Dysmetabolism-related early sensory Deficits and their Relationship with peripheral Neuropathy Development.

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To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development. 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as "healthy" and those with EPSD based on a standardized QST protocol. 196 were followed-up over a mean of 2.64 years for PN occurrence. Among those without T2DM, apart from male gender, height, higher fat and lower lean mass, only higher insulin resistance (IR, HOMA-R: OR 1.70, p=0.009, McAuley index OR: 0.62, p=0.008), was independently associated with EPSD. In T2DM, metabolic syndrome (MetS, OR 18.32, p<0.001) and skin advanced glycation end-products (AGEs, OR 5.66, p=0.003) were independent predictors of EPSD. In longitudinal analysis, T2DM (HR 3.32 vs. no DM, p<0.001), EPSD (aHR 1.88 vs. healthy, p=0.049 adjusted for DM and gender), higher IR and AGEs predicted PN development. Among the three EPSD-associated sensory phenotypes, "sensory loss" was most strongly associated with PN development (aHR 4.35, p=0.011). We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, MetS and higher AGEs which in turn are shown to influence PN development.