Cerebral small-vessel disease is associated with the severity of diabetic retinopathy in type 1 diabetes

Marika I Eriksson; Paula Summanen; Daniel Gordin; Carol Forsblom; Sara Shams; Ron Liebkind; Turgut Tatlisumak; Jukka Putaala; Per-Henrik Groop; Juha Martola; Lena M Thorn; FinnDiane Study Group

doi:10.1136/bmjdrc-2021-002274

Cerebral small-vessel disease is associated with the severity of diabetic retinopathy in type 1 diabetes

BMJ Open Diabetes Res Care. 2021 Aug;9(1):e002274. doi: 10.1136/bmjdrc-2021-002274.

Authors

Marika I Eriksson^{1

2

3}, Paula Summanen^{1

3

4}, Daniel Gordin^{1

2

3

5}, Carol Forsblom^{1

2

3}, Sara Shams^{6

7}, Ron Liebkind⁸, Turgut Tatlisumak^{8

9}, Jukka Putaala⁸, Per-Henrik Groop^{10

2

3

11}, Juha Martola^{6

12}, Lena M Thorn^{1

2

3

13}; FinnDiane Study Group

Affiliations

¹ Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
² Department of Nephrology, Helsinki University Central Hospital, Helsinki, Finland.
³ Research Program in Clinical and Molecular Metabolism, University of Helsinki, Helsinki, Finland.
⁴ Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland.
⁵ Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.
⁶ Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
⁷ Department of Radiology, Stanford Medicine, Stanford, California, USA.
⁸ Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
⁹ Department of Neurology, Sahlgrenska University Hospital, Goteborg, Sweden.
¹⁰ Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland per-henrik.groop@helsinki.fi.
¹¹ Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
¹² Department of Radiology, Helsinki University Central Hospital, Helsinki, Finland.
¹³ Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Abstract

Introduction: Cerebral small-vessel disease is common in neurologically asymptomatic individuals with type 1 diabetes. The retinal vasculature is thought to mirror the brain's vasculature, but data on this association are limited in type 1 diabetes. Our aim was to study associations between diabetic retinopathy severity and cerebral small-vessel disease in type 1 diabetes.

Research design and methods: For this cross-sectional study, we enrolled 189 participants with type 1 diabetes (median age 40 (33-45) years; 53% female; diabetes duration 21.6 (18.2-30.7) years) and 29 healthy age-matched and sex-matched controls as part of the Finnish Diabetic Nephropathy Study. Participants underwent a clinical investigation, brain MRI, and fundus imaging. Signs of cerebral small-vessel disease in brain MRIs were analyzed in relation to diabetic retinopathy severity (Early Treatment Diabetic Retinopathy Study (ETDRS) score).

Results: In type 1 diabetes, participants with cerebral small-vessel disease had higher ETDRS scores (35 (20-61) vs 20 (20-35), p=0.022) and a higher prevalence of proliferative diabetic retinopathy than those without cerebral small-vessel disease (25% vs 9%, p=0.002). In adjusted analysis, proliferative diabetic retinopathy was associated with cerebral small-vessel disease (OR 2.57 (95% CI 1.04 to 6.35)). Median ETDRS score (35 (20-65) vs 20 (20-35), p=0.024) and proliferative diabetic retinopathy prevalence were higher (29% vs 13%, p=0.002) in participants with versus without cerebral microbleeds. ETDRS scores increased by number of cerebral microbleeds (p=0.001), both ETDRS score (OR 1.05 (95% CI 1.02 to 1.09)) and proliferative diabetic retinopathy (8.52 (95% CI 1.91 to 37.94)) were associated with >2 cerebral microbleeds in separate multivariable analysis. We observed no association with white matter hyperintensities or lacunar infarcts.

Conclusions: Presence of cerebral small-vessel disease on brain MRI, particularly cerebral microbleeds, is associated with the severity of diabetic retinopathy.

Keywords: brain; diabetes mellitus; diabetic retinopathy; magnetic resonance imaging; type 1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cerebral Small Vessel Diseases* / complications
Cerebral Small Vessel Diseases* / diagnostic imaging
Cerebral Small Vessel Diseases* / epidemiology
Cross-Sectional Studies
Diabetes Mellitus, Type 1* / complications
Diabetes Mellitus, Type 1* / epidemiology
Diabetic Nephropathies*
Diabetic Retinopathy* / diagnosis
Diabetic Retinopathy* / epidemiology
Female
Humans
Male