Solomon Tesfaye, M.D., Nish Chaturvedi, M.D., Simon E.M. Eaton, D.M., John D. Ward, M.D., Christos Manes, M.D., Constantin Ionescu-Tirgoviste, M.D., Daniel R. Witte, Ph.D., John H. Fuller, M.A., for the EURODIAB Prospective Complications Study Group
Background Other than glycemic control, there are no treatmentsfor diabetic neuropathy. Thus, identifying potentially modifiablerisk factors for neuropathy is crucial. We studied risk factorsfor the development of distal symmetric neuropathy in 1172 patientswith type 1 diabetes mellitus from 31 centers participatingin the European Diabetes (EURODIAB) Prospective ComplicationsStudy.
Methods Neuropathy was assessed at baseline (1989 to 1991) andat follow-up (1997 to 1999), with a mean (±SD) follow-upof 7.3±0.6 years. A standardized protocol included clinicalevaluation, quantitative sensory testing, and autonomic-functiontests. Serum lipids and lipoproteins, glycosylated hemoglobin,and the urinary albumin excretion rate were measured in a centrallaboratory.
ResultsAt follow-up, neuropathy had developed in 276 of 1172 patients without neuropathy at baseline (23.5 percent).Thecumulative incidence of neuropathy was related to the glycosylatedhemoglobin value and the duration of diabetes. After adjustmentfor these factors, we found that higher levels of total andlow-density lipoprotein cholesterol and triglycerides, a higherbody-mass index, higher von Willebrand factor levels and urinaryalbumin excretion rate, hypertension, and smoking were all significantlyassociated with the cumulative incidence of neuropathy. Afteradjustment for other risk factors and diabetic complications,we found that duration of diabetes, current glycosylated hemoglobinvalue, change in glycosylated hemoglobin value during the follow-upperiod, body-mass index, and smoking remained independentlyassociated with the incidence of neuropathy. Cardiovasculardisease at baseline was associated with double the risk of neuropathy,independent of cardiovascular risk factors.
From the Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom (S.T., S.E.M.E., J.D.W.); the Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London (N.C.); the Department of Internal Medicine and Diabetic Center, Papageorgiou General Teaching Hospital, Thessaloniki, Greece (C.M.); the Institute of Diabetes, Nutrition, and Metabolic Diseases, Bucharest, Romania (C.I.-T.); and EURODIAB, Department of Epidemiology and Public Health, Royal Free and University College Medical School, London (D.R.W., J.H.F.).
Address reprint requests to Dr. Tesfaye at the Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield S10 2JF, United Kingdom, or at solomon.tesfaye{at}sth.nhs.uk.
Bruce, S. G., Young, T. K.
(2008). Prevalence and Risk Factors for Neuropathy in a Canadian First Nation Community. Diabetes Care
31: 1837-1841
[Abstract][Full Text]
Ko, S.-H., Park, S.-A., Cho, J.-H., Song, K.-H., Yoon, K.-H., Cha, B.-Y., Son, H.-Y., Yoo, K.-D., Moon, K.-W., Park, Y.-M., Ahn, Y.-B.
(2008). Progression of Cardiovascular Autonomic Dysfunction in Patients With Type 2 Diabetes: A 7-year follow-up study. Diabetes Care
31: 1832-1836
[Abstract][Full Text]
Soedamah-Muthu, S. S., Chaturvedi, N., Witte, D. R., Stevens, L. K., Porta, M., Fuller, J. H., for the EURODIAB Prospective Complications Study G,
(2008). Relationship Between Risk Factors and Mortality in Type 1 Diabetic Patients in Europe: The EURODIAB Prospective Complications Study (PCS). Diabetes Care
31: 1360-1366
[Abstract][Full Text]
Ziegler, D., Rathmann, W., Dickhaus, T., Meisinger, C., Mielck, A., for the KORA Study Group,
(2008). Prevalence of Polyneuropathy in Pre-Diabetes and Diabetes Is Associated With Abdominal Obesity and Macroangiopathy: The MONICA/KORA Augsburg Surveys S2 and S3. Diabetes Care
31: 464-469
[Abstract][Full Text]
Monti, M. C., Lonsdale, J. T., Montomoli, C., Montross, R., Schlag, E., Greenberg, D. A.
(2007). Familial Risk Factors for Microvascular Complications and Differential Male-Female Risk in a Large Cohort of American Families with Type 1 Diabetes. J. Clin. Endocrinol. Metab.
92: 4650-4655
[Abstract][Full Text]
Dyck, P. J., Norell, J. E., Tritschler, H., Schuette, K., Samigullin, R., Ziegler, D., Bastyr, E. J. III, Litchy, W. J., O'Brien, P. C.
(2007). Challenges in Design of Multicenter Trials: End points assessed longitudinally for change and monotonicity. Diabetes Care
30: 2619-2625
[Abstract][Full Text]
Tesfaye, S., Tandan, R., Bastyr, E. J. III, Kles, K. A., Skljarevski, V., Price, K. L., for the Ruboxistaurin Study Group,
(2007). Factors That Impact Symptomatic Diabetic Peripheral Neuropathy in Placebo-Administered Patients From Two 1-Year Clinical Trials. Diabetes Care
30: 2626-2632
[Abstract][Full Text]
Mehra, S., Tavakoli, M., Kallinikos, P. A., Efron, N., Boulton, A. J.M., Augustine, T., Malik, R. A.
(2007). Corneal Confocal Microscopy Detects Early Nerve Regeneration After Pancreas Transplantation in Patients With Type 1 Diabetes. Diabetes Care
30: 2608-2612
[Abstract][Full Text]
Greenstein, A., Tavakoli, M., Mojaddidi, M., Al-Sunni, A., Matfin, G., Malik, R. A
(2007). Review: Microvascular complications: evaluation and monitoring relevance to clinical practice, clinical trials, and drug development. British Journal of Diabetes & Vascular Disease
7: 166-171
[Abstract]
Zandi, M. S, Coles, A. J
(2007). Notes on the kidney and its diseases for the neurologist. J. Neurol. Neurosurg. Psychiatry
78: 444-449
[Abstract][Full Text]
Quattrini, C., Harris, N. D., Malik, R. A., Tesfaye, S.
(2007). Impaired Skin Microvascular Reactivity in Painful Diabetic Neuropathy. Diabetes Care
30: 655-659
[Abstract][Full Text]
Bloomgarden, Z. T.
(2007). Diabetic Retinopathy and Diabetic Neuropathy. Diabetes Care
30: 760-765
[Full Text]
Petitti, D. B., Imperatore, G., Palla, S. L., Daniels, S. R., Dolan, L. M., Kershnar, A. K., Marcovina, S., Pettitt, D. J., Pihoker, C., for the SEARCH for Diabetes in Youth Study Group,
(2007). Serum Lipids and Glucose Control: The SEARCH for Diabetes in Youth Study. Arch Pediatr Adolesc Med
161: 159-165
[Abstract][Full Text]
Samuels, M. A.
(2007). Update in Neurology. ANN INTERN MED
146: 128-132
[Full Text]
Selvarajah, D., Wilkinson, I. D., Emery, C. J., Harris, N. D., Shaw, P. J., Witte, D. R., Griffiths, P. D., Tesfaye, S.
(2006). Early Involvement of the Spinal Cord in Diabetic Peripheral Neuropathy. Diabetes Care
29: 2664-2669
[Abstract][Full Text]
Costacou, T., Chang, Y., Ferrell, R. E., Orchard, T. J.
(2006). Identifying Genetic Susceptibilities to Diabetes-related Complications among Individuals at Low Risk of Complications: An Application of Tree-Structured Survival Analysis. Am J Epidemiol
164: 862-872
[Abstract][Full Text]
Figaro, M. K., Kritchevsky, S. B., Resnick, H. E., Shorr, R. I., Butler, J., Shintani, A., Penninx, B. W., Simonsick, E. M., Goodpaster, B. H., Newman, A. B., Schwartz, A. V., Harris, T. B., for the Health Aging and Body Composition study,
(2006). Diabetes, Inflammation, and Functional Decline in Older Adults: Findings from the Health, Aging and Body Composition (ABC) study.. Diabetes Care
29: 2039-2045
[Abstract][Full Text]
Cho, D. Y., Mold, J. W., Roberts, M.
(2006). Further Investigation of the Negative Association between Hypertension and Peripheral Neuropathy in the Elderly: An Oklahoma Physicians Resource/Research Network (OKPRN) Study.. J Am Board Fam Med
19: 240-250
[Abstract][Full Text]
Pambianco, G., Costacou, T., Ellis, D., Becker, D. J., Klein, R., Orchard, T. J.
(2006). The 30-year natural history of type 1 diabetes complications: the pittsburgh epidemiology of diabetes complications study experience.. Diabetes
55: 1463-1469
[Abstract][Full Text]
Gorson, K C, Ropper, A H
(2006). Additional causes for distal sensory polyneuropathy in diabetic patients.. J. Neurol. Neurosurg. Psychiatry
77: 354-358
[Abstract][Full Text]
Fink, E., Oaklander, A. L.
(2006). Small-fiber neuropathy: answering the burning questions.. Sci Aging Knowl Environ
2006: pe7-pe7
[Abstract][Full Text]
Martin, C. L., Albers, J., Herman, W. H., Cleary, P., Waberski, B., Greene, D. A., Stevens, M. J., Feldman, E. L.
(2006). Neuropathy Among the Diabetes Control and Complications Trial Cohort 8 Years After Trial Completion. Diabetes Care
29: 340-344
[Abstract][Full Text]
Bansal, V, Kalita, J, Misra, U K
(2006). Diabetic neuropathy. Postgrad. Med. J.
82: 95-100
[Abstract][Full Text]
Stults, B., Jones, R. E.
(2006). Management of Hypertension in Diabetes. Diabetes Spectr.
19: 25-31
[Abstract][Full Text]
Maser, R. E., Lenhard, M. J.
(2005). Cardiovascular Autonomic Neuropathy Due to Diabetes Mellitus: Clinical Manifestations, Consequences, and Treatment. J. Clin. Endocrinol. Metab.
90: 5896-5903
[Abstract][Full Text]
Dyck, P. J., O'Brien, P. C., Litchy, W. J., Harper, C. M., Klein, C. J., Dyck, P. J. B.
(2005). Monotonicity of Nerve Tests in Diabetes: Subclinical nerve dysfunction precedes diagnosis of polyneuropathy. Diabetes Care
28: 2192-2200
[Abstract][Full Text]
Abbott, C. A., Garrow, A. P., Carrington, A. L., Morris, J., Van Ross, E. R., Boulton, A. J.
(2005). Foot Ulcer Risk Is Lower in South-Asian and African-Caribbean Compared With European Diabetic Patients in the U.K.: The North-West Diabetes Foot Care Study. Diabetes Care
28: 1869-1875
[Abstract][Full Text]
De Block, C. E.M., De Leeuw, I. H., Van Gaal, L. F.
(2005). Impact of Overweight on Chronic Microvascular Complications in Type 1 Diabetic Patients. Diabetes Care
28: 1649-1655
[Abstract][Full Text]
Rosson, G. D., Dellon, A. L., Gross, R., Sone, H., Mizuno, S., Yamada, N., Tesfaye, S., Witte, D. R., Fuller, J. H.
(2005). Vascular Risk Factors and Diabetic Neuropathy. NEJM
352: 1925-1927
[Full Text]