UKIDS study: Quantitative multi-organ MRI imaging stratifies diabetics with cardiac & abdominal phenotypes specific to proliferative diabetic retinopathy (PDR) & clinically significant diabetic macular edema (CSME, DME)

Abstract

Purpose : Diabetic retinopathy (DR) is a complication of diabetes mellitus associated with increased risk of cardiovascular, renal, pancreatic & liver comorbidities. We hypothesise that severe diabetic retinopathic patients can be stratified using quantitative multi-organ MRI-based imaging in a prospective study.

Methods : Data on multi-organ health (heart, kidneys, liver, pancreas, body composition and aorta) was collected using quantitative MRI from 74 patients with DR (UKIDS NCT05057403). This was compared against 92 healthy volunteers (COVERSCAN, NCT04369807). Wilcoxon rank sum and Fisher’s exact tests were applied for continuous and categorical measures. To control for inter-group differences in age, sex, and BMI we used multivariate linear & logistic regression.

Results : In this group of diabetic patients with DR (38% White, 34% South Asian, 25% Black, 70% male, mean age 63 yr, mean 30kgm² BMI), over half (56%) had cardiac abnormalities suggestive of heart failure with preserved ejection fraction (HFpEF). Prevalent HFpEF & cardiac hypertrophy discriminated grades greater than mild non-proliferative diabetic retinopathy (eg. moderate mild NPDR, >R1 retinopathy) from mild NPDR (ie. R1, p=0.04). Elevated fibroinflammation in the renal cortex was characteristic of moderate, severe NPDR & proliferative retinopathy (ie. >R1 grades), mean cortical T1 1430±72ms vs 1375±48ms for mild NPDR (ie. R1, p=0.004) and discriminated proliferative diabetic retinopathy (ie. PDR, grade R3 retinopathy) mean cortical T1 1435±48ms from mild NPDR (ie. R1, p=0.021). High subcutaneous fat (SAT) and hepatic steatosis discriminated untreated diabetic macular edema (DME, M1 maculopathy) from no DME (ie. M0, 244±101cm² vs 191±76 cm², p=0.046) with 45% vs 13% prevalence (p=0.028). BMI was unaffected by ethnicity; liver fat was highest in White DR (mean 5.3±3.9%) but SAT highest in Black DR patients.

Conclusions : Risk of more DR (ie. more than mild NPDR) was associated with cardiovascular and renal abnormality and severe maculopathy (ie. CSME) with subcutaneous and hepatic fat infiltration. Our UKIDS protocol could be used in future trials of systemic treatments for DR.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Figure 1: Fibro-inflammation in the kidney cortex vs retinopathy grade.

 

Figure 2: Sub-cutaneous fat vs maculopathy grade.