Researchers in France have provided further evidence that duration of diabetes and higher HbA1c levels are primary drivers for diabetic retinopathy among people with type 1 diabetes, and that, to an extent, it can defy improved glucose control.1

The researchers at the University of Paris performed a cross-sectional study of 1,464 T1D patients who were seen at the University Center for Diabetes and its Complications at Lariboisière Hospital from January 2017 to February 2019. Their average HbA1c level was 7.8 ±1.7 percent; the target level for people with diabetes is 7 percent. Their average disease duration was 20.5 years ±13.5 years. Overall, 50.1 percent of the adult T1D patients in the study had DR and 17.6 percent had proliferative DR.

The researchers acknowledged that the reported prevalence of DR in T1D patients has varied widely depending on the study, noting one study that found a rate of any DR of 77.3 percent and PDR of 32.4 percent worldwide,2 while the Meta-Analysis for Eye Disease Study Group reported a prevalence of any DR of 67 percent.3 

Risk Factors and DR Prevalence

The risk factors for DR and PDR the Paris researchers identified are similar to those reported previously.4 Presence of any DR and DR grade were significantly associated with older age, male gender, higher body-mass index, smoking, higher HbA1c levels, diabetes duration, and the presence of nephropathy and neuropathy. 

For example, the risk of developing DR was more 2.2 times greater in T1D patients with HbA1c levels ranging from 8 to 10 percent compared with levels <6.5 percent, results that align with the Diabetes Control and Complications Trial (DCCT) study.5 

As for disease duration, males who had the disease less than 20 years had a 36.7-percent rate of DR vs. a 73.5-percent rate for men who had the disease more than 20 years. For women, the rates were 23.2 and 72.3 percent, respectively. 

The later-in-life onset of DR in women with T1D suggests “a relative protective effect of estrogens against DR in premenopausal women,” the researchers wrote.

The odds ratios for DR in overweight and obese patients were 1.4 and 2.5, respectively, which are in accordance with the European EURODIAB study.6 

Countervailing Findings

However, the Paris researchers also reported a number of findings that run counter to previously reported findings. Their multivariate analysis found no association between hypertension and DR; Wisconsin Epidemiologic Study of Diabetic Retinopathy results suggest the opposite.7 Nor were they able to find a link between DR and dyslipidemia, findings for which, they acknowledged, are “inconsistent in the literature.”

Study strengths the researchers elucidated are its sample size, the standardized DR severity grading scale they used and detailed assessment of many associated factors for any DR and for each DR grade.

But they also acknowledged a number of limitations: its cross-sectional nature; the exclusion of variables because of missing values; and the hospital-based population may not be representative of the overall T1D—although, as they pointed out, most T1D patients in France have hospital follow-up. 

The researchers noted that a survival bias couldn’t be ruled out. “Indeed, although the life expectancy of T1D patients has strongly increased, the micro- and macrovascular clinical complications of this disease are serious and sometimes fatal,” they wrote. “The absence of any significant association between the presence of ischemic heart disease and DR in the multivariate analyses could be explained by a higher and earlier mortality in patients with this condition, preventing them from participating in this study.”

Lead author Abir Zureik and two of 10 co-authors have no disclosures. The remaining authors reported relationships with a number of companies, including Bayer (which holds the European franchise for Eylea), Novartis (which holds the European franchise for Lucentis), Allergan, Alimera, Roche, Alcon and Bausch + Lomb. 




  1. Zureik, A., Julla, JB., Erginay, A. et al. Prevalence, severity stages, and risk factors of diabetic retinopathy in 1464 adult patients with type 1 diabetes. Graefes Arch Clin Exp Ophthalmol. Published online July 15, 2021. https://doi.org/10.1007/s00417-021-05298-7

  2. Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis (Lond). 2015; 2:17.

  3. Yau JW, Kawasaki R, Lamoureux EL, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35:556–564.

  4. Klein R, Knudtson MD, Lee KE, Gangnon R, Klein BE. The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XXII the twenty-five-year progression of retinopathy in persons with type 1 diabetes. Ophthalmology 2008;15:1859–1868.

  5. Lachin JM, White NH, Hainsworth DP, Sun W, Cleary PA, Nathan DM. The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group. Effect of intensive diabetes therapy on the progression of diabetic retinopathy in patients with type 1 diabetes: 18 years of follow-up in the DCCT/EDIC. Diabetes. 2015;64:631–642.

  6. Chaturvedi N, Sjoelie AK, Porta M, et al. Markers of insulin resistance are strong risk factors for retinopathy incidence in type 1 diabetes EURODIAB Prospective Complications Study. Diabetes Care. 2001;24:284–289.

  7. Klein R, Klein BEK, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XVII. The 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes. Ophthalmology. 1998;105:1801–1815.


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