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

Paul Z Benitez-Aguirre; Tien Y Wong; Maria E Craig; Elizabeth A Davis; Andrew Cotterill; Jennifer J Couper; Fergus J Cameron; Farid H Mahmud; Tim W Jones; Lauren A B Hodgson; R Neil Dalton; David B Dunger; Kim C Donaghue; Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT)

doi:10.1007/s00125-017-4538-2

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

Diabetologia. 2018 Apr;61(4):968-976. doi: 10.1007/s00125-017-4538-2. Epub 2018 Feb 2.

Authors

Paul Z Benitez-Aguirre^{1

2}, Tien Y Wong^{3

4

5}, Maria E Craig^{1

2

6}, Elizabeth A Davis^{7

8}, Andrew Cotterill⁹, Jennifer J Couper^{10

11}, Fergus J Cameron^{12

13

14}, Farid H Mahmud¹⁵, Tim W Jones^{7

8}, Lauren A B Hodgson³, R Neil Dalton¹⁶, David B Dunger¹⁷, Kim C Donaghue^{18

19}; Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT)

Collaborators

Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT):
Sally Marshall, Jane Armitage, Polly Bingley, William Van't Hoff, David Dunger, R Neil Dalton, Denis Daneman, Andrew Neil, John Deanfield, Tim Jones, Kim Donaghue

Affiliations

¹ Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, 170 Hawkesbury Rd, Locked Bag 4001, Westmead, NSW, 2145, Australia.
² Discipline of Child and Adolescent Health, University of Sydney, Sydney, NSW, Australia.
³ Centre for Eye Research Australia, Melbourne, VIC, Australia.
⁴ Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore.
⁵ Duke-NUS Medical School, National University of Singapore, Singapore, Republic of Singapore.
⁶ School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.
⁷ Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children, Perth, WA, Australia.
⁸ Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
⁹ University of Queensland, Brisbane, QLD, Australia.
¹⁰ Endocrinology and Diabetes Centre, Women's and Children's Hospital, Adelaide, SA, Australia.
¹¹ Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia.
¹² Department of Endocrinology and Diabetes, Royal Children's Hospital, Melbourne, VIC, Australia.
¹³ Murdoch Children's Research Institute, Melbourne, VIC, Australia.
¹⁴ The University of Melbourne, Melbourne, VIC, Australia.
¹⁵ Division of Endocrinology, Hospital for Sick Children, Toronto, ON, Canada.
¹⁶ WellChild Laboratory, St Thomas' Hospital, King's College London, London, UK.
¹⁷ Department of Paediatrics, University of Cambridge, Box 116, Level 8, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. [email protected].
¹⁸ Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, 170 Hawkesbury Rd, Locked Bag 4001, Westmead, NSW, 2145, Australia. [email protected].
¹⁹ Discipline of Child and Adolescent Health, University of Sydney, Sydney, NSW, Australia. [email protected].

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 log₁₀ 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 log₁₀ ACR and ACR risk groups.

Results: Greater log₁₀ 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-Q5: OR 1.67 [95% CI 1.17, 2.38] and venular OR 1.39 [0.98, 1.99]) and tortuosity in the highest quintile (Q5 vs Q1-Q4: arteriolar OR 2.05 [1.44, 2.92] and venular OR 2.38 [1.67, 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.

Conclusions/interpretation: Higher ACR in adolescents is associated with narrower and more tortuous retinal vessels. Therefore, RVG phenotypes may serve to identify populations at high risk of diabetes complications during adolescence and well before onset of clinical diabetes complications.

Keywords: AdDIT; Adolescents; Diabetic retinopathy; Microvascular complications; Nephropathy; Retinal vascular geometry; Type 1 diabetes.

Publication types

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

MeSH terms

Adolescent
Albumins / analysis
Albuminuria / physiopathology
Arterioles
Blood Pressure
Body Mass Index
Cross-Sectional Studies
Diabetes Mellitus, Type 1 / complications*
Diabetes Mellitus, Type 1 / pathology*
Diabetic Retinopathy / diagnosis*
Female
Humans
Kidney / pathology*
Male
Phenotype
Prospective Studies
Regression Analysis
Retina / physiopathology*
Retinal Vessels / pathology*
Risk Factors

Substances

Albumins

Abstract

Publication types

MeSH terms

Substances

Grants and funding