Diabetes and the Nervous System

  • Aaron I. Vinik
  • Carolina Casellini
  • Serina Neuman
Living reference work entry
Part of the Endocrinology book series (ENDOCR)

Abstract

Diabetic neuropathy is the most common and troublesome complication of diabetes mellitus, leading to the greatest morbidity and mortality and resulting in a huge economic burden for diabetes care. It includes a set of clinical syndromes that affect distinct regions of the nervous system, singly or combined. Current research shows that diabetes can affect brain structure and function, and lead to significant changes in cognition and behavior. Peripheral neuropathy may be silent and go undetected or it may present with clinical symptoms and signs including pain that can significantly affect the patients’ quality of life. It also contributes to additional risks in the aging adult. Loss of sensory perception and muscle strength, and ataxia or incoordination leads to an increased risk of falling in the elderly. However, risk factors for falling are not simply confined to those variables associated with peripheral sensory-motor function. Cognitive decline, particularly related to executive functioning, is a contributing factor to instability. Cardiac autonomic neuropathy is a common complication of diabetes. Early diagnosis is key, as it has been shown to be an independent risk factor for cardiovascular mortality, arrhythmias, major cardiovascular event, and myocardial dysfunction. This chapter will describe our current knowledge on central, peripheral and autonomic nervous system alterations in response to prediabetes and type 1 and type 2 diabetes.

Keywords

Diabetes Diabetic peripheral neuropathy Pain Cardiac autonomic neuropathy Cognitive dysfunction Central nervous system 

References

  1. Abbott CA, Carrington AL, Ashe H, Bath S, Every LC, Griffiths J, et al. The North-West Diabetes Foot Care Study: incidence of, and risk factors for, new diabetic foot ulceration in a community-based patient cohort. Diabet Med. 2002;19(5):377–84.PubMedGoogle Scholar
  2. Abbott CA, Malik RA, Van Ross ER, Kulkarni J, Boulton AJ. Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the U.K. Diabetes Care. 2011;34(10):2220–4.PubMedPubMedCentralGoogle Scholar
  3. Abuaisha BB, Costanzi JB, Boulton AJ. Acupuncture for the treatment of chronic painful peripheral diabetic neuropathy: a long-term study. Diabetes Res Clin Pract. 1998;39(2):115–21.PubMedGoogle Scholar
  4. Adkin AL, Frank JS, Carpenter MG, Peysar GW. Postural control is scaled to level of postural threat. Gait Posture. 2000;12(2):87–93.PubMedGoogle Scholar
  5. ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–72.Google Scholar
  6. Ahmed A, Bril V, Orszag A, Paulson J, Yeung E, Ngo M, et al. Detection of diabetic sensorimotor polyneuropathy by corneal confocal microscopy in type 1 diabetes: a concurrent validity study. Diabetes Care. 2012;35(4):821–8.PubMedPubMedCentralGoogle Scholar
  7. Ajroud-Driss S, Christiansen M, Allen JA, Kessler JA. Phase 1/2 open-label dose-escalation study of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with painful diabetic peripheral neuropathy. Mol Ther. 2013;21:1279.PubMedPubMedCentralGoogle Scholar
  8. Albers JW, Pop-Busui R. Diabetic neuropathy: mechanisms, emerging treatments, and subtypes. Curr Neurol Neurosci Rep. 2014;14(8):473.PubMedPubMedCentralGoogle Scholar
  9. Albers JW, Herman WH, Pop-Busui R, Feldman EL, Martin CL, Cleary PA, et al. Effect of prior intensive insulin treatment during the Diabetes Control and Complications Trial (DCCT) on peripheral neuropathy in type 1 diabetes during the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. Diabetes Care. 2010;33(5):1090–6.PubMedPubMedCentralGoogle Scholar
  10. Allen KV, Frier BM, Strachan MW. The relationship between type 2 diabetes and cognitive dysfunction: longitudinal studies and their methodological limitations. Eur J Pharmacol. 2004;490(1-3):169–75.PubMedGoogle Scholar
  11. Allet L, Armand S, de Bie RA, Golay A, Pataky Z, Aminian K, et al. Clinical factors associated with gait alterations in diabetic patients. Diabet Med. 2009;26(10):1003–9.PubMedGoogle Scholar
  12. Allet L, Armand S, de Bie RA, Golay A, Monnin D, Aminian K, et al. The gait and balance of patients with diabetes can be improved: a randomised controlled trial. Diabetologia. 2010;53(3):458–66.PubMedGoogle Scholar
  13. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2013;36(Suppl 1):S11.Google Scholar
  14. American Diabetes Association American Academy of Neurology. Consensus statement: Report and recommendations of the San Antonio conference on diabetic neuropathy. Diabetes Care. 1988;11(7):592–7.Google Scholar
  15. Ametov AS, Barinov A, Dyck PJ, Hermann R, Kozlova N, Litchy WJ, et al. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care. 2003;26(3):770–6.PubMedGoogle Scholar
  16. Ang L, Jaiswal M, Martin C, Pop-Busui R. Glucose control and diabetic neuropathy: lessons from recent large clinical trials. Curr Diab Rep. 2014;14(9):528.PubMedPubMedCentralGoogle Scholar
  17. Apfel SC, Kessler JA, Adornato BT, Litchy WJ, Sanders C, Rask CA. Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy. NGF Study Group. Neurology. 1998;51(3):695–702.PubMedGoogle Scholar
  18. Arezzo JC, Rosenstock J, LaMoreaux L, Pauer L. Efficacy and safety of pregabalin 600 mg/d for treating painful diabetic peripheral neuropathy: a double-blind placebo-controlled trial. BMC Neurol. 2008;8:33.PubMedPubMedCentralGoogle Scholar
  19. Asghar O, Petropoulos IN, Alam U, Jones W, Jeziorska M, Marshall A, et al. Corneal confocal microscopy detects neuropathy in subjects with impaired glucose tolerance. Diabetes Care. 2014;37(9):2643–6.PubMedPubMedCentralGoogle Scholar
  20. Aung PP, Strachan MW, Frier BM, Butcher I, Deary IJ, Price JF. Severe hypoglycaemia and late-life cognitive ability in older people with Type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Diabet Med. 2012;29(3):328–36.PubMedGoogle Scholar
  21. Ayyar DR, Sharma KR. Chronic inflammatory demyelinating polyradiculoneuropathy in diabetes mellitus. Curr Diab Rep. 2004;4(6):409–12.PubMedGoogle Scholar
  22. Azmi S, Ferdousi M, Petropoulos IN, Ponirakis G, Alam U, Fadavi H, et al. Corneal confocal microscopy identifies small-fiber neuropathy in subjects with impaired glucose tolerance who develop type 2 diabetes. Diabetes Care. 2015;38(8):1502–8.PubMedPubMedCentralGoogle Scholar
  23. Backonja M, Glanzman RL. Gabapentin dosing for neuropathic pain: evidence from randomized, placebo-controlled clinical trials. Clin Ther. 2003;25(1):81–104.PubMedGoogle Scholar
  24. Backonja M, Beydoun A, Edwards KR, Schwartz SL, Fonseca V, Hes M, et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. JAMA. 1998;280(21):1831–6.PubMedGoogle Scholar
  25. Backonja M, Wallace MS, Blonsky ER, Cutler BJ, Malan P Jr, Rauck R, et al. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet Neurol. 2008;7(12):1106–12.PubMedGoogle Scholar
  26. Backonja MM, Attal N, Baron R, Bouhassira D, Drangholt M, Dyck PJ, et al. Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus. Pain. 2013;154(9):1807–19.PubMedGoogle Scholar
  27. Baeuerle PA, Baltimore D. NF-kappa B: ten years after. Cell. 1996;87(1):13–20.PubMedGoogle Scholar
  28. Bakkers M, Merkies IS, Lauria G, Devigili G, Penza P, Lombardi R, et al. Intraepidermal nerve fiber density and its application in sarcoidosis. Neurology. 2009;73(14):1142–8.PubMedGoogle Scholar
  29. Balducci S, Iacobellis G, Parisi L, Di BN, Calandriello E, Leonetti F, et al. Exercise training can modify the natural history of diabetic peripheral neuropathy. J Diabetes Complicat. 2006;20(4):216–23.PubMedGoogle Scholar
  30. Banks WA. The source of cerebral insulin. Eur J Pharmacol. 2004;490(1–3):5–12.PubMedGoogle Scholar
  31. Barada A, Reljanovic M, Milicevic Z, Ljubic S, Car N, Benko B, et al. Proximal diabetic neuropathy-response to immunotherapy. Diabetes. 1999;48(Suppl 1):A148.Google Scholar
  32. Barnett A, Smith B, Lord SR, Williams M, Baumand A. Community-based group exercise improves balance and reduces falls in at-risk older people: a randomised controlled trial. Age Ageing. 2003;32(4):407–14.PubMedGoogle Scholar
  33. Baron R. Mechanisms of disease: neuropathic pain – a clinical perspective. Nat Clin Pract Neurol. 2006;2(2):95–106.PubMedGoogle Scholar
  34. Baron R, Tolle TR, Gockel U, Brosz M, Freynhagen R. A cross-sectional cohort survey in 2100 patients with painful diabetic neuropathy and postherpetic neuralgia: differences in demographic data and sensory symptoms. Pain. 2009;146(1–2):34–40.PubMedGoogle Scholar
  35. Bastyr E, Zhang D, Bril V, The MBBQ Study Group. Neuropathy Total symptom Score-6 Questionnaire (NTSS-6) is a valid instrument for assessing the positive symptoms of diabetic peripheral neuropathy (DPN). Diabetes. 2002;51:A199.Google Scholar
  36. Benedict C, Hallschmid M, Schmitz K, Schultes B, Ratter F, Fehm HL, et al. Intranasal insulin improves memory in humans: superiority of insulin aspart. Neuropsychopharmacology. 2007;32(1):239–43.PubMedGoogle Scholar
  37. Bennett MI, Smith BH, Torrance N, Potter J. The S-LANSS score for identifying pain of predominantly neuropathic origin: validation for use in clinical and postal research. J Pain. 2005;6(3):149–58.PubMedGoogle Scholar
  38. Bennett MI, Attal N, Backonja MM, Baron R, Bouhassira D, Freynhagen R, et al. Using screening tools to identify neuropathic pain. Pain. 2007;127(3):199–203.PubMedGoogle Scholar
  39. Berlie HD, Garwood CL. Diabetes medications related to an increased risk of falls and fall-related morbidity in the elderly. Ann Pharmacother. 2010;44(4):712–7.PubMedGoogle Scholar
  40. Bernardi L, Spallone V, Stevens M, Hilsted J, Frontoni S, Pop-Busui R, et al. Methods of investigation for cardiac autonomic dysfunction in human research studies. Diabetes Metab Res Rev. 2011;27(7):654–64.PubMedGoogle Scholar
  41. Bierhaus A, Schiekofer S, Schwaninger M, Andrassy M, Humpert PM, Chen J, et al. Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB. Diabetes. 2001;50(12):2792–808.PubMedGoogle Scholar
  42. Biesbroeck R, Bril V, Hollander P, Kabadi U, Schwartz S, Singh SP, et al. A double-blind comparison of topical capsaicin and oral amitriptyline in painful diabetic neuropathy. Adv Ther. 1995;12(2):111–20.PubMedGoogle Scholar
  43. Biessels GJ, Reijmer YD. Brain changes underlying cognitive dysfunction in diabetes: what can we learn from MRI? Diabetes. 2014;63(7):2244–52.PubMedGoogle Scholar
  44. Biessels GJ, Bril V, Calcutt NA, Cameron NE, Cotter MA, Dobrowsky R, et al. Phenotyping animal models of diabetic neuropathy: a consensus statement of the diabetic neuropathy study group of the EASD (Neurodiab). J Peripher Nerv Syst. 2014;19(2):77–87.PubMedPubMedCentralGoogle Scholar
  45. Bongaerts BW, Rathmann W, Heier M, Kowall B, Herder C, Stockl D, et al. Older subjects with diabetes and prediabetes are frequently unaware of having distal sensorimotor polyneuropathy: the KORA F4 study. Diabetes Care. 2013;36(5):1141–6.PubMedPubMedCentralGoogle Scholar
  46. Bordier L, Doucet J, Boudet J, Bauduceau B. Update on cognitive decline and dementia in elderly patients with diabetes. Diabete Metab. 2014;40(5):331–7.PubMedGoogle Scholar
  47. Borenstein J, Aronow HU, Bolton LB, Choi J, Bresee C, Braunstein GD. Early recognition of risk factors for adverse outcomes during hospitalization among Medicare patients: a prospective cohort study. BMC Geriatr. 2013;13:72.PubMedPubMedCentralGoogle Scholar
  48. Bosi E, Conti M, Vermigli C, Cazzetta G, Peretti E, Cordoni MC, et al. Effectiveness of frequency-modulated electromagnetic neural stimulation in the treatment of painful diabetic neuropathy. Diabetologia. 2005;48(5):817–23.PubMedGoogle Scholar
  49. Bosi E, Bax G, Scionti L, Spallone V, Tesfaye S, Valensi P, et al. Frequency-modulated electromagnetic neural stimulation (FREMS) as a treatment for symptomatic diabetic neuropathy: results from a double-blind, randomised, multicentre, long-term, placebo-controlled clinical trial. Diabetologia. 2013;56(3):467–75.PubMedGoogle Scholar
  50. Boucher P, Teasdale N, Courtemanche R, Bard C, Fleury M. Postural stability in diabetic polyneuropathy. Diabetes Care. 1995;18(5):638–45.PubMedGoogle Scholar
  51. Bouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E, et al. Development and validation of the neuropathic pain symptom inventory. Pain. 2004;108(3):248–57.PubMedGoogle Scholar
  52. Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain. 2005;114(1–2):29–36.PubMedGoogle Scholar
  53. Bouhassira D, Lanteri-Minet M, Attal N, Laurent B, Touboul C. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain. 2008;136(3):380–7.PubMedGoogle Scholar
  54. Boulanger L, Zhao Y, Foster TS, Fraser K, Bledsoe SL, Russell MW. Impact of comorbid depression or anxiety on patterns of treatment and economic outcomes among patients with diabetic peripheral neuropathic pain. Curr Med Res Opin. 2009;25(7):1763–73.PubMedGoogle Scholar
  55. Boulton AJ. The pathway to foot ulceration in diabetes. Med Clin North Am. 2013;97(5):775–90.PubMedGoogle Scholar
  56. Boulton AJ, Malik RA, Arezzo JC, Sosenko JM. Diabetic somatic neuropathies. Diabetes Care. 2004;27(6):1458–86.PubMedGoogle Scholar
  57. Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005;28(4):956–62.PubMedGoogle Scholar
  58. Bourcier ME, Ullal J, Parson HK, Dublin CB, Witherspoon CA, Ward SA, et al. Diabetic peripheral neuropathy: how reliable is a homemade 1-g monofilament for screening? J Fam Pract. 2006;55(6):505–8.PubMedGoogle Scholar
  59. Boyd R, Stevens JA. Falls and fear of falling: burden, beliefs and behaviours. Age Ageing. 2009;38(4):423–8.PubMedGoogle Scholar
  60. Boyd AL, Barlow PM, Pittenger GL, Simmons KF, Vinik AI. Topiramate improves neurovascular function, epidermal nerve fiber morphology, and metabolism in patients with type 2 diabetes mellitus. Diabetes Metab Syndr Obes. 2010;3:431–7.PubMedPubMedCentralGoogle Scholar
  61. Boyd A, Casellini C, Vinik E, Vinik A. Quality of life and objective measures of diabetic neuropathy in a prospective placebo controlled trial of ruboxistaurin and topiramate. J Diabetes Sci Technol. 2011;5(3):714–22.PubMedPubMedCentralGoogle Scholar
  62. Boyle J, Eriksson ME, Gribble L, Gouni R, Johnsen S, Coppini DV, et al. Randomized, placebo-controlled comparison of amitriptyline, duloxetine, and pregabalin in patients with chronic diabetic peripheral neuropathic pain: impact on pain, polysomnographic sleep, daytime functioning, and quality of life. Diabetes Care. 2012;35(12):2451–8.PubMedPubMedCentralGoogle Scholar
  63. Bril V. NIS-LL: the primary measurement scale for clinical trial endpoints in diabetic peripheral neuropathy. Eur Neurol. 1999;41(Suppl 1):8–13.PubMedGoogle Scholar
  64. Bril V, Perkins BA. Validation of the Toronto clinical scoring system for diabetic polyneuropathy. Diabetes Care. 2002;25(11):2048–52.PubMedGoogle Scholar
  65. Bril V, England J, Franklin GM, Backonja M, Cohen J, Del TD, et al. Evidence-based guideline: treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011;76(20):1758–65.PubMedPubMedCentralGoogle Scholar
  66. Britland ST, Young RJ, Sharma AK, Clarke BF. Acute and remitting painful diabetic polyneuropathy: a comparison of peripheral nerve fibre pathology. Pain. 1992;48:361–70.PubMedGoogle Scholar
  67. Brown SJ, Handsaker JC, Bowling FL, Boulton AJ, Reeves ND. Diabetic peripheral neuropathy compromises balance during daily activities. Diabetes Care. 2015;38(6):1116–22.PubMedGoogle Scholar
  68. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005;54(6):1615–25.PubMedGoogle Scholar
  69. Bruce DG, Davis WA, Casey GP, Clarnette RM, Brown SG, Jacobs IG, et al. Severe hypoglycaemia and cognitive impairment in older patients with diabetes: the Fremantle Diabetes Study. Diabetologia. 2009;52(9):1808–15.PubMedGoogle Scholar
  70. Callaghan BC, Kerber KA, Lisabeth LL, Morgenstern LB, Longoria R, Rodgers A, et al. Role of neurologists and diagnostic tests on the management of distal symmetric polyneuropathy. JAMA Neurol. 2014;71(9):1143–9.PubMedPubMedCentralGoogle Scholar
  71. Callaghan BC, Xia R, Banerjee M, de Rekeneire N, Harris TB, Newman AB, et al. Metabolic syndrome components are associated with symptomatic polyneuropathy independent of glycemic status. Diabetes Care. 2016;39:801.PubMedPubMedCentralGoogle Scholar
  72. Calvet JH, Dupin J, Winiecki H, Schwarz PEH. Assessment of small fiber neuropathy through a quick, simple and non invasive method in a German diabetes outpatient clinic. Exp Clin Endocrinol Diabetes. 2012;120:1–4.Google Scholar
  73. Cameron NE, Eaton SEM, Cotter MA, Tesfaye S. Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia. 2001;44:1973–88.PubMedGoogle Scholar
  74. Cameron FJ, Kean MJ, Wellard RM, Werther GA, Neil JJ, Inder TE. Insights into the acute cerebral metabolic changes associated with childhood diabetes. Diabet Med. 2005;22(5):648–53.PubMedGoogle Scholar
  75. Carnethon MR, Prineas RJ, Temprosa M, Zhang ZM, Uwaifo G, Molitch ME. The association among autonomic nervous system function, incident diabetes, and intervention arm in the Diabetes Prevention Program. Diabetes Care. 2006;29(4):914–9.PubMedPubMedCentralGoogle Scholar
  76. Carpenter MG, Frank JS, Silcher CP, Peysar GW. The influence of postural threat on the control of upright stance. Exp Brain Res. 2001;138(2):210–8.PubMedGoogle Scholar
  77. Carvalho LA, Urbanova L, Hamer M, Hackett RA, Lazzarino AI, Steptoe A. Blunted glucocorticoid and mineralocorticoid sensitivity to stress in people with diabetes. Psychoneuroendocrinology. 2015;51:209–18.PubMedPubMedCentralGoogle Scholar
  78. Casellini CM, Vinik AI. Clinical manifestations and current treatment options for diabetic neuropathies. Endocr Pract. 2007;13(5):550–66.PubMedGoogle Scholar
  79. Casellini CM, Parson HK, Richardson MS, Nevoret ML, Vinik AI. Sudoscan, a noninvasive tool for detecting diabetic small fiber neuropathy and autonomic dysfunction. Diabetes Technol Ther. 2013;15(11):948–53.PubMedPubMedCentralGoogle Scholar
  80. Castro MM, Daltro C. Sleep patterns and symptoms of anxiety and depression in patients with chronic pain. Arq Neuropsiquiatr. 2009;67(1):25–8.PubMedGoogle Scholar
  81. Cavanagh PR, Simoneau GG, Ulbrecht JS. Ulceration, unsteadiness, and uncertainty: the biomechanical consequences of diabetes mellitus. J Biomech. 1993;26(Suppl 1):23–40.PubMedGoogle Scholar
  82. Chan YC, Lo YL, Chan ES. Immunotherapy for diabetic amyotrophy. Cochrane Database Syst Rev. 2012;6:CD006521.Google Scholar
  83. Chao CC, Hsieh SC, Yang WS, Lin YH, Lin WM, Tai TY, et al. Glycemic control is related to the severity of impaired thermal sensations in type 2 diabetes. Diabetes Metab Res Rev. 2007;23(8):612–20.PubMedGoogle Scholar
  84. Chaudhry V, Stevens JC, Kincaid J, So YT. Practice advisory: utility of surgical decompression for treatment of diabetic neuropathy: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2006;66(12):1805–8.PubMedGoogle Scholar
  85. Chaudhry V, Russell J, Belzberg A. Decompressive surgery of lower limbs for symmetrical diabetic peripheral neuropathy. Cochrane Database Syst Rev. 2008;16(3):CD006152.Google Scholar
  86. Chen W, Yang GY, Liu B, Manheimer E, Liu JP. Manual acupuncture for treatment of diabetic peripheral neuropathy: a systematic review of randomized controlled trials. PLoS One. 2013;8(9):e73764.PubMedPubMedCentralGoogle Scholar
  87. Chen YC, Jiao Y, Cui Y, Shang SA, Ding J, Feng Y, et al. Aberrant brain functional connectivity related to insulin resistance in type 2 diabetes: a resting-state fMRI study. Diabetes Care. 2014;37(6):1689–96.PubMedGoogle Scholar
  88. Chen X, Graham J, Dabbah MA, Petropoulos IN, Ponirakis G, Asghar O, et al. Small nerve fiber quantification in the diagnosis of diabetic sensorimotor polyneuropathy: comparing corneal confocal microscopy with intraepidermal nerve fiber density. Diabetes Care. 2015;38(6):1138–44.PubMedPubMedCentralGoogle Scholar
  89. Chiles NS, Phillips CL, Volpato S, Bandinelli S, Ferrucci L, Guralnik JM, et al. Diabetes, peripheral neuropathy, and lower-extremity function. J Diabetes Complicat. 2014;28(1):91–5.PubMedGoogle Scholar
  90. Christmas C, Andersen RA. Exercise and older patients: guidelines for the clinician. J Am Geriatr Soc. 2000;48(3):318–24.PubMedGoogle Scholar
  91. Cohen E, Dillin A. The insulin paradox: aging, proteotoxicity and neurodegeneration. Nat Rev Neurosci. 2008;9(10):759–67.PubMedPubMedCentralGoogle Scholar
  92. Colberg S. The impact of exercise on insulin action in type 2 diabetes mellitus: Relationship to prevention and control. Insulin. 2006;1(3):85–98.Google Scholar
  93. Colberg S, Stansberry K, McNitt P, Vinik A. Chronic exercise is associated with enhanced cutaneous blood flow in type 2 diabetes. J Diabetes Complicat. 2002;16:139–45.PubMedGoogle Scholar
  94. Colberg SR, Parson HK, Nunnold T, Holton DR, Swain DP, Vinik AI. Change in cutaneous perfusion following 10 weeks of aerobic training in type 2 diabetes. J Diabetes Complicat. 2005;19(5):276–83.PubMedGoogle Scholar
  95. Cole BE. Diabetic peripheral neuropathic pain: recognition and management. Pain Med. 2007;8(Suppl 2):S27–32.PubMedGoogle Scholar
  96. Consensus Report of the Peripheral Nerve Society. Diabetic polyneuropathy in controlled clinical trials. Ann Neurol. 1995;38(3):478–82.Google Scholar
  97. Cooper GJ, Leighton B, Dimitriadis GD, Parry Billings M, Kowalchuk JM, Howland K, et al. Amylin found in amyloid deposits in human type 2 diabetes mellitus may be a hormone that regulates glycogen metabolism in skeletal muscle. Proc Natl Acad Sci U S A. 1988;85(20):7763–6.PubMedPubMedCentralGoogle Scholar
  98. Coppin AK, Shumway-Cook A, Saczynski JS, Patel KV, Ble A, Ferrucci L, et al. Association of executive function and performance of dual-task physical tests among older adults: analyses from the InChianti study. Age Ageing. 2006;35(6):619–24.PubMedPubMedCentralGoogle Scholar
  99. Cornblath DR, Vinik A, Feldman E, Freeman R, Boulton AJ. Surgical decompression for diabetic sensorimotor polyneuropathy. Diabetes Care. 2007;30(2):421–2.PubMedGoogle Scholar
  100. Corriveau H, Prince F, Hebert R, Raiche M, Tessier D, Maheux P, et al. Evaluation of postural stability in elderly with diabetic neuropathy. Diabetes Care. 2000;23(8):1187–91.PubMedGoogle Scholar
  101. Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci. 2009;32:1–32.PubMedPubMedCentralGoogle Scholar
  102. Cosway R, Strachan MW, Dougall A, Frier BM, Deary IJ. Cognitive function and information processing in type 2 diabetes. Diabet Med. 2001;18(10):803–10.PubMedGoogle Scholar
  103. Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012;69:29.PubMedGoogle Scholar
  104. Crichton GE, Elias MF, Buckley JD, Murphy KJ, Bryan J, Frisardi V. Metabolic syndrome, cognitive performance, and dementia. J Alzheimers Dis. 2012;30(Suppl 2):S77–87.PubMedGoogle Scholar
  105. Criego AB, Tkac I, Kumar A, Thomas W, Gruetter R, Seaquist ER. Brain glucose concentrations in patients with type 1 diabetes and hypoglycemia unawareness. J Neurosci Res. 2005;79(1–2):42–7.PubMedGoogle Scholar
  106. Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 1995;378(6559):785–9.PubMedGoogle Scholar
  107. Cruccu G, Sommer C, Anand P, Attal N, Baron R, Garcia-Larrea L, et al. EFNS guidelines on neuropathic pain assessment: revised 2009. Eur J Neurol. 2010;17(8):1010–8.PubMedGoogle Scholar
  108. Cruzat A, Qazi Y, Hamrah P. In vivo confocal microscopy of corneal nerves in health and disease. Ocul Surf. 2017;15(1):15–47.PubMedGoogle Scholar
  109. Cui Y, Jiao Y, Chen Y, Wang K, Gao B, Wen S, et al. Altered spontaneous brain activity in type 2 diabetes: a resting-state functional MRI study. Diabetes. 2014;63(2):749–60.PubMedGoogle Scholar
  110. Cukierman-Yaffe T, Gerstein HC, Williamson JD, Lazar RM, Lovato L, Miller ME, et al. Relationship between baseline glycemic control and cognitive function in individuals with type 2 diabetes and other cardiovascular risk factors: the action to control cardiovascular risk in diabetes-memory in diabetes (ACCORD-MIND) trial. Diabetes Care. 2009;32(2):221–6.PubMedPubMedCentralGoogle Scholar
  111. Dabbah MA, Graham J, Petropoulos IN, Tavakoli M, Malik RA. Automatic analysis of diabetic peripheral neuropathy using multi-scale quantitative morphology of nerve fibres in corneal confocal microscopy imaging. Med Image Anal. 2011;15(5):738–47.PubMedGoogle Scholar
  112. Dabby R, Sadeh M, Lampl Y, Gilad R, Watemberg N. Acute painful neuropathy induced by rapid correction of serum glucose levels in diabetic patients. Biomed Pharmacother. 2009;63(10):707–9.PubMedGoogle Scholar
  113. Dallocchio C, Buffa C, Mazzarello P, Chiroli S. Gabapentin vs. amitriptyline in painful diabetic neuropathy: an open-label pilot study. J Pain Symptom Manag. 2000;20(4):280–5.Google Scholar
  114. Daousi C, MacFarlane IA, Woodward A, Nurmikko TJ, Bundred PE, Benbow SJ. Chronic painful peripheral neuropathy in an urban community: a controlled comparison of people with and without diabetes. Diabet Med. 2004;21(9):976–82.PubMedGoogle Scholar
  115. Daut RL, Cleeland CS, Flanery RC. Development of the Wisconsin Brief Pain Questionnaire to assess pain in cancer and other diseases. Pain. 1983;17(2):197–210.PubMedGoogle Scholar
  116. Davies M, Brophy S, Williams R, Taylor A. The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care. 2006;29(7):1518–22.PubMedGoogle Scholar
  117. DCCT Research Group. The effect of intensive diabetes therapy on the development and progression of neuropathy. Ann Intern Med. 1995a;122:561–8.Google Scholar
  118. DCCT Research Group. Effect of intensive diabetes treatment on nerve conduction in the diabetes control and complications trial. Ann Neurol. 1995b;38:869.Google Scholar
  119. de Bresser J, Tiehuis AM, van den BE, Reijmer YD, Jongen C, Kappelle LJ, et al. Progression of cerebral atrophy and white matter hyperintensities in patients with type 2 diabetes. Diabetes Care. 2010;33(6):1309–14.PubMedPubMedCentralGoogle Scholar
  120. de Galan BE, Zoungas S, Chalmers J, Anderson C, Dufouil C, Pillai A, et al. Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Diabetologia. 2009;52(11):2328–36.PubMedGoogle Scholar
  121. De Vos CC, Meier K, Zaalberg PB, Nijhuis HJ, Duyvendak W, Vesper J, et al. Spinal cord stimulation in patients with painful diabetic neuropathy: a multicentre randomized clinical trial. Pain. 2014;155(11):2426–31.PubMedGoogle Scholar
  122. Dehghani C, Pritchard N, Edwards K, Russell AW, Malik RA, Efron N. Fully automated, semiautomated, and manual morphometric analysis of corneal subbasal nerve plexus in individuals with and without diabetes. Cornea. 2014;33(7):696–702.PubMedGoogle Scholar
  123. Delbaere K, Sturnieks DL, Crombez G, Lord SR. Concern about falls elicits changes in gait parameters in conditions of postural threat in older people. J Gerontol A Biol Sci Med Sci. 2009;64(2):237–42.PubMedGoogle Scholar
  124. Derry S, Lloyd R, Moore RA, McQuay HJ. Topical capsaicin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2009;4:CD007393.Google Scholar
  125. Derry S, Wiffen PJ, Aldington D, Moore RA. Nortriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;1:CD011209.PubMedGoogle Scholar
  126. Derry S, Rice AS, Cole P, Tan T, Moore RA. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;1:CD007393.PubMedGoogle Scholar
  127. DeToledo JC, Toledo C, DeCerce J, Ramsay RE. Changes in body weight with chronic, high-dose gabapentin therapy. Ther Drug Monit. 1997;19(4):394–6.PubMedGoogle Scholar
  128. Dieleman JP, Kerklaan J, Huygen FJ, Bouma PA, Sturkenboom MC. Incidence rates and treatment of neuropathic pain conditions in the general population. Pain. 2008;137(3):681–8.PubMedGoogle Scholar
  129. Dogra S, Beydoun S, Mazzola J, Hopwood M, Wan Y. Oxcarbazepine in painful diabetic neuropathy: a randomized, placebo-controlled study. Eur J Pain. 2005;9(5):543–54.PubMedGoogle Scholar
  130. Donofrio PD, Raskin P, Rosenthal NR, Hewitt DJ, Jordan DM, Xiang J, et al. Safety and effectiveness of topiramate for the management of painful diabetic peripheral neuropathy in an open-label extension study. Clin Ther. 2005;27(9):1420–31.PubMedGoogle Scholar
  131. Dore S, Kar S, Quirion R. Insulin-like growth factor I protects and rescues hippocampal neurons against beta-amyloid- and human amylin-induced toxicity. Proc Natl Acad Sci U S A. 1997;94(9):4772–7.PubMedPubMedCentralGoogle Scholar
  132. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360(2):129–39.PubMedGoogle Scholar
  133. Dworkin RH, Corbin AE, Young JP Jr, Sharma U, LaMoreaux L, Bockbrader H, et al. Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology. 2003;60(8):1274–83.PubMedGoogle Scholar
  134. Dworkin RH, O’Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007;132(3):237–51.Google Scholar
  135. Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008;9(2):105–21.PubMedGoogle Scholar
  136. Dworkin RH, Turk DC, Revicki DA, Harding G, Coyne KS, Peirce-Sandner S, et al. Development and initial validation of an expanded and revised version of the Short-form McGill Pain Questionnaire (SF-MPQ-2). Pain. 2009;144(1–2):35–42.PubMedGoogle Scholar
  137. Dworkin RH, O’Connor AB, Audette J, Baron R, Gourlay GK, Haanpaa ML, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc. 2010;85(3 Suppl):S3–14.PubMedPubMedCentralGoogle Scholar
  138. Dyck PJ, Windebank AJ. Diabetic and nondiabetic lumbosacral radiculoplexus neuropathies: new insights into pathophysiology and treatment. Muscle Nerve. 2002;25(4):477–91.PubMedGoogle Scholar
  139. Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: The Rochester Diabetic Neuropathy Study. Neurology. 1993;43:817–24.PubMedGoogle Scholar
  140. Dyck PJ, Overland CJ, Low PA, Litchy WJ, Davies JL, Dyck PJ, et al. Signs and symptoms versus nerve conduction studies to diagnose diabetic sensorimotor polyneuropathy: Cl vs. NPhys trial. Muscle Nerve. 2010;42(2):157–64.PubMedGoogle Scholar
  141. Dyck PJ, Albers JW, Andersen H, Arezzo JC, Biessels GJ, Bril V, et al. Diabetic polyneuropathies: update on research definition, diagnostic criteria and estimation of severity. Diabetes Metab Res Rev. 2011;27(7):620–8.PubMedGoogle Scholar
  142. Dyer CA, Taylor GJ, Reed M, Dyer CA, Robertson DR, Harrington R. Falls prevention in residential care homes: a randomised controlled trial. Age Ageing. 2004;33(6):596–602.PubMedGoogle Scholar
  143. Eaton SE, Harris ND, Rajbhandari SM, Greenwood P, Wilkinson ID, Ward JD, et al. Spinal-cord involvement in diabetic peripheral neuropathy. Lancet. 2001;358(9275):35–6.PubMedGoogle Scholar
  144. Edelsberg J, Oster G. Summary measures of number needed to treat: how much clinical guidance do they provide in neuropathic pain? Eur J Pain. 2009;13:11–6.PubMedGoogle Scholar
  145. Edwards JL, Vincent AM, Cheng HT, Feldman EL. Diabetic neuropathy: mechanisms to management. Pharmacol Ther. 2008;120(1):1–34.PubMedPubMedCentralGoogle Scholar
  146. Edwards K, Pritchard N, Vagenas D, Russell A, Malik RA, Efron N. Utility of corneal confocal microscopy for assessing mild diabetic neuropathy: baseline findings of the LANDMark study. Clin Exp Optom. 2012;95(3):348–54.PubMedGoogle Scholar
  147. Efron N, Edwards K, Roper N, Pritchard N, Sampson GP, Shahidi AM, et al. Repeatability of measuring corneal subbasal nerve fiber length in individuals with type 2 diabetes. Eye Contact Lens. 2010;36(5):245–8.PubMedGoogle Scholar
  148. Elias PK, Elias MF, D’Agostino RB, Cupples LA, Wilson PW, Silbershatz H, et al. NIDDM and blood pressure as risk factors for poor cognitive performance. The Framingham Study. Diabetes Care. 1997;20(9):1388–95.PubMedGoogle Scholar
  149. England JD, Gronseth GS, Franklin G, Carter GT, Kinsella LJ, Cohen JA, et al. Practice Parameter: evaluation of distal symmetric polyneuropathy: role of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based review). Report of the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation. Neurology. 2009;72(2):177–84.PubMedGoogle Scholar
  150. Enzinger C, Fazekas F, Matthews PM, Ropele S, Schmidt H, Smith S, et al. Risk factors for progression of brain atrophy in aging: six-year follow-up of normal subjects. Neurology. 2005;64(10):1704–11.PubMedGoogle Scholar
  151. Farooqi MA, Lovblom LE, Lysy Z, Ostrovski I, Halpern EM, Ngo M, et al. Validation of cooling detection threshold as a marker of sensorimotor polyneuropathy in type 2 diabetes. J Diabetes Complicat. 2016;30(4):716–22.PubMedGoogle Scholar
  152. Feil DG, Rajan M, Soroka O, Tseng CL, Miller DR, Pogach LM. Risk of hypoglycemia in older veterans with dementia and cognitive impairment: implications for practice and policy. J Am Geriatr Soc. 2011;59(12):2263–72.PubMedGoogle Scholar
  153. Feldman EL, Stevens MJ, Thomas PK, Brown MB, Canal N, Greene DA. A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy. Diabetes Care. 1994;17(11):1281–9.PubMedGoogle Scholar
  154. Fiatarone MA, O’Neill EF, Ryan ND, Clements KM, Solares GR, Nelson ME, et al. Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med. 1994;330(25):1769–75.PubMedGoogle Scholar
  155. Finch CE, Cohen DM. Aging metabolism, and Alzheimer disease: review and hypotheses. Exp Neurol. 1997;143(1):82–102.PubMedGoogle Scholar
  156. Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain. 2005;118(3):289–305.PubMedGoogle Scholar
  157. Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain. 2010;150(3):573–81.PubMedGoogle Scholar
  158. Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14:162–73.PubMedPubMedCentralGoogle Scholar
  159. Fioretti S, Scocco M, Ladislao L, Ghetti G, Rabini RA. Identification of peripheral neuropathy in type-2 diabetic subjects by static posturography and linear discriminant analysis. Gait Posture. 2010;32(3):317–20.PubMedGoogle Scholar
  160. Fischer TZ, Waxman SG. Neuropathic pain in diabetes – evidence for a central mechanism. Nat Rev Neurol. 2010;6(8):462–6.PubMedGoogle Scholar
  161. Fonseca V, Lavery L, Thethi TK, et al. Metanx in type 2 diabetes with peripheral neuropathy: a randomized trial. Am J Med. 2013;126(2):141–9.PubMedGoogle Scholar
  162. Francis GJ, Martinez JA, Liu WQ, Xu K, Ayer A, Fine J, et al. Intranasal insulin prevents cognitive decline, cerebral atrophy and white matter changes in murine type I diabetic encephalopathy. Brain. 2008;131(Pt 12):3311–34.PubMedGoogle Scholar
  163. Freedman BI, Bowden DW, Smith SC, Xu J, Divers J. Relationships between electrochemical skin conductance and kidney disease in type 2 diabetes. J Diabetes Complicat. 2014;28(1):56–60.PubMedGoogle Scholar
  164. Freedman BI, Smith SC, Bagwell BM, Xu J, Bowden DW, Divers J. Electrochemical skin conductance in diabetic kidney disease. Am J Nephrol. 2015;41(6):438–47.PubMedPubMedCentralGoogle Scholar
  165. Freeman R, Raskin P, Hewitt DJ, Vorsanger GJ, Jordan DM, Xiang J, et al. Randomized study of tramadol/acetaminophen versus placebo in painful diabetic peripheral neuropathy. Curr Med Res Opin. 2007;23(1):147–61.PubMedGoogle Scholar
  166. Freeman R, Durso-Decruz E, Emir B. Efficacy safety, and tolerability of pregabalin treatment for painful diabetic peripheral neuropathy: findings from seven randomized, controlled trials across a range of doses. Diabetes Care. 2008;31(7):1448–54.PubMedPubMedCentralGoogle Scholar
  167. Freeman R, Baron R, Bouhassira D, Cabrera J, Emir B. Sensory profiles of patients with neuropathic pain based on the neuropathic pain symptoms and signs. Pain. 2014;155(2):367–76.PubMedGoogle Scholar
  168. Freyhagen R, Baron R, Gockel U. Pain detect: a new screening questionnaire to detect neuropathic components in patients with back pain. Curr Med Res Opin. 2006;22:1911–20.Google Scholar
  169. Freynhagen R, Strojek K, Griesing T, Whalen E, Balkenohl M. Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens. Pain. 2005;115(3):254–63.PubMedGoogle Scholar
  170. Frolich L, Blum-Degen D, Bernstein HG, Engelsberger S, Humrich J, Laufer S, et al. Brain insulin and insulin receptors in aging and sporadic Alzheimer’s disease. J Neural Transm (Vienna). 1998;105(4–5):423–38.Google Scholar
  171. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348(5):383–93.PubMedGoogle Scholar
  172. Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358(6):580–91.PubMedGoogle Scholar
  173. Ganz DA, Bao Y, Shekelle PG, Rubenstein LZ. Will my patient fall? JAMA. 2007;297(1):77–86.PubMedGoogle Scholar
  174. Garrow AP, Xing M, Vere J, Verrall B, Wang L, Jude EB. Role of acupuncture in the management of diabetic painful neuropathy (DPN): a pilot RCT. Acupunct Med. 2014;32(3):242–9.PubMedGoogle Scholar
  175. Geber C, Klein T, Azad S, Birklein F, Gierthmuhlen J, Huge V, et al. Test-retest and interobserver reliability of quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain (DFNS): a multi-centre study. Pain. 2011;152(3):548–56.PubMedGoogle Scholar
  176. Geijselaers SL, Sep SJ, Stehouwer CD, Biessels GJ. Glucose regulation, cognition, and brain MRI in type 2 diabetes: a systematic review. Lancet Diabetes Endocrinol. 2015;3(1):75–89.PubMedGoogle Scholar
  177. Gibbons CH. Small fiber neuropathies. Continuum (Minneap Minn). 2014;20(5 Peripheral Nervous System Disorders):1398–412.Google Scholar
  178. Gibbons CH, Freeman R. Treatment-induced neuropathy of diabetes: an acute, iatrogenic complication of diabetes. Brain. 2015;138(Pt 1):43–52.PubMedGoogle Scholar
  179. Gillespie LD, Robertson MC, Gillespie WJ, Lamb SE, Gates S, Cumming RG, et al. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev. 2009; Issue 2. Art. No.: CD007146.  https://doi.org/10.1002/14651858.CD007146.pub2.
  180. Gilron I, Bailey JM, Tu D, Holden RR, Weaver DF, Houlden RL. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med. 2005;352(13):1324–34.PubMedGoogle Scholar
  181. Gimbel JS, Richards P, Portenoy RK. Controlled-release oxycodone for pain in diabetic neuropathy: a randomized controlled trial. Neurology. 2003;60(6):927–34.PubMedGoogle Scholar
  182. Glassman AH, Roose SP, Bigger JT Jr. The safety of tricyclic antidepressants in cardiac patients. Risk-benefit reconsidered. JAMA. 1993;269(20):2673–5.PubMedGoogle Scholar
  183. Goldstein DJ, Lu Y, Detke MJ, Lee TC, Iyengar S. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain. 2005;116(1-2):109–18.PubMedGoogle Scholar
  184. Gore M, Brandenburg NA, Dukes E, Hoffman DL, Tai KS, Stacey B. Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep. J Pain Symptom Manag. 2005;30(4):374–85.Google Scholar
  185. Grant WP, Sullivan R, Sonenshine DE, Adam M, Slusser JH, Carson KA, et al. Electron microscopic investigation of the effects of diabetes mellitus on the Achilles tendon. J Foot Ankle Surg. 1997;36(4):272–8.PubMedGoogle Scholar
  186. Gregg EW, Yaffe K, Cauley JA, Rolka DB, Blackwell TL, Narayan KM, et al. Is diabetes associated with cognitive impairment and cognitive decline among older women? Study of Osteoporotic Fractures Research Group. Arch Intern Med. 2000;160(2):174–80.PubMedGoogle Scholar
  187. Griebeler ML, Morey-Vargas OL, Brito JP, Tsapas A, Wang Z, Carranza Leon BG, et al. Pharmacologic interventions for painful diabetic neuropathy: an umbrella systematic review and comparative effectiveness network meta-analysis. Ann Intern Med. 2014;161(9):639–49.PubMedGoogle Scholar
  188. Gu Y, Dennis S. Are falls prevention programs effective at reducing the risk factors for falls in people with type-2 diabetes mellitus and peripheral neuropathy: a systematic review with narrative synthesis. J Diabetes Complicat. 2017;31(2):504–16.PubMedGoogle Scholar
  189. Gupta A, Silman J, Ray D, Morriss R, Dickens C, MacFarlane GJ, et al. The role of psychosocial factors in predicting the onset of chronic widespread pain: results from a prospective population-based study. Rheumatology. 2007;46:666–71.PubMedGoogle Scholar
  190. Gustafson D. Adiposity indices and dementia. Lancet Neurol. 2006;5(8):713–20.PubMedGoogle Scholar
  191. Haanpaa ML, Backonja MM, Bennett MI, Bouhassira D, Cruccu G, Hansson PT, et al. Assessment of neuropathic pain in primary care. Am J Med. 2009;122(10 Suppl):S13–21.PubMedGoogle Scholar
  192. Handelsman H, Bloomgarden ZT, Grunberger G, Umpierrez U, Zimmerman RS, Bailey TS, et al. American Association of Clinical Endocrinologists Clinical Practice Guidelines for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2015;21(4):413.PubMedGoogle Scholar
  193. Hanewinckel R, van Oijen M, Ikram MA, van Doorn PA. The epidemiology and risk factors of chronic polyneuropathy. Eur J Epidemiol. 2016;31(1):5–20.PubMedGoogle Scholar
  194. Hanlon JT, Boudreau RM, Roumani YF, Newman AB, Ruby CM, Wright RM, et al. Number and dosage of central nervous system medications on recurrent falls in community elders: the Health, Aging and Body Composition study. J Gerontol A Biol Sci Med Sci. 2009;64(4):492–8.PubMedGoogle Scholar
  195. Hanna M, O’Brien C, Wilson MC. Prolonged-release oxycodone enhances the effects of existing gabapentin therapy in painful diabetic neuropathy patients. Eur J Pain. 2008;12(6):804–13.PubMedGoogle Scholar
  196. Harati Y, Gooch C, Swenson M, Edelman S, Greene D, Raskin P, et al. Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy. Neurology. 1998;50:1842–6.PubMedGoogle Scholar
  197. Harati Y, Gooch C, Swenson M, Edelman SV, Greene D, Raskin P, et al. Maintenance of the long-term effectiveness of Tramadol in treatment of the pain of diabetic neuropathy. J Diabetes Complicat. 2000;14:65–70.PubMedGoogle Scholar
  198. Hardy T, Sachson R, Shen S, Armbruster M, Boulton AJ. Does treatment with duloxetine for neuropathic pain impact glycemic control? Diabetes Care. 2007;30(1):21–6.PubMedGoogle Scholar
  199. Hausdorff JM, Yogev G, Springer S, Simon ES, Giladi N. Walking is more like catching than tapping: gait in the elderly as a complex cognitive task. Exp Brain Res. 2005;164(4):541–8.PubMedGoogle Scholar
  200. Havrankova J, Roth J, Brownstein M. Insulin receptors are widely distributed in the central nervous system of the rat. Nature. 1978;272(5656):827–9.PubMedGoogle Scholar
  201. Hearn L, Moore RA, Derry S, Wiffen PJ, Phillips T. Desipramine for neuropathic pain in adults. Cochrane Database Syst Rev. 2014;9:CD011003.Google Scholar
  202. Heath JM, Stuart MR. Prescribing exercise for frail elders. J Am Board Fam Pract. 2002;15(3):218–28.PubMedGoogle Scholar
  203. Herder C, Bongaerts BW, Rathmann W, Heier M, Kowall B, Koenig W, et al. Association of subclinical inflammation with polyneuropathy in the older population: KORA F4 study. Diabetes Care. 2013;36(11):3663–70.PubMedPubMedCentralGoogle Scholar
  204. Herman WH, Kennedy L. Underdiagnosis of peripheral neuropathy in type 2 diabetes. Diabetes Care. 2005;28(6):1480–1.PubMedGoogle Scholar
  205. Herman WH, Pop-Busui R, Braffett BH, Martin CL, Cleary PA, Albers JW, et al. Use of the Michigan Neuropathy Screening Instrument as a measure of distal symmetrical peripheral neuropathy in type 1 diabetes: results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications. Diabet Med. 2012;29(7):937–44.PubMedPubMedCentralGoogle Scholar
  206. Herriott MT, Colberg SR, Parson HK, Nunnold T, Vinik AI. Effects of 8 weeks of flexibility and resistance training in older adults with type 2 diabetes. Diabetes Care. 2004;27(12):2988–9.PubMedGoogle Scholar
  207. Hertz P, Bril V, Orszag A, Ahmed A, Ng E, Nwe P, et al. Reproducibility of in vivo corneal confocal microscopy as a novel screening test for early diabetic sensorimotor polyneuropathy. Diabet Med. 2011;28(10):1253–60.PubMedGoogle Scholar
  208. Hill JM, Lesniak MA, Pert CB, Roth J. Autoradiographic localization of insulin receptors in rat brain: prominence in olfactory and limbic areas. Neuroscience. 1986;17:1127–38.PubMedGoogle Scholar
  209. Holzer SE, Camerota A, Martens L, Cuerdon T, Crystal P, Zagari M. Costs and duration of care for lower extremity ulcers in patients with diabetes. Clin Ther. 1998;20:169–81.PubMedGoogle Scholar
  210. Howe TE, Rochester L, Neil F, Skelton DA, Ballinger C. Exercise for improving balance in older people. Cochrane Database of Systematic Reviews 2011, Issue 11. Art. No.: CD004963.  https://doi.org/10.1002/14651858.CD004963.pub3.
  211. Imms FJ, Edholm OG. Studies of gait and mobility in the elderly. Age Ageing. 1981;10(3):147–56.PubMedGoogle Scholar
  212. Ismail-Beigi F, Craven T, Banerji MA, Basile J, Calles J, Cohen RM, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet. 2010;376(9739):419–30.PubMedPubMedCentralGoogle Scholar
  213. Jacobson AM, Musen G, Ryan CM, Silvers N, Cleary P, Waberski B, et al. Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med. 2007;356(18):1842–52.PubMedGoogle Scholar
  214. Jensen MP, Chodroff MJ, Dworkin RH. The impact of neuropathic pain on health-related quality of life: review and implications. Neurology. 2007;68(15):1178–82.PubMedGoogle Scholar
  215. Jiang M-S. Corneal confocal microscopy for assessment of diabetic peripheral neuropathy: a meta-analysis. Br J Ophthalmol. 2016;100(1):9–14.PubMedGoogle Scholar
  216. Joseph JJ, Wang X, Spanakis E, Seeman T, Wand G, Needham B, et al. Diurnal salivary cortisol, glycemia and insulin resistance: the multi-ethnic study of atherosclerosis. Psychoneuroendocrinology. 2015;62:327–35.PubMedPubMedCentralGoogle Scholar
  217. Joss JD. Tricyclic antidepressant use in diabetic neuropathy. Ann Pharmacother. 1999;33(9):996–1000.PubMedGoogle Scholar
  218. Kajdasz DK, Iyengar S, Desaiah D, Backonja MM, Farrar JT, Fishbain DA, et al. Duloxetine for the management of diabetic peripheral neuropathic pain: evidence-based findings from post hoc analysis of three multicenter, randomized, double-blind, placebo-controlled, parallel-group studies. Clin Ther. 2007;29(Suppl):2536–46.PubMedGoogle Scholar
  219. Kalso E. Sodium channel blockers in neuropathic pain. Curr Pharm Des. 2005;11(23):3005–11.PubMedGoogle Scholar
  220. Karani R, McLaughlin MA, Cassel CK. Exercise in the healthy older adult. Am J Geriatr Cardiol. 2001;10(5):269–73.PubMedGoogle Scholar
  221. Katoulis EC, Ebdon-Parry M, Lanshammar H, Vileikyte L, Kulkarni J, Boulton AJ. Gait abnormalities in diabetic neuropathy. Diabetes Care. 1997;20(12):1904–7.PubMedGoogle Scholar
  222. Kessler JA, Smith AG, Cha BS, Choi SH, Wymer J, Shaibani A, et al. Double-blind, placebo-controlled study of HGF gene therapy in diabetic neuropathy. Ann Clin Transl Neurol. 2015;2(5):465–78.PubMedPubMedCentralGoogle Scholar
  223. Kikta DG, Breuer AC, Wilbourn AJ. Thoracic root pain in diabetes: the spectrum of clinical and electromyographic findings. Ann Neurol. 1982;11:80–5.PubMedGoogle Scholar
  224. Kirkman S, Briscoe V, Clark N, et al. Diabetes in older adults: a consensus report. J Am Geriatr Soc. 2012;60:2342.PubMedPubMedCentralGoogle Scholar
  225. Klein BE, Klein R, Knudtson MD, Lee KE, Danforth LG, Reinke JO, et al. Associations of selected medications and visual function: the Beaver Dam Eye Study. Br J Ophthalmol. 2003;87(4):403–8.PubMedPubMedCentralGoogle Scholar
  226. Kloppenborg RP, van den Berg E, Kappelle LJ, Biessels GJ. Diabetes and other vascular risk factors for dementia: which factor matters most? A systematic review. Eur J Pharmacol. 2008;585(1):97–108.PubMedGoogle Scholar
  227. Kluding PM, Pasnoor M, Singh R, Jernigan S, Farmer K, Rucker J, et al. The effect of exercise on neuropathic symptoms, nerve function, and cutaneous innervation in people with diabetic peripheral neuropathy. J Diabetes Complicat. 2012;26(5):424–9.PubMedPubMedCentralGoogle Scholar
  228. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393–403.PubMedGoogle Scholar
  229. Krause S, Backonja M. Development of a neuropathic pain questionnaire. Clin J Pain. 2003;19:306–14.PubMedGoogle Scholar
  230. Krein SL, Heisler M, Piette JD, Makki F, Kerr EA. The effect of chronic pain on diabetes patients’ self-management. Diabetes Care. 2005;28(1):65–70.PubMedGoogle Scholar
  231. Krendel DA, Costigan DA, Hopkins LC. Successful treatment of neuropathies in patients with diabetes mellitus. Arch Neurol. 1995;52:1053–61.PubMedGoogle Scholar
  232. Krendel DA, Zacharias A, Younger DS. Autoimmune diabetic neuropathy. Neurol Clin. 1997;15:959–71.PubMedGoogle Scholar
  233. Kumar D. Diabetic peripheral neuropathy: effectiveness of electrotherapy and amitriptyline for sympotmatic relief. Diabetes Care. 1998;21:1322–5.PubMedGoogle Scholar
  234. Lafond D, Corriveau H, Prince F. Postural control mechanisms during quiet standing in patients with diabetic sensory neuropathy. Diabetes Care. 2004;27(1):173–8.PubMedGoogle Scholar
  235. Lalli P, Chan A, Garven A, Midha N, Chan C, Brady S, et al. Increased gait variability in diabetes mellitus patients with neuropathic pain. J Diabetes Complicat. 2013;27(3):248–54.PubMedGoogle Scholar
  236. Lamport DJ, Lawton CL, Mansfield MW, Dye L. Impairments in glucose tolerance can have a negative impact on cognitive function: a systematic research review. Neurosci Biobehav Rev. 2009;33(3):394–413.PubMedGoogle Scholar
  237. Landefeld CS, Steinman MA. The Neurontin legacy – marketing through misinformation and manipulation. N Engl J Med. 2009;360(2):103–6.PubMedGoogle Scholar
  238. Laughlin RS, Dyck PJ. Electrodiagnostic testing in lumbosacral plexopathies. Phys Med Rehabil Clin N Am. 2013;24(1):93–105.PubMedGoogle Scholar
  239. Lauria G, Lombardi R. Skin biopsy: a new tool for diagnosing peripheral neuropathy. BMJ. 2007;334(7604):1159–62.PubMedPubMedCentralGoogle Scholar
  240. Lauria G, Hsieh S, Johansson O, Kennedy W, Leger J, Mellgren S, et al. European Federation of Neurological Societies/Peripheral Nerve Society guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol. 2010a;17:903–12.PubMedGoogle Scholar
  241. Lauria G, Bakkers M, Schmitz C, Lombardi R, Penza P, Devigili G, et al. Intraepidermal nerve fiber density at the distal leg: a worldwide normative reference study. J Peripher Nerv Syst. 2010b;15(3):202–7.PubMedGoogle Scholar
  242. Lesser H, Sharma U, LaMoreaux L, Poole RM. Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial. Neurology. 2004;63(11):2104–10.PubMedGoogle Scholar
  243. Lezak MD. Neuropsychological assessment. 4th ed. New York: Oxford University Press; 2004.Google Scholar
  244. Ligthelm RJ, Kaiser M, Vora J, Yale JF. Insulin use in elderly adults: risk of hypoglycemia and strategies for care. J Am Geriatr Soc. 2012;60(8):1564–70.PubMedGoogle Scholar
  245. Lindsay J, Hebert R, Rockwood K. The Canadian Study of Health and Aging: risk factors for vascular dementia. Stroke. 1997;28(3):526–30.PubMedGoogle Scholar
  246. Lloyd BD, Williamson DA, Singh NA, Hansen RD, Diamond TH, Finnegan TP, et al. Recurrent and injurious falls in the year following hip fracture: a prospective study of incidence and risk factors from the Sarcopenia and Hip Fracture study. J Gerontol A Biol Sci Med Sci. 2009;64(5):599–609.PubMedGoogle Scholar
  247. Loeser JD, Treede RD. The Kyoto protocol of IASP basic pain terminology. Pain. 2008;137:473–7.PubMedGoogle Scholar
  248. Lonn EM, Rambihar S, Gao P, Custodis FF, Sliwa K, Teo KK, et al. Heart rate is associated with increased risk of major cardiovascular events, cardiovascular and all-cause death in patients with stable chronic cardiovascular disease: an analysis of ONTARGET/TRANSCEND. Clin Res Cardiol. 2014;103(2):149–59.PubMedGoogle Scholar
  249. Low PA. Diabetic autonomic neuropathy. Semin Neurol. 1996;16(2):143–51.PubMedGoogle Scholar
  250. Low PA, Benrud-Larson LM, Sletten DM, Opfer-Gehrking TL, Weigand SD, O’Brien PC, et al. Autonomic symptoms and diabetic neuropathy: a population-based study. Diabetes Care. 2004;27(12):2942–7.PubMedGoogle Scholar
  251. Luchsinger JA, Tang MX, Stern Y, Shea S, Mayeux R. Diabetes mellitus and risk of Alzheimer’s disease and dementia with stroke in a multiethnic cohort. Am J Epidemiol. 2001;154(7):635–41.PubMedGoogle Scholar
  252. Luchsinger JA, Tang MX, Shea S, Mayeux R. Hyperinsulinemia and risk of Alzheimer disease. Neurology. 2004;63(7):1187–92.PubMedGoogle Scholar
  253. Lykke JA, Tarnow L, Parving HH, Hilsted JA. combined abnormality in heart rate variation and QT corrected interval is a strong predictor of cardiovascular death in type 1 diabetes. Scand J Clin Lab Invest. 2008;68(7):654–9.PubMedGoogle Scholar
  254. Lysy Z, Lovblom LE, Halpern EM, Ngo M, Ng E, Orszag A, et al. Measurement of cooling detection thresholds for identification of diabetic sensorimotor polyneuropathy in type 1 diabetes. PLoS One. 2014;9(9):e106995.PubMedPubMedCentralGoogle Scholar
  255. Maki BE. Gait changes in older adults: predictors of falls or indicators of fear. J Am Geriatr Soc. 1997;45(3):313–20.PubMedGoogle Scholar
  256. Malik RA, Veves A, Tesfaye S, Smith G, Cameron N, Zochodne D, et al. Small fibre neuropathy: role in the diagnosis of diabetic sensorimotor polyneuropathy. Diabetes Metab Res Rev. 2011;27(7):678–84.PubMedGoogle Scholar
  257. Mantyselka P, Ahonen R, Kumpusalo E, Takala J. Variability in prescribing for musculoskeletal pain in Finnish primary health care. Pharm World Sci. 2001;23(6):232–6.PubMedGoogle Scholar
  258. Maraldi C, Volpato S, Penninx BW, Yaffe K, Simonsick EM, Strotmeyer ES, et al. Diabetes mellitus, glycemic control, and incident depressive symptoms among 70- to 79-year-old persons: the health, aging, and body composition study. Arch Intern Med. 2007;167(11):1137–44.PubMedGoogle Scholar
  259. Martin CL, Albers J, Herman WH, Cleary P, Waberski B, Greene DA, et al. Neuropathy among the diabetes control and complications trial cohort 8 years after trial completion. Diabetes Care. 2006;29(2):340–4.PubMedPubMedCentralGoogle Scholar
  260. Martin CL, Albers JW, Pop-Busui R. Neuropathy and related findings in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes Care. 2014;37(1):31–8.PubMedGoogle Scholar
  261. Maser RE, Steenkiste AR, Dorman JS, Nielsen VK, Bass EB, Manjoo Q, et al. Epidemiological correlates of diabetic neuropathy report from Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes. 1989;38:1456–61.PubMedGoogle Scholar
  262. Maser RE, Mitchell BD, Vinik AI, Freeman R. The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis. Diabetes Care. 2003;26(6):1895–901.PubMedGoogle Scholar
  263. Mason L, Moore RA, Derry S, Edwards JE, McQuay HJ. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ. 2004;328(7446):991.PubMedPubMedCentralGoogle Scholar
  264. Mathews VP, Barker PB, Blackband SJ, Chatham JC, Bryan RN. Cerebral metabolites in patients with acute and subacute strokes: concentrations determined by quantitative proton MR spectroscopy. AJR Am J Roentgenol. 1995;165(3):633–8.PubMedGoogle Scholar
  265. Maurer MS, Burcham J, Cheng H. Diabetes mellitus is associated with an increased risk of falls in elderly residents of a long-term care facility. J Gerontol A Biol Sci Med Sci. 2005;60(9):1157–62.PubMedGoogle Scholar
  266. Max MB, Culnane M, Schafer SC, Gracely RH, Walther DJ, Smoller B, et al. Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood. Neurology. 1987;37(4):589–96.PubMedGoogle Scholar
  267. Max MB, Kishore-Kumar R, Schafer SC, Meister B, Gracely RH, Smoller B, et al. Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial. Pain. 1991;45(1):3–9.PubMedGoogle Scholar
  268. Max M, Lynch S, Muir J. Effects of desipramine, amitriptyline and fluoxetine on pain in diabetic neuropathy. N Engl J Med. 1992;326:1250–6.PubMedGoogle Scholar
  269. Mayaudon H, Miloche PO, Bauduceau BA. new simple method for assessing sudomotor function: relevance in type 2 diabetes. Diabete Metab. 2010;36(6 Pt 1):450–4.PubMedGoogle Scholar
  270. McEvoy LK, Laughlin GA, Barrett-Connor E, Bergstrom J, Kritz-Silverstein D, Der-Martirosian C, et al. Metabolic syndrome and 16-year cognitive decline in community-dwelling older adults. Ann Epidemiol. 2012;22(5):310–7.PubMedPubMedCentralGoogle Scholar
  271. McGuire LC, Ford ES, Ajani UA. The impact of cognitive functioning on mortality and the development of functional disability in older adults with diabetes: the second longitudinal study on aging. BMC Geriatr. 2006;6:8.PubMedPubMedCentralGoogle Scholar
  272. McNay EC, Cotero VE. Mini-review: impact of recurrent hypoglycemia on cognitive and brain function. Physiol Behav. 2010;100(3):234–8.PubMedPubMedCentralGoogle Scholar
  273. Menz HB, Lord SR, Fitzpatrick RC. A structural equation model relating impaired sensorimotor function, fear of falling and gait patterns in older people. Gait Posture. 2007;25(2):243–9.PubMedGoogle Scholar
  274. Molnar G, Farago N, Kocsis AK, Rozsa M, Lovas S, Boldog E, et al. GABAergic neurogliaform cells represent local sources of insulin in the cerebral cortex. J Neurosci. 2014;34(4):1133–7.PubMedGoogle Scholar
  275. Moloney NA, Hall TM, Doody CM. Reliability of thermal quantitative sensory testing: a systematic review. J Rehabil Res Dev. 2012;49(2):191–207.PubMedGoogle Scholar
  276. Mooradian AD. Diabetic complications of the central nervous system. Endocr Rev. 1988;9(3):346–56.PubMedGoogle Scholar
  277. Mooradian AD, Perryman K, Fitten J, Kavonian GD, Morley JE. Cortical function in elderly non-insulin dependent diabetic patients. Behavioral and electrophysiologic studies. Arch Intern Med. 1988;148(11):2369–72.PubMedGoogle Scholar
  278. Moreira BS, Dos Anjos DM, Pereira DS, Sampaio RF, Pereira LS, Dias RC, et al. The geriatric depression scale and the timed up and go test predict fear of falling in community-dwelling elderly women with type 2 diabetes mellitus: a cross-sectional study. BMC Geriatr. 2016;16:56.PubMedCentralGoogle Scholar
  279. Morello CM, Leckband SG, Stoner CP, Moorhouse DF, Sahagian GA. Randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain. Arch Intern Med. 1999;159(16):1931–7.PubMedGoogle Scholar
  280. Morrison S, Colberg SR, Mariano M, Parson HK, Vinik AI. Balance training reduces falls risk in older individuals with type 2 diabetes. Diabetes Care. 2010;33(4):748–50.PubMedPubMedCentralGoogle Scholar
  281. Morrison S, Colberg SR, Parson HK, Vinik AI. Relation between risk of falling and postural sway complexity in diabetes. Gait Posture. 2012;35(4):662–8.PubMedGoogle Scholar
  282. Moxey PW, Gogalniceanu P, Hinchliffe RJ, Loftus IM, Jones KJ, Thompson MM, et al. Lower extremity amputations – a review of global variability in incidence. Diabet Med. 2011;28(10):1144–53.PubMedGoogle Scholar
  283. Munshi M, Grande L, Hayes M, Ayres D, Suhl E, Capelson R, et al. Cognitive dysfunction is associated with poor diabetes control in older adults. Diabetes Care. 2006;29(8):1794–9.PubMedPubMedCentralGoogle Scholar
  284. O’Connor AB. Neuropathic pain: quality-of-life impact, costs and cost effectiveness of therapy. PharmacoEconomics. 2009;27(2):95–112.PubMedGoogle Scholar
  285. O’Brien PD, Hinder LM, Sakowski SA, Feldman ELER. stress in diabetic peripheral neuropathy: a new therapeutic target. Antioxid Redox Signal. 2014;21(4):621–33.PubMedGoogle Scholar
  286. Obrosova I, Shevalye H. Metanx alleviates diabetes-induced large and small fiber neuropathies and promotes small sensory nerve fiber regeneration. Diabetes. 2011;60:652-PGoogle Scholar
  287. Ostrovski I, Lovblom LE, Farooqi MA, Scarr D, Boulet G, Hertz P, et al. Reproducibility of in vivo corneal confocal microscopy using an automated analysis program for detection of diabetic sensorimotor polyneuropathy. PLoS One. 2015;10(11):e0142309.PubMedPubMedCentralGoogle Scholar
  288. Ott A, Stolk RP, Hofman A, van Harskamp F, Grobbee DE, Breteler MM. Association of diabetes mellitus and dementia: the Rotterdam Study. Diabetologia. 1996;39(11):1392–7.PubMedGoogle Scholar
  289. Panel on Prevention of Falls in Older Persons AGS, British Geriatrics Society. Summary of the Updated American Geriatrics Society/British Geriatrics Society clinical practice guideline for prevention of falls in older persons. J Am Geriatr Soc. 2011;59(1):148–57.Google Scholar
  290. Parekh PJ, Nayi VR, Johnson DA, Vinik AI. The role of gut microflora and the cholinergic anti-inflammatory neuroendocrine system in diabetes mellitus. Front Endocrinol (Lausanne). 2016;7:55.Google Scholar
  291. Park CR. Cognitive effects of insulin in the central nervous system. Neurosci Biobehav Rev. 2001;25(4):311–23.PubMedGoogle Scholar
  292. Partanen J, Niskanen L, Lehtinen J, Mervaala E, Siitonen O, Uusitupa M. Natural history of peripheral neuropathy in patients with non-insulin-dependent diabetes mellitus. N Engl J Med. 1995;333:89–94.PubMedGoogle Scholar
  293. Perkins ND. The Rel/NF-kappa B family: friend and foe. Trends Biochem Sci. 2000;25(9):434–40.PubMedGoogle Scholar
  294. Perkins BA, Olaleye D, Zinman B, Bril V. Simple screening tests for peripheral neuropathy in the diabetes clinic. Diabetes Care. 2001;24(2):250–6.PubMedGoogle Scholar
  295. Perkins B, Olaleye D, Bril V. Carpal tunnel syndrome in patients with diabetic polyneuropathy. Diabetes Care. 2002;25:565–9.PubMedGoogle Scholar
  296. Perlmuter LC, Tun P, Sizer N, McGlinchey RE, Nathan DM. Age and diabetes related changes in verbal fluency. Exp Aging Res. 1987;13(1–2):9–14.PubMedGoogle Scholar
  297. Peron EP, Ogbonna KC. Diabetic medications and polypharmacy. Clin Geriatr Med. 2015;31(1):17–27.Google Scholar
  298. Peterson MJ, Giuliani C, Morey MC, Pieper CF, Evenson KR, Mercer V, et al. Physical activity as a preventative factor for frailty: the health, aging, and body composition study. J Gerontol A Biol Sci Med Sci. 2009;64(1):61–8.PubMedGoogle Scholar
  299. Petropoulos IN, Manzoor T, Morgan P, Fadavi H, Asghar O, Alam U, et al. Repeatability of in vivo corneal confocal microscopy to quantify corneal nerve morphology. Cornea. 2013a;32(5):e83–9.PubMedGoogle Scholar
  300. Petropoulos IN, Alam U, Fadavi H, Asghar O, Green P, Ponirakis G, et al. Corneal nerve loss detected with corneal confocal microscopy is symmetrical and related to the severity of diabetic polyneuropathy. Diabetes Care. 2013b;36(11):3646–51.PubMedPubMedCentralGoogle Scholar
  301. Piovesan EJ, Teive HG, Kowacs PA, la Coletta MV, Werneck LC, Silberstein SD. An open study of botulinum-A toxin treatment of trigeminal neuralgia. Neurology. 2005;65(8):1306–8.PubMedGoogle Scholar
  302. Pittenger G, Vinik A. Nerve growth factor and diabetic neuropathy. Exp Diabesity Res. 2003;4(4):271–85.PubMedPubMedCentralGoogle Scholar
  303. Pittenger GL, Ray M, Burcus NI, McNulty P, Basta B, Vinik AI. Intraepidermal nerve fibers are indicators of small-fiber neuropathy in both diabetic and nondiabetic patients. Diabetes Care. 2004;27(8):1974–9.PubMedGoogle Scholar
  304. Pittenger G, Mehrabyan A, Simmons K, Rrice A, Dublin C, Barlow P, et al. Small fiber neuropathy is associated with the metabolic syndrome. Metab Syndr Relat Disord. 2005a;3(2):113–21.PubMedGoogle Scholar
  305. Pittenger G, Simmons K, Anandacoomaraswamy D, Rrice A, Barlow P, Vinik A. Topiramate improves intraepidermal nerve fiber morphology and quantitative neuropathy measures in diabetic neuropathy patients. J Peripher Nerv Syst. 2005b;10(Suppl 1):73.Google Scholar
  306. Polydefkis M, Hauer P, Griffin JW, McArthur JC. Skin biopsy as a tool to assess distal small fiber innervation in diabetic neuropathy. Diabetes Technol Ther. 2001;3(1):23–8.PubMedGoogle Scholar
  307. Pop-Busui R. Cardiac autonomic neuropathy in diabetes: a clinical perspective. Diabetes Care. 2010;33(2):434–41.PubMedPubMedCentralGoogle Scholar
  308. Pop-Busui R, Low PA, Waberski BH, Martin CL, Albers JW, Feldman EL, et al. Effects of prior intensive insulin therapy on cardiac autonomic nervous system function in type 1 diabetes mellitus: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study (DCCT/EDIC). Circulation. 2009;119(22):2886–93.PubMedPubMedCentralGoogle Scholar
  309. Pop-Busui R, Evans G, Gerstein H, Fonseca V, Fleg J, Hoogwerf B, et al. Effects of cardiac autonomic dysfunction on mortality risk in the action to control cardiovascular risk in diabetes (ACCORD) trial. Diabetes Care. 2010;33(7):1578–84.PubMedPubMedCentralGoogle Scholar
  310. Pop-Busui R, Lu J, Brooks MM, Albert S, Althouse AD, Escobedo J, et al. Impact of glycemic control strategies on the progression of diabetic peripheral neuropathy in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) cohort. Diabetes Care. 2013a;36(10):3208–15.PubMedPubMedCentralGoogle Scholar
  311. Pop-Busui R, Cleary PA, Braffett BH, Martin CL, Herman WH, Low PA, et al. Association between cardiovascular autonomic neuropathy and left ventricular dysfunction: DCCT/EDIC study (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications). J Am Coll Cardiol. 2013b;61(4):447–54.PubMedGoogle Scholar
  312. Pop-Busui R, Boulton AJ, Feldman EL, Bril V, Freeman R, Malik RA, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care. 2017;40(1):136–54.PubMedGoogle Scholar
  313. Portenoy R. Development and testing of a neuropathic pain screening questionnaire: ID pain. Curr Med Res Opin. 2006;22(8):1555–65.PubMedGoogle Scholar
  314. Punthakee Z, Miller ME, Launer LJ, Williamson JD, Lazar RM, Cukierman-Yaffee T, et al. Poor cognitive function and risk of severe hypoglycemia in type 2 diabetes: post hoc epidemiologic analysis of the ACCORD trial. Diabetes Care. 2012;35(4):787–93.PubMedPubMedCentralGoogle Scholar
  315. Quilici S, Chancellor J, Lothgren M, Simon D, Said G, Le TK, et al. Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain. BMC Neurol. 2009;9:6–19.PubMedPubMedCentralGoogle Scholar
  316. 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.PubMedGoogle Scholar
  317. Raisanen A, Eklund J, Calvet J-H, Tuomilehto J. Sudomotor function as a tool for cardiorespiratory fitness level evaluation: comparison with VO2 max. Int J Environ Res Public Health. 2014;11:5839–48.  https://doi.org/10.3390/ijerph100x000x.CrossRefPubMedPubMedCentralGoogle Scholar
  318. Raskin P, Donofrio PD, Rosenthal NR, Hewitt DJ, Jordan DM, Xiang J, et al. Topiramate vs placebo in painful diabetic neuropathy: analgesic and metabolic effects. Neurology. 2004;63(5):865–73.PubMedGoogle Scholar
  319. Ray WA, Meredith S, Thapa PB, Hall K, Murray KT. Cyclic antidepressants and the risk of sudden cardiac death. Clin Pharmacol Ther. 2004;75:234–41.PubMedGoogle Scholar
  320. Reaven GM, Thompson LW, Nahum D, Haskins E. Relationship between hyperglycemia and cognitive function in older NIDDM patients. Diabetes Care. 1990;13(1):16–21.PubMedGoogle Scholar
  321. Reichard P, Pihl M, Rosenqvist U, Sule J. Complications in IDDM are caused by elevated blood glucose level: the Stockholm Diabetes Intervention Study (SDIS) at 10-year follow up. Diabetologia. 1996;39(12):1483–8.PubMedGoogle Scholar
  322. Reljanovic M, Reichel G, Rett K, Lobisch M, Schuette K, Moller W, et al. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Alpha lipoic acid in diabetic neuropathy. Free Radic Res. 1999;31(3):171–9.PubMedGoogle Scholar
  323. Renard C, Chappey O, Wautier MP, Nagashima M, Lundh E, Morser J, et al. Recombinant advanced glycation end product receptor pharmacokinetics in normal and diabetic rats. Mol Pharmacol. 1997;52(1):54–62.PubMedGoogle Scholar
  324. Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med. 2006;119(1):71–8.PubMedGoogle Scholar
  325. Resnick B. Functional performance of older adults in a long-term care setting. Clin Nurs Res. 1998;7(3):230–46.PubMedGoogle Scholar
  326. Resnick H, Vinik A, Schwartz A, Leveille S, Brancati F, Balfour J, et al. Independent effects of peripheral nerve dysfunction on lower-extremity physical function in old age. Diabetes Care. 2000;23(11):1642–7.PubMedGoogle Scholar
  327. Resnick HE, Stansberry KB, Harris TB, Tirivedi M, Smith K, Morgan P, et al. Diabetes, peripheral neuropathy, and old age disability. Muscle Nerve. 2002;25(1):43–50.PubMedGoogle Scholar
  328. Richardson JK, Hurvitz EA. Peripheral neuropathy: a true risk factor for falls. J Gerontol A Biol Sci Med Sci. 1995;50(4):M211–5.PubMedGoogle Scholar
  329. Richardson JK, Thies SB, DeMott TK, Ashton-Miller JA. Gait analysis in a challenging environment differentiates between fallers and nonfallers among older patients with peripheral neuropathy. Arch Phys Med Rehabil. 2005;86(8):1539–44.PubMedGoogle Scholar
  330. Richardson J, Thies S, Ashton-Miller J. An exploration of step time variability on smooth and irregular surfaces in older persons with neuropathy. Clin Biomech. 2008;23:349–56.Google Scholar
  331. Richter RW, Portenoy R, Sharma U, LaMoreaux L, Bockbrader H, Knapp LE. Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial. J Pain. 2005;6(4):253–60.PubMedGoogle Scholar
  332. Rivard A, Silver M, Chen D, Kearney M, Magner M, Annex B, et al. Rescue of diabetes-related impairment of angiogenesis by intramuscular gene therapy with adeno-VEGF. Am J Pathol. 1999;154(2):355–63.PubMedPubMedCentralGoogle Scholar
  333. Robinovitch SN, Hsiao ET, Sandler R, Cortez J, Liu Q, Paiement GD. Prevention of falls and fall-related fractures through biomechanics. Exerc Sport Sci Rev. 2000;28(2):74–9.PubMedGoogle Scholar
  334. Rolke R, Baron R, Maier C, Tolle TR, Treede RD, Beyer A, et al. Quantitative sensory testing in the German research network on neuropathic pain (DFNS): standardized protocol and reference values. Pain. 2006;123(3):231–43.PubMedGoogle Scholar
  335. Roriz-Filho J, Sa-Roriz T, Rosset I, Camozzato A, Santos A, et al. (Pre)diabetes, brain aging, and cognition. Biochim Biophys Acta. 2009;1792(5):432–43.Google Scholar
  336. Rosenstock J, Tuchman M, LaMoreaux L, Sharma U. Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial. Pain. 2004;110(3):628–38.PubMedGoogle Scholar
  337. Rowbotham MC, Goli V, Kunz NR, Lei D. Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Pain. 2004;110(3):697–706.PubMedGoogle Scholar
  338. Ruhnau KJ, Meissner HP, Finn R, Reljanovic M, Lobisch M, Schutte K, et al. Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Diabet Med. 1999;16(12):1040–3.PubMedGoogle Scholar
  339. Ryan CM, Freed MI, Rood JA, Cobitz AR, Waterhouse BR, Strachan MW. Improving metabolic control leads to better working memory in adults with type 2 diabetes. Diabetes Care. 2006;29(2):345–51.PubMedGoogle Scholar
  340. Sabatowski R, Galvez R, Cherry DA, Jacquot F, Vincent E, Maisonobe P, et al. Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: results of a randomised, placebo-controlled clinical trial. Pain. 2004;109(1-2):26–35.PubMedGoogle Scholar
  341. Sabri O, Ringelstein EB, Hellwig D, Schneider R, Schreckenberger M, Kaiser HJ, et al. Neuropsychological impairment correlates with hypoperfusion and hypometabolism but not with severity of white matter lesions on MRI in patients with cerebral microangiopathy. Stroke. 1999;30(3):556–66.PubMedGoogle Scholar
  342. Said G, Goulon-Goreau C, Lacroix C, Moulonguet A. Nerve biopsy findings in different patterns of proximal diabetic neuropathy. Ann Neurol. 1994;35(5):559–69.PubMedGoogle Scholar
  343. Samaras K, Sachdev PS. Diabetes and the elderly brain: sweet memories? Adv Endocrinol Metab. 2012;3(6):189–96.Google Scholar
  344. Sander HW, Chokroverty S. Diabetic amyotrophy: current concepts. Semin Neurol. 1996;16:173–8.PubMedGoogle Scholar
  345. Sandhu HS, Gilles E, DeVita MV, Panagopoulos G, Michelis MF. Hyponatremia associated with large-bone fracture in elderly patients. Int Urol Nephrol. 2009;41(3):733–7.PubMedGoogle Scholar
  346. Sansone RA, Sansone LA. Pain, pain, go away: antidepressants and pain management. Psychiatry (Edgmont). 2008;5(12):16–9.Google Scholar
  347. Sato N, Morishita R. Brain alterations and clinical symptoms of dementia in diabetes: abeta/tau-dependent and independent mechanisms. Front Endocrinol (Lausanne). 2014;5:143.Google Scholar
  348. Scholz J, Mannion RJ, Hord DE, Griffin RS, Rawal B, Zheng H, et al. A novel tool for the assessment of pain: validation in low back pain. PLoS Med. 2009;6(4):e1000047.PubMedPubMedCentralGoogle Scholar
  349. Schwartz AV, Vittinghoff E, Sellmeyer DE, Feingold KR, de Rekeneire N, Strotmeyer ES, et al. Diabetes-related complications, glycemic control, and falls in older adults. Diabetes Care. 2008;31(3):391–6.PubMedGoogle Scholar
  350. Schwartz S, Etropolski M, Shapiro DY, Okamoto A, Lange R, Haeussler J, et al. Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial. Curr Med Res Opin. 2011;27(1):151–62.PubMedGoogle Scholar
  351. Selvarajah D, Wilkinson ID, Griffiths PD, Shaw PJ, Emery CJ, Tesfaye S. Abnormal Thalamic magnetic resonance spectroscopy: evidence for functional impairment of the thalamus in diabetic neuropathy. Diabet Med. 2004;21(Suppl 2):2–3.Google Scholar
  352. Selvarajah D, Wilkinson ID, Emery CJ, Harris ND, Shaw PJ, Witte DR, et al. Early involvement of the spinal cord in diabetic peripheral neuropathy. Diabetes Care. 2006;29(12):2664–9.PubMedGoogle Scholar
  353. Selvarajah D, Cash T, Davies J, Sankar A, Rao G, Grieg M, et al. SUDOSCAN: a simple, rapid, and objective method with potential for screening for diabetic peripheral neuropathy. PLoS One. 2015;10(10):e0138224.PubMedPubMedCentralGoogle Scholar
  354. Sharma K, Cross J, Farronay O, Ayyar D, Sheber R, Bradley W. Demyelinating neuropathy in diabetes mellitus. Arch Neurol. 2002;59:758–65.PubMedGoogle Scholar
  355. Shemesh E, Rudich A, Harman-Boehm I, Cukierman-Yaffe T. Effect of intranasal insulin on cognitive function: a systematic review. J Clin Endocrinol Metab. 2012;97(2):366–76.PubMedGoogle Scholar
  356. Sherrington C, Lord SR, Herbert RD. A randomised trial of weight-bearing versus non-weight-bearing exercise for improving physical ability in inpatients after hip fracture. Aust J Physiother. 2003;49(1):15–22.PubMedGoogle Scholar
  357. Simoneau GG, Ulbrecht J, Derr JA, Becher MB, Cavanaugh PR. Postural instability in patients with diabetic sensory neuropathy. Diabetes Care. 1994;17:1411–21.PubMedGoogle Scholar
  358. Simpson DA. Gabapentin and venlafaxine for the treatment of painful diabetic neuropathy. J Clin Neuromuscul Dis. 2001;3(2):53–62.PubMedGoogle Scholar
  359. Sindrup SH, Jensen TS. Pharmacologic treatment of pain in polyneuropathy. Neurology. 2000;55(7):915–20.PubMedGoogle Scholar
  360. Singleton JR, Smith AG, Bromberg MB. Increased prevalence of impaired glucose tolerance in patients with painful sensory neuropathy. Diabetes Care. 2001;24(8):1448–53.PubMedGoogle Scholar
  361. Singleton JR, Bixby B, Russell JW, Feldman EL, Peltier A, Goldstein J, et al. The Utah Early Neuropathy Scale: a sensitive clinical scale for early sensory predominant neuropathy. J Peripher Nerv Syst. 2008;13(3):218–27.PubMedGoogle Scholar
  362. Singleton JR, Marcus RL, Jackson JE, Lessard K, Graham TE, Smith AG. Exercise increases cutaneous nerve density in diabetic patients without neuropathy. Ann Clin Transl Neurol. 2014;1(10):844–9.PubMedPubMedCentralGoogle Scholar
  363. Sinnreich M, Taylor BV, Dyck PJ. Diabetic neuropathies. Classification, clinical features, and pathophysiological basis. Neurologist. 2005;11(2):63–79.PubMedGoogle Scholar
  364. Sivaskandarajah GA, Halpern EM, Lovblom LE, Weisman A, Orlov S, Bril V, et al. Structure-function relationship between corneal nerves and conventional small-fiber tests in type 1 diabetes. Diabetes Care. 2013;36(9):2748–55.PubMedPubMedCentralGoogle Scholar
  365. Slangen R, Schaper NC, Faber CG, Joosten EA, Dirksen CD, van Dongen RT, et al. Spinal cord stimulation and pain relief in painful diabetic peripheral neuropathy: a prospective two-center randomized controlled trial. Diabetes Care. 2014;37(11):3016–24.PubMedGoogle Scholar
  366. Smith BE. Focal and entrapment neuropathies. Handb Clin Neurol. 2014;126:31–43.PubMedGoogle Scholar
  367. Smith AG, Singleton JR. Diabetic neuropathy. Continuum (Minneap Minn). 2012;18(1):60–84.Google Scholar
  368. Smith AG, Howard JR, Kroll R, Ramachandran P, Hauer P, et al. The reliability of skin biopsy with measurement of intraepidermal nerve fiber density. J Neurol Sci. 2005;228(1):65–9.PubMedGoogle Scholar
  369. Smith AG, Russell J, Feldman EL, Goldstein J, Peltier A, Smith S, et al. Lifestyle intervention for pre-diabetic neuropathy. Diabetes Care. 2006;29(6):1294–9.PubMedGoogle Scholar
  370. Soedamah-Muthu SS, Chaturvedi N, Witte DR, Stevens LK, Porta M, Fuller JH. Relationship between risk factors and mortality in type 1 diabetic patients in Europe: the EURODIAB Prospective Complications Study (PCS). Diabetes Care. 2008;31(7):1360–6.PubMedPubMedCentralGoogle Scholar
  371. Spallone V. La neuropatia diabetica dolorosa: approccio alla diagnosi e alla terapia di un problema emergente. Media. 2009;9:1–14.Google Scholar
  372. Spallone V, Ziegler D, Freeman R, Bernardi L, Frontoni S, Pop-Busui R, et al. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011a;27:639.PubMedGoogle Scholar
  373. Spallone V, Bellavere F, Scionti L, Maule S, Quadri R, Bax G, et al. Recommendations for the use of cardiovascular tests in diagnosing diabetic autonomic neuropathy. Nutr Metab Cardiovasc Dis. 2011b;21(1):69–78.PubMedGoogle Scholar
  374. Stem MS, Hussain M, Lentz SI, Raval N, Gardner TW, Pop-Busui R, et al. Differential reduction in corneal nerve fiber length in patients with type 1 or type 2 diabetes mellitus. J Diabetes Complicat. 2014;28(5):658–61.PubMedPubMedCentralGoogle Scholar
  375. Steptoe A, Hackett RA, Lazzarino AI, Bostock S, La MR, Carvalho LA, et al. Disruption of multisystem responses to stress in type 2 diabetes: investigating the dynamics of allostatic load. Proc Natl Acad Sci U S A. 2014;111(44):15693–8.PubMedPubMedCentralGoogle Scholar
  376. Stewart R, Liolitsa D. Type 2 diabetes mellitus, cognitive impairment and dementia. Diabet Med. 1999;16(2):93–112.PubMedGoogle Scholar
  377. Strachan MW. R D Lawrence Lecture 2010. The brain as a target organ in type 2 diabetes: exploring the links with cognitive impairment and dementia. Diabet Med. 2011;28(2):141–7.PubMedGoogle Scholar
  378. Strachan MW, Price JF. Diabetes. Cognitive decline and T2DM – a disconnect in the evidence? Nat Rev Endocrinol. 2014;10(5):258–60.PubMedGoogle Scholar
  379. Stranahan AM, Arumugam TV, Cutler RG, Lee K, Egan JM, Mattson MP. Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons. Nat Neurosci. 2008;11(3):309–17.PubMedPubMedCentralGoogle Scholar
  380. Strotmeyer ES, de Rekeneire N, Schwartz AV, Faulkner KA, Resnick HE, Goodpaster BH, et al. The relationship of reduced peripheral nerve function and diabetes with physical performance in older white and black adults: the Health, Aging, and Body Composition (Health ABC) study. Diabetes Care. 2008;31(9):1767–72.PubMedPubMedCentralGoogle Scholar
  381. Strotmeyer ES, de Rekeneire N, Schwartz AV, Resnick HE, Goodpaster BH, Faulkner KA, et al. Sensory and motor peripheral nerve function and lower-extremity quadriceps strength: the health, aging and body composition study. J Am Geriatr Soc. 2009;57(11):2004–10.PubMedPubMedCentralGoogle Scholar
  382. Takeda A, Wakai M, Niwa H, Dei R, Yamamoto M, Li M, et al. Neuronal and glial advanced glycation end product [Nepsilon-(carboxymethyl)lysine] in Alzheimer’s disease brains. Acta Neuropathol. 2001;101(1):27–35.PubMedGoogle Scholar
  383. Tam J, Rosenberg L, Maysinger D. INGAP peptide improves nerve function and enhances regeneration in streptozotocin-induced diabetic C57BL/6 mice. FASEB J. 2004;18(14):1767–9.PubMedGoogle Scholar
  384. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation. 1996;93:1043–65.Google Scholar
  385. Tavakoli M, Malik RA. Corneal confocal microscopy: a novel non-invasive technique to quantify small fibre pathology in peripheral neuropathies. J Vis Exp. 2011;47:2194.Google Scholar
  386. Tavakoli M, Quattrini C, Abbott C, Kallinikos P, Marshall A, Finnigan J, et al. Corneal confocal microscopy: a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy. Diabetes Care. 2010;33(8):1792–7.PubMedPubMedCentralGoogle Scholar
  387. Tesfaye S. Painful diabetic neuropathy. Aetiology and nonpharmacological treatment. In: Veves A, editor. Clinical management of diabetic neuropathy. Totowa: Humana Press; 1998. p. 369–86.Google Scholar
  388. Tesfaye S, Stevens LK, Stephenson JM, Fuller JH, Plater M, Ionescu-Tirgoviste C, et al. Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM Complications Study. Diabetologia. 1996a;39(11):1377–84.PubMedGoogle Scholar
  389. Tesfaye S, Watt J, Benbow SJ, Pang KA, Miles J, MacFarlane IA. Electrical spinal-cord stimulation for painful diabetic peripheral neuropathy. Lancet. 1996b;348:1698–701.PubMedGoogle Scholar
  390. Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010;33(10):2285–93.PubMedPubMedCentralGoogle Scholar
  391. Tesfaye S, Vileikyte L, Rayman G, Sindrup S, Perkins B, Baconja M, et al. Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management. Diabetes Metab Res Rev. 2011;27:629–38.PubMedGoogle Scholar
  392. Tesfaye S, Wilhelm S, Lledo A, Schacht A, Tolle T, Bouhassira D, et al. Duloxetine and pregabalin: high-dose monotherapy or their combination? The “COMBO-DN study” – a multinational, randomized, double-blind, parallel-group study in patients with diabetic peripheral neuropathic pain. Pain. 2013;154(12):2616–25.PubMedGoogle Scholar
  393. Thakral G, Kim PJ, LaFontaine J, Menzies R, Najafi B, Lavery LA. Electrical stimulation as an adjunctive treatment of painful and sensory diabetic neuropathy. J Diabetes Sci Technol. 2013;7(5):1202–9.PubMedPubMedCentralGoogle Scholar
  394. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. Neurology. 1996;46(5):1470.Google Scholar
  395. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977–86.Google Scholar
  396. Tolle T, Freynhagen R, Versavel M, Trostmann U, Young JJP. Pregabalin for relief of neuropathic pain associated with diabetic neuropathy: a randomized, double-blind study. Eur J Pain. 2008;12:203–13.PubMedGoogle Scholar
  397. Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain. 2006;7(4):281–9.PubMedGoogle Scholar
  398. Toth C, Schmidt AM, Tuor UI, Francis G, Foniok T, Brussee V, et al. Diabetes, leukoencephalopathy and rage. Neurobiol Dis. 2006;23(2):445–61.PubMedGoogle Scholar
  399. Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008;70(18):1630–5.PubMedGoogle Scholar
  400. Tsai CP, Liu CY, Lin KP, Wang KC. Efficacy of botulinum toxin type a in the relief of Carpal tunnel syndrome: a preliminary experience. Clin Drug Investig. 2006;26(9):511–5.PubMedGoogle Scholar
  401. Turcot K, Allet L, Golay A, Hoffmeyer P, Armand S. Investigation of standing balance in diabetic patients with and without peripheral neuropathy using accelerometers. Clin Biomech (Bristol, Avon). 2009;24(9):716–21.Google Scholar
  402. Turgut N, Altun BU. Cortical disinhibition in diabetic patients with neuropathic pain. Acta Neurol Scand. 2009;120(6):383–8.PubMedGoogle Scholar
  403. Uccioli L, Giacomini PG, Monticone G, Magrini A, Durola L, Bruno E, et al. Body sway in diabetic neuropathy. Diabetes Care. 1995;18(3):339–44.PubMedGoogle Scholar
  404. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–53.Google Scholar
  405. van den Berg E, de Craen AJ, Biessels GJ, Gussekloo J, Westendorp RG. The impact of diabetes mellitus on cognitive decline in the oldest of the old: a prospective population-based study. Diabetologia. 2006;49(9):2015–23.PubMedGoogle Scholar
  406. van den Berg E, Reijmer YD, de Bresser J, Kessels RP, Kappelle LJ, Biessels GJ. A 4 year follow-up study of cognitive functioning in patients with type 2 diabetes mellitus. Diabetologia. 2010;53(1):58–65.PubMedGoogle Scholar
  407. van Dijk PT, Meulenberg OG, van de Sande HJ, Habbema JD. Falls in dementia patients. Gerontologist. 1993;33(2):200–4.PubMedGoogle Scholar
  408. van Elderen SG, de Roos A, de Craen AJ, Westendorp RG, Blauw GJ, Jukema JW, et al. Progression of brain atrophy and cognitive decline in diabetes mellitus: a 3-year follow-up. Neurology. 2010;75(11):997–1002.PubMedGoogle Scholar
  409. van Seventer R, Feister HA, JrJP Y, Stoker M, Versavel M, Rigaudy L. Efficacy and tolerability of twice-daily pregabalin for treating pain and related sleep interference in postherpetic neuralgia: a 13-week, randomized trial. Curr Med Res Opin. 2006;22:375–84.PubMedGoogle Scholar
  410. Van AK, Bouhassira D, De BD, Weiss S, Matthys K, Raemen H, et al. Prevalence and impact on quality of life of peripheral neuropathy with or without neuropathic pain in type 1 and type 2 diabetic patients attending hospital outpatients clinics. Diabete Metab. 2009;35(3):206–13.Google Scholar
  411. Vellas BJ, Wayne SJ, Romero LJ, Baumgartner RN, Garry PJ. Fear of falling and restriction of mobility in elderly fallers. Age Ageing. 1997;26(3):189–93.PubMedGoogle Scholar
  412. Veresiu AI, Bondor CI, Florea B, Vinik EJ, Vinik AI, Gavan NA. Detection of undisclosed neuropathy and assessment of its impact on quality of life: a survey in 25,000 Romanian patients with diabetes. J Diabetes Complicat. 2015;29(5):644–9.PubMedGoogle Scholar
  413. Veves A, Backonja M, Malik RA. Painful diabetic neuropathy: epidemiology, natural history, early diagnosis, and treatment options. Pain Med. 2008;9(6):660–74.PubMedGoogle Scholar
  414. Vileikyte L, Peyrot M, Bundy C, Rubin RR, Leventhal H, Mora P, et al. The development and validation of a neuropathy- and foot ulcer-specific quality of life instrument. Diabetes Care. 2003;26(9):2549–55.PubMedGoogle Scholar
  415. Vincent AM, Callaghan BC, Smith AL, Feldman EL. Diabetic neuropathy: cellular mechanisms as therapeutic targets. Nat Rev Neurol. 2011;7(10):573–83.PubMedGoogle Scholar
  416. Vinik AI. Treatment of diabetic polyneuropathy (DPN) with recombinant human nerve growth factor (rhNGF). Diabetes. 1999;48(Suppl 1):A54–5.Google Scholar
  417. Vinik AI. Diabetic neuropathies: endpoints in clinical research studies. In: LeRoith D, Vinik AI, editors. Contemporary endocrinology: controversies in treating diabetes: clinical and research aspects. Totowa: Humana Press; 2008. p. 135–56.Google Scholar
  418. Vinik A. The approach to the management of the patient with neuropathic pain. J Clin Endocrinol Metab. 2010;95(11):4802–11.PubMedGoogle Scholar
  419. Vinik AI. The conductor of the autonomic orchestra. Front Endocrinol. 2012;71:1–13.Google Scholar
  420. Vinik AI. Clinical Practice. Diabetic sensory and motor neuropathy. N Engl J Med. 2016;374(15):1455–64.PubMedGoogle Scholar
  421. Vinik AI, Casellini CM. Guidelines in the management of diabetic nerve pain: clinical utility of pregabalin. Diabetes Metab Syndr Obes. 2013;6:57–78.PubMedPubMedCentralGoogle Scholar
  422. Vinik A, Mehrabyan A. Diabetic Neuropathies. Med Clin North Am. 2004;88(4):947–99.PubMedGoogle Scholar
  423. Vinik AI, Ziegler D. Diabetic cardiovascular autonomic neuropathy. Circulation. 2007;115(3):387–97.PubMedGoogle Scholar
  424. Vinik AI, Mitchell BD, Leichter SB, Wagner AL, O’Brian JT, Georges LP. Epidemiology of the complications of diabetes. In: Leslie RDG, Robbins DC, editors. Diabetes: clinical science in practice. Cambridge, UK: Cambridge University Press; 1995a. p. 221–87.Google Scholar
  425. Vinik AI, Suwanwalaikorn S, Stansberry KB, Holland MT, McNitt PM, Colen LE. Quantitative measurement of cutaneous perception in diabetic neuropathy. Muscle Nerve. 1995b;18:574–84.PubMedGoogle Scholar
  426. Vinik A, Mehrabyan A, Colen L, Boulton A. Focal entrapment neuropathies in diabetes. Diabetes Care. 2004;27(7):1783–8.PubMedGoogle Scholar
  427. Vinik EJ, Hayes RP, Oglesby A, Bastyr E, Barlow P, Ford-Molvik SL, et al. The development and validation of the Norfolk QOL-DN, a new measure of patients’ perception of the effects of diabetes and diabetic neuropathy. Diabetes Technol Ther. 2005;7(3):497–508.PubMedGoogle Scholar
  428. Vinik A, Ullal J, Parson HK, Casellini CM. Diabetic neuropathies: clinical manifestations and current treatment options. Nat Clin Pract Endocrinol Metab. 2006;2(5):269–81.PubMedGoogle Scholar
  429. Vinik E, Paulson J, Ford-Molvik S, Vinik A. German-Translated Norfolk Quality of Life (QOL-DN) identifies the same factors as the English version of the tool and discriminates different levels of neuropathy severity. J Diabetes Sci Technol. 2008a;2(6):1075–86.PubMedPubMedCentralGoogle Scholar
  430. Vinik AI, Strotmeyer ES, Nakave AA, Patel CV. Diabetic neuropathy in older adults. Clin Geriatr Med. 2008b;24(3):407–35. vPubMedPubMedCentralGoogle Scholar
  431. Vinik AI, Maser RE, Ziegler D. Neuropathy: the crystal ball for cardiovascular disease? Diabetes Care. 2010a;33(7):1688–90.PubMedPubMedCentralGoogle Scholar
  432. Vinik A, Zlateva G, Cheung R, Murphy K, Emir B, Whalen E. Understanding the impact of pain response on changes in function, quality of life, and sleep interference in patients with painful diabetic peripheral neuropathy and post-herpetic neuralgia treated with pregabalin. In: American Pain Society 29th annual scientific meeting. 2010b. Baltimore. Ref Type: Abstract.Google Scholar
  433. Vinik AI, Maser RE, Ziegler D. Autonomic imbalance: prophet of doom or scope for hope? Diabet Med. 2011;28(6):643–51.PubMedPubMedCentralGoogle Scholar
  434. Vinik A, Nevoret M-L, Casellini C, Parson H. Diabetic neuropathy. In: Poretsky L, Liao E, editors. Acute and chronic complications of diabetes. Philadelphia: Elsevier; 2013. p. 747–87. Endocrinol Metab Clin N Am.Google Scholar
  435. Vinik A, Shapiro D, Rauschkolb C, Lange B, Karcher K, Pennett D. A randomized-withdrawal, placebo-controlled study evaluating the efficacy and tolerability of tapentadol extended release in patient with chronic, painful diabetic peripheral neuropathy. Diabetes Care. 2014;37:2302.PubMedGoogle Scholar
  436. Vinik AI, Vinik EJ, Colberg SR, Morrison S. Falls risk in older adults with type 2 diabetes. In: Strotmeyer S, editor. Diabetes and aging, Clinics in geriatric medicine. Philadelphia: Elsevier; 2015. p. 89–99.Google Scholar
  437. Vinik AI, Perrot S, Vinik EJ, Pazdera L, Jacobs H, Stoker M, et al. Capsaicin 8% patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy: a randomised, 52-week, open-label, safety study. BMC Neurol. 2016;16(1):251.PubMedPubMedCentralGoogle Scholar
  438. Vischer UM, Bauduceau B, Bourdel-Marchasson I, Blickle JF, Constans T, Fagot-Campagna A, et al. A call to incorporate the prevention and treatment of geriatric disorders in the management of diabetes in the elderly. Diabete Metab. 2009;35(3):168–77.PubMedGoogle Scholar
  439. Volpato S, Leveille SG, Blaum C, Fried LP, Guralnik JM. Risk factors for falls in older disabled women with diabetes: the women’s health and aging study. J Gerontol A Biol Sci Med Sci. 2005;60(12):1539–45.PubMedPubMedCentralGoogle Scholar
  440. Volpato S, Maraldi C, Fellin R. Type 2 diabetes and risk for functional decline and disability in older persons. Curr Diabetes Rev. 2010;6(3):134–43.PubMedGoogle Scholar
  441. Wackers FJ, Young LH, Inzucchi SE, Chyun DA, Davey JA, Barrett EJ, et al. Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD study. Diabetes Care. 2004;27(8):1954–61.PubMedGoogle Scholar
  442. Walker ML, Morrison S, Colberg SR. Supervised exercise leads to improved reactions, balance and reduced falls risk in older adults with type 2 diabetes: 2946 board #11 June 3, 2: 00 PM – 3: 30 PM. Med Sci Sports Exerc. 2016;48(5 Suppl 1):828.Google Scholar
  443. Watanabe K, Hagura R, Akanuma Y, Takasu T, Kajinuma H, Kuzuya N, et al. Characteristics of cranial nerve palsies in diabetic patients. Diabetes Res Clin Pract. 1990;10(1):19–27.PubMedGoogle Scholar
  444. Watson CP, Moulin D, Watt-Watson J, Gordon A, Eisenhoffer J. Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy. Pain. 2003;105(1-2):71–8.PubMedGoogle Scholar
  445. Wautier JL, Guillausseau PJ. Advanced glycation end products, their receptors and diabetic angiopathy. Diabete Metab. 2001;27:535–42. Ref Type: GenericPubMedGoogle Scholar
  446. Wernicke JF, Pritchett YL, D’Souza DN, Waninger A, Tran P, Iyengar S, et al. A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain. Neurology. 2006;67(8):1411–20.PubMedGoogle Scholar
  447. Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA. 2009;301(15):1565–72.PubMedPubMedCentralGoogle Scholar
  448. WHO Press Conference. Global report on diabetes. Geneva. http://www.who.int/diabetes/global-report/en/2016. Accessed Jan 26 2017.
  449. Wilbourn AJ. Diabetic entrapment and compression neuropathies. In: Dyck PJ, Thomas PK, editors. Diabetic neuropathy. Philadelphia: Saunders; 1999. p. 481–508.Google Scholar
  450. Witzke KA, Vinik AI. Diabetic neuropathy in older adults. Rev Endocr Metab Disord. 2005;6(2):117–27.PubMedGoogle Scholar
  451. Witzke KA, Vinik AI. Charcot neuroarthropathy may be the RAGE. Diabetes Technol Ther. 2012;S1:005.Google Scholar
  452. Witzke K, Vinik A, Grant L, Parson H, Pittenger G. Loss of RAGE defense: a cause of charcot neuroarthropathy? Diabetes Care. 2011;34:1617. SubmittedPubMedPubMedCentralGoogle Scholar
  453. Woolcott JC, Richardson KJ, Wiens MO, Patel B, Marin J, Khan KM, et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Intern Med. 2009;169(21):1952–60.PubMedGoogle Scholar
  454. Wootton-Gorges SL, Buonocore MH, Kuppermann N, Marcin J, Dicarlo J, Neely EK, et al. Detection of cerebral {beta}-hydroxy butyrate, acetoacetate, and lactate on proton MR spectroscopy in children with diabetic ketoacidosis. AJNR Am J Neuroradiol. 2005;26(5):1286–91.PubMedGoogle Scholar
  455. Wu T, Ahmed A, Bril V, Orszag A, Ng E, Nwe P, et al. Variables associated with corneal confocal microscopy parameters in healthy volunteers: implications for diabetic neuropathy screening. Diabet Med. 2012;29(9):e297–303.PubMedGoogle Scholar
  456. Wulsin LR, Horn PS, Perry JL, Massaro J, D’Agostino R. Autonomic imbalance as a predictor of metabolic risks, cardiovascular disease, diabetes, and mortality autonomic imbalance predicts CVD, DM, mortality. J Clin Endocrinol Metab. 2015;100(6):2443–8.Google Scholar
  457. Yaffe K, Falvey C, Hamilton N, Schwartz AV, Simonsick EM, Satterfield S, et al. Diabetes, glucose control, and 9-year cognitive decline among older adults without dementia. Arch Neurol. 2012;69(9):1170–5.PubMedPubMedCentralGoogle Scholar
  458. Yan SD, Fu J, Soto C, Chen X, Zhu H, Al-Mohanna F, et al. An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer’s disease. Nature. 1997;389(6652):689–95.PubMedGoogle Scholar
  459. Yan SF, Ramasamy R, Schmidt AM. Receptor for AGE (RAGE) and its ligands-cast into leading roles in diabetes and the inflammatory response. J Mol Med. 2009;87(3):235–47.PubMedPubMedCentralGoogle Scholar
  460. Yoshitake T, Kiyohara Y, Kato I, Ohmura T, Iwamoto H, Nakayama K, et al. Incidence and risk factors of vascular dementia and Alzheimer’s disease in a defined elderly Japanese population: the Hisayama Study. Neurology. 1995;45(6):1161–8.PubMedGoogle Scholar
  461. Young RJ. Structural functional interactions in the natural history of diabetic polyneuropathy: a key to the understanding of neuropathic pain? Diabet Med. 1993;10(Suppl 2):89S–90S.PubMedGoogle Scholar
  462. Young RJ, Ewing DJ, Clarke BF. Chronic and remitting painful diabetic polyneuropathy. Correlations with clinical features and subsequent changes in neurophysiology. Diabetes Care. 1988;11(1):34–40.PubMedGoogle Scholar
  463. Young MJ, Boulton AJM, MacLeod AF, Williams DRR, Sonksen PH. A multicenter study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia. 1993;36:150–4.PubMedGoogle Scholar
  464. Young LH, Wackers FJ, Chyun DA, Davey JA, Barrett EJ, Taillefer R, et al. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA. 2009;301(15):1547–55.PubMedPubMedCentralGoogle Scholar
  465. Yuan RY, Sheu JJ, Yu JM, Chen WT, Tseng IJ, Chang HH, et al. Botulinum toxin for diabetic neuropathic pain: a randomized double-blind crossover trial. Neurology. 2009;72(17):1473–8.PubMedGoogle Scholar
  466. Zafrir B, Azencot M, Dobrecky-Mery I, Lewis BS, Flugelman MY, Halon DA. Resting heart rate and measures of effort-related cardiac autonomic dysfunction predict cardiovascular events in asymptomatic type 2 diabetes. Eur J Prev Cardiol. 2016;23(12):1298–306.PubMedGoogle Scholar
  467. Zelman DC, Brandenburg NA, Gore M. Sleep impairment in patients with painful diabetic peripheral neuropathy. Clin J Pain. 2006;22(8):681–5.PubMedGoogle Scholar
  468. Zenker J, Ziegler D, Chrast R. Novel pathogenic pathways in diabetic neuropathy. Trends Neurosci. 2013;36(8):439–49.PubMedGoogle Scholar
  469. Zhao WQ, Townsend M. Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer’s disease. Biochim Biophys Acta. 2009;1792(5):482–96.PubMedGoogle Scholar
  470. Ziegler D, Hanefeld M, Ruhnau KJ, Meissner HP, Lobisch M, Schutte K, et al. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN study). Diabetologia. 1995;38(12):1425–33.PubMedGoogle Scholar
  471. Ziegler D, Sohr CG, Nourooz-Zadeh J. Oxidative stress and antioxidant defense in relation to the severity of diabetic polyneuropathy and cardiovascular autonomic neuropathy. Diabetes Care. 2004a;27(9):2178–83.PubMedGoogle Scholar
  472. Ziegler D, Nowak H, Kempler P, Vargha P, Low PA. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis. Diabet Med. 2004b;21(2):114–21.PubMedGoogle Scholar
  473. Ziegler D, Ametov A, Barinov A, Dyck PJ, Gurieva I, Low PA, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. 2006;29(11):2365–70.PubMedGoogle Scholar
  474. Ziegler D, Pritchett YL, Wang F, Desaiah D, Robinson MJ, Hall JA, et al. Impact of disease characteristics on the efficacy of duloxetine in diabetic peripheral neuropathic pain. Diabetes Care. 2007;30(3):664–9.PubMedGoogle Scholar
  475. Ziegler D, Rathmann W, Dickhaus T, Meisinger C, Mielck A. 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. 2008a;31(3):464–9.PubMedGoogle Scholar
  476. Ziegler D, Zentai CP, Perz S, Rathmann W, Haastert B, Doring A, et al. Prediction of mortality using measures of cardiac autonomic dysfunction in the diabetic and nondiabetic population: the MONICA/KORA Augsburg cohort study. Diabetes Care. 2008b;31(3):556–61.PubMedGoogle Scholar
  477. Ziegler D, Rathmann W, Dickhaus T, Meisinger C, Mielck A. Neuropathic pain in diabetes, prediabetes and normal glucose tolerance: the MONICA/KORA Augsburg Surveys S2 and S3. Pain Med. 2009a;10(2):393–400.PubMedGoogle Scholar
  478. Ziegler D, Rathmann W, Meisinger C, Dickhaus T, Mielck A. Prevalence and risk factors of neuropathic pain in survivors of myocardial infarction with pre-diabetes and diabetes. The KORA Myocardial Infarction Registry. Eur J Pain. 2009b;13(6):582–7.PubMedGoogle Scholar
  479. Ziegler D, Low PA, Litchy WJ, Boulton AJ, Vinik AI, Freeman R, et al. Efficacy and safety of antioxidant treatment with alpha-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care. 2011;34(9):2054–60.PubMedPubMedCentralGoogle Scholar
  480. Ziegler D, Papanas N, Vinik AI, Shaw JE. Epidemiology of polyneuropathy in diabetes and prediabetes. In: Zochodne DW, Malik RA, editors. Diabetes and the nervous system, Handbook of clinical neurology. 3rd ed. Edinburgh: Elsevier; 2014a. p. 3–22.Google Scholar
  481. Ziegler D, Papanas N, Zhivov A, Allgeier S, Winter K, Ziegler I, et al. Early detection of nerve fiber loss by corneal confocal microscopy and skin biopsy in recently diagnosed type 2 diabetes. Diabetes. 2014b;63(7):2454–63.PubMedGoogle Scholar
  482. Ziegler D, Voss A, Rathmann W, Strom A, Perz S, Roden M, et al. Increased prevalence of cardiac autonomic dysfunction at different degrees of glucose intolerance in the general population: the KORA S4 survey. Diabetologia. 2015a;58(5):1118–28.PubMedGoogle Scholar
  483. Ziegler D, Duan WR, An G, Thomas JW, Nothaft W. A randomized double-blind, placebo-, and active-controlled study of T-type calcium channel blocker ABT-639 in patients with diabetic peripheral neuropathic pain. Pain. 2015b;156(10):2013–20.PubMedPubMedCentralGoogle Scholar
  484. Ziegler D, Low PA, Freeman R, Tritschler H, Vinik AI. Predictors of improvement and progression of diabetic polyneuropathy following treatment with alpha-lipoic acid for 4years in the NATHAN 1 trial. J Diabetes Complicat. 2016;30(2):350–6.PubMedGoogle Scholar
  485. Zinman LH, Bril V, Perkins BA. Cooling detection thresholds in the assessment of diabetic sensory polyneuropathy: comparison of CASE IV and Medoc instruments. Diabetes Care. 2004;27(7):1674–9.PubMedGoogle Scholar
  486. Zochodne D, Toth C. Diabetes and the nervous system. In: Aminoff’s neurology and general medicine. 5th ed. Amsterdam: Academic; 2014. p. 351–68.Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Aaron I. Vinik
    • 1
  • Carolina Casellini
    • 1
  • Serina Neuman
    • 2
  1. 1.Strelitz Diabetes Center & The Neuroendocrine UnitEastern Virginia Medical SchoolNorfolkUSA
  2. 2.Psychiatry & Behavioral Sciences/ Behavioral Medicine Program/Therapeutic Brain Stimulation ProgramEastern Virginia Medical SchoolNorfolkUSA

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