To explore the clinical significance of seven diabetes-related serum microRNAs (miR-9, miR-29a, miR-30d, miR34a, miR-124a, miR146a and miR375) during the pathogenesis of type 2 diabetes (T2D), 56 subjects were recruited to this study: 18 cases of newly diagnosed T2D (n-T2D) patients, 19 cases of pre-diabetes individuals (impaired glucose tolerance [IGT] and/or impaired fasting glucose [IFG]) and 19 cases of T2D-susceptible individuals with normal glucose tolerance (s-NGT). Serum miRNAs were determined by real-time RT-PCR. Expression levels of single miRNAs and the expression signatures of miRNAs as a panel were analysed among the three groups. In n-T2D, all 7 miRNAs were significantly up-regulated compared with s-NGT and five were significantly up-regulated compared with pre-diabetes, while miRNA expression was not significantly different between s-NGT and pre-diabetes. By Canonical discriminant analysis, 70.6% of n-T2D subjects (12/17) were recognized by canonical discriminant function, while s-NGT and pre-diabetes subjects could not be discriminated from each other. Similar results were found in Hierarchical Clustering analysis based on the expression levels of all seven miRNAs. In different statistical analysis, miR-34a always showed the most significant differences. We conclude that the expression levels of seven diabetes-related miRNAs in serum were significantly elevated in n-T2D compared with pre-diabetes and/or s-NGT, and the latter two groups featured similar expression patterns of these miRNAs, suggesting that during the pathogenesis of T2D, the peripheral diabetes-related miRNAs have not changed significantly from s-NGT at pre-diabetic stage.

Grouped according to BMI, overweight and obese subjects have similar thyroid hormones compared to those with normal weight. Body composition parameters increase with the elevation of FT3, and FT3 is associated with body fat parameters in euthyroid subjects.

Supplementary key words adenosine 5 ′ -monophosphate-activated protein kinase • cholesterol • hydroxy-methylglutaryl coenzyme A reductaseThe liver plays a vital role in regulating cholesterol homeostasis in the body. HMG-CoA reductase (HMGCR) is the rate-limiting enzyme in cholesterol biosynthesis ( 1 ), so its activity is instrumental in controlling de novo cholesterol synthesis. To maintain cholesterol homeostasis, HMGCR could be regulated by multiple mechanisms such as transcription, translation ( 2 ), enzyme degradation rate ( 3 ), phosphorylation-dephosphorylation ( 4 ), and feedback inhibition ( 5 ). Hormones could regulate the expression of HMGCR by acting at different levels. For example, glucocorticoids act at a posttranslational level ( 1 ), whereas insulin reportedly affects both the transcriptional and posttranslational processes ( 6 ). Recently, Wu et al. ( 7 ) found that the changes of the phosphorylated HMGCR play an important role in regulation of the hepatic cholesterol biosynthesis process. The site of phosphorylation on HMGCR has been identifi ed as serine 871 in rodents ( 8 ) and serine 872 in humans ( 9 ). The HMGCR is physiologically present in the cell in unphosphorylated active form and phosphorylated inactive form. In general, phosphorylation of HMGCR leads to inactivation of the enzyme, while dephosphorylation activates it. The ratio of the phosphorylated form to total form indicates an inactivation state of HMGCR. Abstract