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

Metabolomic profile predicts development of microalbuminuria in individuals with type 1 diabetes

Elevated urinary albumin excretion (microalbuminuria) is an early marker of diabetic nephropathy, but there is an unmet need for better biomarkers that capture the individuals at risk with higher accuracy and earlier than the current markers do. We performed an untargeted metabolomic study to assess baseline differences between individuals with type 1 diabetes who either developed microalbuminuria or remained normoalbuminuric. A total of 102 individuals progressed to microalbuminuria during a median follow-up of 3.2 years, whereas 98 sex-, age- and body mass index (BMI) matched nonprogressors remained normoalbuminuric during a median follow-up of 7.1 years. Metabolomic screening identified 1,242 metabolites, out of which 111 differed significantly between progressors and non-progressors after adjustment for age of diabetes onset, baseline glycosylated hemoglobin A1c (HbA(1c)), and albumin excretion rate (AER). The metabolites that predicted development of microalbumiuria included several uremic toxins and carnitine metabolism related molecules. Iterative variable selection indicated erythritol, 3-phenylpropionate, and N-trimethyl-5-aminovalerate as the best set of variables to predict development of microalbuminuria. A metabolomic index based on these metabolites improved the prediction of incident microalbuminuria on top of the clinical variables age of diabetes onset, baseline HbA1c and AER (ROCAUC = 0.842 vs 0.797), highlighting their ability to predict early-phase diabetic nephropathy.Peer reviewe

Differential metabolomic signatures of declining renal function in Types 1 and 2 diabetes

Publisher Copyright: © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.Background: Chronic kidney disease (CKD) shows different clinical features in Types1 (T1D) and 2 diabetes (T2D). Metabolomics have recently provided useful contribution to the identification of biomarkers of CKD progression in either form of the disease. However, no studies have so far compared plasma metabolomics between T1D and T2D in order to identify differential signatures of progression of estimated glomerular filtration rate (eGFR) decline. Methods: We used two large cohorts of T1D (from Finland) and T2D (from Italy) patients followed up to 7 and 3 years, respectively. In both groups, progression was defined as the top quartile of yearly decline in eGFR. Pooled data from the two groups were analysed by univariate and bivariate random forest (RF), and confirmed by bivariate partial least squares (PLS) analysis, the response variables being type of diabetes and eGFR progression. Results: In progressors, yearly eGFR loss was significantly larger in T2D [-5.3 (3.0), median (interquartile range)mL/min/1.73 m2/year] than T1D [-3.7 (3.1) mL/min/1.73 m2/year; P = 0.018]. Out of several hundreds, bivariate RF extracted 22 metabolites associated with diabetes type (all higher in T1D than T2D except for 5-methylthioadenosine, pyruvate and β-hydroxypyruvate) and 13 molecules associated with eGFR progression (all higher in progressors than non-progressors except for sphyngomyelin). Three of the selected metabolites (histidylphenylalanine, leucylphenylalanine, tryptophylasparagine) showed a significant interaction between disease type and progression. Only eight metabolites were common to both bivariate RF and PLS. Conclusions: Identification of metabolomic signatures of CKD progression is partially dependent on the statistical model. Dual analysis identified molecules specifically associated with progressive renal impairment in both T1D and T2D.Peer reviewe

GLP-1 and glucose tolerance after sleeve gastrectomy in morbidly obese subjects with type 2 diabetes.

Although GLP-1 has been suggested as a major factor for the marked improvement of glucose tolerance commonly seen after sleeve gastrectomy (SG), several observations challenge this hypothesis. To better understand the role of GLP-1 in the remission of type 2 diabetes mellitus (T2DM) long term after SG in humans, we conducted two separate cross-sectional studies: 1) the GLP-1 response to a standardized mixed liquid meal (SMLM) was compared in subjects with T2DM antedating SG but with different long-term (>2 years) T2DM outcomes (remission, relapse, or lack of remission) (study 1) and 2) the effect of GLP-1 receptor blockade with exendin (9-39) on glucose tolerance was examined in subjects with T2DM antedating surgery, who had undergone SG and presented with long-term T2DM remission (study 2). In study 1, we observed a comparable GLP-1 response to the SMLM regardless of the post-SG outcome of T2DM. In study 2, the blockade of GLP-1 action resulted in impaired insulin secretion but limited deterioration of glucose tolerance. Thus, our data suggest the enhanced GLP-1 secretion observed long term after SG is neither sufficient nor critical to maintain normal glucose tolerance in subjects with T2DM antedating the surgery