Comparison between Friedewald's and Sampson's formulas in the estimation of high levels of measured LDL-cholesterol in youth with obesity.

BACKGROUND AND AIM: To assess the performance of Friedewald's and Sampson's formulas in relation to high or borderline-high levels of measured LDL-Cholesterol (LDL-C) in youths with overweight/obesity (OW/OB). METHODS AND RESULTS: A cross-sectional study was performed in 1694 youths (age 5-17 years) with OW/OB observed in Italian centers of Messina (group 1) and Naples (group 2). LDL-C levels were both measured and calculated using Friedewald's (LDL-CF) and Sampson's (LDL-CS) formulas. The two groups were similar for sex, age, BMI, BMI Z-score, and measured LDL-C. Levels of LDL-CF and LDL-CS were higher in group 1 than group 2. In the overall sample, 9.9 % youths had measured LDL-C ≥130 mg/dL and 27.8 % ≥ 110 mg/dL, without differences between centers. The two formulas showed comparable high sensitivity and specificity in relation to levels of measured LDL-C ≥130 mg/dL or ≥110 mg/dL. However, LDL-CF showed a higher positive predictive value than LDL-CS. CONCLUSIONS: Both formulas estimate with high accuracy measured LDL-C levels in youths with OW/OB. Therefore, calculated LDL-C can be a useful tool for universal screening when direct LDL-C measurement is not available. The Friedewald's formula is more feasible in clinical practice for simplicity of calculation.

Cardiometabolic risk in children and adolescents with obesity: a position paper of the Italian Society for Pediatric Endocrinology and Diabetology.

Despite the implementation of preventive measures to counteract the obesity epidemics, the prevalence of childhood obesity is still alarming all over the world. Childhood obesity is the most common risk factor for both cardiovascular and metabolic diseases. In fact, an earlier onset of obesity can cause a greater risk of adiposity tracking across the lifespan and consequently a longer exposure to cardiometabolic risk factors. Accumulating evidence provided by prospective and intervention studies demonstrated the link between pediatric obesity and selected subclinical signs of cardiovascular damage (atherosclerosis and left ventricular hypertrophy), or fatal and not fatal cardiovascular events as early as 40 years of age.The numerous guidelines and scientific documents published in the last years demonstrate the relevance of assessing cardiometabolic risk factors in children and adolescents with OB.This Position paper, released by experts of the "Childhood Obesity study group" within the Italian Society for Pediatric Endocrinology and Diabetology, aims to review the assessment of cardiometabolic risk factors and comorbidities in children and adolescents with OW/OB on the light of the most recent scientific evidence.The main recommendations are: (a) early detection of comorbidities, including hypertension, dyslipidemia, prediabetes/type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, polycystic ovary syndrome, inactivity, obstructive sleep apnea and decline in kidney function; (b) weight loss treatment, which is associated with a reduction of all cardiometabolic risk factors; (c) specific treatment of comorbidities, through lifestyle modifications or pharmacological treatment added to lifestyle for suitable individuals; d). monitoring comorbidities for mitigating future morbidity and mortality.

Sex-Related Differences in Cardiovascular Risk in Adolescents with Overweight or Obesity.

Background: Pediatric obesity is closely associated with cardiometabolic comorbidities, but the role of sex in this relationship is less investigated. We aimed to evaluate sex-related differences on cardiometabolic risk factors and preclinical signs of target organ damage in adolescents with overweight/obesity (OW/OB). Methods: The main cross-sectional study included 988 adolescents (510 boys and 478 girls) with OW/OB aged 10-18 years. In all youths clinical and biochemical variables were evaluated and an abdominal echography was performed. Echocardiographic data for the assessment of left ventricular mass (LVM) and relative wall thickness (RWT) were available in an independent sample of 142 youths (67 boys and 75 girls), while echographic data of carotid intima media thickness (cIMT) were available in 107 youths (59 boys and 48 girls). Results: The three samples did not differ for age, body mass index, and sex distribution. In the main sample, boys showed higher waist-to-height ratio (WHtR) values (p < 0.0001) and fasting glucose levels (p = 0.002) than girls. Lower levels of estimates glomerular filtration rate (eGFR) were found in girls vs boys (p < 0.0001). No sex-related differences for prediabetes and hyperlipidemia were observed. A higher prevalence of WHtR ≥ 0.60 (57.3% vs 49.6%, p = 0.016) and fatty liver disease (FLD) (54.5% vs 38.3%, p < 0.0001) as well as a trend for high prevalence of hypertension (40.4 vs 34.7%, p = 0.06) were observed in boys vs girls. More, a higher prevalence of mild reduced eGFR (MReGFR) ( < 90 mL/min/1.73 m 2 ) was observed in girls vs boys (14.6% vs 9.6 %, p < 0.0001). In the sample with echocardiographic evaluation, boys showed higher levels of LVM (p = 0.046), and RWT (p = 0.003) than girls. Again, in the sample with carotid echography, boys showed higher levels of cIMT as compared to girls (p = 0.011). Conclusions: Adolescent boys with OW/OB showed higher risk of abdominal adiposity, FLD, and increased cardiac and vascular impairment than girls, whereas the latter had a higher risk of MReGFR. Risk stratification by sex for cardiometabolic risk factors or preclinical signs of target organ damage should be considered in youths with OW/OB.

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.

Sensitivity to thyroid hormones and reduced glomerular filtration in children and adolescents with overweight or obesity.

BACKGROUND: Reduced central sensitivity to thyroid hormones (TH) has been observed in euthyroid adults with reduced renal function. This topic is unexplored in young people with overweight or obesity (OW/OB). OBJECTIVE: To evaluate the association between sensitivity to TH and mild reduced estimated glomerular filtration rate (MReGFR) in euthyroid children and adolescents with OW/OB. METHODS: Data of 788 euthyroid children and adolescents with OW/OB (aged 6-16 years), recruited from seven Italian centers for the care of OW/OB, were evaluated. Peripheral sensitivity to TH was estimated through the FT3/FT4 ratio, while central sensitivity was assessed by estimating TSH index (TSHI), Thyrotroph T4 Resistance Index (TT4RI), Thyroid Feedback Quantile-based Index (TFQI), Parametric Thyroid Feedback Quantile-based Index (PTFQI). MReGFR was defined by an eGFR value ≥60 and ≤90 mL/min/1.73 m2. RESULTS: Subjects with MReGFR had significantly lower levels of FT3/FT4 ratio (0.43±0.09 vs 0.44±0.10; p=0.028) and higher levels of TSH (2.89±1.00 vs 2.68±0.99; p=0.019), TSH Index (2.95±0.45 vs 2.85±0.55; p=0.031), TFQI [1.00 (0.98-1.00) vs 1.00 (0.97-1.00); p=0.046] and PTFQI (0.66±0.17 vs 0.60±0.23; p=0.006) compared with individuals with normal eGFR. Odds ratio of MReGFR raised of 1.2-3.2-fold for each increase of 1 mIU/L in TSH, 1 unit in TSHI, and PTFQI, but not for FT3/FT4 ratio. CONCLUSION: MReGFR is associated with reduced indices of central sensitivity to TH in euthyroid children and adolescents with OW/OB. This preliminary observation should be confirmed in prospective studies.

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.

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.

Skeptical Look at the Clinical Implication of Metabolic Syndrome in Childhood Obesity.

Metabolic syndrome (MetS) is defined by a cluster of several cardio-metabolic risk factors, specifically visceral obesity, hypertension, dyslipidemia, and impaired glucose metabolism, which together increase risks of developing future cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D). This article is a narrative review of the literature and a summary of the main observations, conclusions, and perspectives raised in the literature and the study projects of the Working Group of Childhood Obesity (WGChO) of the Italian Society of Paediatric Endocrinology and Diabetology (ISPED) on MetS in childhood obesity. Although there is an agreement on the distinctive features of MetS, no international diagnostic criteria in a pediatric population exist. Moreover, to date, the prevalence of MetS in childhood is not certain and thus the true value of diagnosis of MetS in youth as well as its clinical implications, is unclear. The aim of this narrative review is to summarize the pathogenesis and current role of MetS in children and adolescents with particular reference to applicability in clinical practice in childhood obesity.

Central sensitivity to thyroid hormones is reduced in youths with overweight or obesity and impaired glucose tolerance.

Background: Thyroid hormones (TH) play multiple effects on glucose metabolism. Some recent studies carried out in adult patients suggested an association between altered sensitivity to TH and type 2 diabetes, obesity, and metabolic syndrome. No studies are currently available on the presence of altered sensitivity to the action of TH in youths with prediabetes. Objective: To evaluate the relationship between sensitivity to TH and impaired glucose tolerance (IGT), impaired fasting glucose (IFG), or glycosylated hemoglobin (HbA1c) ≥ 5.7% in youths with overweight/obesity (OW/OB). Materials and methods: This cross-sectional study included 805 Caucasian youths with OW or OB (aged 6-18 years) recruited at seven Italian centers for the care of OW/OB. Individuals with TH out of the normal range of TH in each center were excluded. The fT3/fT4 ratio was evaluated to assess peripheral sensitivity, while TSH index (TSHI), Thyrotroph T4 Resistance Index (TT4RI), Thyroid Feedback Quantile-based Index (TFQI) and Parametric TFQI were calculated to assess central sensitivity. Results: Youths with IGT (n =72) showed higher levels of TSH (3.08 ± 0.98 vs 2.68 ± 0.98 mIU/L, P =0.001), TSHI (3.06 ± 0.51 vs 2.85 ± 0.53, P =0.001), TT4RI (46.00 ± 17.87 vs 38.65 ± 16.27, P <0.0001), TFQI [1.00 (0.97-1.00) vs 1.00 (0.99-1.00)], P=0.034), PTFQI (0.67 ± 0.20 vs 0.60 ± 0.22, P =0.007) compared to youths without IGT (n =733), independently of centers and age. No differences were observed for fT3/fT4-ratio. The others phenotypes of prediabetes were not associated with altered sensitivity to TH. Odds ratio of IGT raised of 1-7-fold for each increase of 1 mIU/L in TSH (P =0.010), 1 unit in TSH Index (P =0.004), TT4RI (P =0.003) or PTFQI (P =0.018), independently of centers, age, and prepubertal stage. Conclusion: IGT was associated with a reduced central sensitivity to TH in youths with OW/OB. Our finding suggests that IGT phenotype, known to be associated with an altered cardiometabolic risk profile, might also be associated with an impaired TH homeostasis in youths with OW/OB.

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.

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.

Static cutoffs or tables for the diagnosis of hypertension? Effect on identification of organ damage in youths with obesity.

BACKGROUND AND AIM: Recently, the European Society of Cardiology task force released a Consensus document (ESC-CD) on pediatric hypertension (HTN) supporting the use of normative tables (age range 6-16 years) for the diagnosis of HTN, while the Hypertension Canada Guidelines (HTN-CGs) proposed static cutoffs. We aimed to assess the prevalence of HTN by ESC-CD or HTN-CGs and their association with glomerular function and left ventricular (LV) geometry in youths with overweight/obesity (OW/OB). METHODS AND RESULTS: Data of 3446 youths were analyzed. HTN by was defined using normative tables (ESC-CD) or static cutoffs of BP ≥ 120/80 in children (age <12 years) and ≥130/85 mmHg in adolescents (age ≥12 years) (HTN-CGs). Mildly reduced glomerular filtration rate was defined by GFR <90 ≥ 60 mL/min/1.73 m2. Concentric LV hypertrophy (cLVH) was assessed in 500 youths and defined by LVH and high relative wall thickness as proposed by ESC-CD. Prevalence of HTN was 27.9% by ESC-CD and 22.7% by HTN-CGs. The association with mildly reduced glomerular filtration rate was significant only in hypertensive adolescents classified by HTN-CGs [Odds Ratio (OR), 95%Cl] 2.16 (1.44-3.24), whereas the association with cLVH was significant using both criteria: children OR 2.18 (1.29-3.67) by ESC-CD and 2.27 (1.32-3.89) by HTN-CGs; adolescents OR 2.62 (1.17-5.84) by ESC-CD and 2.83 (1.14-7.02) by HTN-CGs. CONCLUSION: Although static cutoffs may represent a simplification for HTN identification, tables by ESC-CD detect a higher number of hypertensive youths before a clear appearance of glomerular impairment, which offers advantages in terms of primary cardiovascular prevention.

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.

Hypertension in children and adolescents.

Definition and management of arterial hypertension in children and adolescents are uncertain, due to different positions of current guidelines. The European Society of Cardiology task-force, constituted by Associations and Councils with interest in arterial hypertension, has reviewed current literature and evidence, to produce a Consensus Document focused on aspects of hypertension in the age range of 6-16 years, including definition, methods of measurement of blood pressure, clinical evaluation, assessment of hypertension-mediated target organ damage, evaluation of possible vascular, renal and hormonal causes, assessment and management of concomitant risk factors with specific attention for obesity, and anti-hypertensive strategies, especially focused on life-style modifications. The Consensus Panel also suggests aspects that should be studied with high priority, including generation of multi-ethnic sex, age and height specific European normative tables, implementation of randomized clinical trials on different diagnostic and therapeutic aspects, and long-term cohort studies to link with adult cardiovascular risk. Finally, suggestions for the successful implementation of the contents of the present Consensus document are also given.

Uric acid and cardiometabolic risk by gender in youth with type 1 diabetes.

The aim of this study was to investigate the association between uric acid (UA) and cardiometabolic risk factors (CMRFs) by sex in youth with type 1 diabetes (T1D). Retrospective data collected from 1323 children and adolescents (5-18 years; 716 boys) with T1D recruited in 9 Italian Pediatric Diabetes Centers were analyzed. CMRFs included UA, HbA1c, blood pressure (BP), cholesterol (TC), HDL, triglycerides (TG), neutrophils (N) and lymphocytes (L) count, glomerular filtration rate (eGFR) (calculated using Schwartz-Lyon equation). In boys, we found a higher age, daily insulin dose, TG, TG/HDL ratio, TC/HDL ratio, systolic BP, N/L ratio and lower HDL, and eGFR across UA tertiles (p = 0.01-0.0001). Similar results were found in girls but not for TG and systolic BP. In boys, the odds ratio (OR) of high levels of TG/HDL ratio, TC/HDL ratio, BP and mildly reduced eGFR (MRGFR) increased for 0.5 mg/dL of UA. Instead, in girls an increased levels of 0.5 mg/dL of UA were associated with high OR of TC/HDL ratio, N/L ratio and MRGFR. Uric acid may represent a useful marker for identifying youth with T1D at high cardiometabolic risk, and this association appears to vary by sex.

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.

Albuminuric and non-albuminuric reduced eGFR phenotypes in youth with type 1 diabetes: Factors associated with cardiometabolic risk.

BACKGROUND AND AIM: Albuminuria and reduced eGFR are hallmarks of Diabetic Kidney Disease in adults. Our aim was to analyze factors associated with albuminuric and non-albuminuric mildly reduced eGFR phenotypes in youths with type 1 diabetes. METHODS AND RESULTS: This multicenter cross-sectional study included 1549 youths (age 5-17 years) with type 1 diabetes enrolled at 14 Italian Pediatric Diabetes Centers. Albuminuria, creatinine, glycosylated hemoglobin (HbA1c), lipids, blood pressure (BP), neutrophils (N) and lymphocytes (L) count were analyzed. Uric acid (UA) was available in 848 individuals. Estimated GFR (eGFR) was calculated using bedside Schwartz's equation. The sample was divided in three phenotypes: 1) normoalbuminuria and eGFR ≥90 mL/min/1.73 m2 (reference category, n = 1204), 2) albuminuric and normal GFR phenotype (n = 106), 3) non-albuminuric mildly reduced GFR (MRGFR) phenotype (eGFR 60-89 mL/min/1.73 m2, n = 239). Albuminuric and non-albuminuric reduced eGFR phenotypes were significantly associated with autoimmune thyroiditis (P =0.028 and P=0.044, respectively). Albuminuric phenotype showed high risk of high HbA1c (P=0.029), high BP (P < 0.001), and low HDL-C (P =0.045) vs reference category. Non-albuminuric MRGFR phenotype showed high risk of high BP (P < 0.0001), low HDL-C (P =0.042), high Triglycerides/HDL-C ratio (P =0.019), and high UA (P < 0.0001) vs reference category. CONCLUSION: Non albuminuric MRGFR phenotype is more prevalent than albuminuric phenotype and shows a worst cardiometabolic risk (CMR) profile). Both phenotypes are associated with autoimmune thyroiditis. Our data suggest to evaluate both albuminuria and eGFR earlier in type 1 diabetes to timely identify young people with altered CMR profile.

Prevalence of Mildly Reduced Estimated GFR by Height- or Age-Related Equations in Young People With Obesity and Its Association with Cardiometabolic Risk Factors.

OBJECTIVE: To compare the prevalence of mildly reduced estimated glomerular filtration rate (MRGFR) (eGFR >60 and < 90 mL/min/1.73 m2), calculated by two creatinine-based equations, and its association with cardiometabolic risk factors (CMRF) in youth with overweight (OW)/obesity (OB). METHODS: This is a multicenter cross-sectional study involving university and non-university hospital pediatrics departments. We enrolled 3,118 youth with OW/OB (5-14 years) and 286 healthy normal weight (NW) youth. eGFR was calculated using bedside Schwartz equation (eGFRBSE) and Full Age Spectrum equation (eGFRFAS). In OW/OB group we analyzed the association between eGFR calculated by both equations and CMRF. Uric acid (UA) and birth weight were available in 2,135 and in 1,460 youth. RESULTS: The prevalence of MRGFR was 3.8% in NW versus 7.8% in OW/OB (P = .016) by eGFRBSE, and 8.7% in NW versus 19.4% in OW/OB (P < .0001) by eGFRFAS. eGFRBSE and eGFRFAS identified 242 and 605 young people with OW/OB with MRGFR, respectively. Individuals with MRGFR according with both equations showed lower birth weight, younger age, higher BMI-SDS, non-high-density lipoprotein-cholesterol and UA as compared to those with normal eGFR. To examine whether the eGFRFAS was associated with a worse CMR profile also in the range of normal eGFRBSE, we reclassified young people with normal eGFRBSE (n = 2,876) according with eGFRFAS. Out of youth with normal eGFRBSE, 366 (12.7%) presented MRGFR by eGFRFAS and had lower age, higher BMI-SDS, BP and UA than the remaining youth reclassified as normal eGFRFAS. CONCLUSION: MRGFR is associated with an altered CMR profile in a large sample of young people with overweight (OW)/obesity (OB). The eGFRFAS equation identifies a higher prevalence of youth with MRGFR, compared to eGFRBSE equation.

Uric acid, impaired fasting glucose and impaired glucose tolerance in youth with overweight and obesity.

BACKGROUND AND AIM: The relationships between uric acid (UA) and prediabetes is poorly explored in youth. We investigated the association between UA, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), insulin resistance (IR) and low insulin sensitivity (IS) in youth with overweight/obesity (OW/OB). METHODS AND RESULTS: A cross-sectional study was performed in 2248 youths with OW/OB (age 5-17 years). The sample was stratified in sex-specific quintiles (Q1 to Q5) of UA and the associations with fasting (FG), 2-h post-load glucose (2H-PG), IR and low IS were investigated. IR and low IS were estimated by assessment model of insulin resistance (HOMA-IR) and whole-body IS index (WBISI), respectively. IFG was defined as FG ≥ 100 < 126 mg/dL, IGT as 2H-PG ≥140 < 200 mg/dL, IR as HOMA-IR ≥75th percentile and low IS as WBISI ≤25th percentile by sex. Age, body mass index z-score, 2H-PG, HOMA-IR and WBISI, increased across sex-quintiles of UA while FG did not. The prevalence of IFG and IR were significantly increased in Q5 vs Q1 (reference quartile, P < 0.025). The prevalence of IGT increased from Q3 to Q5 vs Q1 (P < 0.025-0.0001) and that of low IS from Q2 to Q5 vs Q1 (P < 0.005-0.0001). CONCLUSIONS: In youth with OW/OB, rates of IGT and low IS increased progressively across quintiles of UA. On the contrary, IFG and IR were associated only with the highest quintile of UA. Our data suggest that UA is a biomarker of impaired glucose metabolism prevalently in post-challenge condition rather than in fasting state.