Feasibility and effectiveness of a distance-adapted physical activity intervention in adolescents with obesity during the COVID-19 pandemic.

BACKGROUND: Pediatric obesity represents one of the most important public health challenges and its prevalence significantly increased during the COVID-19 pandemic. Our prospective study aimed to assess the feasibility of a remote adapted physical activity (PA) intervention and its effectiveness in improving anthropometric indices, metabolic health parameters, as well as cardiopulmonary function and fitness in adolescents with obesity. METHODS: A PA intervention involving synchronous online lessons combined with asynchronous sessions and promotion of independent PA and "active breaks" to interrupt prolonged sedentary behaviors was proposed to 20 adolescents aged 11-17 years with obesity over a 4-month period. Clinical and anthropometric parameters (weight, height, waist, body composition, blood pressure), metabolic parameters (glycemia, insulinemia, glycated hemoglobin, oral glucose tolerance test [OGTT], lipid profile, presence of hepatic steatosis), cardiopulmonary function and fitness indices (VO2max, six-minute walking test [6MWT], upper and lower limb strength test) were evaluated before and after the intervention. RESULTS: Twenty adolescents with obesity were enrolled (11 male [55%], aged 14.1±1.5 years, BMI SDS 3.1±0.5). Eighteen participants (90%) successfully completed the project, and no adverse events were reported. We observed an increase in cardiovascular and muscle fitness [higher VO2peak, maximal workload, better performance at limb strength and 6MWT (all P<0.05)], increased lean body mass (P=0.005), and an improvement of glucose metabolism response with a reduction of insulin concentrations during OGTT (P=0.043). CONCLUSIONS: Participation in the training program was feasible and effective in improving cardiovascular fitness, glucose metabolism, body composition, strength, and endurance in adolescents with obesity during the COVID-19 pandemic.

Glucose sensor with predictive alarm for hypoglycaemia: Improved glycaemic control in adolescents with type 1 diabetes.

AIM: Hypoglycaemic events are linked to microvascular and macrovascular complications in people with type 1 diabetes. We aimed to evaluate the efficacy of glucose sensor [real-time continuous glucose monitoring (RT-CGM)] with predictive alarm (PA) in reducing the time spent below the range (%TBR <70 mg/dl) in a group of adolescents with type 1 diabetes (AwD). MATERIALS AND METHODS: This was a crossover, monocentric and randomized study. RT-CGM was set with Alarm on Threshold (AoT) at 70 mg/dl) or PA for hypoglycaemia (20 m before threshold). Twenty AwD were enrolled and randomized to either a PA/AoT or AoT/PA treatment sequence, in a 1:1 ratio. The two groups (PA vs. AoT) were compared using two-way repeated measures ANOVA taking account of the carryover effect. RESULTS: AwD using PA for hypoglycaemia spent less time in severe hypoglycaemia (%TBR2 <54 mg/dl; 0.32 ± 0.31 vs. 0.91 ± 0.90; p < .02) and hypoglycaemia (%TBR <70 mg/dl; 1.68 ± 1.06 vs. 2.90 ± 2.05; p < .02), with better glycaemia risk index (51.3 ± 11.0 vs. 61.5 ± 12.6; p ≤ .01). CONCLUSION: The use of RT-CGM with PA for hypoglycaemia technology in AwD using multiple daily insulin injection treatment could significantly reduce the risk of having hypoglycaemic events resulting in an improved quality of glucose control. CLINICAL TRIAL REGISTRATION NUMBER: NCT05574023.

Association of HDL-Cholesterol, hypertension and left ventricular hypertrophy in youths with overweight or obesity.

BACKGROUND AND AIM: To evaluate the relationship between HDL-Cholesterol (HDL-C), hypertension, and left ventricular hypertrophy (LVH) in a large sample of Caucasian youths with overweight/obesity (OW/OB). METHODS AND RESULTS: A cross-sectional multicenter study was performed in 1469 youths (age 6-16 years) with OW/OB observed in the period 2016-2020. An additional independent sample of 244 youths with an echocardiographic evaluation, observed in a single center was analyzed. The sample was divided in six quantiles (Q) of HDL-C: Q1: >56, Q2: ≤56 > 51, Q3: ≤51 > 45, Q4: ≤45 > 41, Q5: ≤41 > 39, Q6: <39 mg/dL. The nadir of the relationship was identified in youths in the first quantile. Among HDL-Cholesterol quantiles the distribution of hypertension was non-linear with a percentage of 25.0%, 40.1%, 33.6%, 31.3%, 35.2% and 39.7% in the six quantiles, respectively. The percentage of LVH was 21.8%, 43.6%, 48.8%, 35.5%, 38.5% and 52.0% in the six quantiles, respectively. The highest odds [95%Cl] of hypertension were 2.05 (1.33-3.16) (P < 0.01) in Q2, 1.67 (1.10-2.55) (P < 0.05) in Q3 and 1.59 (1.05-2.41) (P < 0.05) in Q6 vs Q1. The odds of LVH were 3.86 (1.15-10.24) (P < 0.05) in Q2, 4.16 (1.58-10.91) (P < 0.05) in Q3 and 3.60 (1.44-9.02) (P < 0.05) in Q6 vs Q1, independently by centers, age, sex, prepubertal stage, and body mass index. CONCLUSION: Contrary to the common belief, the present study shows that high levels of HDL-C may be not considered a negative predictor of hypertension and LVH, two risk factors for future CV disease.

Aiming for the Best Glycemic Control Beyond Time in Range: Time in Tight Range as a New Continuous Glucose Monitoring Metric in Children and Adolescents with Type 1 Diabetes Using Different Treatment Modalities.

Introduction: To evaluate time in tight range (TITR) 70-140 mg/dL (3.9-7.8 mmol/L), its correlation with standard continuous glucose monitoring (CGM) metrics and the clinical variables that possibly have a substantial impact on its value, in a large cohort of pediatric subjects using different treatment strategies. Materials and Methods: A total of 854 children and adolescents with type 1 diabetes were consecutively recruited in this real world, dual center, cross-sectional study. Participants were categorized into four treatment groups (multiple daily injections [MDI] + real-time CGM, MDI + intermittently scanned CGM, sensor augmented pump, and hybrid closed loop [HCL]). Demographical and clinical data, including CGM data, were collected and analyzed. Results: The overall study population exhibited an average TITR of 36.4% ± 12.8%. HCL users showed higher TITR levels compared to the other treatment groups (P < 0.001). A time in range (TIR) cut-off value of 71.9% identified subjects achieving a TITR ≥50% (area under curve [AUC] 0.98; 95% confidence interval 0.97-0.99, P < 0.001), and a strong positive correlation between these two metrics was observed (r = 0.95, P < 0.001). An increase in TIR of 1% was associated with 1.84 (R2 Nagelkerke = 0.35, P < 0.001) increased likelihood of achieving TITR ≥50%. Use of HCL systems (B = 7.78; P < 0.001), disease duration (B = -0.26, P = 0.006), coefficient of variation (B = -0.30, P = 0.004), and glycated hemoglobin (B = -8.82; P < 0.001) emerged as significant predictors of TITR levels. Conclusions: Our study highlights that most children and adolescents with type 1 diabetes present TITR levels below 50%, except those using HCL. Tailored interventions and strategies should be implemented to increase TITR.

IGF1 and PPARG polymorphisms are associated with reduced estimated glomerular filtration rate in a cohort of children and adolescents with type 1 diabetes.

INTRODUCTION: Several genetic loci have been associated with diabetic nephropathy; however, the underlying genetic mechanisms are still poorly understood, with no robust candidate genes identified yet. AIM: We aimed to determine whether two polymorphisms, previously associated with renal decline, influence kidney impairment evaluating their association with markers of renal function in a pediatric population with type 1 diabetes (T1D). MATERIAL AND METHODS: Renal function was evaluated by glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) in a cohort of pediatric subjects with T1D (n = 278). Risk factors for diabetes complications (diabetes duration, blood pressure, HbA1c) were assessed. The IGF1 rs35767 and PPARG rs1801282 SNPs were genotyped by TaqMan RT-PCR system. An additive genetic interaction was calculated. Association analysis between markers of renal function and both SNPs or their additive interaction were performed. RESULTS: Both SNPs showed a significant association with eGFR: the A allele of rs35767 or the C allele of rs1801282 were associated to reduced eGFR compared to G alleles. Multivariate regression analysis adjusted for age, sex, z-BMI, T1D duration, blood pressure and Hba1c values showed that the additive genetic interaction was independently associated with lower eGFR (ß = -3.59 [-6.52 to -0.66], p = 0.017). No associations were detected between SNPs, their additive interaction and ACR. CONCLUSIONS: These results provide new insight into the genetic predisposition to renal dysfunction, showing that two polymorphisms in IGF1 and PPARG genes can lead to a reduction in renal filtration rate leading these patients to be exposed to a higher risk of early renal complications.

One-Hour Post-Load Plasma Glucose and Altered Glucometabolic Profile in Youths with Overweight or Obesity.

In youths, two cut-offs (133 and 155 mg/dL) have been proposed to identify high glucose levels at the 1 h (G60) mark during an oral glucose tolerance test (OGTT). We evaluated which cut-off was more closely associated with isolated impaired glucose tolerance (IGT) and cardiometabolic risk (CMR) in 1199 youth with overweight/obesity (OW/OB) and normal fasting glucose and/or HbA1c. The disposition index (DI) was available in 724 youths. The sample was divided by two cut-offs of G60: <133 mg/dL (n = 853) and ≥133 mg/dL (n = 346), or G60 < 155 mg/dL (n = 1050) and ≥155 mg/dL (n = 149). Independent of the cut-off, youths with high levels of G60 showed higher levels of G120, insulin resistance (IR), triglycerides to HDL ratio (TG/HDL), alanine aminotransferase (ALT), and lower insulin sensitivity (IS) and DI than youths with lower levels of G60. The percentage of youths showing IGT, IR, low IS, high TG/HDL ratio, high ALT, and low DI was 50% higher in the G60 ≥ 133 mg/dL group than in the G60 ≥ 155 mg/dL one. In youths with OW/OB and IGT, a cut-off of G60 ≥ 133 mg/dL is more useful than G60 ≥ 155 mg/dL to identify those at high risk of IGT and altered CMR profile.

The treatment of obesity in children and adolescents: consensus position statement of the Italian society of pediatric endocrinology and diabetology, Italian Society of Pediatrics and Italian Society of Pediatric Surgery.

This Position Statement updates the different components of the therapy of obesity (lifestyle intervention, drugs, and surgery) in children and adolescents, previously reported in the consensus position statement on pediatric obesity of the Italian Society of Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics. Lifestyle intervention is the first step of treatment. In children older than 12 years, pharmacotherapy is the second step, and bariatric surgery is the third one, in selected cases. Novelties are available in the field of the medical treatment of obesity. In particular, new drugs demonstrated their efficacy and safety and have been approved in adolescents. Moreover, several randomized control trials with other drugs are in process and it is likely that some of them will become available in the future. The increase of the portfolio of treatment options for obesity in children and adolescents is promising for a more effective treatment of this disorder.

Risk factors for pre-clinical atherosclerosis in adolescents with type 1 diabetes.

AIMS: To assess whether, besides "traditional" risk factors, overall oxidative stress, oxidized lipoproteins, and glycemic variability are associated with early macro-vascular damage in type 1 diabetes (T1D). METHODS: In 267 children/adolescents with T1D (130 girls, age 9.1-23.0 years) we evaluated: derivatives of reactive oxygen metabolites [d-ROMs], serum total antioxidant capacity [TAC] and oxidized LDL-cholesterol [oxLDL]; markers of early vascular damage (Lipoprotein-associated phospholipase A2 [Lp-PLA2], z-score of carotid intima-media thickness [z-cIMT] and carotid-femoral pulse wave velocity [z-PWV]); CGM metrics of four weeks preceding the visit, central systolic/diastolic blood pressures (cSBP/cDBP), and HbA1c, z-score of BP (z-SBP/z-DBP) and circulating lipids longitudinally collected since T1D onset.. Three general linear models were built with z-cIMT, z-PWV adjusted for current cDBP, and Lp-PLA2 as independent variables. RESULTS: The z-cIMT was associated with male gender (B = 0.491, η2 = 0.029, p = 0.005), cSBP (B = 0.023, η2 = 0.026, p = 0.008) and oxLDL (B = 0.022, η2 = 0.022, p = 0.014). The z-PWV was associated with diabetes duration (B = 0.054, η2 = 0.024, p = 0.016), daily insulin dose (B = 0.52, η2 = 0.018, p = 0.045), longitudinal z-SBP (B = 0.18, η2 = 0.018, p = 0.045) and dROMs (B = 0.003, η2 = 0.037, p = 0.004). Lp-PLA2 was associated with age (B = 0.221, η2 = 0.079, p = 3*10-6), oxLDL (B = 0.081, η2 = 0.050, p = 2*10-4), longitudinal LDL-cholesterol (B = 0.031, η2 = 0.043, p = 0.001) and male gender (B = -1.62, η2 = 0.10, p = 1.3*107). CONCLUSIONS: Oxidative stress, male gender, insulin dose, diabetes duration and longitudinal lipids and blood pressure, contributed to the variance of early vascular damage in young patients with T1D.

Is Metabolic Syndrome Useful for Identifying Youths with Obesity at Risk for NAFLD?

The definition of metabolic syndrome (MetS) in childhood is controversial. Recently, a modified version of the International Diabetes Federation (IDF) definition was proposed using reference data from an international population for high waist circumference (WC) and blood pressure (BP), while the fixed cutoffs for lipids and glucose were not changed. We analyzed MetS prevalence using this modified definition (MetS-IDFm) and its association with non-alcoholic fatty liver disease (NAFLD) in 1057 youths (age 6-17 years) with overweight/obesity (OW/OB). A comparison with another modified definition of MetS according to the Adult Treatment Panel III (MetS-ATPIIIm) was performed. The prevalence of MetS-IDFm was 27.8% and 28.9% by MetS-ATPIIIm. The Odds (95% Confidence Intervals) of NAFLD was 2.70 (1.30-5.60) (p = 0.008) for high WC, 1.68 (1.25-2.26)(p = 0.001) for MetS, 1.54 (1.12-2.11)(p = 0.007) for low HDL-Cholesterol, 1.49 (1.04-2.13)(p = 0.032) for high triglycerides and 1.37 (1.03-1.82)(p = 0.033) for high BP. No substantial difference was found in the prevalence of MetS-IDFm and frequency of NAFLD compared to Mets-ATPIIIm definition. Our data demonstrate that one third of youths with OW/OB have MetS, whichever was the criterion. Neither definition was superior to some of their components in identifying youths with OW/OB at risk for NAFLD.

A new proposal for a second insulin bolus to optimize postprandial glucose profile in adolescents with type 1 diabetes.

AIMS: To evaluate whether a second insulin bolus, calculated with a new approach, could improve postprandial glucose (PPG) after the intake of real-life high-fat (HF) and high-protein (HP) mixed meals. METHODS: Fifteen adolescents with T1D treated with non-automated insulin pumps and CGM were enrolled. Patients received standard, HF and HP mixed meals treated with one pre-meal insulin bolus; based on differences in PPG between standard, HF and HP meals, correction boluses were calculated (30% and 60% of pre-meal bolus for HF and HP meals, respectively). Then patients received the same HF or HP meal treated with pre-meal bolus plus second insulin bolus after 3 h. Differences between postprandial variables after HF and HP meals treated with one or two insulin boluses were assessed by paired Student's t-test. RESULTS: Treating HF and HP meals with two insulin boluses significantly reduced the postprandial BG-AUC (21% and 26% respectively, p < 0.05), increased %TIR (from 52.5 to 78.3% for HF meal; from 32.7 to 57.1% for HP meal; p < 0.01), and reduced mean BG and %TAR (p < 0.01), with no differences in %TBR. CONCLUSIONS: The new way to calculate and administer correction boluses 3 h after HF and HP meals is effective and safe in reducing PPG and the hypoglycemia risk.

Which Is the Most Appropriate Cut-Off of HbA1c for Prediabetes Screening in Caucasian Youths with Overweight or Obesity?

This cross-sectional study aimed to assess the best cut-off of HbA1c for detection of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), beta-cell impairment and cardiometabolic risk (CMR) profile in overweight or obese (OW/OB) Caucasian youths. Two-hour oral glucose tolerance test was available in 1549 youths, one-hour glucose (G60) in 1430 youths and disposition index (DI) in 972 youths. Insulin resistance (IR) was calculated as Homeostatic Model Assessment for IR and insulin sensitivity (IS) as 1/fasting insulin. High G60 was defined by a value ≥ 133 mg/dL. The best cut-off of HbA1c for IFG or IGT was 5.5%. The frequency of individuals with HbA1c ≥ 5.5% was 32.5%, compared to 16.3% with HbA1c ≥ 5.7% (as proposed by the American Diabetes Association). HbA1c ≥ 5.5% showed higher sensitivity and lower specificity with respect to HbA1c ≥ 5.7% for all the abnormalities examined (IFG, IGT, high G60, IR, low IS, DI and CMR factors). In conclusion, this lower cut-off might represent a more appropriate screening marker of glucose dysmetabolism in youths with OW/OB. Prospective studies are needed to validate this cut-off for predicting prediabetes/diabetes in youths with OW/OB.

Cardiovascular Risk Factors in Children and Adolescents with Type 1 Diabetes Mellitus: The Role of Insulin Resistance and Associated Genetic Variants.

INTRODUCTION: Type 1 diabetes (T1D) is associated with an increased risk of cardiovascular disease. Insulin resistance is an important cardiovascular risk factor (CVRF), also in subjects with T1D, but the influence of the genetic predisposition of insulin resistance on cardiovascular risk is still unknown in T1D. We aimed to determine whether a genetic score composed of six variants, previously associated with insulin resistance and type 2 diabetes (T2D) risk, associates with insulin sensitivity and known CVRFs in children and adolescents with T1D. MATERIALS AND METHODS: 330 children and adolescents (174 males; mean age 15.7 ± 3.5 years) with T1D were genotyped for the following genetic variants: rs1801278 (IRS1), rs1044498 (ENPP1), rs2295490 (TRIB3), rs1801282 (PPARG), rs780094 (GCKR), and rs35767 (IGF1). An additive genetic risk score (GRS) and cardiovascular risk score (CVRS) were calculated. Anthropometric, glycemic control, insulin sensitivity, blood pressure, and biochemical parameters were assessed. Multivariate regression between evaluated phenotypes and GRS was performed. RESULTS: We found a significant association between the GRS and estimated insulin sensitivity (ß = -0.027 [-0.040 to -0.013], R2 = 0.86, p≤ 0.001), diastolic blood pressure (ß = 0.68 [0.08-1.27], R2 = 0.20, p = 0.026), triglycerides (ß = 4.26 [1.74-6.77], R2 = 0.13, p = 0.001), waist to height ratio (ß = 0.003 [0.001-0.006], R2 = 0.75, p = 0.010), non-HDL-cholesterol (ß = 3.63 [1.39-5.87], R2 = 0.12, p = 0.002), and CVRS (ß = 0.063 [0.008-0.118], R2 = 0.19, p = 0.025), independent of age, sex, BMI, pubertal stage, diabetes duration, glycated hemoglobin, type of treatment, and total insulin requirement. The addition of the GRS to established clinical risk factors significantly improved the discriminatory capability of the regression model for predicting subjects with more CVRFs (C-statistic 0.89 [95% CI: 0.84-0.95] versus 0.83 (0.73-0.93); p = 0.037). CONCLUSIONS: Insulin resistance and T2D risk-associated genetic variants influence insulin sensitivity and known CVRFs in children and adolescents with T1D.

A new formula to improve the screening of impaired glucose tolerance in youths with overweight or obesity.

AIM: To assess a new formula to improve the screening of isolated impaired glucose tolerance (IGT) in youth with overweight/obesity (OW/OB). METHODS AND RESULTS: A cross-sectional study was performed in 1189 Caucasian youths with OW/OB aged 5-17 years, in whom impaired fasting glucose and high glycosylated hemoglobin were excluded. The sample was divided into training set (TS) (n = 883) and validation set (VS) (n = 306). Fasting (FG) and post-load plasma glucose, alanine aminotransferase (ALT), lipids and familial history for type 2 diabetes (FD) were available in all individuals. In the TS youths with IGT (n = 58, 7.0%) showed higher prevalence of female sex (FS), FD, and higher levels of FG, post-load glucose, ALT and lower levels of HDL-cholesterol vs individuals without IGT. The linear formula was obtained by logistic regression analysis in the TS: 0.05∗ALT + 0.07∗FG + 0.87∗FD + (0.06∗HDL∗ - 1) + 1∗FS. The best cut-off was 5.84. The performance of the formula vs IGT was: sensitivity: 0.74 and specificity: 0.71. Similar results were obtained in the VS. CONCLUSIONS: Using metabolic and anamnestic data we obtained a simple formula with a good performance for screening isolated IGT. This formula may support pediatricians to identify youths with OW/OB in whom the OGTT may be useful for detecting IGT.

Genetic Variation in Antioxidant Response Modulates the Level of Oxidative Stress in Youth with Type 1 Diabetes and Poor Glycemic Control.

BACKGROUND: The minor allele of the single nucleotide polymorphism (SNP) rs2364723 of NFE2L2, a gene encoding a master antioxidant transcription factor, has been associated with poor cardiovascular outcomes and with complications of type 2 diabetes. We assessed the association between rs2364723 of NFE2L2 and oxidative stress in children/adolescents with type 1 diabetes (T1D). METHODS: In 384 children/adolescents with T1D (age 15.7 ± 3.2 years, 207 males), we assessed the oxidative stress by measuring the concentration of derivatives of reactive oxygen metabolites (d-ROMs) and we genotyped the rs2364723 SNP by real time polymerase chain reaction. RESULTS: The concentration of d-ROMs was 372.8 ± 64.6 Carratelli units. The minor genotype (CC) of rs2364723 at NFE2L2 was associated with higher concentration of derivatives of d-ROMs in the subgroup with HbA1c ≥ 8% (B = 47.85, p for genotype ∗ HbA1c interaction = 0.019). CONCLUSIONS: The carriers of the minor genotype of rs2364723 may have increased oxidative stress compared to their counterparts with other genotypes, especially in case of poor glycemic control. This observation needs to be replicated and confirmed in larger independent cohorts of youth with T1D.

Markers of subclinical vascular damage in young adults with type 1 diabetes mellitus: the role of central blood pressure.

INTRODUCTION: Type 1 diabetes mellitus (T1D) is a chronic disease leading to cardiovascular complications that can be diagnosed early as subclinical vascular damage. To prevent such damage, it is important to increase knowledge of the effects of the different cardiovascular risk factors in patients with T1D. The aim of our study was to assess possible associations between markers of subclinical arterial damage and traditional cardiovascular risk factors, with a special focus on peripheral blood pressure and central blood pressure (cBP), in a sample of young adults with T1D. PATIENTS AND METHODS: The study included 172 T1D patients (mean age 24.7 ±â€Š8.7 years, duration of T1D 13.5 ±â€Š9.6 years). Pulse wave velocity (PWV), pulse wave analysis and cBP were assessed by tonometry (SphygmoCor Xcel). Carotid intima-media thickness (cIMT) and carotid distensibility coefficient (cDC) were assessed by high-resolution echo-Doppler analysis and further examined with dedicated hardware. RESULTS: Seventeen patients (10.1%) were classified as hypertensive by office peripheral blood pressure, and 48 patients (27.9%) were classified as hypertensive by cBP. One hundred sixteen patients (68.8%) had cDC under the range of normality, one patient had a PWV (0.6%) above 10 m/s, and no patients had a cIMT above 0.9 mm. In multivariable analysis, central SBP, but not metabolic parameters, remained associated with all the markers of subclinical arterial damage [cIMT ( ß â€Š= 0.288 ±â€Š0.001; P  < 0.001), PWV ( ß â€Š= 0.374 ±â€Š0.007; P  < 0.001), cDC ( ß â€Š= -0.149 ±â€Š0.055; P  = 0.029)]. CONCLUSION: The independent association between cBP and markers of subclinical vascular damage underlines the importance of haemodynamic factors in the development of early signs of macrovascular disease in T1D patients. Further studies are warranted to better define the role of cBP to stratify cardiovascular risk, to individualize the need for follow-up and to tailor preventive strategies in T1D patients.

Early marker of ocular neurodegeneration in children and adolescents with type 1 diabetes: the contributing role of polymorphisms in mir146a and mir128a genes.

BACKGROUND: Early ocular neurodegenerative signs of diabetic neuropathy (DN) can be found in children and adolescents with type 1 diabetes (T1D). No data are available on the potential role of polymorphisms in miRNAs genes in predisposing T1D subjects to these signs. AIMS: To determine whether MIR146A rs2910164 and MIR128A rs11888095 polymorphisms are associated with early retinal and corneal neurodegenerative changes in pediatric patients with T1D. METHODS: A total of 140 T1D children/adolescents underwent spectral domain-optical coherence tomography (SD-OCT) and in vivo confocal microscopy (IVCM) with measurement of retinal and corneal nerve fiber parameters. Risk factors for diabetes complications (diabetes duration, blood pressure, HbA1c) were recorded. Genotyping of rs2910164 and rs1188095 SNPs and genotype-phenotype association analysis were performed. RESULTS: The C allele of rs2910164 in MIR146A was associated with higher values of IVCM parameters and minimum rim width (MRW) of the peripapillary region of optic nerve head measured in the retina, whereas the T allele of rs1188095 in MIR128A was associated with a significant impairment of them. Multiple regression analysis showed that MIR146A and MIR128A polymorphisms were significantly associated with corneal nerve fiber length (beta = 0.225 and - 0.204, respectively) and other IVCM parameters, independently from age, diabetes duration, HbA1c and systolic blood pressure percentile. Similar results were found for MRW (beta = 0.213 and - 0.286, respectively). CONCLUSIONS: These results provide new insight into the genetic predisposition to DN showing that two polymorphisms in MIR146A and MIR128A genes could significantly contribute to the development of early ocular preclinical signs of DN.

FADS cluster variants are associated with insulin sensitivity in children and adolescents with overweight and obesity.

Changes in the desaturation activity of LC-PUFAs may influence insulin sensitivity by modulating the relative abundance of omega-3. The aim of this cross-sectional study was to assess the association between genetic variants of fatty acid desaturase cluster genes (FADS1, FADS2, FADS3) and insulin sensitivity in a cohort of children and adolescents with obesity. Anthropometric evaluation, lipid profile, glucose metabolism parameters and the genotype of rs1535 on FADS2 gene were assessed. In 162 obese children and adolescents (12.6 ± 2.3 years; BMI 30.9 ± 7.3), we found a significant association between an index of insulin sensitivity, i.e., Matsuda index, and rs1535 (B = -0,192; p = 0.008), BMI (B = -0,003; p < 0.001), and triglycerides (B = -0,034; p < 0.001), independent of age and sex [R² = 0.35; p = <0.001]. In conclusion, FADS cluster variants were associated with insulin sensitivity in a population of children and adolescents with obesity, contributing to identify individuals who may benefit from personalised prevention and treatment nutritional strategies since childhood.

Serum zonulin as an index of glucose dysregulation in children and adolescents with overweight and obesity.

Increased intestinal permeability has an important role in metabolic dysregulation. In this cross-sectional study, we examined whether serum intestinal permeability marker zonulin and related pro-inflammatory molecules were associated with the oral disposition index, a predictor for the development of type 2 diabetes, in a cohort of children and adolescents with overweight and obesity. Ninety-two children and adolescents were recruited [Male: 43; 12.7 (2.35) years; BMI SDS: 2.7 (0.96)]. Anthropometric and clinical parameters, lipid profile, glucose metabolism and plasma levels of zonulin, lipopolysaccharide-binding protein and Interleukin-6 were measured. We found an association between oral disposition index and zonulin (ß = -0.243; p = 0.019) and age (ß = -0.307; p = 0.004), independent of sex and BMI SDS [R2  = 0.16; p = 0.005]. Our results show an association between serum zonulin concentration and oral disposition index supporting the hypothesis of increased intestinal permeability as a possible risk factor for glucose metabolism dysregulation in children and adolescents with obesity.

Uric acid versus metabolic syndrome as markers of fatty liver disease in young people with overweight/obesity.

AIMS: To compare the association of high serum uric acid (HUA) or metabolic syndrome (MetS) with fatty liver disease (FLD) in youths with overweight/obesity (OW/OB). MATERIALS AND METHODS: Cross-sectional study of anthropometrics, biochemical variables, and liver ultrasound of 3104 individuals with OW/OB (age 5-17 years). Metabolic syndrome was defined by ≥ 3 criteria among (1) high waist circumference; (2) high triglycerides; (3) low high-density lipoproteins; (4) fasting glucose ≥100 mg/dl; (5) blood pressure ≥95th percentile in children, and ≥130/80 mmHg in adolescents. High serum uric acid was defined as serum UA value ≥ 75th percentile adjusted for sex. Fatty liver disease was determined by echography. RESULTS: The sample was stratified in four categories: (1) no HUA, no MetS (reference category); (2) MetS; (3) HUA; (4) HUA and MetS (HUA + MetS). The prevalence of FLD increased across the four categories from 29.9%, 44.0%, 52.2%, to 67.1%, respectively (p < 0.0001). The ORs for the categorical variables were 1.33 (1.06-1.68) for MetS (p = 0.02), 3.19 (2.51-4.05) for HUA (p < 0.0001) and 3.72 (2.65-5.21) for HUA + MetS (p < 0.0001), versus the reference category regardless of the body mass index. CONCLUSIONS: HUA represents a useful marker of FLD in youths with OW/OB, given its greater ability to identify those at increased risk of the disease compared to MetS. The ability of both to predict incident FLD must be investigated in longitudinal study.