Changes of transforming growth factor beta 1 in patients with type 2 diabetes and diabetic nephropathy

Abstract

Background:The existing evidence indicates increased levels of transforming growth factor beta 1 (TGF-β1) in patients with type 2 diabetes mellitus (T2DM) and those with type 2 diabetic nephropathy (T2DN); yet no meta-analysis displays a reliable result. Here we conducted a meta-analysis to evaluate characteristic changes of TGF-β1 in T2DM and diabetic nephropathy.Methods:A systematic search was conducted for eligible studies, which reported the association of TGF-β1 withT2DM and T2DN patients, in PubMed, Wangfang, Chinese-Cqvip, and China National Knowledge Infrastructure database, from February 1, 1991 to December 15, 2015. The association of serum and urine TGF-β1 in T2DM and T2DN patients should be evaluated in case-control studies. The Newcastle-Ottawa Scale was used to access the quality of the included studies, and pooling data were synthesized as standard mean difference (SMD) and 95% confidence interval (CI). The collected data were synthesized according to Cochrane Handbook for Systematic Reviews criteria. Subgroup analysis was conducted by albuminuria and ethnicity. Regression analysis and sensitivity analysis were used to explore the sources of heterogeneity. Publication bias was judged by the Egger test.Results:Sixty-three case-control studies of 364 T2DM patients (1604 T2DN patients) and 2100 healthy controls were included for meta-analysis. Compared with the controls, the cases had increased TGF-β1 levels in both serum (T2DM: SMD 1.78 μg/L; 95% CI 0.98–2.59, P < .001; T2DN: SMD 4.70 μg/L, 95% CI 3.55–5.85, P < .001) and urine samples (T2DM: SMD 1.27 pg/mg.creatinine, 95% CI 0.16–2.38, P < .001; SMD 1.19 ng/L, 95% CI 0.77–1.62, P < .001; T2DN: SMD 3.14 pg/mg.creatinine, 95% CI 2.15–4.13, P < .001; SMD 4.50 ng/L, 95% CI 3.16–5.83, P < .001). The increase of serum TGF-β1 persisted in patients with either microalbuminuria or macroalbuminuria (all P < .001) in Chinese and non-Chinese population. High heterogeneity exists in some comparisons and small-sample studies.Conclusions:Patients with T2DM and those with albuminuria, Chinese or non-Chinese, had increased serum and urine TGF-β1 levels.

Effect of Oral Carnosine Supplementation on Urinary TGF-β in Diabetic Nephropathy: a Randomized Controlled Trial

“…Reduced urinary TGF-β is a biomarker for CKD progression. [7] It has been shown that carnosine may have a reno-protective effect on ischemia/reperfusion-induced acute kidney injury in animal models [15] and attenuates the development of patients with T2DM and nephropathy [16]. Whereas, we found that oral carnosine supplementation did not reduce urine albumin, which differed from one related study [12].…”

Molecular evidence of field cancerization initiated by diabetes in colon cancer patients

“…This increased phosphorylation has been reported in diabetics compared to healthy subjects (Fr€ ojd€ o et al, 2009) and is largely involved in cell proliferation (Mebratu and Tesfaigzi, 2009;Wagner and Nebreda, 2009). Upstream effectors of this signaling cascade include deregulation of the TGF-b pathway, increased in T2DM patients (Qiao et al, 2017) and described as a CC oncogene (Xu and Pasche, 2007); and Wnt activation, postulated as a possible link between diabetes and cancer (Garc ıa-Jim enez et al, 2014). Two additional pathways cooperate with Wnt in CC tumorigenesis: Hippo (Rosenbluh et al, 2012), proposed as potential target in diabetes (S.-P. Wang and Wang, 2016), and Notch (Vinson et al, 2016) that plays an important role in B cells under hyperglycemia (Darville and Eizirik, 2006).…”

Adjuvant Therapy With Mushroom Polysaccharides for Diabetic Complications

“…As the research progressed, researchers have begun to believe that abnormal expression of growth factors plays a role in the development of diabetic complications (Shi et al, 2018). TGF-b1, a fibrotic cytokine, can cause renal cell hypertrophy, regulate the generation of extracellular matrix molecules and induce the production of chemokines in the proximal tubules of the kidney, which promotes DN to some extent (Qiao et al, 2017). Experiments have shown that streptozotocin (STZ) triggers DR by increasing the levels of TNF-a, IL-1b, and IL-6 (Gao et al, 2017).…”