Retinopathy as an independent predictor of all-cause mortality in individuals with type 2 diabetes - 29/11/22

Doi : 10.1016/j.diabet.2022.101413

Emanuela Orsi ¹, Anna Solini ², Enzo Bonora ³, Martina Vitale ⁴, Monia Garofolo ⁵, Cecilia Fondelli ⁶, Roberto Trevisan ⁷, Monica Vedovato ⁸, Franco Cavalot ⁹, Gianpaolo Zerbini ¹⁰, Antonio Nicolucci ¹¹, Giuseppe Pugliese ^4,^⁎
for the
Renal Insufficiency And Cardiovascular Events (RIACE) Study Group^{^#}
See Appendix 1 for a complete list of the RIACE Investigators (see supplementary materials associated with this article on line).
¹ Diabetes Unit, IRCCS “Cà Granda - Ospedale Maggiore Policlinico” Foundation, Milan
² Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa
³ Division of Endocrinology, Diabetes and Metabolism, University and Hospital Trust of Verona, Verona
⁴ Department of Clinical and Molecular Medicine, “La Sapienza” University, Rome, Italy
⁵ Department of Clinical and Experimental Medicine, University of Pisa, Pisa
⁶ Diabetes Unit, University of Siena, Siena
⁷ Endocrinology and Diabetes Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo
⁸ Department of Clinical and Experimental Medicine, University of Padua, Padua
⁹ Department of Clinical and Biological Sciences, University of Turin, Orbassano
¹⁰ Complications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milan
¹¹ Centre for Outcomes Research and Clinical Epidemiology (CORESEARCH), Pescara, Italy

^⁎Corresponding author: Giuseppe Pugliese, MD, PhD, Department of Clinical and Molecular Medicine, “La Sapienza” University, Via di Grottarossa, 1035-1039 00189 Rome, Italy; Phone: +39-0633775440; Fax: +39-0633776327Department of Clinical and Molecular Medicine“La Sapienza” UniversityVia di Grottarossa, 1035-1039Rome00189Italy

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Abstract

Aims

To assess whether the presence and grade of diabetic retinopathy (DR) predict all-cause mortality, independent of risk factors for cardiovascular disease (CVD) and other complications, including diabetes-related kidney disease (DKD) and CVD, in individuals with type 2 diabetes mellitus.

Methods

Prospective cohort study that enrolled 15,773 patients in 19 Italian centers in 2006-2008. DR ascertained by fundoscopy, DKD by albuminuria and estimated glomerular filtration rate, and prior CVD by hospital discharge records. All-cause mortality retrieved for 15,656 patients on 31 October 2015.

Results

The adjusted risk of death was increased in patients with any DR (hazard ratio, 1.136 [95% confidence interval, 1.054;1.224] P < 0.0001), advanced DR, including severe non-proliferative and proliferative DR and diabetic macula edema (1.213 [1.097;1.340] P < 0.0001), and especially proliferative DR alone (1.381 [1.207;1.580] P < 0.0001), compared with those without DR. The impact of DR was more evident in patients without than in those with DKD or CVD. Mortality risk was increased in participants with DR alone, though much less than in those with DKD or CVD alone and particularly in those with both DR and DKD or CVD. DR grade was related to mortality in individuals without DKD or CVD, whereas it conferred no additional risk to those with albuminuric or nonalbuminuric DKD or established CVD.

Conclusions

In patients with type 2 diabetes mellitus, the excess mortality risk conferred by DR is relatively small and higher in those without DKD and CVD, suggesting that it may be mediated by the concurrent presence of these complications, even at a subclinical level.

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Key words : All-cause mortality, Cardiovascular disease Diabetic retinopathy, Diabetes-related kidney disease, Type 2 diabetes

Abbreviations : Alb, BMI, BP, CI, CVD, DKD, DME, DPN, DR, eGFR, HbA_1c, HDL, HR, IQR, LDL, NPDR, PDR, SD, RIACE, T2DM