Aims/hypothesis: We examined whether retinal vessel diameter in persons with type 1 diabetes mellitus is associated with changes in subclinical anatomical and functional indicators of diabetic nephropathy. Methods: Persons with type 1 diabetes mellitus had gradable fundus photographs and renal biopsy data at baseline and 5-year follow-up (n∈=∈234). Retinal arteriolar and venular diameters were measured at baseline and follow-up. Central retinal arteriole equivalent (CRAE) and central retinal venule equivalent (CRVE) were computed. Baseline and 5-year follow-up renal structural variables were assessed by masked electron microscopic morphometric analyses from percutaneous renal biopsy specimens. Variables assessed included: mesangial fractional volume, glomerular basement membrane width, mesangial matrix fractional volume and glomerular basement membrane width composite glomerulopathy index. Results: While controlling for other covariates, baseline CRAE was positively associated with change in the glomerulopathy index over the 5-year period. Change in CRAE was inversely related to a change in mesangial matrix fractional volume and abnormal mesangial matrix fractional volume, while change in CRVE was directly related to change in the volume fraction of cortex that was interstitium [Vv (Int/cortex)] over the 5-year period. Baseline CRAE or CRVE or changes in these diameters were not related to changes in other anatomical or functional renal endpoints. Conclusions/interpretation: Independently of other factors, baseline CRAE correlated with changes in glomerulopathy index, a composite measure of extracellular matrix accumulation in the mesangium and glomerular basement membrane. A narrowing of the CRAE was related to mesangial matrix accumulation. Changes in CRVE were related to changes in Vv (Int/cortex), a measure of interstitial expansion in persons with type 1 diabetes mellitus.
Bibliographical noteFunding Information:
Acknowledgements This study was funded by research grants from the Juvenile Diabetes Research Foundation (R. Klein) and the National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Disease (NIH DK51975). Work was also supported by Merck (in the USA), Merck Frosst (in Canada) and the Canadian Institutes of Health Research (CIHR) (DCT 14281). The University of Minnesota General Clinical Research Center is supported by the NIH (M01 RR 00400). Additional support was given by the National Institutes of Health, National Eye Institute (EY12198) and Research to Prevent Blindness (Senior Scientific Investigator Award to R. Klein) (New York, USA). S. Suissa was the recipient of a Distinguished Investigator Award from the CIHR. The sponsors and funding organisations had no role in the design or conduct of this research.
Duality of interest B. Zinman has received lecture fees, consulting fees and research grants from Merck. R. Klein is an Advisory Board member for AstraZeneca (through the DIRECT study), Pfizer, Lilly and Novartis. All other authors declare that there is no duality of interest associated with this manuscript.
- Microvascular disease
- Retinal blood vessel diameters
- Risk indicators
- Type 1 diabetes mellitus