The Oscillometric Pulse Wave Analysis Is Useful in Evaluating the Arterial Stiffness of Obese Children with Relevant Cardiometabolic Risks.

Early detection of all complications of childhood obesity is imperative in order to minimize effects. Obesity causes vascular disruptions, including early increased arterial stiffness and high blood pressure. This study's aim is to assess the reliability of pulse wave analysis (PWA) in obese children and how additional risk factors influence the evaluated parameters. We analyzed 55 children aged 6-18 years old by measuring their pulse wave velocity (PWV), augmentation index (AIx), peripheral blood pressure (SBP, DBP), heart rate, central blood pressure (cSBP, cDBP) and central pulse pressure (cPP). We used the oscillometric IEM Mobil-O-Graph and performed a single-point brachial measurement. The subjects were divided into two groups: obese (n = 30) and normal-weight (n = 25) and were clinically and anamnestically assessed. BMI and waist circumference are significantly correlated to higher values for PWV, SBP, DBP, cSBP, and cDBP. Weight significantly predicts PWV, SBP, DBP and cPP. The risk factors that significantly influence the PWA and BP values are: a cardiometabolically risky pregnancy (higher PWV, AIx, SBP), active and passive smoking (higher PWV, SBP, cSBP, cDBP), sleep deprivation (higher PWV, SBP, cSBP) and sedentariness (higher PWV, AIx, peripheral and central BP). We conclude that obese children with specific additional cardiometabolic risk factors present increased arterial stiffness and higher blood pressure values.

CHDH-PNPLA3 Gene-Gene Interactions Predict Insulin Resistance in Children with Obesity.

INTRODUCTION: Insulin resistance plays a major role in metabolic syndrome and is recognized as the most common risk factor for non-alcoholic fatty liver disease (NAFLD). Identifying predictors for insulin resistance could optimize screening and prevention. PURPOSE: To evaluate the contribution of multiple single nucleotide polymorphisms across genes related to NAFLD and choline metabolism, in predicting insulin resistance in children with obesity. METHODS: One hundred fifty-three children with obesity (73 girls), aged 7-18 years, were evaluated within the NutriGen Study (ClinicalTrials.gov-NCT02837367). Insulin resistance was defined by Homeostatic Model Assessment for insulin-resistance cut-offs that accommodated pubertal and gender differences. Anthropometric, metabolic, intake-related variables, and 55 single nucleotide polymorphisms related to NAFLD and choline metabolism were evaluated. Gene-gene interaction effects were assessed using Multiple Data Reduction Software. RESULTS: Sixty percent (93/153) of participants showed insulin resistance (58.7% of boys, 63% of girls). Children with insulin resistance presented significantly higher values for standardized body mass index, triglycerides, transaminases and plasma choline when compared to those without insulin resistance. Out of 52 single nucleotide polymorphisms analysed, the interaction between genotypes CHDH(rs12676) and PNPLA3(rs738409) predicted insulin resistance. The model presented a 6/10 cross-validation consistency and 0.58 testing accuracy. Plasma choline levels and alanine aminotransferase modulated the gene interaction effect, significantly improving the model. CONCLUSION: The interaction between genotypes in CHDH and PNPLA3 genes, modulated by choline and alanine aminotransferase levels, predicted insulin-resistance status in children with obesity. If replicated in larger cohorts, these findings could help identify metabolic risk in children with obesity.

Single Nucleotide Polymorphisms in PEMT and MTHFR Genes are Associated with Omega 3 and 6 Fatty Acid Levels in the Red Blood Cells of Children with Obesity.

Polyunsaturated fatty acids (PUFAs) play important roles in health and disease. PUFA levels are influenced by nutrition and genetic factors. The relationship between PUFA composition in red blood cells (RBCs) and genetic variations involved in PUFA metabolism has not been investigated in children with obesity. This study evaluated the association between several genetic variations and PUFA levels in RBCs in children with obesity. One hundred ninety-six children with obesity (101 females, 95 males) were evaluated using anthropometric measurements, dietary intakes, plasma and RBC PUFA quantification, blood biochemistry, and 55 single nucleotide polymorphisms within 14 genes. phosphatidylethanolamine N-methyltransferase (PEMT) rs1109859 and methylenetetrahydrofolate reductase gene (MTHFR) rs4846052 genotypes were associated with PUFA levels in RBCs. PUFA intake did not influence the RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels. Higher RBC DHA and EPA levels were observed for PEMT rs1109859 GG and GA genotypes versus the AA genotype. Higher levels of RBC DHA, EPA, arachidonic acid (ARA), and linoleic acid (LA) and were observed for MTHFR rs4846052 TT genotype versus TC and CC genotypes. Genetic variations in PEMT rs1109859 and MTHFR rs4846052 were associated with different PUFA levels in RBC membranes and are estimators for PUFA species in RBCs. Further research is needed to establish whether these genotype-specific alterations are specific to overweight children.

No clinical utility of common polymorphisms in IGF1, IRS1, GCKR, PPARG, GCK1 and KCTD1 genes previously associated with insulin resistance in overweight children from Romania and Moldova.

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.

Development and Validation of a LC⁻MS/MS-Based Assay for Quantification of Free and Total Omega 3 and 6 Fatty Acids from Human Plasma.

Few high-performance liquid chromatography⁻tandem mass spectrometry (LC-MS/MS) methods have been developed for the full quantitation of fatty acids from human plasma without derivatization. Therefore, we propose a method that requires fewer sample preparation steps, which can be used for the quantitation of several polyunsaturated fatty acids in human plasma. The method offers rapid, accurate, sensitive, and simultaneous quantification of omega 3 (α-linolenic, eicosapentaenoic, and docosahexaenoic acids) and omega 6 fatty acids (arachidonic and linoleic acids) using high-performance LC-MS/MS. The selected fatty acids were analysed in lipid extracts from both free and total forms. Chromatographic separation was achieved using a reversed phase C18 column with isocratic flow using ammonium acetate for improving negative electrospray ionization (ESI) response. Mass detection was performed in multiple reaction monitoring (MRM) mode, and deuterated internal standards were used for each target compound. The limits of quantification were situated in the low nanomolar range, excepting linoleic acid, for which the limit was in the high nanomolar range. The method was validated according to the U.S. Department of Health and Human Services guidelines, and offers a fast, sensitive, and reliable quantification of selected omega 3 and 6 fatty acids in human plasma.

A novel method for measuring subcutaneous adipose tissue using ultrasound in children - interobserver consistency.

BACKGROUND: Currently, sufficiently accurate field methods for body composition assessment in children are missing. The ultrasound method for assessing adipose tissue thickness has been used extensively in sport medicine. However, there are no studies looking at the reliability of this method in non-athletic children. This paper aims to determine the inter-observer reliability in measuring the uncompressed subcutaneous adipose tissue thickness using ultrasound, in children. SUBJECTS, MATERIALS AND METHODS: Forty healthy children (20 males, 20 females), median age 11.85 years (5.3 to 18.1 years) were evaluated. Median body mass index standard deviation score (BMI SDS) was -0.13 (-3.9 to 4). Three observers used a Hosand BX 2000 Ultrasonic Adipometer to measure uncompressed subcutaneous adipose tissue thickness at three sites: triceps, subscapular, supraspinale. A single experienced observer used the three sites to also measure the compressed adipose thickness using a skinfold caliper. RESULTS: Individual observer deviations from the mean value of the three observers in adipometer measurement had a standard deviation of 1.74 mm, 92.8% were less than 3 mm. Analysis separated by individual anatomical sites showed high reliability values for triceps: linear regression R²=0.84, p=0.000; intraclass correlation coefficient (ICC)=0.92 and standard error of measurement (SEM)=0.63. The values at supraspinale site were R²=0.82, p=0.000, ICC=0.89 and SEM=1.17, while for subscapular the values were lower: R²=0.79, p=0.000, ICC=0.78 and SEM=1.02. The body fat percentage (BF%) calculated using skinfold measurements was highly correlated with the BF% calculated by the adipometer (R=0.92, R²=0.83, p=0.000). The Pearson's correlation between BMI SDS and BF% calculated from skinfold was R=0.52, R²=0.28, p=0.001, while for the adipometer it was R=0.53, R²=0.27, p=0.000. CONCLUSIONS: This novel ultrasound measurement technique can be used with good accuracy and reliability to measure uncompressed subcutaneous adipose tissue thickness in children, sustaining its application for research and clinical purposes, however larger studies are needed.

Factors influencing the quality of life perception in patients with type 2 diabetes mellitus.

PURPOSE: To evaluate the impact of several factors on the patient's perception on quality of life in a group of patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: In this cross-sectional study, 198 patients with T2DM were enrolled according to a consecutive-case population-based study design. In all participants, the perception on the quality of life was measured using the quality of life index - diabetes version III proposed by Ferrans and Powers. We evaluated the impact of several anthropometric and diabetes-related (ie, diabetes history and quality of glycemic control) factors on the patient's perception on the quality of life. RESULTS: The presence of diabetes complications was associated with a decreased quality of life: retinopathy (1 vs 5 points; P<0.001), chronic kidney disease (-1 vs 5 points; P<0.001), and neuropathy (-1 vs 5 points; P<0.001). A significant reverse correlation was found between the patient's quality of life and depression's severity (Spearman's r=-0.345; P<0.001) and body mass index (Spearman's r=-0.158; P=0.026). A positive association between the quality of life and the quality of diabetes-related self-care activities was found (Spearman's r=0.338; P<0.001). No significant association was found between the patient's quality of life and the quality of glycemic control, diabetes duration, age, gender, or smoking status. CONCLUSION: To improve the patient's quality of life, special care should be given to the modifiable diabetes-related factors: the prevention and treatment of diabetes complications, treatment of depression, and weight loss in obese and overweight patients.

Age as an independent factor for the development of neuropathy in diabetic patients.

Population aging is unprecedented, without parallel in the history of humanity. As type 2 diabetes mellitus is predominantly more prevalent in aging populations, this creates a major public health burden. Older adults with diabetes have the highest rates of major lower-extremity amputation, myocardial infarction, visual impairment, and end-stage renal disease of any age group. The aims of our study were to assess whether age is an independent factor for the occurrence of diabetic neuropathy (DN), and to evaluate the relationship between the presence and the severity of DN and the diabetes duration and blood glucose level. In this study, we enrolled 198 patients, previously diagnosed with type 2 diabetes mellitus. For all patients, we measured hemoglobin A1c (HbA1c), lipid profile, and body mass index and we assessed the presence and severity of DN using the evaluation of clinical signs and symptoms. Patients had a median age of 62 years, with a median of diabetes duration of 7 years; 55.1% of the patients were men and the average HbA1c in the cohort was 8.2%. The prevalence of DN according to Michigan Neuropathy Screening Instrument was 28.8%, being significantly and positively correlated with higher age (65 vs 59 years; P=0.001) and HbA1c (8.6% vs 8.0%; P=0.027). No significant correlations were observed between the severity of DN and diabetes duration, body mass index (31.9 vs 29.9 kg/m(2)), or the number of centimeters exceeding the normal waist circumference (25.2 vs 17.3 cm; P=0.003). In conclusion, age influences the presence of DN, independent on other risk factors. This influence persists even after adjusting for other, very important risk factors, like blood glucose level or diabetes duration.