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BackgroundDysregulation of microRNA (miRNA) expression in various tissues and body fluids has been demonstrated to be associated with several diseases, including Type 2 Diabetes mellitus (T2D). Here, we compare miRNA expression profiles in different tissues (pancreas, liver, adipose and skeletal muscle) as well as in blood samples from T2D rat model and highlight the potential of circulating miRNAs as biomarkers of T2D. In parallel, we have examined the expression profiles of miRNAs in blood samples from Impaired Fasting Glucose (IFG) and T2D male patients.Methodology/Principal FindingsEmploying miRNA microarray and stem-loop real-time RT-PCR, we identify four novel miRNAs, miR-144, miR-146a, miR-150 and miR-182 in addition to four previously reported diabetes-related miRNAs, miR-192, miR-29a, miR-30d and miR-320a, as potential signature miRNAs that distinguished IFG and T2D. Of these microRNAs, miR-144 that promotes erythropoiesis has been found to be highly up-regulated. Increased circulating level of miR-144 has been found to correlate with down-regulation of its predicted target, insulin receptor substrate 1 (IRS1) at both mRNA and protein levels. We could also experimentally demonstrate that IRS1 is indeed the target of miR-144.ConclusionWe demonstrate that peripheral blood microRNAs can be developed as unique biomarkers that are reflective and predictive of metabolic health and disorder. We have also identified signature miRNAs which could possibly explain the pathogenesis of T2D and the significance of miR-144 in insulin signaling.

Significant dysregulation of seven candidate microRNAs has been found to be associated with risks involved in the manifestation of metabolic syndrome.

Using 2 highly sensitive metabolomic techniques, we report distinct serum profile change of a wide range of metabolites from healthy persons to type 2 diabetes mellitus. Apart from glucose, IFG and diabetes mellitus are characterized by abnormalities in amino acid, fatty acids, glycerophospholipids, and sphingomyelin metabolism. These early broad-spectrum metabolic changes emphasize the complex abnormalities present in a disease defined mainly by elevated blood glucose levels.

The level of glycaemic control as measured by HbA1c emerged as the most consistent risk factor associated with the extent and severity of periodontal disease in this study cohort.

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IntroductionPathophysiology of diabetic kidney disease (DKD) is incompletely understood. We aim to elucidate metabolic abnormalities associated with DKD in type 2 diabetes mellitus (T2DM) by targeted plasma metabolomics.MethodsA total of 126 T2DM participants with early DKD (urinary albumin-to-creatinine ratio [ACR] 30−299 mg/g and eGFR ≥ 60 ml/min/1.73 m2), 154 overt DKD (ACR ≥ 300 mg/g or eGFR < 60 ml/min/1.73 m2), and 129 non-DKD T2DM controls (ACR < 30 mg/g and eGFR ≥ 60 ml/min/1.73 m2) were included in discovery study. Findings were subsequently validated in 149 T2DM with macroalbuminuria (ACR ≥ 300 mg/g) and 149 matched non-DKD T2DM controls. Plasma amino acid, acylcarnitine, Krebs cycle organic acid, and sphingolipids/ceramide levels were quantified by liquid chromatography−mass spectrometry and gas chromatography−mass spectrometry.ResultsOf 123 metabolites included in the data analysis, 24 differed significantly between DKD and controls in the same direction in both discovery and validation subpopulations. A number of short acylcarnitines including their dicarboxylic derivatives (C2−C6) were elevated in DKD, suggesting abnormalities in fatty acids and amino acids metabolic pathways. Five phosphatidylcholines were lower whereas 4 metabolites in the sphingomyelin−ceramide subfamily were higher in DKD. Principal component regression revealed that long-chain ceramides were independently associated with ACR but not eGFR. Conversely, essential amino acids catabolism and short dicarboxylacylcarnitine accumulation were associated with eGFR but not ACR.DiscussionDKD is associated with altered fuel substrate use and remodeling of sphingolipid metabolism in T2DM with DKD. Associations of albuminuria and impaired filtration function with distinct metabolomic signatures suggest different pathophysiology underlying these 2 manifestations of DKD.