DN is the most common complication of diabetes. DN is the primary cause of diabetic foot problems and ulceration, the leading causes of diabetes-related hospital admissions and nontraumatic amputation.[4]Vinik AI, Nevoret ML, Casellini C, et al. Diabetic neuropathy. Endocrinol Metab Clin North Am. 2013 Dec;42(4):747-87.
http://www.ncbi.nlm.nih.gov/pubmed/24286949?tool=bestpractice.com
Approximately 50% of people with diabetes will develop DN during their lifetime, although estimates vary depending on the diagnostic criteria used.[5]Young MJ, Boulton AJ, MacLeod AF, et al. A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia. 1993 Feb;36(2):150-4.
http://www.ncbi.nlm.nih.gov/pubmed/8458529?tool=bestpractice.com
[6]Iqbal Z, Azmi S, Yadav R, et al. Diabetic peripheral neuropathy: epidemiology, diagnosis, and pharmacotherapy. Clin Ther. 2018 Apr 30;40(6):828-49.
https://www.clinicaltherapeutics.com/article/S0149-2918(18)30140-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29709457?tool=bestpractice.com
A systematic review and meta-analysis found that individuals with type 2 diabetes had a higher prevalence (31.5%) of DN than those with type 1 diabetes (17.5%).[7]Sun J, Wang Y, Zhang X, et al. Prevalence of peripheral neuropathy in patients with diabetes: a systematic review and meta-analysis. Prim Care Diabetes. 2020 Oct;14(5):435-44.
http://www.ncbi.nlm.nih.gov/pubmed/31917119?tool=bestpractice.com
Although there are no major differences in nerve pathology between type 1 and type 2 diabetes, small-fiber neuropathy may be more severe in latent autoimmune diabetes in adults (LADA).[8]Alam U, Asghar O, Petropoulos IN, et al. Small fiber neuropathy in patients with latent autoimmune diabetes in adults. Diabetes Care. 2015 Jul;38(7):e102-3.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876746
http://www.ncbi.nlm.nih.gov/pubmed/26106229?tool=bestpractice.com
The prevalence of DN is considered to be low in patients with early type 1 diabetes. However, among participants in the Diabetes Control and Complications Trial (DCCT) who were considered to be non-neuropathic at baseline, the prevalence of an abnormal neurologic exam was almost 20% in those on conventional treatment and almost 10% in those on intensive treatment after approximately 5 years of follow-up.[9]Nathan DM, Genuth S, Lachin J, et al; 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 Sep 30;329(14):977-86.
https://www.nejm.org/doi/full/10.1056/NEJM199309303291401
http://www.ncbi.nlm.nih.gov/pubmed/8366922?tool=bestpractice.com
The prevalence of both distal symmetric polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) increased during the observational follow-up of the DCCT cohort, Epidemiology of Diabetes Interventions and Complications (EDIC). At EDIC years 13 to 14, after a mean diabetes duration of 26 years, reported prevalence rates were 25% and 35% for diabetic peripheral neuropathy (DPN), and 29% and 35% for CAN, in the former intensive and conventional control treatment groups with type 1 diabetes, respectively.[10]Albers JW, Herman WH, Pop-Busui R, et al; Diabetes Control and Complications Trial /Epidemiology of Diabetes Interventions and Complications Research Group. 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 May;33(5):1090-6.
https://diabetesjournals.org/care/article/33/5/1090/27031/Effect-of-Prior-Intensive-Insulin-Treatment-During
http://www.ncbi.nlm.nih.gov/pubmed/20150297?tool=bestpractice.com
[11]Pop-Busui R, Low PA, Waberski BH, et al; DCCT/EDIC Research Group. 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 Jun 9;119(22):2886-93.
https://www.ahajournals.org/doi/full/10.1161/circulationaha.108.837369
http://www.ncbi.nlm.nih.gov/pubmed/19470886?tool=bestpractice.com
The EURODIAB IDDM Complications Study found that the prevalence of DN, across randomly selected patients with type 1 diabetes from 16 European countries, was 28%, with no significant geographic differences.[12]Tesfaye S, Stevens LK, Stephenson JM, et al. Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM Complications Study. Diabetologia. 1996 Nov;39(11):1377-84.
http://www.ncbi.nlm.nih.gov/pubmed/8933008?tool=bestpractice.com
In the Pittsburgh Epidemiology of Diabetes Complications Study, in which patients with type 1 diabetes were followed, the cumulative incidence of DPN over a period of 5.3 years was 29%.[13]Maser RE, Steenkiste AR, Dorman JS, et al. Epidemiological correlates of diabetic neuropathy. Report from Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes. 1989 Nov;38(11):1456-61.
http://www.ncbi.nlm.nih.gov/pubmed/2620781?tool=bestpractice.com
A prospective study of outpatients with type 1 or type 2 diabetes found an increase in the prevalence of DN from 10% (at the time of diagnosis) to 50% after 25 years of diabetes.[14]Pirart J, Lauvaux JP, Rey W. Blood sugar and diabetic complications. N Engl J Med. 1978 May 18;298(20):1149.
http://www.ncbi.nlm.nih.gov/pubmed/643042?tool=bestpractice.com
A similar prevalence was reported in the Rochester Diabetic Study, in which 59% of patients with type 2 and 66% of patients with type 1 diabetes had DN.[15]Dyck PJ, Kratz KM, Karnes JL, 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 Apr;43(4):817-24.
http://www.ncbi.nlm.nih.gov/pubmed/8469345?tool=bestpractice.com
Another large cross-sectional study of people with type 1 and type 2 diabetes in the UK found the prevalence of DN to be 29%.[5]Young MJ, Boulton AJ, MacLeod AF, et al. A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia. 1993 Feb;36(2):150-4.
http://www.ncbi.nlm.nih.gov/pubmed/8458529?tool=bestpractice.com
There was no benefit on incidence of DN in people undergoing a multifactorial intervention for screen-detected type 2 diabetes.[16]Sandbæk A, Griffin SJ, Sharp SJ, et al. Effect of early multifactorial therapy compared with routine care on microvascular outcomes at 5 years in people with screen-detected diabetes: a randomized controlled trial: the ADDITION-Europe study. Diabetes Care. 2014 Jul;37(7):2015-23.
https://diabetesjournals.org/care/article/37/7/2015/37792/Effect-of-Early-Multifactorial-Therapy-Compared
http://www.ncbi.nlm.nih.gov/pubmed/24784827?tool=bestpractice.com
[17]Charles M, Ejskjaer N, Witte DR, et al. Prevalence of neuropathy and peripheral arterial disease and the impact of treatment in people with screen-detected type 2 diabetes: the ADDITION-Denmark study. Diabetes Care. 2011 Oct;34(10):2244-9.
https://diabetesjournals.org/care/article/34/10/2244/26920/Prevalence-of-Neuropathy-and-Peripheral-Arterial
http://www.ncbi.nlm.nih.gov/pubmed/21816977?tool=bestpractice.com
In one large study that enrolled more than 2300 participants with type 2 diabetes with a mean diabetes duration of approximately 10 years and confirmed coronary artery disease, the prevalence of confirmed DPN was approximately 50%.[18]Pop-Busui R, Lu J, Lopes N, et al; BARI 2D Investigators. Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort. J Peripher Nerv Syst. 2009 Mar;14(1):1-13.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2692660
http://www.ncbi.nlm.nih.gov/pubmed/19335534?tool=bestpractice.com
[19]Pop-Busui R, Lu J, Brooks MM, et al; BARI 2D Study Group. 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. 2013 Oct;36(10):3208-15.
https://diabetesjournals.org/care/article/36/10/3208/30388/Impact-of-Glycemic-Control-Strategies-on-the
http://www.ncbi.nlm.nih.gov/pubmed/23757426?tool=bestpractice.com
Among those participants who were free of DPN at baseline, the cumulative incidence of DPN over 4 years of follow-up was 69%.[19]Pop-Busui R, Lu J, Brooks MM, et al; BARI 2D Study Group. 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. 2013 Oct;36(10):3208-15.
https://diabetesjournals.org/care/article/36/10/3208/30388/Impact-of-Glycemic-Control-Strategies-on-the
http://www.ncbi.nlm.nih.gov/pubmed/23757426?tool=bestpractice.com
In two longitudinal studies of patients with type 1 diabetes, approximately 18% developed DPN over 3 years.[20]Pritchard N, Edwards K, Russell AW, et al. Corneal confocal microscopy predicts 4-year incident peripheral neuropathy in type 1 diabetes. Diabetes Care. 2015 Apr;38(4):671-5.
https://diabetesjournals.org/care/article/38/4/671/37524/Corneal-Confocal-Microscopy-Predicts-4-Year
http://www.ncbi.nlm.nih.gov/pubmed/25573881?tool=bestpractice.com
[21]Lovblom LE, Halpern EM, Wu T, et al. In vivo corneal confocal microscopy and prediction of future-incident neuropathy in type 1 diabetes: a preliminary longitudinal analysis. Can J Diabetes. 2015 Oct;39(5):390-7.
http://www.ncbi.nlm.nih.gov/pubmed/25936902?tool=bestpractice.com
In the NHANES study, the prevalence of DPN was found to be 28%.[22]Gregg EW, Sorlie P, Paulose-Ram R, et al; 1999-2000 national health and nutrition examination survey. Prevalence of lower-extremity disease in the US adult population ≥40 years of age with and without diabetes: 1999-2000 National Health and Nutrition Examination Survey. Diabetes Care. 2004 Jul;27(7):1591-7.
https://diabetesjournals.org/care/article/27/7/1591/24507/Prevalence-of-Lower-Extremity-Disease-in-the-U-S
http://www.ncbi.nlm.nih.gov/pubmed/15220233?tool=bestpractice.com
Longitudinal studies indicate an annual increase in prevalence of CAN of about 6% in type 2 diabetes and of about 2% in type 1 diabetes.[23]Spallone V, Ziegler D, Freeman R, et al; Toronto Consensus Panel on Diabetic Neuropathy. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011 Oct;27(7):639-53.
https://onlinelibrary.wiley.com/doi/full/10.1002/dmrr.1239
http://www.ncbi.nlm.nih.gov/pubmed/21695768?tool=bestpractice.com
Prevalence increases with age (up to 38% in type 1 and 44% in type 2 diabetes patients ages 40-70 years) and diabetes duration (up to 35% in type 1 and 65% in type 2 diabetes patients with long-standing diabetes).[23]Spallone V, Ziegler D, Freeman R, et al; Toronto Consensus Panel on Diabetic Neuropathy. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011 Oct;27(7):639-53.
https://onlinelibrary.wiley.com/doi/full/10.1002/dmrr.1239
http://www.ncbi.nlm.nih.gov/pubmed/21695768?tool=bestpractice.com
Due to its broad clinical consequences and high morbidity, DN is associated with a poor quality of life.[24]Vileikyte L, Leventhal H, Gonzalez JS, et al. Diabetic peripheral neuropathy and depressive symptoms: the association revisited. Diabetes Care. 2005 Oct;28(10):2378-83.
https://diabetesjournals.org/care/article/28/10/2378/23961/Diabetic-Peripheral-Neuropathy-and-Depressive
http://www.ncbi.nlm.nih.gov/pubmed/16186266?tool=bestpractice.com
[25]Vileikyte L, Rubin RR, Leventhal H. Psychological aspects of diabetic neuropathic foot complications: an overview. Diabetes Metab Res Rev. 2004 May-Jun;20 Suppl 1:S13-8.
http://www.ncbi.nlm.nih.gov/pubmed/15150807?tool=bestpractice.com
The SEARCH for Diabetes in Youth study reported that signs for both cardiac autonomic neuropathy and DPN are found in youth with type 1 diabetes.[26]Jaiswal M, Urbina EM, Wadwa RP, et al. Reduced heart rate variability among youth with type 1 diabetes: the SEARCH CVD study. Diabetes Care. 2013 Jan;36(1):157-62.
https://diabetesjournals.org/care/article/36/1/157/38298/Reduced-Heart-Rate-Variability-Among-Youth-With
http://www.ncbi.nlm.nih.gov/pubmed/22961570?tool=bestpractice.com
In this study, DPN prevalence in youth ages under 20 years based in the US was high, with a significant excess preponderance in those with type 2 diabetes even with a short duration of disease.[27]Jaiswal M, Divers J, Dabelea D, et al. Prevalence of and risk factors for diabetic peripheral neuropathy in youth with type 1 and type 2 diabetes: SEARCH for Diabetes in Youth study. Diabetes Care. 2017 Sep;40(9):1226-32.
https://diabetesjournals.org/care/article/40/9/1226/36722/Prevalence-of-and-Risk-Factors-for-Diabetic
http://www.ncbi.nlm.nih.gov/pubmed/28674076?tool=bestpractice.com
The prevalence of DPN was 7% in youth with type 1 diabetes and 22% in youth with type 2 diabetes.[27]Jaiswal M, Divers J, Dabelea D, et al. Prevalence of and risk factors for diabetic peripheral neuropathy in youth with type 1 and type 2 diabetes: SEARCH for Diabetes in Youth study. Diabetes Care. 2017 Sep;40(9):1226-32.
https://diabetesjournals.org/care/article/40/9/1226/36722/Prevalence-of-and-Risk-Factors-for-Diabetic
http://www.ncbi.nlm.nih.gov/pubmed/28674076?tool=bestpractice.com
Studies also show evidence of small-fiber neuropathy in people with impaired glucose tolerance.[28]Asghar O, Petropoulos IN, Alam U, et al. Corneal confocal microscopy detects neuropathy in subjects with impaired glucose tolerance. Diabetes Care. 2014 Sep;37(9):2643-6.
https://diabetesjournals.org/care/article/37/9/2643/28987/Corneal-Confocal-Microscopy-Detects-Neuropathy-in
http://www.ncbi.nlm.nih.gov/pubmed/24969581?tool=bestpractice.com
[29]Zilliox LA, Ruby SK, Singh S, et al. Clinical neuropathy scales in neuropathy associated with impaired glucose tolerance. J Diabetes Complications. 2015 Apr;29(3):372-7.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558101
http://www.ncbi.nlm.nih.gov/pubmed/25690405?tool=bestpractice.com