Early electrophysiological abnormalities and clinical neuropathy: a prospective study in patients with type 1 diabetes

Lars Hyllienmark, Nils Alstrand, Björn Jonsson, Johnny Ludvigsson, Gerald Cooray, Jeanette Wahlberg-Topp, Lars Hyllienmark, Nils Alstrand, Björn Jonsson, Johnny Ludvigsson, Gerald Cooray, Jeanette Wahlberg-Topp

Abstract

Objective: The aim of this study was to elucidate whether subclinical nerve dysfunction as reflected by neurophysiological testing predicts the development of clinical neuropathy in patients with type 1 diabetes.

Research design and methods: Fifty-nine patients were studied twice with neurophysiological measurements at baseline and at follow-up. At baseline, patients were 15.5±3.22 years (range 7-22 years) of age, and duration of diabetes was 6.8±3.3 years. At follow-up, patients were 20-35 years of age, and disease duration was 20±5.3 years (range 10-31 years).

Results: At baseline, patients showed modestly reduced nerve conduction velocities and amplitudes compared with healthy subjects, but all were free of clinical neuropathy. At follow-up, clinical neuropathy was present in nine (15%) patients. These patients had a more pronounced reduction in peroneal motor nerve conduction velocity (MCV), median MCV, and sural sensory nerve action potential at baseline (P<0.010-0.003). In simple logistic regression analyses, the predictor with the strongest association with clinical neuropathy was baseline HbA1c (R2=48%, odds ratio 7.9, P<0.002) followed by peroneal MCV at baseline (R2=38%, odds ratio 0.6, P<0.006). With the use of a stepwise forward analysis that included all predictors, first baseline HbA1c and then only peroneal MCV at baseline entered significantly (R2=61%). Neuropathy impairment assessment showed a stronger correlation with baseline HbA1c (ρ=0.40, P<0.002) than with follow-up HbA1c (ρ=0.034, P<0.007).

Conclusions: Early defects in nerve conduction velocity predict the development of diabetic neuropathy. However, the strongest predictor was HbA1c during the first years of the disease.

Figures

Figure 1
Figure 1
Predicted probability (from logistic regression) of having clinical neuropathy after an average of 20 years with type 1 diabetes as a function of peroneal MCV at baseline, where duration of disease was an average of 7 years. Data are from 59 patients with type 1 diabetes. DPN, diabetic peripheral neuropathy.

References

    1. Pirart J. Diabetes mellitus and its degenerative complications. A prospective study of 4,400 patients observed between 1947 and 1973. Diabetes Care 1978;1:168–188, 252–263
    1. Ziegler D, Mayer P, Muhlen H, Gries A. The natural history of somatosensory and autonomic nerve dysfunction in relation to glycaemic control during the first 5 years after diagnosis of type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1991;34:822–829
    1. Tesfaye S, Boulton AJ, Dyck PJ, et al. Toronto Diabetic Neuropathy Expert Group Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 2010;33:2285–2293
    1. Dyck PJ, Albers JW, Andersen H, et al. Diabetic polyneuropathies: update on research definition, diagnostic criteria and estimation of severity. Diabetes Metab Res Rev 2011;27:620–628
    1. The Diabetes Control and Complications Trial Research Group The effect of intensive diabetes therapy on the development and progression of neuropathy. Ann Intern Med 1995;122:561–568
    1. Albers JW, Herman WH, Pop-Busui R, Martin CL, Cleary P, Waberski B; Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Intervention and Complications (EDIC) Research Group. Subclinical neuropathy among Diabetes Control and Complications Trial participants without diagnosable neuropathy at trial completion: possible factors of incipient neuropathy? Diabetes Care 2007;30:2613–2618
    1. Martin CL, Albers J, Herman WH, et al. DCCT/EDIC Research Group Neuropathy among the diabetes control and complications trial cohort 8 years after trial completion. Diabetes Care 2006;29:340–344
    1. White NH, Sun W, Cleary PA, et al. DCCT-EDIC Research Group Effect of prior intensive therapy in type 1 diabetes on 10-year progression of retinopathy in the DCCT/EDIC: comparison of adults and adolescents. Diabetes 2010;59:1244–1253
    1. de Boer IH, Sun W, Cleary PA, et al. DCCT/EDIC Research Group Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. N Engl J Med 2011;365:2366–2376
    1. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577–1589
    1. Hyllienmark L, Brismar T, Ludvigsson J. Subclinical nerve dysfunction in children and adolescents with IDDM. Diabetologia 1995;38:685–692
    1. Hyllienmark L, Maltez J, Dandenell A, Ludvigsson J, Brismar T. EEG abnormalities with and without relation to severe hypoglycaemia in adolescents with type 1 diabetes. Diabetologia 2005;48:412–419
    1. Dyck PJ, Karnes J, O’Brien PC, Swanson CJ. Neuropathy Symptom Profile in health, motor neuron disease, diabetic neuropathy, and amyloidosis. Neurology 1986;36:1300–1308
    1. Hyllienmark L, Ludvigsson J, Brismar T. Normal values of nerve conduction in children and adolescents. Electroencephalogr Clin Neurophysiol 1995;97:208–214
    1. Ekberg K, Brismar T, Johansson BL, et al. C-Peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy. Diabetes Care 2007;30:71–76
    1. Hansson P, Lindblom U, Lindström P. Graded assessment and classification of impaired temperature sensibility in patients with diabetic polyneuropathy. J Neurol Neurosurg Psychiatry 1991;54:527–530
    1. Hyllienmark L, Jonsson B, Ekberg K, Lindström P. Abnormal cold perception in the lower limbs: a sensitive indicator for detection of polyneuropathy in patients with type 1 diabetes mellitus. Diabetes Res Clin Pract 2009;85:298–303
    1. England JD, Gronseth GS, Franklin G, et al. American Academy of Neurology. American Association of Electrodiagnostic Medicine. American Academy of Physical Medicine and Rehabilitation Distal symmetric polyneuropathy: a definition for clinical research: report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 2005;64:199–207
    1. Boulton AJ, Vinik AI, Arezzo JC, et al. ; American Diabetes Association. Diabetic neuropathies: a statement bythe American Diabetes Association Diabetes Care 2005;28:956–962
    1. Dyck PJ. Detection, characterization, and staging of polyneuropathy: assessed in diabetics. Muscle Nerve 1988;11:21–32
    1. Tesfaye S, Chaturvedi N, Eaton SE, et al. EURODIAB Prospective Complications Study Group Vascular risk factors and diabetic neuropathy. N Engl J Med 2005;352:341–350
    1. Dyck PJ, Carter RE, Litchy WJ. Modeling nerve conduction criteria for diagnosis of diabetic polyneuropathy. Muscle Nerve 2011;44:340–345
    1. Dyck PJ, Davies JL, Litchy WJ, O’Brien PC. Longitudinal assessment of diabetic polyneuropathy using a composite score in the Rochester Diabetic Neuropathy Study cohort. Neurology 1997;49:229–239
    1. Burke D, Skuse NF, Lethlean AK. Sensory conduction of the sural nerve in polyneuropathy. J Neurol Neurosurg Psychiatry 1974;37:647–652
    1. Taylor PK. Non-linear effects of age on nerve conduction in adults. J Neurol Sci 1984;66:223–234
    1. Gregersen G. Variations in motor conduction velocity produced by acute changes of the metabolic state in diabetic patients. Diabetologia 1968;4:273–277
    1. Amthor KF, Dahl-Jørgensen K, Berg TJ, et al. The effect of 8 years of strict glycaemic control on peripheral nerve function in IDDM patients: the Oslo Study. Diabetologia 1994;37:579–584
    1. Boulton AJ, Knight G, Drury J, Ward JD. The prevalence of symptomatic, diabetic neuropathy in an insulin-treated population. Diabetes Care 1985;8:125–128
    1. Dyck PJ, O’Brien PC, Litchy WJ, Harper CM, Klein CJ, Dyck PJB. Monotonicity of nerve tests in diabetes: subclinical nerve dysfunction precedes diagnosis of polyneuropathy. Diabetes Care 2005;28:2192–2200

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe