Skip to main content
SpringerLink
Log in

Diabetic Neuropathy in Elderly Patients

What Can Be Done?

  • Review Article
  • Disease Management
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Summary

The prevalence of diabetes mellitus increases markedly with age. Furthermore, advancing age is a strong risk factor for diabetic neuropathy, independent of the duration of diabetes mellitus and glycaemic control. Several biological changes occurring during the aging process may account for the facilitating effect of age on diabetic neuropathy. These include an increase in the production of advanced glycosylation end-products (AGEs), a defect in the polyol pathway, nerve vascular alterations and impaired resistance to oxidative stress.

The clinical diagnosis of diabetic neuropathy is often difficult in elderly patients. The relationship between symptoms and neuropathy and that between neuropathy and diabetes mellitus are more difficult to ascertain in elderly patients due to age-related changes in the peripheral and autonomic nervous system and associated diseases frequently encountered in this population. Diagnosis of diabetic neuropathy is based on nerve conduction studies, vibratory perception threshold determination and assessment of autonomic function. For most of these tests, reference values are markedly influenced by age and their interpretation should use carefully age-adjusted reference intervals.

Identification of peripheral diabetic neuropathy indicates a high risk of foot complications, such as ulcers and gangrene, often resulting in amputation, whereas cardiovascular autonomic neuropathy is associated with an increased risk of postural hypotension and coronary events. All these risks increase markedly with aging.

Therapeutic trials in elderly patients with diabetic neuropathy are lacking. Treatment of diabetic neuropathy consists of achievement of better glycaemic control and treatment of symptoms related to neuropathy. Specific treatments capable of preventing or curing neuropathy are under investigation. The interesting results obtained with aldose reductase inhibitors in animal studies contrast with disappointing results in patients with diabetes mellitus. Other metabolic approaches, like antioxidants and γ-linolenic acid, seem promising.

Clinical complications of diabetic neuropathy in the elderly are often severe. Early detection is required, since at the present time a preventive approach is the most effective way to avoid or postpone debilitating complications. More research is needed to make effective curative treatments of diabetic neuropathy available.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Morrow LA, Herman WH, Halter JB. Diabetes mellitus. In: Evans JG, William TF, editors. Oxford textbook of geriatric medicine. Oxford: Oxford University Press, 1992: 131–40

    Google Scholar 

  2. Harris MI, Hadden WC, Knowler WC, et al. Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in US population aged 20–74 years. Diabetes 1987; 36: 523–34

    Article  PubMed  CAS  Google Scholar 

  3. Morley JE, Mooradian AD, Rosenthal MJ, et al. Diabetes mellitus in elderly patients: is it different? Am J Med 1987; 83: 533–44

    Article  PubMed  CAS  Google Scholar 

  4. Tattersall RB. Diabetes in the elderly: a neglected area? Diabetologia 1984; 27: 167–73

    PubMed  CAS  Google Scholar 

  5. Dornan TL, Peck GM, Dow JDC, et al. A community survey of diabetes in the elderly. Diabetic Med 1992; 9: 860–5

    Article  PubMed  CAS  Google Scholar 

  6. Morst RS, Sinnock P. The epidemiology of lower extremity amputation in diabetic individuals. Diabetes Care 1983; 6: 87–91

    Article  Google Scholar 

  7. Deerochanawong C, Home PD, Alberti KGMM. A survey of lower limb amputation in diabetic patients. Diabetic Med 1992; 9: 942–6

    Article  PubMed  CAS  Google Scholar 

  8. Ewing DJ, Campbell D, Clarke BF. The natural history of diabetic autonomic neuropathy. Q J Med 1980; 49: 95–100

    PubMed  CAS  Google Scholar 

  9. Sampson MJ, Wilson S, Karagiannis R, et al. Progression of diabetic autonomic neuropathy over a decade in insulin dependent diabetics. Q J Med 1990; 75: 635–46

    PubMed  CAS  Google Scholar 

  10. Diabetes Control and Complications Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes. N Engl J Med 1993; 329: 977–86

    Article  Google Scholar 

  11. Reichard P, Nilsson BY, Rosenqvist U. The effect of long term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med 1993; 329: 304–9

    Article  PubMed  CAS  Google Scholar 

  12. DeFronzo R. Glucose intolerance and aging. Diabetes Care 1981; 4: 493–501

    Article  PubMed  CAS  Google Scholar 

  13. Valensi P, Giroux C, Seeboth-Galayini B, et al. Diabetic peripheral neuropathy: effects of age, duration of diabetes, glycemic control and vascular factors. J Diabetes Complications. In press

  14. Ziegler D, Gries FA, Spüler M, et al. The epidemiology of diabetic neuropathy. Diabetic Med 1993; 10 Suppl. 2: 82S–6S

    Article  PubMed  Google Scholar 

  15. Monnier V. Nonenzymatic glycosylation, the Maillard reaction and the aging process. J Gerontol Biol Sci 1990; 45: 105–11

    Google Scholar 

  16. Belmin J, Tedgui A. Le vieillissement artériel. Médecine/Sciences 1993; 10: 1068–78

    Google Scholar 

  17. Vlassara H, Brownlee M, Manogue KR, et al. Cachectin/TNF and IL-1 induced by glucose-modified proteins: role in normal tissue remodeling. Science 1988; 240: 1546–8

    Article  PubMed  CAS  Google Scholar 

  18. Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med 1988; 318: 1315–21

    Article  PubMed  CAS  Google Scholar 

  19. Brownlee M. Glycation and diabetic complications. Diabetes 1994; 43: 836–41

    PubMed  CAS  Google Scholar 

  20. Funasako M, Fujimoto K, Taniji M, et al. Effect of ageing on erythrocyte aldose reductase and sorbitol dehydrogenase activity. Mech Ageing Dev 1994; 73: 137–43

    Article  PubMed  CAS  Google Scholar 

  21. Vracko R. A comparison of the microvascular lesions in diabetes mellitus with those of normal aging. J Am Geriatr Soc 1982; 30: 201–5

    PubMed  CAS  Google Scholar 

  22. Sima AAF, Nathaniel V, Prashar A, et al. Endoneural microvessels in human diabetic neuropathy: endothelial cell dysfunction and lack of treatment effect by aldose reductase inhibitors. Diabetes 1991; 40: 1090–9

    Article  PubMed  CAS  Google Scholar 

  23. Greene DA, Sima AAF, Stevens MJ, et al. Complications: neuropathy, pathogenetic considerations. Diabetes Care 1992; 15: 1902–25

    Article  PubMed  CAS  Google Scholar 

  24. Cameron NE, Cotter MA, Archibald V, et al. Anti-oxidant and pro-oxidant effects on nerve conduction velocity, endoneurial blood flow and oxygen tension in non-diabetic and streptozocin rats. Diabetologica 1994; 37: 449–59

    Article  CAS  Google Scholar 

  25. Martin GM. Biological mechanisms of ageing. In: Evans JG, William TF, editors. Oxford textbook of geriatric medicine. Oxford: Oxford University Press, 1992: 41–8

    Google Scholar 

  26. Vaughan DW. Effects of advancing age on peripheral nerve regeneration. J Comp Neurol 1992; 323: 219–37

    Article  PubMed  CAS  Google Scholar 

  27. O’Keeffe ST, Smith T, Valacio R, et al. A comparison of two techniques for ankle jerk assessment in elderly subjects. Lancet 1994; 344: 1619–20

    Article  PubMed  Google Scholar 

  28. Impallomeni M, Kenny RA, Flynn MD, et al. The elderly and their ankle jerks. Lancet 1984; 1: 670–2

    Article  PubMed  CAS  Google Scholar 

  29. Oh SJ. Clinical electromyography: nerve conduction studies. Baltimore: University Park Press, 1984

    Google Scholar 

  30. Buchtal F, Rosenfalck A, Behse F. Sensory potentials of normal and diseased nerves. In: Dyck PJ, Thomas PK, Lambert EH, et al., editors. Peripheral neuropathy. Philadelphia: WB Saunders, 1984: 981–1015

    Google Scholar 

  31. Bouche P, Cattelin F, Saint-Jean O, et al. Clinical and electrophysiological study of the peripheral nervous system in the elderly. J Neurol 1993; 240: 263–8

    Article  PubMed  CAS  Google Scholar 

  32. Taylor PK. Non-linear effects of age on nerve conduction in adults. J Neurol Sci 1984; 66: 223–34

    Article  PubMed  CAS  Google Scholar 

  33. Maser RE, Laudadio C, DeCherney GS. The effects of age and diabetes mellitus on nerve function. J Am Geriatr Soc 1993; 41: 1202–4

    PubMed  CAS  Google Scholar 

  34. Wiles PG, Pearce SM, Rice PJS, et al. Vibration perception threshold: influence of age, height, sex, and smoking, and calculation of accurate centile values. Diabetic Med 1991; 8: 157–61

    Article  PubMed  CAS  Google Scholar 

  35. Armstrong FM, Bradbury JE, Ellis SH, et al. A study of peripheral diabetic neuropathy: the application of age-related reference values. Diabetic Med 1991; 8 Suppl.: S94–9

    Article  PubMed  Google Scholar 

  36. Thomson FJ, Masson EA, Boulton AJM. Quantitative vibration perception testing in elderly preople: an assessment of variability. Age Ageing 1992; 21: 171–4

    Article  PubMed  CAS  Google Scholar 

  37. Rowe JW, Troen BR. Sympathetic nervous system and aging in man. Endocrine Rev 1980; 1: 167–79

    Article  CAS  Google Scholar 

  38. Collins KJ, Exton-Smith AN, James MH, et al. Functional changes in autonomic nervous responses with aging. Age Ageing 1980; 9: 17–24

    Article  PubMed  CAS  Google Scholar 

  39. Christiensen NJ. Sympathetic nervous activity and age. Eur J Clin Invest 1982; 12: 91–2

    Google Scholar 

  40. Pfeifer MA, Weinberg CG, Cook D, et al. Differential changes of autonomic nervous system with age in man. Am J Med 1983; 75: 249–58

    Article  PubMed  CAS  Google Scholar 

  41. Mets TF. Drug-induced orthostatic hypotension in older patients. Drugs Aging 1995; 6: 219–28

    Article  PubMed  CAS  Google Scholar 

  42. Evans JG, William TF, editors. Oxford textbook of geriatric medicine. Oxford: Oxford University Press, 1992

    Google Scholar 

  43. Veerman DP, Imholz BPM, Wieling W, et al. Effects of aging on blood pressure variability in resting conditions. Hypertension 1994; 24: 120–30

    Article  PubMed  CAS  Google Scholar 

  44. Pagani M, Lombardi R, Guzetti S, et al. Power spectral analysis of heart rate and arterial pressure in man and conscious dog. Circ Res 1986; 59: 178–93

    Article  PubMed  CAS  Google Scholar 

  45. Lipsitz LA, Ryan SM, Parker JA, et al. Hemodynamic and autonomic nervous system responses to mixed meal ingestion in healthy young and old subjects and dysautonomic patients with postprandial hypotension. Circulation 1993; 87: 391–400

    Article  PubMed  CAS  Google Scholar 

  46. Wieling W, Veerman DP, Dambrink JHA, et al. Disparities in circulatory adaptation upon standing between young and old subjects explained by pulse contour analysis. Clin Sci 1992; 83: 149–55

    PubMed  CAS  Google Scholar 

  47. Ziegler D, Laux G, Dannehl K, et al. 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. Diabetic Med 1992; 9: 166–75

    Article  PubMed  CAS  Google Scholar 

  48. Siehé JP, de Gaudemaris R, Chevalier M, et al. Evaluation de l’altération du système nerveux autonome cardiaque avec l’âge par mesure clinique automatisée. Arch Mal Coeur Vaiss 1993; 86: 1187–91

    Google Scholar 

  49. Smagghue O, Pichart C, Attali JR, et al. Altérations de la fonction sympathique chez les diabétiques [abstract]. Diabete Metab 1993; 19: 33

    Google Scholar 

  50. Ziegler MG, Lake CR, Kopin IJ. Plasma noradrenaline increase with age. Nature 1976; 261: 333–5

    Article  PubMed  CAS  Google Scholar 

  51. Rubin PC, Scott PJW, McLean K, et al. Noradrenaline release and clearance in relation to age and blood pressure in man. Eur J Clin Invest 1982; 12: 121–5

    Article  PubMed  CAS  Google Scholar 

  52. Ng AV, Callister R, Johnson DG, et al. Age and gender influence muscle sympathetic nerve activity at rest in healthy humans. Hypertension 1993; 21: 498–503

    Article  PubMed  CAS  Google Scholar 

  53. Wallin BG, Sundlöf G, Eriksson BM, et al. Plasma noradrenaline correlates to sympathetic muscle nerve activity in normotensive man. Acta Physiol Scand 1981; 111: 69–73

    Article  PubMed  CAS  Google Scholar 

  54. White M, Roden R, Minobe W, et al. Age-related changes in β-adrenergic neuroeffector systems in the human heart. Circulation 1994; 90: 1225–38

    Article  PubMed  CAS  Google Scholar 

  55. Lakatta EG. Cardiovascular regulation in aging. Physiol Rev 1993; 73: 413–67

    PubMed  CAS  Google Scholar 

  56. Dobson JR, Fenton RA, Romano FD. Increased myocardial adenosine production and reduction of β-adrenergic contractile response in aged hearts. Circ Res 1990; 66: 1381–90

    Article  PubMed  CAS  Google Scholar 

  57. Folkow B, Svanborg A. Physiology of cardiovascular aging. Physiol Rev 1993; 73: 725–64

    PubMed  CAS  Google Scholar 

  58. Ford GA, Hoffman BB, Blaschke TF. Cardiac chronotropic and vascular smooth muscle beta-adrenergic responses during propanolol therapy and withdrawal in young and elderly persons. J Gerontol Med Sci 1992; 47: M56–8

    Google Scholar 

  59. Bays HE, Pfeifer MA. Peripheral diabetic neuropathy. Med Clin North Am 1988; 72: 1439–64

    PubMed  CAS  Google Scholar 

  60. Ellenberg M. Diabetic neuropathic cachexia. Diabetes 1974; 23: 418–23

    PubMed  CAS  Google Scholar 

  61. Ewing DJ, Martyn CN, Young RJ, et al. The value of cardiovascular autonomic tests: 10 years experience in diabetes. Diabetes Care 1985; 8: 481–98

    Article  Google Scholar 

  62. Consensus statement. Report and recommendations of the San Antonio conference on diabetic neuropathy. Diabetes 1988; 37: 1000–4

    Google Scholar 

  63. Valensi P, Attali JR, Gagant S, et al. Reproducibility of parameters for assessment of diabetic neuropathy. Diabetic Med 1993; 10: 933–9

    Article  PubMed  CAS  Google Scholar 

  64. Valensi P, Sachs RN, Attali JR. L’ischémie myocardique silencieuse chez le diabétique: problèmes diagnostiques. Diabete Metab 1989; 15: 204–5

    PubMed  CAS  Google Scholar 

  65. Moss S, Klein R, Klein B. The prevalence and incidence of lower extremity amputation in a diabetic population. Arch Intern Med 1992; 152: 610–6

    Article  PubMed  CAS  Google Scholar 

  66. Waugh NR. Amputations in diabetic patients: a review of rates relative risks and resource use. Community Med 1988; 10: 279–88

    PubMed  CAS  Google Scholar 

  67. Vogt MT, Cauley JA, Neuman AB, et al. Decreased ankle/arm pressure index and mortality in elderly women. JAMA 1993; 270: 465–9

    Article  PubMed  CAS  Google Scholar 

  68. White EG, Mulley GP. Footcare for very elderly people: a community survey. Age Ageing 1989; 18: 275–8

    Article  Google Scholar 

  69. Edmonds ME, Blundell MP, Morris HE, et al. The diabetic foot: impact of a foot clinic. Q J Med 1986; 232: 761–3

    Google Scholar 

  70. Thomson FJ, Masson EA. Can elderly diabetic patients co-operate with routine foot care? Age Ageing 1992; 21: 333–7

    Article  PubMed  CAS  Google Scholar 

  71. Van Weel C, Vermeulen H, van den Bosch W. Falls: a community care perspective. Lancet 1995; 345: 1549–51

    Article  PubMed  Google Scholar 

  72. Valensi P, Miossec P, Attali JR. Vidange gastrique et instabilité du diabète. In: Selam JL, editor. Journées annuelles de diabétologie de l’Hotel-Dieu. Paris: Médecine-Sciences Flammarion, 1995: 257–70

    Google Scholar 

  73. Archer AG, Watkins PJ, Thomas PK, et al. The natural history of acute painful neuropathy in diabetes mellitus. J Neurol Neurosurg Psychaitry 1983; 46: 491–9

    Article  CAS  Google Scholar 

  74. Young RL, Clarke BF. Pain relief in diabetic neuropathy: the effectiveness of imipramine and related drugs. Diabet Med 1985; 2: 363–6

    Article  PubMed  CAS  Google Scholar 

  75. Rains C, Bryson HM. Topical capsaicin: a review of its pharmacological properties and therapeutic potential in post-herpetic neuralgia, diabetic neuropathy and osteoarthritis. Drugs Aging 1995; 7: 317–28

    Article  PubMed  CAS  Google Scholar 

  76. Shade RR, Dugas MC, Lhotsky DM, et al. Effect of metoclopramine on gastric liquid emptying in patients with diabetic gastroparesis. Dig Dis Sci 1985; 30: 10–5

    Article  Google Scholar 

  77. Horowitz M, Harding PE, Chatterton BE, et al. Acute and chronic effects of domperidone on gastric emptying in diabetic autonomic neuropathy. Dig Dis Sci 1985; 30: 1–9

    Article  PubMed  CAS  Google Scholar 

  78. Horowitz M, Maddox A, Harding PE, et al. Effect of cisapride on gastric and oesophageal emptying in insulin-dependent diabetes mellitus. Gastroenterology 1987; 92: 1899–907

    PubMed  CAS  Google Scholar 

  79. Janssens J, Peeters TL, Vantrappen G, et al. Improvement of gastric emptying in diabetic gastroparesis by erythromycine. N Engl J Med 1990; 322: 1028–31

    Article  PubMed  CAS  Google Scholar 

  80. Thomas M, Verges M. Traitement par la phénytoïne de la diarrhée motrice du diabétique. Presse Med 1986; 15: 11–4

    PubMed  CAS  Google Scholar 

  81. Fedorak RN, Field M, Chang EB. Treatment of diabetic diarrhea with Clonidine. Ann Intern Med 1985; 102: 197–9

    PubMed  CAS  Google Scholar 

  82. Condon JR, Suleman MI, Fan YS, et al. Cholestyramine and diabetic and post-vagotomy diarrhoea [letter]. BMJ 1973; 4: 423

    Article  PubMed  CAS  Google Scholar 

  83. Belmin J, Pangrazzi JP, Salvatore R, et al. Intoxication muscarinique induite par le béthanechol au cours d’une insuffisance rénale [letter]. Presse Med 1988; 17: 213

    PubMed  CAS  Google Scholar 

  84. Dejgard A, Hilsted J. No effect of pindolol on postural hypotension in type 1 (insulin-dependent) diabetic patients with autonomic neuropathy. A randomised double-blind controlled study. Diabetologia 1988; 31: 281–4

    PubMed  CAS  Google Scholar 

  85. Diabetes Control and Complications Research Group. Factors in development of diabetic neuropathy: baseline analysis of neuropathy in the feasibility phase of diabetes control and complications trial (DCCT). Diabetes 1988; 37: 476–81

    Article  Google Scholar 

  86. Service FJ, Daube JR, O’Brien PC, et al. Effect of artificial pancreas treatment on peripheral nerve function in diabetics. Neurology 1981; 31: 1375–80

    Article  PubMed  CAS  Google Scholar 

  87. Ziegler D, Mayer P, Mühlen H, et al. 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: 822–9

    Article  PubMed  CAS  Google Scholar 

  88. Fedele D, Bellavere F, Cardone C, et al. Short and long term continuous insulin infusion system treatment in patients with autonomic diabetic neuropathy. Horm Metab Res 1985; 17: 410–3

    Article  PubMed  CAS  Google Scholar 

  89. Jakobsen J, Christiansen JS, Kristoffersen I, et al. Autonomic and somatosensory nerve function after 2 years of continuous insulin infusion in type 1 diabetes. Diabetes 1988; 37: 452–5

    Article  PubMed  CAS  Google Scholar 

  90. Jaspan J, Maselli R, Hoerold K, et al. Treatment of severely painful diabetic neuropathy with an aldose reductase inhibitor: relief of pain and improved somatic and autonomic function. Lancet 1983; II: 758–62

    Article  Google Scholar 

  91. Guy RCJ, Gilbey SG, Sheehy M, et al. Diabetic neuropathy in the upper limb and the effect of twelve months sorbitol treatment. Diabetologia 1988; 31: 214–20

    Article  PubMed  CAS  Google Scholar 

  92. Sundkvist G, Lila B, Rosen I, et al. Autonomic and peripheral nerve function in early diabetic neuropathy: possible influence of a novel aldose reductase inhibitor on autonomic function. Acta Med Scand 1987; 221: 445–53

    Article  PubMed  CAS  Google Scholar 

  93. Cameron NE, Cotter MA. Potential therapeutic approaches to the treatment or prevention of diabetic neuropathy: evidence from experimental studies. Diabetic Med 1993; 10: 593–605

    Article  PubMed  CAS  Google Scholar 

  94. Steele JW, Faulds D, Goa KL. Epalrestat: a review of its pharmacology, and therapeutic potential in late-onset complications of diabetes mellitus. Drugs Aging 1993; 3: 532–55

    Article  PubMed  CAS  Google Scholar 

  95. Jamal GA, Carmichael H. The effect of γ-linolenic acid on human diabetic peripheral neuropathy: a double-blind placebo controlled trial. Diabetic Med 1990; 7: 319–23

    Article  PubMed  CAS  Google Scholar 

  96. Tesfaye S, Malik R, Ward JD. Vascular factors in diabetic neuropathy. Diabetologia 1994; 37: 847–54

    Article  PubMed  CAS  Google Scholar 

  97. Morley JE, Perry HM. The management of diabetes mellitus in older individuals. Drugs 1991; 41: 356–60

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Service de Médecine Interne Gériatrique, Hôpital René Muret-Bigottini-Assistance Publique-Hôpitaux de Paris and Université Paris-Nord, Sevran, France

    Joël Belmin

  2. Service d’Endocrinologie-Diabétologie-Nutrition, Hôpital Jean Verdier and Université Paris-Nord, Bondy, France

    Paul Valensi

Authors
  1. Joël Belmin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul Valensi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Belmin, J., Valensi, P. Diabetic Neuropathy in Elderly Patients. Drugs & Aging 8, 416–429 (1996). https://doi.org/10.2165/00002512-199608060-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-199608060-00003

Keywords

Search

Navigation