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Non-albuminuric reduced eGFR phenotype in children and adolescents with type 1 diabetes
Glucose and gluconeogenic substrate exchange by the forearm skeletal muscle in hyperglycemic and insulin treated type II diabetic patients.
Glycemic control and microvascular complications in adults with type 1 diabetes and long-lasting treated celiac disease: A case-control study
Aims: To investigate whether in type 1 diabetes (T1DM) patients the concomitance of long-lasting celiac disease (CD) treated with a gluten free diet (GFD) impacts glycaemic control and the prevalence/severity of microvascular complications.
Methods: A case-control, observational study was performed in 34 patients with T1DM and GFD-treated CD and 66 patients with T1DM alone matched for age, gender, and T1DM duration. Anthropometric parameters, glucose control (HbA1c), status of chronic complications and concomitant autoimmune diseases were evaluated.
Results: HbA1c level was similar in T1DM + CD and T1DM alone (7.8 ± 1.0 vs 7.7 ± 1.1%, P = 0.57); insulin requirement was significantly higher in T1DM + CD compared with T1DM (P = 0.04). There were no differences in systolic blood pressure while diastolic blood pressure was significantly lower in T1DM + CD (P = 0.003). The prevalence/severity of microvascular complications was similar between the two groups. Glomerular filtration rate (eGFR) was significantly lower in T1DM + CD (100 ± 20 vs 110 ± 16 ml/min/1.73 m2, P = 0.007).
Conclusions: In patients with T1DM, the co-occurrence of long-term GFD-treated CD neither worsens glycemic control nor negatively impacts chronic microvascular complications. However, patients with T1DM + CD have lower eGFR values than those with T1DM alone
A new simple formula built on the American Academy of Pediatrics criteria for the screening of hypertension in overweight/obese children
We evaluated the performance of a new simple formula (NSF) for the screening of hypertension by American Academy of Pediatrics Guidelines 2017 (AAPG2017) in children with overweight/obesity (OW/OB). The performance of the NSF and the modified blood pressure to height ratio (MBPHR3) thresholds against AAPG2017 was evaluated; both methods were also compared to assess the association with concentric left ventricular hypertrophy (cLVH). The study included 3259 OW/OB children (5-13 years). Two centers served as learning sample (LS) (n = 1428), four centers served as validation sample (VS) (n = 1831), and the echocardiographic evaluation was available in 409 children in VS. The NSF was [1.5 × systolic blood pressure (mmHg) + diastolic blood pressure (mmHg)] - [(26 × height (m)] - age (years). A cut-off of the NSF ≥ 193 mmHg showed sensitivity, specificity, positive, and negative predictive values of 0.92, 0.93, 0.83, and 0.97, respectively, versus the standard procedure. Against AAPG2017, the NSF showed higher specificity and positive predictive values than the MBPHR3 thresholds. Among hypertensive children defined by AAPG2017, NSF, or MBPHR3, the odds ratio (95%CI) for cLVH was respectively 1.73 (1.06-2.83), 1.69 (1.05-2.75), and 1.18 (0.75-1.85).Conclusions: The NSF shows a very high performance for the screening of OW/OB children at risk of hypertension and cLVH. What is Known: • The American Academy of Pediatrics released updated guidelines (AAPG 2017) to classify hypertension (HTN) in children. • The process needs categorization of height percentiles and comparison of blood pressure versus gender and age-adjusted values. What is New: • A user-friendly formula built on the AAPG 2017 was validated for the categorization of HTN in children with overweight/obesity. • The formula showed high performance in identifying children with HTN versus the standard procedure (sensitivity 0.92, specificity 0.93) and similar ability in identifying hypertensive children with concentric left ventricular hypertrophy versus the standard procedure (40% and 39% respectively)
High normal post-load plasma glucose, cardiometabolic risk factors and signs of organ damage in obese children
Objective To evaluate normoglycemic overweight/obese (Ow/Ob) children whose post-load plasma glucose (2hPG) cut-point may be significantly associated with cardiometabolic risk factors (CMRFs) and whether this cut-point predicts preclinical signs of organ damage. Methods One thousand seven hundred and thrity four normoglycemic Ow/Ob children were stratified into quintiles of 2hPG, the sixth group was constituted by 101 children with impaired glucose tolerance (IGT). Results Moving from the lower quintiles of 2hPG to IGT, the groups differed for Prepubertal stage, BMI, fasting PG, insulin levels, blood pressure, and lipids. To evaluate the best cut-off of 2hPG related to CMRFs, the area under the receiver operating characteristic curve and the Youden's index was calculated. Insulin resistance, high blood pressure, and high triglyceride/HDL-C ratio were associated with a 2hPG cut-off of 110 mg/dl. Children with 2hPG ≥110 mg/dl showed 1.3-3.2 fold higher risk to have high levels of ALT (as surrogate of nonalcoholic fatty liver disease) or increased carotid intima-media thickness. Conclusions This study, performed in a large cohort of Ow/Ob children, shows that an atherogenic risk profile and preclinical signs of organ damage are associated with post-challenge elevations in plasma glucose still considered in the high normal range
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
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
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
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
Triglycerides-to-HDL cholesterol ratio as screening tool for impaired glucose tolerance in obese children and adolescents
To identify metabolic phenotypes at increased risk of impaired glucose tolerance (IGT) in Italian overweight/obese children (n = 148, age 5-10 years) and adolescents (n = 531, age 10-17.9 year)
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