Glucose lowering strategies and cardiovascular disease in type 2 diabetes – teachings from the TOSCA.IT study

TOSCA.IT is an institutional, non-industry-supported, head-to-head study comparing long term cardiovascular effects, efficacy and safety of two antidiabetes drugs (pioglitazone vs sulphonylureas) used in combination with metformin in patients with type 2 diabetes mellitus. The study results show that in the absence of clinically evident cardiovascular disease both treatment strategies represent suitable alternatives; however, in consideration of the greater durability of the metabolic effects, the lower risk of hypoglycemia and the potential benefit on atherosclerotic cardiovascular disease, the combination of metformin and pioglitazone may be considered as the preferential therapeutic option. In this review the study is critically evaluated against the background of the evidence accumulated over the last decade on the impact of different glucose lowering drugs on cardiovascular events in people with type 2 diabetes

Association between Diet Quality and Index of Non-Alcoholic Steatohepatitis in a Large Population of People with Type 2 Diabetes: Data from the TOSCA.IT Study

Background: There are still open questions with respect to the optimal dietary treatment in patients with type 2 diabetes (T2D) and coexisting non-alcoholic steatohepatitis (NASH). The aim of this study is to investigate, in patients with T2D, the association between NASH, dietary component intake, food groups and adherence to the Mediterranean diet. Methods: Cross-sectional analysis of 2026 people with T2D (1136 men and 890 women). The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. NASH was identified by the Index Of NASH (ION). Based on the cluster analysis two dietary patterns were identified: the NASH and the NO-NASH pattern. Results: The macronutrient composition of the diet was similar in the two patterns. However, the NASH pattern compared with the NO-NASH pattern was characterized by a significantly lower content of fibre (p < 0.001), β-carotene (p < 0.001), vitamin C (p < 0.001), vitamin E (p < 0.001), polyphenols (p = 0.026) and antioxidant capacity (p < 0.001). With regard to food consumption, the NASH pattern compared with NO-NASH pattern was characterized by higher intake of rice (p = 0.021), potatoes (p = 0.013), red (p = 0.004) and processed meat (p = 0.003), and a lower intake of wholegrain bread (p = 0.019), legumes and nuts (p = 0.049), vegetables (p = 0.047), fruits (p = 0.002), white meat (p = 0.001), fatty fish (p = 0.005), milk and yogurt (p < 0.001). Conclusions: NO-NASH dietary pattern was characterized by a food consumption close to the Mediterranean dietary model, resulting in a higher content of polyphenols, vitamins, and fibre. These finding highlight the potential for dietary components in the prevention/treatment of NASH in people with T2D

Development and analytical performance of an automated screening method for cannabinoids on the Dimension clinical chemistry system

A fully automated, random access method for the determination of cannabinoids (UTHC) was developed for the Dimension AR and XL clinical chemistry systems. The method utilizes Abuscreen ONLINE reagents and a multianalyte liquid calibrator containing 11-nor-Δ9-THC-9-carboxylic acid. Within-run and total reproducibility, determined using NCCLS protocol EP5- T2, was less than 0.6% and 1.6% CV, respectively, at all concentrations. Calibration stability was retained for at least 30 days. An extensive evaluation of non-structurally related drugs and various physiological substances indicated lack of interference in the method. No sample carry-over was observed following a specimen containing 1886 ng/ml 11-nor-Δ9-THC-9-carboxylic acid. A 99.1% agreement (N = 445 samples) was found between an EMIT based method on the aca discrete clinical analyser and the Dimension UTHC method

Pasta consumption and connected dietary habits: Associations with glucose control, adiposity measures, and cardiovascular risk factors in people with type 2 diabetes—TOSCA.IT study

Background: Pasta is a refined carbohydrate with a low glycemic index. Whether pasta shares the metabolic advantages of other low glycemic index foods has not really been investigated. The aim of this study is to document, in people with type-2 diabetes, the consumption of pasta, the connected dietary habits, and the association with glucose control, measures of adiposity, and major cardiovascular risk factors. Methods: We studied 2562 participants. The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. Sex-specific quartiles of pasta consumption were created in order to explore the study aims. Results: A higher pasta consumption was associated with a lower intake of proteins, total and saturated fat, cholesterol, added sugar, and fiber. Glucose control, body mass index, prevalence of obesity, and visceral obesity were not significantly different across the quartiles of pasta intake. No relation was found with LDL cholesterol and triglycerides, but there was an inverse relation with HDL-cholesterol. Systolic blood pressure increased with pasta consumption; but this relation was not confirmed after correction for confounders. Conclusions: In people with type-2 diabetes, the consumption of pasta, within the limits recommended for total carbohydrates intake, is not associated with worsening of glucose control, measures of adiposity, and major cardiovascular risk factors

The Pro12Ala polymorphism of PPARγ2 modulates beta cell function and failure to oral glucose-lowering drugs in patients with type 2 diabetes

Background: We evaluate whether the Pro12Ala polymorphism of peroxisome proliferator-activated receptor γ2 (PPARγ2) has a role in the progression of diabetes by modulating the occurrence of treatment failure to glucose-lowering drugs. Methods: We studied 215 patients with type 2 diabetes participating in the Thiazolidinediones Or Sulphonylureas and Cardiovascular Accidents Intervention Trial study. All participants were insufficiently controlled (glycated haemoglobin [HbA1c] 7.0%-9.0%) with metformin 2 g/day and were randomly allocated to add-on pioglitazone or a sulfonylurea. Treatment failure was defined as HbA1c ≥8% on two consecutive visits, 3 months apart. Results: Carriers or non-carriers of the polymorphism had similar age, body mass index, and diabetes duration. Ala carriers had lower fasting plasma insulin, better insulin sensitivity (Homeostasis Model Assessment [HOMA]2-%S), and worse beta cell secretion (HOMA2-%B) than non-carriers. During 24 months of follow-up, 32.5% among the Ala carriers and 8.6% among non-carriers (P < 0.001) developed treatment failure with a cumulative incidence of 18.6 vs 4.6/100 person-years. Those patients who developed treatment failure were older, had a younger age at diabetes diagnosis (48 ± 10 vs 52 ± 7 years; P = 0.032), higher HbA1c (8.1 ± 0.5 vs 7.7 ± 0.5%; P < 0.001), and lower HOMA2-%B (30 ± 12 vs 46 ± 29; P = 0.015) at study entry, as compared to those who did not develop treatment failure. At multivariate analysis, the Pro12Ala polymorphism was significantly associated with treatment failure (hazard ratio [HR] 4.45; 95% confidence interval [CI] 1.79-11.1; P < 0.001); HbA1c at study entry was the other independent predictor of failure in this study population. Conclusion: The Pro12Ala polymorphism is associated with a greater insulin sensitivity, reduced beta cell function and a substantially increased risk of treatment failure

Structural characterization of the Xi class glutathione transferase from the haloalkaliphilic archaeon Natrialba magadii

Xi class glutathione transferases (GSTs) are a recently identified group, within this large superfamily of enzymes, specifically endowed with glutathione-dependent reductase activity on glutathionyl-hydroquinone. Enzymes belonging to this group are widely distributed in bacteria, fungi, and plants but not in higher eukaryotes. Xi class GSTs are also frequently found in archaea and here we focus on the enzyme produced by the extreme haloalkaliphilic archaeon Natrialba magadii (NmGHR). We investigated its function and stability and determined its 3D structure in the apo form by X-ray crystallography. NmGHR displays the same fold of its mesophilic counterparts, is enriched in negatively charged residues, which are evenly distributed along the surface of the protein, and is characterized by a peculiar distribution of hydrophobic residues. A distinctive feature of haloalkaliphilic archaea is their preference for γ-glutamyl-cysteine over glutathione as a reducing thiol. Indeed we found that the N. magadii genome lacks a gene coding for glutathione synthase. Analysis of NmGHR structure suggests that the thiol binding site (G-site) of the enzyme is well suited for hosting γ-glutamyl-cysteine

Evaluation of cardiovascular risk in adults with type 1 diabetes: Poor concordance between the 2019 ESC risk classification and 10-year cardiovascular risk prediction according to the Steno Type 1 Risk Engine

Background: Patients with type 1 diabetes (T1D) have higher mortality risk compared to the general population; this is largely due to increased rates of cardiovascular disease (CVD). As accurate CVD risk stratification is essential for an appropriate preventive strategy, we aimed to evaluate the concordance between 2019 European Society of Cardiology (ESC) CVD risk classification and the 10-year CVD risk prediction according to the Steno Type 1 Risk Engine (ST1RE) in adults with T1D. Methods: A cohort of 575 adults with T1D (272F/303M, mean age 36 ± 12 years) were studied. Patients were stratified in different CVD risk categories according to ESC criteria and the 10-year CVD risk prediction was estimated with ST1RE within each category. Results: Men had higher BMI, WC, SBP than women, while no difference was found in HbA1c levels between genders. According to the ESC classification, 92.5% of patients aged 20 years) alone identified few patients (< 30%) among those aged ≥35 years, who were at very high risk according to ESC, in whom this condition was confirmed by ST1RE; conversely, the coexistence of two or more of these criteria identified about half of the patients at high/very high risk also according to this predicting algorithm. When only patients aged ≥ 50 years were considered, there was greater concordance between ESC classification and ST1RE prediction, since as many as 78% of those at high/very high risk according to ESC were confirmed as such also by ST1RE. Conclusions: Using ESC criteria, a large proportion (45%) of T1D patients without CVD are classified at very high CVD risk; however, among them, none of those < 35 years and only 12% of those ≥ 35 years could be confirmed at very high CVD risk by the ST1RE predicting algorithm. More studies are needed to characterize the clinical and metabolic features of T1D patients that identify those at very high CVD risk, in whom a very aggressive cardioprotective treatment would be justified