Diabetologia. 2025 Apr 29. doi: 10.1007/s00125-025-06440-4. Online ahead of print.
ABSTRACT
AIMS/HYPOTHESIS: Soluble receptor for advanced glycation end products (sRAGE) has been inversely linked to obesity, which is defined by excess of total body fat. However, body fat accumulation is also relevant for health. In this study, we investigated associations between sRAGE and obesity in individuals with type 1 diabetes over 6.3 years of follow-up.
METHODS: The study included 3886 adults with type 1 diabetes from the FinnDiane study. Serum sRAGE concentrations were determined by ELISA. Central obesity was defined on the basis of waist/height ratio (WHtR), and general obesity on the basis of BMI. The Kruskal-Wallis test was used to assess the differences in baseline BMI, WHtR and sRAGE concentrations, comparing the groups stratified by albuminuria status. Changes in BMI and WHtR were calculated over time and Wilcoxon rank test was used for comparisons. Linear regression, adjusted for sex, age, albuminuria and HbA1c, was used for assessing the association of sRAGE with obesity measures at baseline, and with changes over time.
RESULTS: Over a median follow-up of 6.3 years, BMI changed by a median Δ of 0.76 kg/m2 (IQR -0.39 to 2.07; p<0.001) and WHtR by a median Δ of 0.019 (IQR -0.007 to 0.05; p<0.001). The change in BMI was observed in 67% of the individuals, and WHtR in 68% of them. Baseline sRAGE was inversely associated with BMI (r2=0.07, β -0.174; p<0.001) and WHtR (r2=0.16, β -0.179; p<0.001) in the overall cohort. These relationships remained consistent across subgroups stratified by albuminuria status, including no, moderate and severe albuminuria (all p<0.001). However, sRAGE was not associated with changes in BMI or WHtR over time.
CONCLUSIONS/INTERPRETATION: sRAGE is inversely associated with both general and central obesity, as represented by BMI and WHtR, independent of kidney disease, suggesting sRAGE is a biomarker of obesity. However, sRAGE is not associated with the changes in BMI and WHtR over a 6.3 year follow-up. Future research with longer follow-up is merited to understand how sRAGE correlates with body fat accumulation.
PMID:40301129 | DOI:10.1007/s00125-025-06440-4