Polymorphism of the FTO Gene Influences Body Weight in Children with Type 1 Diabetes without Severe Obesity

The objective was to compare the impact of clinical and genetic factors on body mass index (BMI) in children with type 1 diabetes (T1DM) without severe obesity. A total of 1,119 children with T1DM (aged 4-18 years) were qualified to take part in the study. All children were genotyped for variants of FTO, MC4R, INSIG2, FASN, NPC1, PTER, SIRT1, MAF, IRT1, and CD36. Results. Variants of FTO showed significant association with BMI-SDS in the T1DM group. The main factors influencing BMI-SDS in children with T1DM included female gender ( = 0.0003), poor metabolic control ( = 0.0001), and carriage of the A allele of the FTO rs9939609 gene ( = 0.02). Conclusion. Our research indicates, when assessing, the risk of overweight and obesity carriage of the A allele in the rs9939609 site of the FTO gene adds to that of female gender and poor metabolic control. This trial is registered with ClinicalTrials.gov (NCT01279161)

Visfatin in juvenile obesity - the effect of obesity intervention and sex

Background The association of visfatin, an adipocytokine relevant to the development of inflammation and metabolic disorders, with juvenile obesity needs to be re-established as previously used tests occurred to be nonspecific. Objective To evaluate visfatin association with a metabolic profile of 88 overweight / obese and 26 lean children / adolescents as well as changes in its levels following weight reduction programme (diet + enhanced physical activity +/- metformin). Design A case-control and cohort study. Results Visfatin was higher in obese than lean and overweight individuals (2 07 vs. 1 53 and 1 47 ng mL) 1, P = 0 034). Of metabolic syndrome components, central obesity combined with either insulin resistance (IR) or hyperinsulinemia (HI) was associated with increases in circulating visfatin. In girls, visfatin correlated with leptin (r = 0 40, P = 0 009) and thiols (r =) 0 36, P = 0 009), which explained 24% in visfatin variability. In boys, visfatin correlated with waist circumference (r = 0 36, P = 0 036), BMI% (r = 0 38, P = 0 025), whole body insulin sensitivity index (r =) 0 36, P = 0 036), IL-6 (r = 0 38, P = 0 024) and thiobarbituric acid reactive substances (TBARS) (r = 0 52, P = 0 001), of which IL-6 and TBARS were independent predictors of visfatin elevation, explaining 42% in data variability. Visfatin was significantly lower following weight reduction programme than at baseline (1 43 vs. 1 83 ng mL) 1, P = 0 033). Visfatin reduction correlated neither with changes in metabolic parameters nor was it affected by metformin. DVisfatin correlated exclusively with baseline visfatin (r = 0 612, P <0 0001), which explained 38% in data variability. Conclusions Central obesity combined with HI / IR contributes to visfatin elevation. Visfatin association with metabolic / biochemical variables is gender dependent. Diet + enhanced physical activity are effective in visfatin reduction, the degree of which depends on baseline visfati

The broad phenotypic spectrum of 17α-hydroxylase/ 17,20-lyase (CYP17A1) deficiency: a case series.

CONTEXT 17α-hydroxylase/17,20-lyase deficiency (17OHD) caused by mutations in the CYP17A1 gene is a rare form of congenital adrenal hyperplasia typically characterized by cortisol deficiency, mineralocorticoid excess and sex steroid deficiency. OBJECTIVE To examine the phenotypic spectrum of 17OHD by clinical and biochemical assessment and corresponding in silico and in vitro functional analysis. DESIGN Case series Patients and Results: We assessed eight patients with 17OHD, including four with extreme 17OHD phenotypes: two siblings presented with failure to thrive in early infancy and two with isolated sex steroid deficiency and normal cortisol reserve. Diagnosis was established by mass spectrometry-based urinary steroid profiling and confirmed by genetic CYP17A1 analysis, revealing homozygous and compound heterozygous sequence variants. We found novel (p.Gly111Val, p.Ala398Glu, p.Ile371Thr), and previously described sequence variants (p.Pro409Leu, p.Arg347His, p.Gly436Arg, p.Phe53/54del, p.Tyr60IlefsLys88X). In vitro functional studies employing an overexpression system in HEK293 cells showed that 17,20-lyase activity was invariably decreased while mutant 17α-hydroxylase activity retained up to 14% of wild-type activity in the two patients with intact cortisol reserve. A ratio of urinary corticosterone over cortisol metabolites reflective of 17α-hydroxylase activity correlated well with clinical phenotype severity. CONCLUSION Our findings illustrate the broad phenotypic spectrum of 17OHD. Isolated sex steroid deficiency with normal stimulated cortisol have not been reported before. Attenuation of 17α-hydroxylase activity is readily detected by urinary steroid profiling and predicts phenotype severity