Antidiabetic Medications for Type 2 Diabetics with Nonalcoholic Fatty Liver Disease: Evidence From a Network Meta-Analysis of Randomized Controlled Trials

ObjectiveType 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD) are closely related, and antidiabetic medications have been shown to be potential therapeutics in NAFLD. Using a network meta-analysis, we sought to examine the effectiveness of antidiabetic agents for the treatment of NAFLD in patients with type 2 diabetes mellitus.MethodsMedline and Embase were searched for randomized controlled trials relating to the use of antidiabetic agents, including sodium-glucose transport protein 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists, and peroxisome proliferator-activated receptor gamma (PPARγ) agonists, biguanides, sulfonylureas and insulin, on NAFLD in patients with diabetes. The p-score was used as a surrogate marker of effectiveness.ResultsA total of 14 articles were included in the analysis. PPARγ agonists were ranked as the best treatment in steatosis reduction, resulting in the greatest reduction of steatosis. There was statistical significance between PPARγ agonists [mean difference (MD): ?6.02%, confidence interval (CI): ?10.37% to ?1.67%] and SGLT2 inhibitors (MD: ?2.60%, CI: ?4.87% to ?0.33%) compared with standard of care for steatosis reduction. Compared with PPARγ agonists, SGLT2 inhibitors resulted in a statistical significant reduction in fibrosis (MD: ?0.06, CI: ?0.10 to ?0.02). Body mass index reduction was highest in SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists. Additionally, SGLT2 inhibitors were ranked as the best treatment for increasing high-density lipoprotein and reducing low-density lipoprotein.ConclusionGlucagon-like peptide-1 receptor agonists and SGLT2 inhibitors were suitable alternatives for the treatment of NAFLD in those with type 2 diabetes mellitus with a reduction in body mass index, fibrosis, and steatosis. SGLT2 inhibitors also have the added benefit of lipid modulation.     

Isolation of Legume Glycosyltransferases and Active Site Mapping of the <Emphasis Type="Italic">Phaseolus lunatus</Emphasis> Zeatin O-glucosyltransferase ZOG1

O-Glycosides of the cytokinin zeatin are found in many plant tissues. They provide protection against degradative enzymes and may serve as cytokinin reserves. Two zeatin glycosyltransferase (GT) genes, an O-glucosyltransferase (ZOG1) from Phaseolus lunatus and an O-xylosyltransferase (ZOX1) from P. vulgaris, were previously isolated. Five novel bean and soybean GT genes with high sequence identity to ZOG1 were isolated, sequenced, and expressed, along with two such genes from rice and one from tomato. None of the recombinant proteins showed GT activity with zeatin. By comparing the ZOG1 sequence to the 3D model of Medicago truncatula UGT71G1, four regions possibly important to zeatin binding were identified, and mutation studies identified one amino acid within each region (R59, D87, L127, and F149) whose mutation strongly impaired enzyme activity. The new bean and soybean GTs differ from ZOG1 in one (PlGT2 and GmGT2) to three (GmGT1) of these residues. Mutation of one such GT (PlGT2) to render it identical to ZOG1 at the four implicated residues conferred low enzyme activity, providing further support for the importance of these amino acids in recognizing zeatin as substrate. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.