The potential role of angiopoietin-like protein-8 in type 2 diabetes mellitus: a possibility for predictive diagnosis and targeted preventive measures?

Background Previous studies showed altered angiopoietin-like protein-8 (ANGPTL-8) circulating levels in type 2 diabetes mellitus (DM). Whether or not the alteration in ANGPTL-8 level can be a predictive maker for increased DM risk remains unclear. Aim Investigating possible role of ANGPTL-8 as a risk predictor of type2 DM, in addition to a set of factors likely to affect ANGPTL-8 level. Methods One hundred recently diagnosed persons with type 2 DM and 100 sex- and age-matched healthy controls were enrolled. Exclusion criteria included type 1 DM, acute infections, history of chronic kidney disease, malignancy, and blood loss or transfusion. Serum levels of ANGPTL-8, blood pressure, weight, height, glycosylated hemoglobin (HbA1c), fasting blood glucose, cystatin C, lipid profile, liver, and kidney function tests were assessed. The independent relationship between DM and ANGPTL-8 was tested in the unadjusted and multiple-adjusted regression models. Results Serum ANGPTL-8 levels showed significant elevation among persons with vs. without DM (p = 0.006), positive correlation with HbA1c (p < 0.001), and negative correlation with estimated GFR (eGFR) (p = 0.003) but no significant correlation to fasting glucose level. In the unadjusted model, patients in the third tertile of ANGPTL-8 had 4 times risk of DM (OR 4.03; 95% CI = 1.37-11.84). Data adjustment for cardiovascular diseases, smoking, body mass index, systolic blood pressure, alanine transaminase (ALT), and low-density lipoprotein (LDL) increased the direct relationship between ANGPTL-8 and DM (OR 6.26; 95% CI = 1.21-32.50). However, the risk significantly decreased after adjustment of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR creatinine-cystatin (OR 2.17; 95% CI = 0.10-49.84). Conclusion This study highlights a possible predictive role of ANGPTL-8 in diabetic complications, particularly nephropathy. Larger prognostic studies are needed to validate the cause-effect relationship between ANGPTL-8 and deteriorated kidney functions.