Background and aims: To evaluate the level of tubular and glomerular biomarkers of kidney injury as potential nephroprorotective effects of GLP-1R agonist (liraglutide) addition in type 1 diabetic patients compared to standard insulin therapy.
Materials and methods: 12 T1DM patients with normo-(AER <20 mg/l, n=7) and microalbuminuria (AER<199 mg/l, n=5) with liraglutide 1.2 mg as add on to insulin for 6 month and 12 patients with normo-(AER <20 mg/l, n=8) and microalbuminuria(AER<199 mg/l, n=4) on standard insulin therapy. Biomarkers of kidney damage (collagen i.v., nephrin, podocin, cystatin C, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), uromodulin, osteopontin) were measured by enzyme-linked immunosorbent assay ELISA in the morning urine and fasting plasma; overnight AER by immunoturbidimetry assay; glomerular filtration rate (GFR) by CKD-EPI formula were measured before and after 6-month treatment. Concomitant RAAS blockage-drugs given in stable doses. Differences were examined for statistical significanse (P<0.05) using Wilcoxon Signed-Rank Test.
Results: Initially the groups were similar by average age, HbA1c, plazma glucose, BP, lipids, uric acid, C-reactive protein, creatinine, eGFR. HbA1c before and after 6 month treatment. There were no significant differences in BP, albuminuria, creatinine, eGFR, HbA1c in 6 month. BMI decreased from 29 (22;38) to 26.8 (21;34.7) kg/m2, P=0.01 in GLP1 group. Urinary levels of podocin, KIM-1 and collagen did not changed before and after therapy. In GLP1 group observed significant reduction in the urinary levels of NGAL/creatinine 1.48(0.81;2.29) vs 0.65(0.34;0.74) ng/mmol, P=0.015; KIM-1/creatinine 115(35;328) vs 47(21;116) ng/mmol, P=0.02; cystatin C 881(464;1579) vs 136(91;205) ng/mmol, P=0.01; nephrin 0.1(0.09;0.15) vs 0.004(0.01;0.1), uromodulicreatinine rised from 175(82;278) to 458 (235;754); and plazma levels of cystatin and osteopontin after treatment: 1264 (877;1472) vs 722 (672;848) ng/ml, P=0.007; 126.8 (45;161) vs 65 (45;74), P=0.02, respectively compared to the stable levels of markers in the standard insulin treatment group.
Conclusion: The present data suggest that GLP-1R adding to standard insulin therapy might be effective for the weight reduction and as potential nephroprotective strategy for attenuating the chronic kidney injury in T1DM.
20 - 23 May 2017
European Society of Endocrinology