OBJECTIVE-Vaspin was identified as an adipokine with insulin-sensitizing effects, which is predominantly secreted from visceral adipose tissue in a rat model of type 2 diabetes. We have recently shown that vaspin mRNA expression in adipose tissue is related to parameters of obesity and glucose metabolism. However, the regulation of vaspin serum concentrations in human obesity and type 2 diabetes is unknown.RESEARCH DESIGN AND METHODS-For the measurement of vaspin serum concentrations, we developed an enzyme-linked immunosorbent assay (ELISA). Using this ELISA, we assessed circulating vaspin in a cross-sectional study of 187 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance and in 60 individuals with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes before and after a 4-week physical training program.RESULTS-Vaspin serum concentrations were significantly higher in female compared with male subjects. There was no difference in circulating vaspin between individuals with NGT and type 2 diabetes. In the normal glucose-tolerant group, circulating vaspin significantly correlated with BMI and insulin sensitivity. Moreover, physical training for 4 weeks resulted in significantly increased circulating vaspin levels.CONCLUSIONS-We found a sexual dimorphism in circulating vaspin. Elevated vaspin serum concentrations are associated with obesity and impaired insulin sensitivity, whereas type 2 diabetes seems to abrogate the correlation between increased circulating vaspin, higher body weight, and decreased insulin sensitivity. Low circulating vaspin correlates with a high fitness level, whereas physical training in untrained individuals causes increased vaspin serum concentrations.

OBJECTIVE -The dysregulation of adipokines is closely associated with the pathogenesis of insulin resistance and type 2 diabetes. Retinol-binding protein-4 (RBP4), a new adipokine, was recently reported to provide a link between obesity and insulin resistance. Here, we examined the relation between plasma RBP4 concentrations and various metabolic parameters in humans.RESEARCH DESIGN AND METHODS -An enzyme-linked immunosorbent assay was developed to measure human RBP4 plasma concentrations, which were then compared with various parameters related to insulin resistance in subjects with normal glucose tolerance (NGT; n ϭ 57), impaired glucose tolerance (IGT; n ϭ 48), and type 2 diabetes (n ϭ 49).RESULTS -Plasma RBP4 concentrations were higher in the IGT and type 2 diabetic groups than in the NGT group (median 18.9 [range 11.2-45.8], 20.9 [9.9 -48.5], and 18.1 g/ml [9.3-30.5], respectively). However, no difference was found between plasma RBP4 concentrations in the IGT and type 2 diabetic groups. Plasma RBP4 concentrations were found to be associated with sex, waist circumference, fasting plasma glucose, and insulin resistance. Of these, sex and fasting plasma glucose levels were found to be independent determinants of plasma RBP4 concentration.CONCLUSIONS -Plasma RBP4 concentrations were found to be elevated in subjects with IGT or type 2 diabetes and to be related to various clinical parameters known to be associated with insulin resistance. Diabetes Care 29:2457-2461, 2006A n increased adipose tissue mass is strongly associated with the pathogenesis of insulin resistance and type 2 diabetes (1). Adipose tissue may be viewed as an endocrine organ that secretes many types of adipokines (such as leptin, tumor necrosis factor ␣, interleukin 6, and adiponectin) that modulate the action of insulin in other tissues (2-5). Moreover, retinol-binding protein-4 (RBP4), a new fat-derived adipokine that specifically binds to retinol (6), has recently been reported to provide a link between obesity and insulin resistance (7). RBP4 was discovered while trying to identify the substance responsible for regulating insulin sensitivity in mice either lacking or overexpressing GLUT4 in adipose tissues (8,9). It is regulated reciproc a l l y i n a d i p o s e t i s s u e o f m i c e overexpressing or lacking GLUT4. Circulating RBP4 levels were reported to be raised in several different mouse models of obesity and insulin resistance (7). In mice lacking GLUT4, rosiglitazone (a peroxisome proliferator-activated receptor ␥ agonist) was found to lower circulating levels of RBP4 and to reduce insulin resistance. Increasing the circulating levels of RBP4 leads to glucose intolerance, whereas knock out of the RBP4 gene increases insulin sensitivity. In addition, treatment of mice with fenretinide (which facilitates the excretion of RBP4 into urine) decreased the insulin resistance induced by a high-fat diet (7).A mechanism whereby RBP4 modulates insulin sensitivity in muscle and liver has been suggested. In skeletal muscle, RBP4 reduces insu...

OBJECTIVE-Progranulin is an important molecule in inflammatory response. Chronic inflammation is frequently associated with central obesity and associated disturbances; however, the role of circulating progranulin in human obesity, type 2 diabetes, and dyslipidemia is unknown.RESEARCH DESIGN AND METHODS-For the measurement of progranulin serum concentrations, we developed an enzymelinked immunosorbent assay (ELISA). Using this ELISA, we assessed circulating progranulin in a cross-sectional study of 209 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance and in 60 individuals with normal (NGT) or impaired (IGT) glucose tolerance or type 2 diabetes before and after a 4-week physical training program. Progranulin mRNA and protein expression was measured in paired samples of omental and subcutaneous adipose tissue (adipocytes and cells of the stromal vascular fraction) from 55 lean or obese individuals. Measurement of Erk activation and chemotactic activity induced by progranulin in vitro was performed using THP-1-based cell migration assays.RESULTS-Progranulin serum concentrations were significantly higher in individuals with type 2 diabetes compared with NGT and in obese subjects with predominant visceral fat accumulation. Circulating progranulin significantly correlates with BMI, macrophage infiltration in omental adipose tissue, C-reactive protein (CRP) serum concentrations, A1C values, and total cholesterol. Multivariable linear regression analyses revealed CRP levels as the strongest independent predictor of circulating progranulin. The extent of in vitro progranulin-mediated chemotaxis is similar to that of monocyte chemoattractant protein-1 but independent of G␣. Moreover, in type 2 diabetes, but not in IGT and NGT individuals, physical training for 4 weeks resulted in significantly decreased circulating progranulin levels.CONCLUSIONS-Elevated progranulin serum concentrations are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. We identified progranulin as a novel marker of chronic inflammation in obesity and type 2 diabetes that closely reflects omental adipose tissue macrophage infiltration. Physical training significantly reduces elevated circulating progranulin in patients with type 2 diabetes. Diabetes 58:627-636, 2009

Context:Women with previous gestational diabetes mellitus (pGDM) are at high risk of developing type 2 diabetes mellitus in the future. The role of adipokines in women with pGDM has not been established. Objective:We investigated whether circulating adipokine concentration is associated with abnormal glucose homeostasis in women with pGDM.Design, Setting, Patients, and Main Outcome Measures: We measured the plasma concentrations of retinol-binding protein-4 (RBP4), transthyretin (TTR), and adiponectin and metabolic parameters in four groups of women who exhibited normal glucose tolerance (NGT) during a previous pregnancy (NP, n ϭ 17), NGT after GDM (GDM-NGT, n ϭ 72), impaired glucose tolerance after GDM (GDM-IGT, n ϭ 60), and type 2 diabetes after GDM (GDM-DM, n ϭ 8).Results: Plasma RBP4 concentration was significantly higher in women with GDM-DM, GDM-IGT, and GDM-NGT than in those with NP. RBP4 concentration correlated positively with TTR concentration; fasting plasma glucose, insulin, and triglyceride concentrations; blood pressure; abdominal fat area; and homeostasis model assessment of insulin resistance. Plasma TTR concentration was elevated in women with GDM-DM compared with other groups. In contrast, adiponectin concentration was lowest in the GDM-DM group and correlated inversely with parameters of insulin resistance. Resistin concentration was higher only in the GDM-NGT and GDM-IGT groups, whereas leptin did not differ between groups. Plasma RBP4 and adiponectin concentrations were inversely correlated. Conclusions:The severity of glucose intolerance in women with pGDM is associated with high RBP4 and low adiponectin concentrations. (J Clin Endocrinol Metab 93: 3142-3148, 2008) G estational diabetes mellitus (GDM) is defined as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy (1). Women with GDM have prominent insulin resistance regardless of compensatory insulin secretion and are at high risk for developing type 2 diabetes (2). Women with GDM have a 17-63% increased risk of type 2 diabetes within 5-16 yr postpartum (3, 4). In Korean women with GDM, the conversion rate to type 2 diabetes is as high as

Our data suggest that the urinary ACE2 level is closely associated with T2DM and is an independent risk factor for microalbuminuria.