Background: Dapagliflozin, a novel inhibitor of sodium-glucose cotransporter-2 (SGLT-2), lowers blood glucose level by specifically inhibiting the activity of SGLT-2. Previous studies showed efficacy and safety of dapagliflozin combined with other antihyperglycemic agents in type 2 diabetes (T2DM), however, there are few studies for dapagliflozin as monotherapy. The aim of this study was to assess the efficacy and safety of dapagliflozin as a monotherapy in T2DM and provide theoretical basis for clinical rational use of drugs. Methods: We did a systematic review and meta-analysis of randomized, placbo-controlled clinical studies in patients with type 2 diabetes. We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP database through October 2018, we also manually screened list of references to the previous meta-analysis of dapagliflozin in the treatment of type 2 diabetes. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. A meta-analysis was conducted by using RevMan 5.3 software. Results: Six randomized controlled trials (RCTs) including 2033 patients were analyzed. Compared with placebo, dapagliflozin monotherapy was associated with a reduction in glycosylated hemoglobin A1c (HbA1c) (weighted mean difference [WMD]: -0.60%; 95% confidence interval [CI]: -0.67%, -0.52%; P<.00001), fasting plasam glucose (FPG) (WMD: -1.30 mmol/L; 95% CI: -1.52, 1.08; P<.00001), and body weight (WMD: -1.50 kg; 95% CI: -1.67, -1.32; P<.00001). Dapagliflozin was associated with an increased risk of urinary tract infections (relative risk [RR]: 1.74; 95% CI: 1.21, 2.49; P=.003) and genital tract infections (RR: 3.52; 95% CI: 2.06, 6.03; P<.00001). Conclusions: Dapagliflozin monotherapy was well tolerated and effective in reducing the level of HbA1c, FPG, and body weight in patients with T2DM without increasing hypoglycaemia, although it may increase the risk of urinary tract infections and genital tract infections. This meta-analysis provides an evidence for the treatment in patients with T2DM. However, more randomized clinical evidences are still needed to verify the results.

Objective: The aim of this study was to assess the prevalence of thyroid autoimmunity in T2DM with NAFLD, furthermore explore the relationship between elevated TPOAb titer and the severity of NAFLD. Methods: A total of 400 patients with T2DM were divided into two groups according to NAFLD. Thyroid function and other metabolic indicators were measured. Results: There were more TPOAb-positive patients in both groups, and the prevalence of TPOAb positive was significantly different in two groups (17% vs 6.9%, p< 0.01). FT4 was significantly lower in patients with T2DM with NAFLD (median FT4 0.89 vs 1.08, p < 0.001), while TSH was increased (median TSH 2.85 vs 2.28, p < 0.05). In patients with T2DM with NAFLD, the proportion of women in the thyroid autoimmune-positive group was significantly higher than the negative (71.1% vs 46%, p < 0.01). Similarly, thyroid autoimmune-positive T2DM and NAFLD patients had lower FT4 levels (median FT4 0.59 vs 0.92, p < 0.001), higher TSH levels (median TSH 3.65 vs 2.67, p < 0.001), and much higher TPOAb/TGAb (median TPOAb/TGAb 6.8 vs 1.46, p < 0.001). The increase of TPOAb was significantly correlated with the severity of fatty liver. HbA1c, TC, TG, TSH, TPOAb/TGAb and severity of fatty liver were risk factors of thyroid autoimmunity. Conclusion: Autoimmune thyroid disease is more common in patients with T2DM complicated with NAFLD. Elevated TPOAb titer is closely related to fatty liver, suggesting that elevated TPOAb titer is a predictor of autoimmune development in T2DM with NAFLD.

Puerarin, a major active isoflavone extracted from the Traditional Chinese Medicine Radix Puerariae, has been studied for its comprehensive biological effects. However, to date, its effect on bone formation and the underlying mechanism of action have not been well investigated. The present study investigated the effect of puerarin on cell proliferation and osteoblastic maturation in cultured human bone marrow stromal cells (hBMSC) in vitro. Puerarin (2.5-100 µM) increased hBMSC growth in a dose-dependent manner, as indicated by an MTT assay, and stimulated osteoblastic maturation as indicated by assessment of alkaline phosphatase (ALP) activity, as well as calcium deposition into the extracellular matrix detected by alizarin red S staining. Furthermore, polymerase chain reaction analysis showed that the expression of osteoblastic markers, including Runt-related transcription factor 2/core-binding factor alpha 1, osterix and osteocalcin, were increased in hBMSCs following incubation with puerarin. Further experiments indicated that puerarin increased the nitric oxide (NO) production and cyclic guanosine monophosphate (cGMP) content in hBMSCs. The effects of puerarin were mimicked by 17β-estrodiol (10(-8) M) and were abolished in the presence of estrogen receptor antagonist ICI182780 (10(-7) M). A NO synthase inhibitor, Nx-nitro-L-arginine methylester (6 x 10(-3) M), significantly attenuated puerarin-induced increases in NO production and cGMP content, in parallel with a reduction of cell proliferation and osteoblastic differentiation as well as the expression of osteoblastic markers. These results suggested that puerarin may prevent osteoporosis by exerting stimulatory effects on bone formation and the NO/cGMP pathway, which has an important role in puerarin-induced hBMSC proliferation and osteoblastic differentiation.