Urinary albumin/creatinine ratio tertiles predict risk of diabetic retinopathy progression: a natural history study from the Adolescent Cardio-Renal Intervention Trial (AdDIT) observational cohort

Paul Z Benitez-Aguirre; M Loredana Marcovecchio; Scott T Chiesa; Maria E Craig; Tien Y Wong; Elizabeth A Davis; Andrew Cotterill; Jenny J Couper; Fergus J Cameron; Farid H Mahmud; H Andrew W Neil; Timothy W Jones; Lauren A B Hodgson; R Neil Dalton; Sally M Marshall; John Deanfield; David B Dunger; Kim C Donaghue; Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT)

doi:10.1007/s00125-022-05661-1

Urinary albumin/creatinine ratio tertiles predict risk of diabetic retinopathy progression: a natural history study from the Adolescent Cardio-Renal Intervention Trial (AdDIT) observational cohort

Diabetologia. 2022 May;65(5):872-878. doi: 10.1007/s00125-022-05661-1. Epub 2022 Feb 19.

Authors

Paul Z Benitez-Aguirre^{1

2}, M Loredana Marcovecchio³, Scott T Chiesa⁴, Maria E Craig^{1

2

5}, Tien Y Wong^{6

7

8}, Elizabeth A Davis^{9

10}, Andrew Cotterill¹¹, Jenny J Couper¹², Fergus J Cameron^{13

14

15}, Farid H Mahmud¹⁶, H Andrew W Neil¹⁷, Timothy W Jones^{9

10}, Lauren A B Hodgson⁶, R Neil Dalton¹⁸, Sally M Marshall¹⁹, John Deanfield⁴, David B Dunger^{20

21}, Kim C Donaghue^{22

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

Affiliations

¹ Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, Australia.
² Discipline of Child and Adolescent Health, University of Sydney, Sydney, NSW, Australia.
³ Department of Paediatrics, University of Cambridge, Cambridge, UK. [email protected].
⁴ Institute of Cardiovascular Science, University College London, London, UK.
⁵ School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.
⁶ Centre for Eye Research Australia, Melbourne, VIC, Australia.
⁷ Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
⁸ Duke-NUS Medical School, National University of Singapore, Singapore, Singapore.
⁹ Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children, Perth, WA, Australia.
¹⁰ Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
¹¹ University of Queensland, Brisbane, QLD, Australia.
¹² Endocrinology and Diabetes Centre, Women's and Children's Hospital, and Robinson Institute, University of Adelaide, Adelaide, SA, Australia.
¹³ Department of Endocrinology and Diabetes, Royal Children's Hospital, Melbourne, VIC, Australia.
¹⁴ Murdoch Children's Research Institute, Melbourne, VIC, Australia.
¹⁵ The University of Melbourne, Melbourne, VIC, Australia.
¹⁶ Division of Endocrinology, Hospital for Sick Children, Toronto, ON, Canada.
¹⁷ Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
¹⁸ St Thomas' Hospital, Well Child Laboratory, Evelina London Children's Hospital, London, UK.
¹⁹ Translational and Clinical Research Institute, Newcastle University, Newcastle, UK.
²⁰ Department of Paediatrics, University of Cambridge, Cambridge, UK.
²¹ Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
²² Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, Australia. [email protected].
²³ Discipline of Child and Adolescent Health, University of Sydney, Sydney, NSW, Australia. [email protected].

Abstract

Aims/hypothesis: We hypothesised that adolescents with type 1 diabetes with a urinary albumin/creatinine ratio (ACR) in the upper tertile of the normal range (high ACR) are at greater risk of three-step diabetic retinopathy progression (3DR) independent of glycaemic control.

Methods: This was a prospective observational study in 710 normoalbuminuric adolescents with type 1 diabetes from the non-intervention cohorts of the Adolescent Cardio-Renal Intervention Trial (AdDIT). Participants were classified as 'high ACR' or 'low ACR' (lowest and middle ACR tertiles) using baseline standardised log₁₀ ACR. The primary outcome, 3DR, was determined from centrally graded, standardised two-field retinal photographs. 3DR risk was determined using multivariable Cox regression for the effect of high ACR, with HbA_1c, BP, LDL-cholesterol and BMI as covariates; diabetes duration was the time-dependent variable.

Results: At baseline mean ± SD age was 14.3 ± 1.6 years and mean ± SD diabetes duration was 7.2 ± 3.3 years. After a median of 3.2 years, 83/710 (12%) had developed 3DR. In multivariable analysis, high ACR (HR 2.1 [1.3, 3.3], p=0.001), higher mean IFCC HbA_1c (HR 1.03 [1.01, 1.04], p=0.001) and higher baseline diastolic BP SD score (HR 1.43 [1.08, 1.89], p=0.01) were independently associated with 3DR risk.

Conclusions/interpretation: High ACR is associated with greater risk of 3DR in adolescents, providing a target for future intervention studies.

Trial registration: isrctn.org ISRCTN91419926.

Keywords: AdDIT; Adolescents; Diabetic nephropathy; Diabetic retinopathy progression; Kidney function; Microvascular complications; Type 1 diabetes.

Publication types

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

MeSH terms

Adolescent
Albumins / analysis
Albuminuria
Child
Creatinine / urine
Diabetes Mellitus, Type 1* / complications
Diabetic Nephropathies*
Diabetic Retinopathy*
Humans
Risk Factors

Substances

Albumins
Creatinine

Associated data

ISRCTN/ISRCTN91419926