Prevalence of peripheral neuropathy in pre-diabetes: a systematic review

There is growing evidence of excess peripheral neuropathy in pre-diabetes. We aimed to determine its prevalence, including the impact of diagnostic methodology on prevalence rates, through a systematic review conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive electronic bibliographic search was performed in MEDLINE, EMBASE, PubMed, Web of Science and the Cochrane Central Register of Controlled Trials from inception to June 1, 2020. Two reviewers independently selected studies, extracted data and assessed risk of bias. An evaluation was undertaken by method of neuropathy assessment. After screening 1784 abstracts and reviewing 84 full-text records, 29 studies (9351 participants) were included. There was a wide range of prevalence estimates (2%-77%, IQR: 6%-34%), but the majority of studies (n=21, 72%) reported a prevalence ≥10%. The three highest prevalence estimates of 77% (95% CI: 54% to 100%), 71% (95% CI: 55% to 88%) and 66% (95% CI: 53% to 78%) were reported using plantar thermography, multimodal quantitative sensory testing and nerve conduction tests, respectively. In general, studies evaluating small nerve fiber parameters yielded a higher prevalence of peripheral neuropathy. Due to a variety of study populations and methods of assessing neuropathy, there was marked heterogeneity in the prevalence estimates. Most studies reported a higher prevalence of peripheral neuropathy in pre-diabetes, primarily of a small nerve fiber origin, than would be expected in the background population. Given the marked rise in pre-diabetes, further consideration of targeting screening in this population is required. Development of risk-stratification tools may facilitate earlier interventions.