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.

Aim/introductionCirculating levels of N-terminal fragment of probrain natriuretic peptide (NT-proBNP) are established as a risk factor for cardiovascular disease and mortality in patients with diabetes, as well as in the general population. We sought to examine the possibility of NT-proBNP as a biomarker of microvascular complications in patients with type 2 diabetes.Materials and methodsIn total, 277 outpatients with type 2 diabetes were consecutively enrolled as a hospital cohort. Two hundred and seventeen of these patients (132 males; mean age, 63.4 years) were designated as cases with any of the diabetic complications (retinopathy, neuropathy, nephropathy, ischemic heart disease, strokes, peripheral artery disease), and 60 (42 males; mean age, 54.1 years) were set as controls without clinical evidence of diabetic complications. Diabetic complications were evaluated by medical record and routine laboratory examinations. NT-proBNP was measured and investigated with regard to the associations with diabetic complications.ResultsMean NT-proBNP levels were significantly higher in patients with any of the diabetic complications (59 versus 33 pg/mL; P<0.0001). In logistic regression analysis, NT-proBNP levels >79 pg/mL, which was the highest tertile, were independently associated with a 5.04 fold increased risk of all complications (P<0.0051) compared to the lowest tertile (NT-proBNP levels <31 pg/mL). Odd ratios of cardiovascular disease and nephropathy, neuropathy, and retinopathy were 9.33, 6.23, 6.6 and 13.78 respectively, in patients with NT-proBNP values in the highest tertile (>79 pg/mL), independently of age, sex, duration of diabetes or other risk factors, such as body mass index or hemoglobin A1c. In addition, NT-proBNP levels were associated with surrogate markers of atherosclerosis, such as brachial-ankle pulse wave velocity (r=0.449, P<0.0001) and left ventricular hypertrophy (r=0.212, P<0.001).ConclusionIn this hospital-based cohort of type 2 diabetes, the NT-proBNP levels were associated with systemic atherosclerosis and comorbid diabetic microvascular as well as macrovascular complications. It is useful to stratify high-risk diabetic patients by measuring NT-proBNP and to start comprehensive care for preventing the progression of diabetic complications. It is necessary to elucidate the underlying mechanism for the progression of diabetic complications represented by an elevation of NT-proBNP and to demonstrate the ability of NT-proBNP as a predictive global biomarker for diabetic complications in Japanese type 2 diabetic patients.

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