Gut microbiota affects the host's metabolism, and it is suggested that there are differences in gut microbiota composition between patients with type 2 diabetes and healthy individuals. Additionally, dysbiosis may increase the concentration of lipopolysaccharides (LPS), causing metabolic endotoxemia, which induces impaired glucose tolerance. Several studies have reported relationships between metabolic diseases and the gut microbiota; and prebiotics, such as oligosaccharides, are commonly consumed to regulate gut microbiotas in healthy individuals. Galacto-oligosaccharides (GOS) are a major prebiotic, which specifically increase Bifidobacteriaceae abundance. Recent studies have reported that Bifidobacteriaceae improved metabolic endotoxemia or impaired glucose tolerance. However, there are few studies reporting the effects of GOS on patients with type 2 diabetes. In the current study, we compared clinical parameters, faecal gut microbiota, their associated metabolic products and their components such as LPS, and LPS-binding protein (LBP) produced by the host, between patients with diabetes and healthy controls. We then assessed the effects of GOS on glycaemic control, and gut microbiotas and metabolites in patients with type 2 diabetes in a double-blind controlled manner. LBP levels were significantly higher in patients with diabetes than those of healthy subjects, which was consistent with previous reports. The abundance of Bifidobacteriaceae and the diversity of intestinal microbiota were significantly lower in patients with diabetes than in healthy subjects. Interestingly, Bifidobacteriaceae was markedly restored in patients with diabetes after consumption of GOS, whereas LBP and glucose tolerance did not improve during this short-term trial period. In the present study, we demonstrated that GOS can ameliorate dysbiosis in patients with diabetes, and continuous intake of GOS may be a promising method for managing type 2 diabetes.

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Background: Hyperglycemia in type 2 diabetes causes glucotoxicity, which can be treated with intensive insulin therapy. However, this treatment can lead to weight gain and hypoglycemia. The present study investigated the efficacy and safety of combination therapy with liraglutide and insulin glargine as the initial treatment for patients with moderate or severe hyperglycemia. Methods:Changes in clinical indexes such as glycated hemoglobin (HbA1c) and body mass index (BMI) were retrospectively investigated in 20 patients under combination therapy with liraglutide and insulin glargine and 10 patients treated with intensive insulin therapy.Results: Combination therapy with liraglutide and insulin glargine significantly improved HbA1c and BMI at 3 months compared with baseline. However, BMI was not improved in patients treated with intensive insulin therapy. Severe hypoglycemia was not observed in the combination therapy group during the observation period, and no patients required switching because of gastrointestinal symptoms. Conclusion:Combination therapy with liraglutide and insulin glargine demonstrated a superior glucoselowering effect, safety, and convenience without increasing body weight in poorly controlled patients with type 2 diabetes under hyperglycemic conditions. These results suggest that combination therapy could be considered an alternative to intensive insulin therapy. Effects of Combination Short CommunicationOpen Access IntroductionType 2 diabetes is a progressive disease that creates a vicious cycle of glucotoxicity, and it is important to break the cycle and normalize glucose metabolism by initiating early treatment. Intensive insulin therapy with multiple insulin injections is considered effective for removing the glucotoxicity caused by hyperglycemia [1], and such removal has been performed in many patients with hyperglycemia under hospitalization and frequent self-monitoring of glucose. However, intensive insulin therapy can increase the risk of adverse reactions such as hypoglycemia and body weight gain.Glucagon-like peptide-1 (GLP-1) receptor agonists are type 2 diabetes drugs that can be used in combination with insulin therapy and contribute to the improvement of not only fasting blood glucose levels, but also postprandial blood glucose levels. Therefore, combined use of a GLP-1 receptor agonist with insulin,which mainly improves fasting blood glucose levels may enable better glycemic control [2]. In fact, greater reductions in glycated hemoglobin(HbA1c) were seen in patients who added a GLP-1 receptor agonist to insulin therapy and in those who added insulin therapy to a GLP-1 receptor agonist, compared with those who did not add either of these therapies [3][4][5]. However, the clinical effects of such combination therapies with simultaneous initiation of both drugs as the initial treatment have not been fully investigated.In the present study, we retrospectively investigated the efficacy and safety of combination therapy with a GLP-1 receptor agonist (liraglutide) and long-...