Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.
PROSPERO. Unique identifier: CRD42013004501.
ObjectivesThe aim of this study was to systematically review data regarding pharmacokinetic (PK)-pharmacodynamic (PD) parameters from randomized controlled trials relating to interactions between herbal medicines and warfarin.MethodsThree electronic databases were searched to identify relevant trials. Two reviewers independently performed the study selection and data extraction. The risk of bias and reporting quality were also assessed independently by two reviewers using the Cochrane risk of bias tool and the consolidated standards of reporting trials (CONSORT). Outcomes were measured for all reported PK-PD parameters and adverse events.ResultsNine randomized controlled trials met our inclusion criteria. Most of the included studies were unclear regarding the risk of bias and had a low quality of methodology. Using CONSORT, the reporting percentages for the articles ranged from 36.5% to 61.5% and the mean percentage for all articles was 45.6%. St John’s wort and echinacea affected the PK parameters of warfarin. Ginseng, ginger, garlic, and cranberry had no significant effect on the PK parameters. American ginseng altered the PD parameters of warfarin. St John’s wort, ginseng, Korea red ginseng, ginkgo, ginger, garlic, aged garlic, and echincea did not significantly alter the PD parameters. Studies of ginkgo and cranberry showed conflicting results on the PK parameters and PD parameters, respectively. The incidence of adverse events in all trials was low and no major adverse events were reported.ConclusionsIt was difficult to determine whether ten herbal medicines had significant effects on the PK-PD parameters of warfarin. Low quality of evidence, different compounds within and different compositions of the herbs, and methodological limitations of the crossover study, which is a clinical study in which subjects receive a sequence of different interventions, made it difficult to form conclusions. Additional studies that remedy these vulnerabilities are necessary to verify these results.
BackgroundNoninvasive and easy-to-use surface electromyography (EMG) is frequently utilized for the diagnosis of temporomandibular disorders (TMDs). However, few EMG parameters that consider TMDs in addition to the cranio-cervical-mandibular system have been regarded as important in traditional Korean medicine.MethodsThis clinical trial will be conducted as an assessor-blinded cross-sectional study. The participants will be classified based on the Diagnostic Criteria for TMDs Symptom Questionnaire (DC/TMD SQ) and 30 TMD patients and 30 healthy controls will be enrolled. The primary outcome will be the percentage overlapping coefficient (POC; %) in the masseter and sternocleidomastoid muscles between the patient group and healthy control group in clenching and cervical side flexion. The secondary outcomes include the score from temporomandibular joint-related questionnaires, the difference in the absolute values of EMG for the healthy group and TMD group before/after wearing intraoral appliances, and the change in the location of the temporomandibular joint as determined by X-ray imaging and 3D face photography.DiscussionThis study will provide information about the objective diagnostic method for TMD using surface EMG and will verify the effectiveness of surface EMG in diagnosing TMD. Furthermore, the method or device for diagnosis TMD will improve the expansion of treatment area to TMD by accumulating evidence for the efficacy of TKM treatment.
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