Adeshara Krishna, Parente Erika B, Harjutsalo Valma, Lehto Markku, Sandholm Niina, Groop Per-Henrik
Folkhälsan Research Center, Helsinki, Finland.
Research Program for Clinical and Molecular Metabolism, University of Helsinki, Helsinki, Finland.
Diabetologia. 2025 Apr 29. doi: 10.1007/s00125-025-06440-4.
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.
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 HbA, was used for assessing the association of sRAGE with obesity measures at baseline, and with changes over time.
Over a median follow-up of 6.3 years, BMI changed by a median Δ of 0.76 kg/m (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 (r=0.07, β -0.174; p<0.001) and WHtR (r=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.
目的/假设：晚期糖基化终产物可溶性受体（sRAGE）与肥胖呈负相关，肥胖的定义是全身脂肪过多。然而，体脂积累也与健康相关。在本研究中，我们在6.3年的随访期内调查了1型糖尿病患者中sRAGE与肥胖之间的关联。
该研究纳入了来自芬兰糖尿病预防研究（FinnDiane study）的3886名1型糖尿病成年患者。通过酶联免疫吸附测定法（ELISA）测定血清sRAGE浓度。中心性肥胖根据腰高比（WHtR）定义，全身性肥胖根据体重指数（BMI）定义。采用Kruskal-Wallis检验评估基线BMI、WHtR和sRAGE浓度的差异，比较按蛋白尿状态分层的各组。计算随时间变化的BMI和WHtR变化，并使用Wilcoxon秩和检验进行比较。采用经性别、年龄、蛋白尿和糖化血红蛋白（HbA）校正的线性回归分析，评估sRAGE与基线时肥胖指标以及随时间变化的关联。
在中位随访期6.3年期间，BMI的中位变化量为0.76 kg/m²（四分位间距-IQR为-0.39至2.07；p<0.001），WHtR的中位变化量为0.019（IQR为-0.007至0.05；p<0.001）。67%的个体观察到BMI有变化，68%的个体观察到WHtR有变化。在整个队列中，基线sRAGE与BMI（r=0.07，β=-0.174；p<0.001）和WHtR（r=0.16，β=-0.179；p<0.001）呈负相关。在按蛋白尿状态分层的亚组中，包括无蛋白尿、中度蛋白尿和重度蛋白尿亚组，这些关系均保持一致（所有p<0.001）。然而，sRAGE与BMI或WHtR随时间的变化无关。
结论/解读：sRAGE与以BMI和WHtR表示的全身性肥胖和中心性肥胖均呈负相关，且独立于肾脏疾病，提示sRAGE是肥胖的生物标志物。然而，在6.3年的随访期内，sRAGE与BMI和WHtR的变化无关。值得进行更长随访期的未来研究，以了解sRAGE与体脂积累之间的关联。
