Circulating and dietary advanced glycation end products and obesity in an adult population: A paradox of their detrimental effects in obesity.

Background: The detrimental role of advanced glycation end products (AGEs) against cardio-metabolic health has been revealed in several previous reports. However, the results of studies regarding the association between AGEs and obesity measurements are inconsistent. In the current meta-analysis, we aimed to quantitatively summarize the results of studies that evaluated the association between circulating and dietary AGEs with obesity measurements among the adult population. Methods: A systematic search from PubMed, Embase, and Scopus electronic databases until 30 October 2022 retrieved a total of 21,429 observational studies. After duplicate removal, title/abstract screening, and full-text reading by two independent researchers, a final number of 18 manuscripts remained to be included in the meta-analysis. Results: Those in the highest category of circulating AGEs had ~1.5 kg/m2 reduced BMI compared with those in the lowest AGEs category [weighted mean difference (WMD): -1.485; CI: -2.459, -0.511; p = 0.003], while a nonsignificant increase in BMI was observed in the highest versus lowest category of dietary AGEs (WMD: 0.864, CI: -0.365, 2.094; p = 0.186). Also, lower amounts of circulating AGEs in individuals with obesity versus individuals without obesity were observed (WMD: -57.220, CI: -84.290, -30.149; p < 0.001). AGE type can be considered as a possible source of heterogeneity. Conclusion: In the current meta-analysis, we observed an inverse association between circulating AGEs and body mass index among adults. Due to low study numbers, further studies are warranted to better elucidate these results.

Genetic variants in the receptor for advanced glycation end products (RAGE) gene were associated with circulating soluble RAGE level but not with renal function among Asians with type 2 diabetes: a genome-wide association study.

BACKGROUND: The soluble receptor for advanced glycation end products (sRAGE) has been shown to play an important role in diabetic complications. We conducted genome-wide association study (GWAS) of sRAGE in Asian type 2 diabetes mellitus (T2DM) patient and validated the association in an independent cohort of T2DM. METHODS: GWAS for sRAGE was performed in 2058 T2DM patients. Associations between single-nucleotide polymorphisms (SNPs) and plasma sRAGE level were analyzed in an additive model using a linear mixed model. To validate the associations, we performed de novo genotyping in an independent cohort (n = 1984). We selected the top SNP for assessment with diabetic kidney disease (DKD). RESULTS: The strongest SNP, rs2070600C>T (P = 1.21 × 10-52), was a genotyped, missense SNP located on chromosome 6, corresponding to the RAGE (AGER) gene locus, the gene encoding RAGE. Conditioning analysis on rs2070600 revealed that rs2071288C>T was the top genotyped independent SNP (P = 8.36 × 10-10). Both SNPs were strongly and dose-dependently correlated with sRAGE level (TT = 399.6 pg/mL, CT = 737.0 pg/mL and CC = 967.0 pg/mL, P < 0.001 for rs2070600; TT = 687.9 pg/mL, CT = 737.6 pg/mL and CC = 904.7 pg/mL, P < 0.001 for rs2072188). Both SNPs were robustly replicated in the independent cohort, especially among Chinese patients (P = 9.02 × 10-72 for rs2070600; P = 1.13 × 10-9 for rs2071288). Log-transformed sRAGE was associated with DKD after adjustment for age, gender and ethnicity in pooled cohorts [odds ratio 2.536 (95% confidence interval 1.864-3.450), P < 0.001]. However, we did not observe any significant association between rs2070600 and DKD. CONCLUSIONS: Common variants in RAGE are strongly associated with plasma sRAGE level, which is associated with DKD. However, we did not find a causal link between sRAGE and renal function by Mendelian randomization.