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Abstract
To examine if skin autofluorescence (sAF) differed in early adulthood between individuals with type 1 diabetes and age-matched controls and to ascertain if sAF aligned with risk for kidney disease. Young adults with type 1 diabetes (N = 100; 20.0 ± 2.8 years; M:F 54:46; FBG-11.6 ± 4.9 mmol/mol; diabetes duration 10.7 ± 5.2 years; BMI 24.5(5.3) kg/m2) and healthy controls (N = 299; 20.3 ± 1.8 years; M:F-83:116; FBG 5.2 ± 0.8 mmol/L; BMI 22.5(3.3) kg/m2) were recruited. Skin autofluorescence (sAF) and circulating AGEs were measured. In a subset of both groups, kidney function was estimated by GFRCKD-EPI CysC and uACR, and DKD risk defined by uACR tertiles. Youth with type 1 diabetes had higher sAF and BMI, and were taller than controls. For sAF, 13.6% of variance was explained by diabetes duration, height and BMI (Pmodel = 1.5 × 10–12). In the sub-set examining kidney function, eGFR and sAF were higher in type 1 diabetes versus controls. eGFR and sAF predicted 24.5% of variance in DKD risk (Pmodel = 2.2 × 10–9), which increased with diabetes duration (51%; Pmodel < 2.2 × 10–16) and random blood glucose concentrations (56%; Pmodel < 2.2 × 10–16). HbA1C and circulating fructosamine albumin were higher in individuals with type 1 diabetes at high versus low DKD risk. eGFR was independently associated with DKD risk in all models. Higher eGFR and longer diabetes duration are associated with DKD risk in youth with type 1 diabetes. sAF, circulating AGEs, and urinary AGEs were not independent predictors of DKD risk. Changes in eGFR should be monitored early, in addition to uACR, for determining DKD risk in type 1 diabetes.
Highlights
To examine if skin autofluorescence differed in early adulthood between individuals with type 1 diabetes and age-matched controls and to ascertain if sAF aligned with risk for kidney disease
Holm’s corrected Spearman’s correlations in the full sAF and renal sub-set showed that sAF was positively associated with age, Body mass index (BMI) and diabetes duration and negatively correlated with height (Fig. 1C)
The limitations of the advanced glycation end products (AGEs) reader used to measure sAF have been previously described, but it has been validated as a reliable surrogate marker of AGE burden in an adolescent p opulation[46]. Given that this was a cross-sectional observational study, we did not have follow up data for these individuals to determine if/when they developed diabetic kidney disease. These studies suggest that greater eGFR and diabetes duration in youth with type 1 diabetes without previously diagnosed complications are markers of DKD risk, which are not improved by measurement of sAF nor other markers of AGE burden
Summary
To examine if skin autofluorescence (sAF) differed in early adulthood between individuals with type 1 diabetes and age-matched controls and to ascertain if sAF aligned with risk for kidney disease. Despite there being increasing scrutiny of childhood and adolescence, there is a paucity of data available examining risk for DKD in young adults with type 1 diabetes prior to the onset of chronic complications. These young people are often lost to follow up in the transition from pediatric to adult clinical c are[5], and commonly. Greater accumulation of skin collagen AGEs, such as carboxymethyllysine (CML), predicted faster progression to DKD in young people with type 1 diabetes aged 20–30 y ears[10] These quantitative studies of punch skin biopsies have evolved into non-invasive skin autofluorescence (sAF), a tool for assessing AGE-associated disease r isk[11]. Studies in adolescents and young people have mostly shown increases in c irculating[16,17] or urinary AGE c oncentrations[18] with diabetes, but no independent association with diabetes complications[19,20]
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