1997) 24-h blood pressure and autonomic function is related to albumin excretion within the normoalbuminuric range in IDDM patients. Diabetologia 40: 718–725

    Article  Google Scholar 

  • Tesfaye S, Chaturvedi N, Eaton SEM, Ward JD, Manes CH, Tirgoviste CI, et al; EURODIAB Prospective Complications Study Group (2005) Vascular risk factors and diabetic neuropathy. N Engl J Med 352: 341–350

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Maser RE, Lenhard MJ (2005) Cardiovascular autonomic neuropathy due to diabetes mellitus: clinical manifestations, consequences, and treatment. J Clin Endocrinol Metab 90: 5896–5903

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Silvie Lacigová.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lacigová, S., Šafránek, P., Čechurová, D. et al. Could we predict asymptomatic cardiovascular autonomic neuropathy in type 1 diabetic patients attending out-patients clinics?. Wien Klin Wochenschr 119, 303–308 (2007). https://doi.org/10.1007/s00508-007-0789-0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00508-007-0789-0

Key words

Navigation