The Adolescent Cardio-Renal Intervention Trial (AdDIT): retinal vascular geometry and renal function in adolescents with type 1 diabetes

Abstract

Aims/hypothesis We examined the hypothesis that elevation in urinary albumin creatinine ratio (ACR) in adolescents with type 1 diabetes is associated with abnormal retinal vascular geometry (RVG) phenotypes. Methods A cross-sectional study at baseline of the relationship between ACR within the normoalbuminuric range and RVG in 963 adolescents aged 14.4 ± 1.6 years with type 1 diabetes (median duration 6.5 years) screened for participation in AdDIT. A validated algorithm was used to categorise log 10 ACR into tertiles: upper tertile ACR was defined as 'high-risk' for future albuminuria and the lower two tertiles were deemed 'low-risk'. RVG analysis, using a semi-automated computer program, determined retinal vascular calibres (standard and extended zones) and tortuosity. RVG measures were analysed continuously and categorically (in quintiles: Q1-Q5) for associations with log 10 ACR and ACR risk groups. Results Greater log 10 ACR was associated with narrower vessel calibres and greater tortuosity. The high-risk group was more likely to have extended zone vessel calibres in the lowest quintile (arteriolar Q1 vs Q2 67, 3.40]). The effects of retinal vascular calibres and tortuosity were additive such that the participants with the narrowest and most tortuous vessels were more likely to be in the high-risk group (OR 3.32 [1.84, 5.96]). These effects were independent of duration, blood pressure, BMI and blood glucose control.A list of AdDIT investigators is included in the Appendix and members of the Trial Steering Committee are listed in the Acknowledgements.

Microvascular Dysfunction and Hyperglycemia: A Vicious Cycle With Widespread Consequences

“…In addition, arteriolar widening and increased blood flow are not constant findings (18,22,31-33). This is perhaps related in part to the co-occurrence of other risk factors that are associated with smaller diameters, such as hypertension (20), insulin resistance (9), and progression of MVD (34). Greater fractal dimension, which represents greater geometric density of the vascular branching pattern (a fractal structure because it exhibits the property of self-similarity), and greater arteriolar tortuosity (vessel undulation) have Table 1-Causal inference in human studies on the pathogenesis of diabetes and its complications: problems, pitfalls, and potential solutions A general model of causation: definitions (3) c A cause of a disease event (or (patho)physiological phenomenon) is an event, condition, or characteristic that preceded the disease event and without which the disease event either would not have occurred at all or would not have occurred until some later time.…”

A new strategy for vascular complications in young people with type 1 diabetes mellitus

“…In the AdDIT study, at baseline, adolescents in the highest tertile for ACR showed renal hyperfiltration, dyslipidaemia, early retinal vessel abnormalities and increased pulse wave velocity 65,66 . In a subgroup of the AdDIT cohort, where data on aIMT and autonomic function measures were available, a higher ACR at baseline was also associated with thicker aIMT and the presence of markers of autonomic dysfunction 67,68 .…”

“…The results of both the AdDIT Intervention and AdDIT Observational studies have now been published 63,65,66,69 and it is important to consider how these results could influence screening and intervention strategies in high-risk and low-risk adolescents with T1DM.…”

Comprehensive retinal vascular measurements: a novel association with renal function in type 2 diabetic patients in China

“…Previous studies have been focusing on central retinal vessels proximal to optic disc 19 . As discussed in a recent study, reducing the measurement area would result in an enormous data reduction that may miss vessel changes occurring elsewhere in the retina 20 .…”

“…For example, caliber measurements were restricted to retinal vessels proximal to the optic 5 The authors contributed equally: Xiayu Xu and Fei Sun. * email: bingao@fmmu.edu.cn measurements were restricted to manually selected vascular branches 19 . However, a few recent studies have suggested that more peripheral retinal vessels may signify an even earlier change than central retinal vessels in microvascular complications of diabetes 20 .…”