Association between Serum Galectin-3 and Advanced Glycation End Products in Type 2 Diabetes

Abstract

Galectin-3, a member of the multifunctional galectin family, acts a broad-spectrum biological response modifier and is involved in tissue fibrosis, immunity, and inflammatory response. The role of galectin-3 in diabetic complications is unclear and animal studies have provided evidence for protective and detrimental functions of galectin-3. Although galectin-3 is a mediator of inflammation and fibrosis, it is also a scavenger receptor for advanced glycation end products (AGEs) and stimulates their degradation. We have investigated whether serum galectin-3 level is related to circulating AGEs and/or inflammation in type 2 diabetic patients with and without chronic kidney disease (CKD). 270 type 2 diabetic patients (30% with CKD and eGFR <60 ml/min/1.73m2) and 230 controls were recruited. Serum galectin-3 and AGEs were assayed by ELISA and plasma high sensitivity C-reactive protein (CRP) was measured by immunoturbidimetric assay. Diabetic patients had higher HbA1c, AGEs (4.46 ± 1.06 unit/ml (CKD+); 4.10 ± 0.98 (CKD-); 3.56 ± 0.99 (control); ANOVA p<0.01) and CRP levels than controls. Serum galectin-3 was highest in those with CKD (9.07 ± 2.64 ng/ml (CKD+); 7.48 ± 2.36 (CKD-); 5.36 ± 1.65 (control); ANOVA p<0.01). Serum glaectin-3 correlated with AGEs (r=0.34, p<0.01), eGFR (r=-0.35, p<0.01) and age (r=0.25, p<0.01) but there were no associations with duration of diabetes, HbA1c or CRP. The association with AGEs remained significant even after excluding subjects with CKD (r=0.30, p<0.01). On linear regression analysis, serum AGEs and eGFR were independent determinants of serum galectin-3 after adjusting for age, gender, body mass index, and smoking, accounting for 10% and 12% of the variability respectively (p<0.01). In conclusion, serum galectin-3 was increased in type 2 diabetic patients with and without CKD, and serum level was associated with AGEs and renal function but not with inflammation. The role of galectin-3 in diabetic complications in humans remains to be determined.