Metformin Decreases Urinary Cytokines Excretion In The Patients With Type 2 Diabetes

Objective:To observe the effects of metformin treatment on urinary cytokines (including TNF-a, MCP-1 and CRP) excretion in type 2 diabetic patients (T2DM) and explore its possible reno-protective mechanisms.Methods:Firstly,121 patients with type 2 diabetes (DM group) were divided into insulingroup (INS group) and Sulfonylurea group(SU group), and then another two subgroups were divided according to whether or not they were combined by metformin, grouped as follows:INS group I (insulin only) and INS group Ⅱ (insulin combined bymetformin), SU group I (sulfonylurea only) and SU group Ⅱ (sulfonylurea combined bymetformin). At the same period,24 healthy subjects were selected as normal control group (NC group). Urinary cytokines, including tumor necrosis factor-a(TNF-a), monocyte chemoattractant protein-1 (MCP-1) and C-reactive protein(CRP), were measured and expressed as a ratio of urinary creatinine excretion (abbreviated as UTCR、 UMCR and UCCR). Urinary albumin/creatinine ratio(UACR), age, course of disease, BMI, blood pressure, serum creatinine, FBG, PBG and HbAlc also were determined at the same time.Results:1 Comparisons between group DM and group NC1. There was no significant difference in age, BMI, blood pressure or serum creatinine between group DM and group NC (P>0.05). However, when compared with group NC, the level of FBG in DM group got significantly increase (7.21±0.14,4.85±0.10) mmol/L, P<0.05. And PBG also got elevated(9.71±0.31,5.24±0.22) mmol/L. Besides, we found HbA1c 、UACR、UTCR、UMCR、UCCR in group DM were also significantly higher than those in NC group, (7.03±0.10,5.22±0.06)%, (27.68±3.99, 13.63±1.03) mg/gCr and (95.96±17.10,30.71±1.83) pg/ngCr, respectively. (P<0.05 or 0.01).2. When compared with INS group Ⅰ, UTCR、UMCR、UCCR and UACR were significantly decreased in INS group Ⅱ, (152±34.43,60.23±12.27), (116.2±10.47, 27.42±4.45), (10.04±2.96,2.83±0.43), (42.96±6.24,10.48±1.98), respectively (P<0.05), while there was no significant difference in age、course of disease、BMI、 blood pressure、serum creatinine、FBG、PBG or HbAlc between two subgroups(P>0.05).3. When compared with SU group Ⅰ, UTCR、UMCR、UCCR and UACR decreased significantly in SU group Ⅱ,110.4±14.27,62.14±7.38), (240.8±12.77,53.58±8.11), (11.26±3.18,3.11±0.68), (52.43±7.80,18.31±5.70), respectively (P<0.05), while there was no significant difference in age、course of disease、 BMI、blood pressure、 serum creatinine、FBG、PBG or HbAlc between two subgroups(P>0.05).4. There was a positive correlation between the excretion of cytokines UTCR、UMCR、 UCCR and UACR(r=0.73,P<0.01; r=0.79, P<0.01; r=0.53, P<0.01;).Conclusions:Metformin can reduce the excretion of urinary cytokines in type 2 diabetics, which may be associated with its renal protection.