Impact of glucose-lowering drugs on cardiovascular disease in type 2 diabetes

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Assessing Insulin Secretion by Modeling in Multiple-Meal Tests

We developed a mathematical model of the glucose control of insulin secretion capable of quantifying β-cell function from a physiological meal test. The model includes a static control, i.e., a secretion component that is a function of plasma glucose concentration (the dose-response function), and a dynamic control, i.e., a secretion component that is proportional to the positive values of the glucose concentration derivative. Furthermore, the dose-response function is assumed to be modulated by a time-varying potentiation factor. To test the model, nine nondiabetic control subjects and nine type 2 diabetic patients received three standardized mixed meals over a period of 14–15 h. Blood samples were drawn for the measurement of glucose, insulin, and C-peptide concentration. The dose-response function, the parameter of the dynamic control, and the potentiation factor were determined by fitting the model to glucose and C-peptide concentrations. In diabetic patients, the dose-response function was shifted to the right (glucose concentration at a reference insulin secretion of 300 pmol · min−1 · m−2 was 11.7 ± 1.1 vs. 7.2 ± 0.7 mmol/l; P < 0.05), and decreased in slope (53 ± 15 vs. 148 ± 38 pmol · min−1 · m−2 · mmol−1 · l; P < 0.05) and the parameter of the dynamic control was decreased (220 ± 67 vs. 908 ± 276 pmol · m−2 · mmol−1 · l; P < 0.05) compared with the nondiabetic control subjects. Furthermore, potentiation was markedly blunted and delayed: maximum potentiation was observed at the first meal in normal subjects and at the second meal (about 4 h later) in diabetic subjects; the mean time for the potentiation factor was higher (7.1 ± 0.2 vs. 5.9 ± 0.2 h; P < 0.01), and the size of potentiation was reduced (2.6 ± 0.5 vs. 7.2 ± 1.5 fold increase; P < 0.005). In conclusion, our model of insulin secretion extracts multiple indexes of β-cell function from a physiological meal test. Use of the model in patients with type 2 diabetes retrieves known defects in insulin secretion but also uncovers new facets of β-cell dysfunction

Bariatric surgery as a treatment of type 2 diabetes

Obesity has reached epidemic proportions, predisposing to the development of type 2 diabetes and cardiovascular diseases. Weight loss is a major objective, although often difficult to achieve with medical treatments. Bariatric surgery has proven its efficacy in obtaining marked and sustained weight loss, and is also associated with a significant improvement in insulin resistance, beta cell function, lipid metabolism, blood pressure and even diabetes remission. We examined the long-term effect of Roux-en-Y gastric bypass (RYGB, a predominantly restrictive procedure) in a patient with uncontrolled type 2 diabetes. One year after surgery, the patient had lost 30% of initial weight with a significant improvement in blood pressure, withdrawal of cholesterol-lowering therapy, complete remission of diabetes

Anti-inflammatory and antioxidant properties of HDLs are impaired in type 2 diabetes.

ObjectiveIn mice, 4F, an apolipoprotein A-I mimetic peptide that restores HDL function, prevents diabetes-induced atherosclerosis. We sought to determine whether HDL function is impaired in type 2 diabetic (T2D) patients and whether 4F treatment improves HDL function in T2D patient plasma in vitro.Research design and methodsHDL anti-inflammatory function was determined in 93 T2D patients and 31 control subjects as the ability of test HDLs to inhibit LDL-induced monocyte chemotactic activity in human aortic endothelial cell monolayers. The HDL antioxidant properties were measured using a cell-free assay that uses dichlorofluorescein diacetate. Oxidized fatty acids in HDLs were measured by liquid chromatography-tandem mass spectrometry. In subgroups of patients and control subjects, the HDL inflammatory index was repeated after incubation with L-4F.ResultsThe HDL inflammatory index was 1.42 ± 0.29 in T2D patients and 0.70 ± 0.19 in control subjects (P < 0.001). The cell-free assay was impaired in T2D patients compared with control subjects (2.03 ± 1.35 vs. 1.60 ± 0.80, P < 0.05), and also HDL intrinsic oxidation (cell-free assay without LDL) was higher in T2D patients (1,708 ± 739 vs. 1,233 ± 601 relative fluorescence units, P < 0.001). All measured oxidized fatty acids were significantly higher in the HDLs of T2D patients. There was a significant correlation between the cell-free assay values and the content of oxidized fatty acids in HDL fractions. L-4F treatment restored the HDL inflammatory index in diabetic plasma samples (from 1.26 ± 0.17 to 0.71 ± 0.11, P < 0.001) and marginally affected it in healthy subjects (from 0.81 ± 0.16 to 0.66 ± 0.10, P < 0.05).ConclusionsIn patients with T2D, the content of oxidized fatty acids is increased and the anti-inflammatory and antioxidant activities of HDLs are impaired

Hepatitis C Virus Infection: Evidence for an Association With Type 2 Diabetes: Response to Skowroński et al.

We agree with Skowronski et al. (1) that the type of diabetes manifested by patients with HCV chronic infection (HCV+) may not be classical type 2 diabetes, and the phenotypic characterization of our patients shows just that. The labeling of HCV+ patients as type 2 diabetes is purely conventional and possibly inaccurate: the lines separating type 1 diabetes, from latent autoimmune diabetes in

Hepatitis C Virus Infection: Evidence for an Association With Type 2 Diabetes

An increased prevalence of type 2 diabetes and impaired glucose tolerance has been consistently found in liver cirrhosis from any cause (1–3). Less clear is whether hepatitis C virus (HCV) infection is associated with type 2 diabetes in the absence of cirrhosis. Several reports have claimed a specific association between HCV infection and type 2 diabetes, but in most instances, patients were a mixture of cases with cirrhosis and hepatitis (4–6). Two clinic-based studies found an excess of type 2 diabetes in noncirrhotic HCV+ (NC-HCV+) patients compared with patients with chronic hepatitis of other origin (7–9), but another large study could not detect it (10). Furthermore, one clinic-based small study found a specific association with type 2 diabetes in NC-HCV+ patients (11) compared with a general population sample. The aim of this study was to establish the prevalence and clinical phenotype of type 2 diabetes in a large series of NC-HCV+ patients. A sample of the general population or patients with hepatitis B virus (HBV)-related noncirrhotic chronic hepatitis (NC-HBV+) was used as control subjects. From January 1995 to December 2001, 564 NC-HCV+ patients were consecutively examined at our center (none had been previously treated with interferon). Diagnosis of HCV infection was based on abnormal serum aminotransferases levels of >6 months' duration and positive testing for serum anti-HCV markers and

Impact of Treatment on Islet Function in Type 2 Diabetes

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