Background: The United Arab Emirates is experiencing increasing rates of type 2 diabetes (T2D) and its complications. As soluble levels of the receptor for advanced glycation end products, (sRAGE), and endogenous secretory RAGE (esRAGE), the latter an alternatively spliced form of AGER (the gene encoding RAGE), have been reported to be associated with T2D and its complications, we tested for potential relationships between these factors and T2D status in Emirati subjects.
Methods: In a case-control study, we recruited Emirati subjects with T2D and controls from the Sheikh Khalifa Medical City in Abu Dhabi. Anthropomorphic characteristics, levels of plasma sRAGE and esRAGE, and routine chemistry variables were measured.
Results: Two hundred and sixteen T2D subjects and 215 control subjects (mean age, 57.4 ± 12.1 vs. 50.7 ± 15.4 years; P < 0.0001, respectively) were enrolled. Univariate analyses showed that levels of sRAGE were significantly lower in the T2D vs. control subjects (1033.9 ± 545.3 vs. 1169.2 ± 664.1 pg/ml, respectively; P = 0.02). Multivariate analyses adjusting for age, sex, systolic blood pressure, pulse, body mass index, Waist/Hip circumference ratio, fasting blood glucose, HDL, LDL, insulin, triglycerides, Vitamin D and urea levels revealed that the difference in sRAGE levels between T2D and control subjects remained statistically-significant, P = 0.03, but not after including estimated glomerular filtration rate in the model, P = 0.14. There were no significant differences in levels of esRAGE. Levels of plasma insulin were significantly higher in the control vs. the T2D subjects (133.6 ± 149.9 vs. 107.6 ± 93.3 pg/L. respectively; P = 0.01, after adjustment for age and sex).
Conclusion/discussion: Levels of sRAGE, but not esRAGE, were associated with T2D status in Abu Dhabi, but not after correction for eGFR. Elevated levels of plasma insulin in both control and T2D subjects suggests the presence of metabolic dysfunction, even in subjects without diabetes.
Keywords: ADAM10, a disintegrin and metalloproteinase domain-containing protein 10; AGEs, advanced glycation endproducts; ARIC, Atherosclerosis Risk in Communities; BMI, body mass index; CARDS, Collaborative Atorvastatin Diabetes Study; CV, coefficient of variation; DBP, diastolic blood pressure; ELISA, enzyme-linked immunosorbent assay; ESRD, end stage renal disease; FBG, fasting blood glucose; HDL, high density lipoprotein; HbA1c, glycosylated hemoglobin; Insulin resistance; Kidney function; LADA, latent autoimmune diabetes of the adult; LDL, low density lipoprotein; MMP, matrix metalloproteinase; RAGE, receptor for advanced glycation endproducts; Receptor for advanced glycation endproducts (RAGE); SBP, systolic blood pressure; SKMC, Sheikh Khalifa Medical City; Soluble RAGE (sRAGE); T2D, type 2 diabetes; TG, triglycerides; Type 2 diabetes; UAE, United Arab Emirates; UAEHFS, United Arab Emirates Healthy Futures Study; W/H ratio, Waist/Hip circumference ratio; eGFR, estimated glomerular filtration rate; esRAGE (endogenous secretory RAGE); esRAGE, endogenous secretory RAGE; hsCRP, high sensitivity C-reactive protein; sRAGE, soluble RAGE.