Epidemiology

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] Approximately 50% of people with diabetes will develop DN during their lifetime, although estimates vary depending on the diagnostic criteria used.[5][6] 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] 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]

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] 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][11] 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] 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]

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] 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] 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] There was no benefit on incidence of DN in people undergoing a multifactorial intervention for screen-detected type 2 diabetes.[16][17] 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][19] Among those participants who were free of DPN at baseline, the cumulative incidence of DPN over 4 years of follow-up was 69%.[19] In two longitudinal studies of patients with type 1 diabetes, approximately 18% developed DPN over 3 years.[20][21] In the NHANES study, the prevalence of DPN was found to be 28%.[22]

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] 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]

Due to its broad clinical consequences and high morbidity, DN is associated with a poor quality of life.[24][25] 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] 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] The prevalence of DPN was 7% in youth with type 1 diabetes and 22% in youth with type 2 diabetes.[27] Studies also show evidence of small-fiber neuropathy in people with impaired glucose tolerance.[28][29]

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