(Pre)diabetes, glycemia, and daily glucose variability are associated with retinal nerve fiber layer thickness in The Maastricht Study

Author:

van der Heide Frank C. T.ORCID,Foreman Yuri D.ORCID,Franken Iris W. M.,Henry Ronald M. A.ORCID,Kroon Abraham A.ORCID,Dagnelie Pieter C.ORCID,Eussen Simone J. P. M.ORCID,Berendschot Tos T. J. M.ORCID,Schouten Jan S. A. G.ORCID,Webers Carroll A. B.ORCID,Schram Miranda T.ORCID,van der Kallen Carla J. H.ORCID,van Greevenbroek Marleen M. J.ORCID,Wesselius AnkeORCID,Schalkwijk Casper G.ORCID,Schaper Nicolaas C.ORCID,Brouwers Martijn C. G. J.ORCID,Stehouwer Coen D. A.ORCID

Abstract

AbstractRetinopathy and neuropathy in type 2 diabetes are preceded by retinal nerve fibre layer (RNFL) thinning, an index of neurodegeneration. We investigated whether glucose metabolism status (GMS), measures of glycaemia, and daily glucose variability (GV) are associated with RNFL thickness over the entire range of glucose tolerance. We used cross-sectional data from The Maastricht Study (up to 5455 participants, 48.9% men, mean age 59.5 years and 22.7% with type 2 diabetes) to investigate the associations of GMS, measures of glycaemia (fasting plasma glucose [FPG], 2-h post-load glucose [2-h PG], HbA1c, advanced glycation endproducts [AGEs] assessed as skin autofluorescence [SAF]) and indices of daily GV (incremental glucose peak [IGP] and continuous glucose monitoring [CGM]-assessed standard deviation [SD]) with mean RNFL thickness. We used linear regression analyses and, for GMS, P for trend analyses. We adjusted associations for demographic, cardiovascular risk and lifestyle factors, and, only for measures of GV, for indices of mean glycaemia. After full adjustment, type 2 diabetes and prediabetes (versus normal glucose metabolism) were associated with lower RNFL thickness (standardized beta [95% CI], respectively − 0.16 [− 0.25; − 0.08]; − 0.05 [− 0.13;  0.03]; Ptrend = 0.001). Greater FPG, 2-h PG, HbA1c, SAF, IGP, but not CGM-assessed SD, were also associated with lower RNFL thickness (per SD, respectively − 0.05 [− 0.08; − 0.01]; − 0.06 [− 0.09; − 0.02]; − 0.05 [− 0.08; − 0.02]; − 0.04 [− 0.07; − 0.01]; − 0.06 [− 0.12; − 0.01]; and − 0.07 [− 0.21; 0.07]). In this population-based study, a more adverse GMS and, over the entire range of glucose tolerance, greater glycaemia and daily GV were associated with lower RNFL thickness. Hence, early identification of individuals with hyperglycaemia, early glucose-lowering treatment, and early monitoring of daily GV may contribute to the prevention of RNFL thinning, an index of neurodegeneration and precursor of retinopathy and neuropathy.

Funder

Diabetes fonds

Oogfonds

Medtronic

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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