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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]

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]

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]