Non-standardizes residuals were then taken forward as a new dependent variable in the ANOVA analysis for all four groups (NGT, IFG, IGT, T2D)

Non-standardizes residuals were then taken forward as a new dependent variable in the ANOVA analysis for all four groups (NGT, IFG, IGT, T2D). 56 subjects with T2D were included. Serum concentrations of adiponectin, chemerin, fetuin-A, leptin, interleukin (IL)-6, retinol-binding protein 4 (RBP4), monocyte chemoattractant protein (MCP)-1, vaspin, progranulin, and soluble leptin receptor (sOBR) were measured by ELISAs. == Results == Chemerin, progranulin, fetuin-A, and RBP4, IL-6, adiponectin and leptin serum concentrations were differentially regulated among the four investigated groups but only circulating chemerin was significantly different in patients with IGT compared to those with IFG. Compared to T2D the IFG subjects had higher serum chemerin, progranulin, fetuin-A and RBP4 levels which was not detectable in the comparison of the T2D and IGT group. == Conclusion == Alterations in adipokine serum concentrations are already detectable in prediabetic states, mainly for chemerin, and may reflect adipose tissue dysfunction as an early pathogenetic event in T2D development. In addition, distinct adipokine serum patterns in individuals with IFG and IGT suggest a specific role of adipose tissue in the pathogenesis of these prediabetic states. == Introduction == Adipose tissue dysfunction belongs to the primary defects in obesity and may link obesity to several health problems including increased risk of type 2 diabetes, fatty liver, and cardiovascular disease[1][6]. Altered adipokine serum concentrations are an early symptom of impaired adipose tissue function and GSK3368715 may contribute to the development of obesity-associated disorders. In patients with type 2 diabetes, elevated tumor necrosis factor (TNF), C-reactive protein (CRP), interleukin (IL) -1, -6, -8, plasminogen activator inhibitor-1 (PAI-1), retinol binding protein 4 (RBP4), chemerin, fetuin-A, visfatin/Nampt, resistin and reduced adiponectin and IL-10 serum concentrations have been reported[7][11], reviewed in[1],[5]. However, it is not entirely clear whether these alterations in adipokine serum concentrations are already present in prediabetic states of isolated impaired fasting glycemia (IFG), isolated impaired glucose tolerance (IGT), or combined IFG/IGT. Furthermore, at present there is no comprehensive comparison of adipokine pattern across all stages of glucose intolerance starting from NGT status available. Here, we sought to identify adipokines, which are either increased or decreased in individuals with the prediabetic states IFG and IGT compared to normal glucose tolerant (NGT) healthy controls and GSK3368715 subjects with type 2 diabetes. In addition, we tested the hypothesis that isolated IFG and IGT are associated with distinct adipokine patterns which reflect the pathophysiological differences between IFG and IGT. Taking into account the dominant effect of obesity, age and gender on adipokine levels we present all analyses adjusted for these factors. Key defects in IFG include reduced hepatic insulin sensitivity, beta cell dysfunction, and/or chronic low beta cell mass, altered glucagon-like peptide-1 secretion, and inappropriately elevated glucagon secretion. In contrast, IGT is characterised by reduced peripheral insulin sensitivity, near-normal hepatic insulin sensitivity, progressive loss of beta cell function, reduced secretion of glucose-dependent insulinotropic polypeptide, and inappropriately elevated glucagon secretion[12],[13]. In addition, the aetiologies of IFG and IGT seem to differ, with IFG being predominantly related to Rabbit polyclonal to PABPC3 genetic factors, smoking, and male gender, while IGT is predominantly related to physical inactivity, unhealthy diet, and short stature[13]. Our aim is to elucidate distinct pathomechanisms for either IFG or IGT by comparing GSK3368715 adipokine serum patterns between these prediabetic states and NGT and T2D. Furthermore, we aim to provide a broad overview of adipokine profiles across all stages of glucose intolerance. == Methods == == Subjects == A total of 864 Caucasian men (n = 413) and women (n = 451) have been consecutively recruited in the context of a study on insulin resistance at the Department of Medicine, University of Leipzig, to represent a wide range of obesity, insulin sensitivity, and glucose tolerance. On the basis GSK3368715 of a 75-g oral glucose tolerance test (OGTT) according to the criteria of the American Diabetes Association[14], 179 individuals for whom complete data sets for the described parameters were available, were selected from this cohort and divided into groups of.