1) To evaluate whether peripheral blood mononuclear cells (PBMCs) from type 2 diabetic patients present an impairment of phagocytic activity; 2) To determine whether the eventual impairment in phagocytic activity is related to glycemic control and can be reversed by improving blood glucose levels. 21 type 2 diabetic patients and 21 healthy volunteers were prospectively recruited for a case-control study. In addition, those patients in whom HbA1c was higher than 8% (n = 12) were hospitalized in order to complete a 5-day intensification treatment of blood glucose. Phagocytic activity was assessed by using a modified flow cytometry procedure developed in our laboratory based on DNA/RNA viable staining to discriminate erythrocytes and debris. This method is simple, highly sensitive and reproducible and it takes advantage of classic methods that are widely used in flow cytometry. Type 2 diabetic patients showed a lower percentage of activated macrophages in comparison with non-diabetic subjects (54.00±18.93 vs 68.53±12.77%; p = 0.006) Significant negative correlations between phagocytic activity and fasting glucose (r = −0.619, p = 0.004) and HbA1c (r = −0.506, p = 0.019) were detected. In addition, multiple linear regression analyses showed that either fasting plasma glucose or HbA1c were independently associated with phagocytic activity. Furthermore, in the subset of patients who underwent metabolic optimization a significant increase in phagocytic activity was observed (p = 0.029). Glycemic control is related to phagocytic activity in type 2 diabetes. Our results suggest that improvement in phagocytic activity can be added to the beneficial effects of metabolic optimization.

OBJECTIVE—The aim of this study was to compare the prevalence of both impaired fasting glucose (IFG) and diabetes between hepatitis C virus (HCV)-infected patients and patients with other liver diseases but anti-HCV⁻, taking into account the degree of liver damage. RESEARCH DESIGN AND METHODS—A total of 642 consecutive patients attending the outpatient liver unit of a university hospital (498 anti-HCV⁺ and 144 anti-HCV⁻) were prospectively recruited. Patients were classified as having chronic hepatitis (n = 472) or cirrhosis (n = 170) by means of the result of either a liver biopsy or by typical clinical features. A logistic regression model was used to determine independent associations of covariates (age, sex, BMI, HCV antibody status, and triglycerides) with the presence of glucose abnormalities. RESULTS—A threefold increase in the prevalence of glucose abnormalities was observed in HCV⁺ patients with chronic hepatitis in comparison with HCV⁻ subjects (32 vs. 12%; P = 0.0003). In contrast, among patients with cirrhosis, although both diabetes and IFG were more prevalent in anti-HCV⁺ patients (40%) than in anti-HCV⁻ patients (36%), the differences were not statistically significant. Finally, the logistic regression analysis showed that HCV infection was independently related to glucose abnormalities in those patients with chronic hepatitis (odds ratio 4.26 [95% CI 2.03–8.93]). In contrast, HCV was not an independent predictor of glucose abnormalities in cirrhotic patients. CONCLUSIONS—The high prevalence of IFG and diabetes found in HCV-infected patients observed in our study suggests that screening for glucose abnormalities should be indicated in these patients. In addition, we provide evidence that the genuine connection between HCV infection and diabetes is initiated at early stages of hepatic disease.

Low plasma sex hormone–binding globulin (SHBG) levels are associated with obesity and predict the development of type 2 diabetes. The reason why obese individuals have low circulating SHBG has been attributed to hyperinsulinemia, but no mechanistic evidence has been described. The aim of the current study is to explore whether tumor necrosis factor-α (TNF-α) rather than insulin could be the main factor accounting for low SHBG levels in obesity. We performed in vitro and in vivo studies using human HepG2 cells and human SHBG transgenic mice. In addition, a cross-sectional study to explore the relationship between TNF-α and SHBG in obese patients and an interventional study to examine the effect of insulin administration on circulating SHBG in type 2 diabetic patients were performed. We provide evidence that TNF-α, but not insulin, is the main factor by which SHBG is reduced in obesity. Plasma SHBG was significantly increased rather than decreased after insulin treatment in diabetic patients. TNF-α–induced reduction of SHBG expression was mediated by downregulating HNF4A. Finally, a negative and independent correlation was found between plasma TNF-α receptor 1 and SHBG levels in obese patients. Our results suggest that TNF-α plays an important role downregulating SHBG in chronic low-grade inflammatory diseases such as obesity and type 2 diabetes.

OBJECTIVE—There is evidence to suggest that hepatitis C virus (HCV) infection is a high-risk condition for developing type 2 diabetes. However, there are no interventional studies that confirm that HCV infection causes diabetes. The main aim of this study was to compare the incidence of glucose abnormalities (diabetes plus impaired fasting glucose) between HCV-infected patients with or without sustained virological response (SVR) after antiviral therapy.

Context: Zinc-α2 glycoprotein (ZAG) has been proposed as a new candidate in the pathogenesis of obesity, but most of the information stems from studies performed in rodents and in vitro assays. Objective: The main aim of the study was to compare serum levels of ZAG and its expression (mRNA levels and protein) in adipose tissue and the liver between obese and nonobese subjects. The relationship between ZAG and insulin resistance was also explored. Design: This was a case-control study. Setting: The study was conducted at a university referral center. Patients and Methods: Samples of serum, sc adipose tissue (SAT), visceral adipose tissue (VAT), and liver were obtained from 20 obese subjects during bariatric surgery. Samples from 10 nonobese patients matched by age and gender were used as a control group. Serum ZAG levels were determined by ELISA. ZAG mRNA levels were measured by real-time PCR and protein content by Western blot. The effect of insulin on liver production of ZAG was assessed using HepG2 cultures. Results: Serum concentration of ZAG (micrograms per milliliter) was significantly lower in obese subjects (40.87 ± 10.45 vs. 63.26 ± 16.40; P = 0.002). ZAG expression was significantly lower in the adipose tissue (SAT and VAT) and liver of obese patients than in control subjects. Significant negative correlations between body mass index and circulating ZAG (r = −0.65, P < 0.001) as well as between body mass index and mRNA ZAG levels in SAT (r = −0.68, P < 0.001) and VAT were detected (r = −0.64, P < 0.001). No relationship was found between ZAG and homeostasis model assessment for insulin resistance and insulin had no effect on ZAG production in vitro. Conclusion: A down-regulation of ZAG in SAT, VAT, and liver exists in obese patients but seems unrelated to insulin resistance. A downregulation of zinc-α2 glycoprotein in adipose tissue and liver exists in obese patients, and it is unrelated to insulin resistance.