128-OR: The Ipswich Neurodiab Study: A 5-Year Longitudinal Study Examining Natural History of Diabetes Polyneuropathy (DPN)

Abstract

This longitudinal, case-control study compares the progression of Small and Large Fibre Neuropathy (SFN and LFN respectively) in T1DM and T2DM and examines determinants of progression. T1DM, T2DM and healthy controls (HC) groups each with 50 subjects were evaluated annually (2014-19). Functional SFN was assessed using the LDIFLARE test in the foot and structural SFN in the cornea [corneal nerve fibre density using confocal microscopy (CCMCNFD)]. LFN was assessed using vibration perception threshold (VPT) and sural nerve conduction velocity (SNCV) and amplitude (SNAP). At year 5 DPN was diagnosed if the Neurology Disability score (NDS) was ≥3 (DPN+). Mean (±SD) age and sex distribution at baseline for T1DM was (41.4±15.0 yr; 27 males), T2DM (54.38±9.1; 25m) and HC (40.7±15.1; 24m). T1DM with DPN+ had a significantly greater decline of LDIFLARE size compared to DPN- [0.15 v 0.08 cm2/yr; p=0.001] and of CCMCNFD (0.16v 0.10 fibres/mm2/yr; p=0.005). In contrast in T2DM there was no difference between DPN+ and DPN- groups in LDIFLARE size (0.22v 0.15cm2/yr; p=0.09) and CCMCNFD (0.23v 0.16 fibres/mm2/yr; p=0.06). Decline in small fibre function and structure in T1DM DPN- was no different from HCs. (LDIFLARE - 0.07cm2/yr; CCMCNFD - 0.05 fibres/mm2/yr) in contrast to all other groups. In T1DM, the decline of LDIFLARE size and CCMCNFD correlated only with HbA1c change (p=<0.05). In T2DM they correlated with HbA1c, triglycerides and BP changes (p=<0.05). There was no significant change of LFN indices (VPT, SNCV and SNAP; p=>0.05) over the 5yrs. This - the first longitudinal comparative study of changes in small fibre nerve structure and function in T1DM and T2DM - demonstrates changes in SFN in both groups that are not paralleled by changes in LFN, supporting the concept that SFN precedes LFN in DPN, It further demonstrates important differences in determinants of progression between T1DM and T2DM; the former being related to glycaemic control and the latter to multiple metabolic factors. Disclosure S. Sharma: None. J. Cross: None. P.R. Vas: None. G. Rayman: None.