Background Previous genome-wide association studies (GWAS) identified IGF1, IRS1, GCKR, PPARG, GCK1 and KCTD1 as candidate genes for insulin resistance and type 2 diabetes (T2D). We investigated the associations of these previously reported common variants in these genes with insulin resistance in overweight children from Romania and Moldova. Methods Six single nucleotide polymorphisms (SNPs), IGF1 (rs35767), IRS1 (rs2943634), GCKR (rs780094), PPARG (rs1801282), GCK1 (rs1799884) and KCTD15 (rs29941), were genotyped in 100 overweight children along with clinical and metabolic parameters. Homeostatic model assessment of insulin resistance (HOMA-IR) above 3.4 (defining insulin resistance) was used as the outcome. Results Children differed in insulin resistance status despite having similar body mass index (BMI) standard deviation scores (SDS) (World Health Organization, [WHO] reference). The identified predictors for altered insulin metabolism were higher cholesterol levels, higher diastolic blood pressure and higher waist-to-hip-ratio (as a marker for increased abdominal fat). None of the SNPs showed significant association with increase in the risk for insulin resistance in children (p range=0.478–0.724; odds ratio [OR] range=1.924–4.842); however, the risk allele in GCKR (rs780094, p=0.06, OR=6.871) demonstrated near statistical significance. Conclusions The interrogated risk alleles did not show any significant association with insulin resistance in children in our cohort; however, the GCKR (rs780094) might be a viable candidate in larger cohorts. The lack of replication of the proposed association may point to differences in linkage disequilibrium or effect modifiers across studies.

Background: Cardiomyopathy (CM) associated with Duchenne muscular dystrophy (DMD) is a commonly recognized appearance of this neuromuscular disease, significantly increased morbidity and mortality, as well as the necessity for cardiological management. CM in DMD is defined by left ventricular (LV) systolic dysfunction and both atrial and ventricular dysrhythmias and is associated with higher mortality than other cases of pediatric dilated CMs. Notwithstanding the high rate of cardiac involvement, patients are usually asymptomatic despite significant LV dysfunction, because of likely poor mobility that masks the usual heart failure (HF) symptoms. Also, imagistic predictors are provided to be very helpful in defining early LV dysfunction, especially electrocardiogram and cardiac imaging (transthoracic echocardiography, speckle-tracking, cardiac magnetic resonance) are used to detect the onset and progression of dilated cardiomyopathy (DCM) in DMD. Conclusions: As most DMD patients are asymptomatic for a long time of their life, so identifying predictors of HF is crucial to support these patients. Ventricular dysfunction based on the ejection fraction (EF) measurement helps to choose therapy. In the case of early DCM (LVEF≥50%) the great purpose is to prevent ventricular dysfunction incipience with first-line HF therapy with Angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARBs). Current guidelines recommend the use of conventional HF medication in case of disease progression and DCM with MidRange Reduction of LV EF (40-49%). The therapeutic approach for patients with DCM and severe ventricular dysfunction (<40%) has been studied less profoundly and contemporary guidelines recommend all drugs used for HF treatment

No abstract

No abstract

Objective: Introduction: Duchenne muscular dystrophy (DMD) is one of many neuromuscular diseases, that commonly creates severe disability and early death. Cardiomyopathy associated with DMD is an increasingly acknowledged presentation of this neuromuscular disorder, significantly increasing morbidity and mortality, as well as the requirement for cardiological treatment. Design and method: Purpose: is to review literature data relatively the presence of elevated blood pressure values and body mass index in children with DMD and their impact on the development of heart disease. Results: Several studies have published cross-sectional data about the prevalence of hypertension and increased BMI in children with DMD. Wong et al., 2017 reported that 25.5% of patients on daily steroids aged 10–13 years had systolic hypertension. In patients aged 13–16 years, they reported systolic hypertension in 10.3% of patients. Corticosteroid treatment is thus an essential part of the standards of care in DMD and is recommended from the age of 4 to 5 years onward. Ricotti et al., 2013 observed hypertension in 5% of the patients aged 3–15 years on intermittent steroids while in a study by Braat et al., 2015, 45% of the patients had hypertension. In N.M. van de Velde et al., 2019, study increased BMI, but not systolic blood pressure, was related to early myocardial deformation defined by peak systolic GLS in young DMD patients < 11 years of age. Prevalence of obesity has been described up to 73% in steroid-native DMD patients < 13 years and higher BMI was associated with longer duration and higher cumulative dose in ambulant DMD patients using prednisone (Lamb et al., 2016). In Barber et al. study, 2013 use of corticosteroids has managed to prolongation of the ambulant stage in DMD by almost 3 years. It has also been correlated with a delayed onset of dystrophinic cardiomyopathy in Markham et al., 2008 and Davidson et al., 2014 studies. Conclusions: The results of this review suggest that factors influencing afterload, such as increased blood pressure and BMI, may play a role in the deterioration of cardiac function in DMD.