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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. [ABSTRACT FROM AUTHOR]

Aims: Due to their different chemical structures and metabolism, polyphenol subclasses may have specific impact on cardiometabolic risk factors. Our aim was to evaluate whether the intake of different polyphenol subclasses is associated with clinical outcomes beneficially improved by polyphenols in a nutritional trial performed by our group (postprandial lipid response, glucose homeostasis, early insulin secretion and oxidative stress).Methods: The present study is a secondary analysis of a nutritional intervention study with a diet naturally rich in polyphenols. The data are derived from 78 participants at high cardiovascular risk who completed the ETHERPATH trial. The associations between variations in polyphenol subclasses (phenolic acids, anthocyanidins, flavones, flavan-3-ols, flavonols and flavanones) and clinical outcomes beneficially influenced by polyphenols were firstly explored by Spearman’s correlation. Thereafter, adjustment for gender, age and body mass index (BMI) was run. Linear regression analysis was used to assess the class of polyphenols that best predicted the outcome. Results: Flavanone intake was inversely correlated with postprandial lipid response, whereas flavone intake was related to postchallenge glucose response. Anthocyanidins and flavan-3-ols associated positively with early insulin secretion. The decrease in urinary isoprostanes correlated with anthocyanidins, flavan-3-ols and flavonols. Correlations did not change after adjustment for gender, age, and BMI. Linear regression analysis showed an independent association between flavonols and urinary isoprostanes, whereas early insulin secretion was mainly associated with flavan-3-ols intake. Conclusions: The results of this study show that a polyphenol-rich diet may have a pleiotropic effect on cardiometabolic risk factors thanks to the specific action of different polyphenol subclasses. [ABSTRACT FROM AUTHOR]

Background Mucopolysaccharidoses ( MPS) are inherited lysosomal storage disorders caused by deficiency of required glycosaminoglycans breakdown enzymes, inducing cardiac involvement. Little is known about myocardial deformation involvement in MPS. Our aim was to assess biventricular structure and function in asymptomatic children with MPS using standard echo Doppler and 2D speckle tracking ( STE). Methods Fifteen MPS children (one type I, six type II, three type III A, one III B, three IV A, one VI), asymptomatic for cardiac symptoms, and 15 age and sex-matched healthy controls underwent echo Doppler and STE. Left ventricular ( LV) wall thicknesses, diameters, and mass were normalized by z-score. LV global longitudinal strain ( GLS), global circumferential strain ( GCS), global radial strain ( GRS) at papillary muscles, LV twisting, and right ventricular ( RV) GLS were measured. Results The two groups were comparable for body mass index, heart rate, and blood pressure. LV mass index and relative wall thickness were higher in MPS. Ejection fraction (EF), and s′ velocity did not differ between the two groups. E/A ratio was lower and E/e′ higher in MPS. Tricuspid annular plane systolic excursion, RV s′ and e′ were lower in MPS. LV GLS did not differ between the two groups, but GCS ( P=.014), GRS ( P=.023), twisting ( P=.012), and RV GLS ( P<.001) were lower in the MPS group. Conclusions LV strain abnormalities are detectable in MPS pediatric patients, independently of MPS type, when EF is still normal. RV GLS is also involved consensually with TAPSE reduction. STE can be useful for detection of subclinical myocardial damage in MPS. [ABSTRACT FROM AUTHOR]

Background: The role of thyrotropin (TSH) on the cardiovascular system has been poorly investigated. It is unknown whether the changes in the vasculature associated with thyroid diseases result from altered thyroid hormone action or whether they are a consequence of a direct effect of TSH on endothelial cells. The present study was designed to evaluate the endothelial response of coronary flow to TSH in patients with differentiated thyroid cancer (DTC) without cardiovascular risk factors. Methods: The study population consisted of threemen and seven women (Mage = 32.6 - 8 years) who underwent total thyroidectomy for DTC. All were receiving therapy with L-thyroxine tomaintain TSH within the reference range. No patient was obese, or had hypertension, diabetes, or dyslipidemia. Patients underwent standard echo-Doppler examination with evaluation of the coronary flow reserve (CFR) of the distal left anterior descending artery obtained by cold pressure test (CPT) before and 24 h after the second recombinant human TSH (rhTSH) injection. Results: Left ventricularmorphology and systolic and diastolic function were normal in all patients. Levels of thyroid hormones and thyroglobulin and antithyroglobulin antibodies did not differ significantly pre- versus post-rhTSH treatment, whereas TSH levels were higher after rhTSH administration. Blood pressure and heart rate were not affected by rhTSH. Coronary flow peak velocity at rest (22.3 -6 vs 23.2- 8.7; p = 0.66) did not differ between baseline and 24 h after rhTSH, while post-CPT velocity (29.3 - 6.8 vs 34.4 - 10.9; p < 0.05) and the CFR were higher after rhTSH administration (1.32 - 0.2 vs. 1.53 - 0.2; p < 0.01). Conclusions: rhTSH administration may improve the CFR after the non-pharmacological stressor CPT in DTC patients. The increase of coronary blood flow after rhTSH suggests that TSH may exert a protective effect on the coronary endothelium. [ABSTRACT FROM AUTHOR]

We show the long-term efficacy and safety of modified biliopancreatic diversion for the treatment of LPL-deficiency. How this option compares with gene therapy is difficult to evaluate due to limited experience. Surgery may be the first option in patients in whom medical therapy is ineffective and gene therapy not applicable. [ABSTRACT FROM AUTHOR]

Aim/hypothesis: Dietary polyphenols and long chain n-3 polyunsaturated fatty acids (LCn3) are associated with lower cardiovascular risk. This may relate to their influence on glucose metabolism and diabetes risk. We evaluated the effects of diets naturally rich in polyphenols and/or LCn3 of marine origin on glucose metabolism in people at high cardiometabolic risk. Methods: According to a 2 × 2 factorial design, individuals with high waist circumference and at least one more component of the metabolic syndrome were recruited at the obesity outpatient clinic. Eighty-six participants were randomly assigned by MINIM software to an isoenergetic diet: (1) control, low in LCn3 and polyphenol (analysed n = 20); (2) rich in LCn3 ( n = 19); (3) rich in polyphenols ( n = 19); or (4) rich in LCn3 and polyphenols ( n = 19). The assigned diets were known for the participants and blinded for people doing measurements. Before and after the 8 week intervention, participants underwent a 3 h OGTT and a test meal with a similar composition as the assigned diet for the evaluation of plasma glucose, insulin and glucagon-like peptide 1 (GLP-1) concentrations, and indices of insulin sensitivity and beta cell function. Results: During OGTT, polyphenols significantly reduced plasma glucose total AUC ( p = 0.038) and increased early insulin secretion ( p = 0.048), while LCn3 significantly reduced beta cell function ( p = 0.031) (two-factor ANOVA). Moreover, polyphenols improved post-challenge oral glucose insulin sensitivity (OGIS; p = 0.05 vs control diet by post hoc ANOVA). At test meal, LCn3 significantly reduced GLP-1 total postprandial AUC ( p < 0.001; two-factor ANOVA). Conclusion/interpretation: Diets naturally rich in polyphenols reduce blood glucose response, likely by increasing early insulin secretion and insulin sensitivity. These effects may favourably influence diabetes and cardiovascular risk. The implications of the decrease in insulin secretion and postprandial GLP-1 observed with diets rich in marine LCn3 need further clarification. Trial registration: ClinicalTrials.gov NCT01154478 Funding: The trial was funded by European Community's Seventh Framework Programme FP7/2009-2012 under grant agreement FP7-KBBE-222639, Etherpaths Project and 'Ministero Istruzione Università e Ricerca' PRIN 2010-2011 - 2010JCWWKM. [ABSTRACT FROM AUTHOR]

Objective: Cross-sectional studies suggest the association between diabetic nephropathy and the PPARγ2 Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 (PPARγ2). Prospective data are limited to microalbuminuria and no information on renal function is available to date. The present study evaluates the association between the Pro12Ala polymorphism of PPARγ2 and the progression of albuminuria and decay in glomerular filtration rate (GFR) in type 2 diabetes. Patients and measurements: We studied 256 patients with an average 5-year follow-up. Among others, urinary albumin excretion rate (UAER) was measured on spot sample, GFR was estimated with the CKD-EPI Equation. Results: Baseline UAER and GFR were similar for carriers or non-carriers of the polymorphism. At follow-up no significant changes from baseline were observed for UAER or eGFR in carriers of the Pro12Ala polymorphism whereas a significant increase in UAER [17 (11.3-37.9) versus 24.5 (13.8-49.9) μg/mg, p < 0.006)] and a significant reduction in the eGFR (82.8 ± 14.5 versus 80.3 ± 17.3 ml/min/1.73, m2 p = 0.02), were observed in non carriers of the Pro12Ala polymorphism. Progression of nephropathy - defined according to a combined end point of UAER and eGFR- i.e. doubling of baseline UAER to at least 100 μg/mg, or new onset microalbuminuria, or progression from micro to macroalbuminuria, or 25% reduction of eGFR, or annualized eGFR decline >3 ml/min/year - was significantly less frequent in Ala carriers than non carriers (11.4% vs 35.8%; p < 0.01); HR adjusted for baseline age, AER, eGFR, HbA1c, diabetes duration and blood pressure was 0.32 (0.12-0.80). Conclusions: This study found that among patients with type 2 diabetes, the PPARγ2 Pro12Ala polymorphism is protective against progression of nephropathy and decay of renal function independent of major confounders. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Peroxisome Proliferator-Activated Receptor ϒ Polymorphism Pro 12Ala Is Associated With Nephropathy in Type 2 Diabetes: Evidence From Meta-Analysis of 18 Studies," by H. Zhang and colleagues, published in a 2012 issue of the journal.