HIGH EXTRACELLULAR WATER TO TOTAL BODY WATER RATIO AND DIABETIC RETINOPATHY PROGRESSION IN TYPE 2 DIABETES

Abstract

OBJECTIVES
Excess extracellular water is associated with chronic kidney disease progression. It is not known if it is associated with diabetic retinopathy (DR) progression. We aim to investigate the relationship between the ratio of extracellular-water to total-body-water (ECW/TBW), an indicator of fluid balance, and DR progression in type 2 diabetes mellitus (T2DM), and elucidate its role as a potential mediator in the relationship between matrix metallo-proteinase-2 (MMP2) and DR progression.

METHODOLOGY
We conducted a prospective study on 1,041 patients (mean age 56.5 ± 10.7 years) from the SMART2D cohort. ECW/TBW ratio was measured using bio-impedance analysis. Digital colour fundus photographs were examined for DR in a masked fashion. DR progression was defined as increase in severity across categories - normal, non-proliferative DR and proliferative DR. This research has been approved by an ethical committee.

RESULTS
After 7.8 years’ follow-up, 15.5% of 1,041 participants experienced DR progression. Logistic regression showed that Tertile 3 ECW/TBW ratio, indicative of higher ECW/ TBW ratio, was associated with 129% higher odds of DR progression with unadjusted Odds Ratio (OR) 2.29 (95% CI 1.49-3.52, p<0.001) compared with Tertile 1 ECW/TBW ratio. Having adjusted for demographics, clinical co-variables and medications, the positive association persisted for Tertile 3 ECW/TBW ratio with OR 2.79 (95% CI 1.58-4.89, p<0.001). Binary mediation revealed that ECW/TBW ratio accounted for 41.5% of the relationship between MMP2 and DR progression (p=0.001).

CONCLUSION
The novel finding of the association between a higher ECW/ TBW ratio and DR progression highlights the importance of extracellular fluid excess as a potential marker of DR progression for future studies and interventions.