Calcium, Phosphate, and Vitamin D in Children and Adolescents with Chronic Diseases: A Cross-Sectional Study.

Chronic diseases may affect the nutritional status of children and adolescents. Calcium (Ca), phosphorus (P), and vitamin D (Vit-D) are crucial nutrients for their growth and development. Proper diagnosis and treatment are critical components of personalized and precision medicine. Hence, we conducted a cross-sectional and comparative study to evaluate Ca, P, and Vit-D levels in their non-skeletal functions and their association with health and nutritional biomarkers in children and adolescents with diverse chronic conditions. We performed anthropometric, body composition, clinical evaluation, biochemical analysis, and dietary survey methods. A total of 78 patients (1-19 years, 43 females, 42 children) took part in this study. Overall, 24, 30, and 24 participants were obese, undernourished, and eutrophic, respectively. Results found that 74% and 35% of individuals had deficient Vit-D and Ca intake, respectively. Most cases were normocalcemic. Results also found that 47% of the subjects had Vit-D deficiency (VDD), 37% were insufficient, and 37% had hypophosphatemia. Of the 46% and 31% of patients with VDD and insufficient levels, 19% and 11% were hypophosphatemic, respectively. Calcium, P, and Vit-D levels were associated with anthropometric parameters, body mass index, body composition, physical activity, diet, growth hormones, and the immune, liver, and kidney systems. These results show the coincident risk of altered Ca, P, and Vit-D metabolism in children and adolescents with chronic diseases.

Utility of time in tight range (TITR) in evaluating metabolic control in pediatric and adult patients with type 1 diabetes in treatment with advanced hybrid closed-loop systems.

PURPOSE: To analyze the time in tight range (TITR), and its relationship with other glucometric parameters in patients with type 1 diabetes (T1D) treated with advanced hybrid closed-loop (AHCL) systems. METHODS: A prospective observational study was conducted on pediatric and adult patients with T1D undergoing treatment with AHCL systems for at least 3 months. Clinical variables and glucometric parameters before and after AHCL initiation were collected. RESULTS: A total of 117 patients were evaluated. Comparison of metabolic control after AHCL initiation showed significant improvements in HbA1c (6.9 ± 0.9 vs. 6.6 ± 0.5%, p < 0.001), time in range (TIR) (68.2 ± 11.5 vs. 82.5 ± 6.9%, p < 0.001), TITR (43.7 ± 10.8 vs. 57.3 ± 9.7%, p < 0.001), glucose management indicator (GMI) (6.9 ± 0.4 vs. 6.6 ± 0.3%, p < 0.001), time below range (TBR) 70-54 mg/dl (4.3 ± 4.5 vs. 2.0 ± 1.4%, p < 0.001), and time above range (TAR) > 180 mg/dl (36.0 ± 7.6 vs. 15.1 ± 6.4%, p < 0.001). Coefficient of variation (CV) also improved (36.3 ± 5.7 vs. 30.6 ± 3.7, p < 0.001), while time between 140-180 mg/dl remained unchanged. In total, 76.3% achieved TITR > 50% (100% pediatric). Correlation analysis between TITR and TIR and GRI showed a strong positive correlation, modified by glycemic variability. CONCLUSIONS: AHCL systems achieve significant improvements in metabolic control (TIR > 70% in 93.9% patients). The increase in TIR was not related to an increase in TIR 140-180 mg/dl. Despite being closely related to TIR, TITR allows for a more adequate discrimination of the achieved control level, especially in a population with good initial metabolic control. The correlation between TIR and TITR is directly influenced by the degree of glycemic variability.

Quality of life, diabetes-related stress and treatment satisfaction are correlated with glycemia risk index (GRI), time in range and hypoglycemia/hyperglycemia components in type 1 diabetes.

INTRODUCTION: To evaluate the relationship between the GRI -component of hypoglycemia (CHypo) and hyperglycemia (CHyper)- with diabetes quality of life (DQoL), diabetes-related stress (DDS), perception of hypoglycemia (Clarke Test), visual analogic scale (VAS) and diabetes-knowledge (DKQ2) in T1D. METHODS: Cross-sectional study in 92 patients with T1D under intensive insulin treatment (21.7% CSII) and flash glucose monitoring (isCGM). Clinical, metabolic and glycometric parameters and quality of life/satisfaction questionnaires were analyzed. RESULTS: 92 patients (54.3% male, BMI 25.4 ± 4.5 kg/m2, HbA1c 7.5 ± 1.0%, TIR 53.9 ± 15.9%) with mean age 36.1 ± 12.6years and 17.8 ± 11.3 T1D duration. The mean GRI was 60.6 ± 22.2 with a CHypo and CHyper of 5.9 ± 4.8 and 27.3 ± 14.4, respectively. 19.1% presented a pathological Clarke's test. Patients with TIR > 70% and GRI < 40 showed better VAS (8.8 ± 1.3 vs 9.3 ± 0.9, p < 0.05) and DDS (46.4 ± 22.1 vs 36.7 ± 16.6, p < 0.05) scores, showing no differences between groups. CHyper > 15 and Chypo > 3.4 were related to worse levels of DQoL (91.1 ± 23.9 vs 76.6 ± 18.6 and 94.6 ± 24.8 vs 79.8 ± 20.1, p < 0.01), DDS(49.8 ± 22.4 vs 35.7 ± 16.5 and 49.8 ± 22.4 vs 35.7 ± 16.5, p < 0.01),and DKQ2 (24.4 ± 4.3 vs 26.8 ± 5.2 and 24.1 ± 4.8 vs 26.0 ± 4.6, p < 0.05), respectively. Worse metabolic control defined by GRI correlated with worse scores in VAS (r = -0.209, p < 0.05), DQoL (r = 0.205, p < 0.05), and DDS (r = 0.205, p < 0.05). No difference was observed in knowledge´s scale. CHyper correlated with worse scores in VAS (r = -0.231, p < 0.05), DQoL (r = 0.422, p < 0.01), and DDS (r = 0.341, p < 0.01) and lower degree of knowledge DKQ2 (r = -0.231, p < 0.05). When analyzing DQoL as a dependent variable in a multiple lineal regression, only age (ß = 0.747; p < 0.001) and CHyper (ß = 0.717; p < 0.001) maintained statistical significance. CONCLUSIONS: Higher GRI was related to worse quality of life, diabetes-related stress and satisfaction with treatment, analogous to the TIR results.CHyper an Chypo were related to a greater decline in quality of life, diabetes-related stress, and lower satisfaction with treatment.However, in a multiple linear regression, only CHyper maintained statistical significance.

Clinical, glycometric features and treatment in a family with monogenic diabetes due to a new mutation in the insulin gene.

Monogenic diabetes caused by changes in the gene that encodes insulin (INS) is a very rare form of monogenic diabetes (<1%). The aim of this work is to describe the clinical and glycaemic control characteristics over time from four members of a family diagnosed with monogenic diabetes with the novel mutation: c.206del,p.(Gly69Aalfs*62) located in exon 3 of the gene INS. 75% are females, with debut in adolescence and negative autoimmunity. In all cases, C-peptide is detectable decades after diagnosis (>0.6ng/ml). Currently, patients are being treated either with insulin in a bolus-basal regimen, oral antidiabetics or hybrid closed loop system. Monogenic diabetes due to mutation in the INS is an entity with heterogeneous presentation, whose diagnosis requires high suspicion and presents an important clinical impact. Given the lack of standards in this regard, therapy must be individualized, although insulin therapy could help preserve beta cell functionality in these subjects.

Impact of glucose variability on the assessment of the glycemia risk index (GRI) and classic glycemic metrics.

OBJECTIVE: To evaluate the impact of glucose variability on the relationship between the GRI and other glycemic metrics in a cohort of pediatric and adult patients with type 1 diabetes (T1D) using intermittent scanning continuous glucose monitoring (isCGM). METHODS: We performed a cross-sectional study of 202 patients with T1D under intensive insulin treatment (25.2% CSII) using isCGM. Clinical, metabolic, and glycemic metrics were collected, and the GRI was calculated with its hypoglycemia (CHypo) and hyperglycemia (CHyper) components. The correlation between the GRI and other classical glycometrics in relation to the coefficient of variation (CV) was evaluated. RESULTS: A total of 202 patients were included (53% male; 67.8% adults) with a mean age of 28.6 ± 15.7 years and 12.5 ± 10.9 years of T1D evolution (TIR 59.0 ± 17.0%; CV 39.8 ± 8.0%; GMI 7.3 ± 1.1%). The mean GRI was 54.0 ± 23.3 with a CHypo and CHyper component of 5.7 ± 4.8 and 23.4 ± 14.3, respectively. A strong negative correlation was observed between the GRI and TIR (R = -0.917; R2 = 0.840; p < 0.001), showing differences when dividing patients with low glycemic variability (CV < 36%) (R = -0.974; R2 = 0.948; p < 0.001) compared to those with greater CV instability (≥36%) (R = -0.885; R2 = 0.784; p < 0.001). The relationship of GRI with its two components was strongly positive with CHyper (R = 0.801; R2 = 0.641; p < 0.001) and moderately positive with CHypo (R = 0.398; R2 = 0.158; p < 0.001). When the GRI was evaluated with the rest of the classic glycemic metrics, a strong positive correlation was observed with HbA1c (R = 0.617; R2 = 0.380; p < 0.001), mean glucose (R = 0.677; R2 = 0.458; p < 0.001), glucose standard deviation (R = 0.778; R2 = 0.605; p < 0.001), TAR > 250 (R = 0.801; R2 = 0.641; p < 0.001), and TBR < 54 (R = 0.481; R2 = 0.231; p < 0.001). CONCLUSIONS: The GRI correlated significantly with all the glycemic metrics analyzed, especially with the TIR. Glycemic variability (GV) significantly affected the correlation of the GRI with other parameters and should be taken into consideration.

Glycemia Risk Index Assessment in a Pediatric and Adult Patient Cohort With Type 1 Diabetes Mellitus.

BACKGROUND: To evaluate the glycemia risk index (GRI) as a new glucometry in pediatric and adult populations with type 1 diabetes (T1D) in clinical practice. METHODS: A cross-sectional study of 202 patients with T1D receiving intensive treatment with insulin (25.2% continuous subcutaneous insulin infusion [CSII]) and intermittent scanning (flash) glucose monitoring (isCGM). Clinical and glucometric isCGM data were collected, as well as the component of hypoglycemia (CHypo) and component of hyperglycemia (CHyper) of the GRI. RESULTS: A total of 202 patients (53% males and 67.8% adults) with a mean age of 28.6 ± 15.7 years and 12.5 ± 10.9 years of T1D evolution were evaluated.Adult patients (>19 years) presented higher glycated hemoglobin (HbA1c) (7.4 ± 1.1 vs 6.7 ± 0.6%; P < .01) and lower time in range (TIR) (55.4 ± 17.5 vs 66.5 ± 13.1%; P < .01) values than the pediatric population, with lower coefficient of variation (CV) (38.6 ± 7.2 vs 42.4 ± 8.9%; P < .05). The GRI was significantly lower in pediatric patients (48.0 ± 22.2 vs 56.8 ± 23.4; P < .05) associated with higher CHypo (7.1 ± 5.1 vs 5.0 ± 4.5; P < .01) and lower CHyper (16.8 ± 9.8 vs 26.5 ± 15.1; P < .01) than in adults.When analyzing treatment with CSII compared with multiple doses of insulin (MDI), a nonsignificant trend to a lower GRI was observed in CSII (51.0 ± 15.3 vs 55.0 ± 25.4; P= .162), with higher levels of CHypo (6.5 ± 4.1 vs 5.4 ± 5.0; P < .01) and lower CHyper (19.6 ± 10.6 vs 24.6 ± 15.2; P < .05) compared with MDI. CONCLUSIONS: In pediatric patients and in those with CSII treatment, despite a better control by classical and GRI parameters, higher overall CHypo was observed than in adults and MDI, respectively. The present study supports the usefulness of the GRI as a new glucometric parameter to evaluate the global risk of hypoglycemia-hyperglycemia in both pediatric and adult patients with T1D.

Increased Presentation of Diabetic Ketoacidosis and Changes in Age and Month of Type 1 Diabetes at Onset during the COVID-19 Pandemic in Spain.

Objective: To assess the impact of the COVID-19 pandemic and lockdown measures on the presenting characteristics (age at diagnosis, severity, monthly distribution) of newly diagnosed type 1 diabetes in Spanish children. Research Design and Methods: An ambispective observational multicenter study was conducted in nine Spanish tertiary-level hospitals between January 2015 and March 2021. Inclusion criteria: new cases of type 1 diabetes in children (0-14 years) recording age, sex, date of diagnosis, presence of diabetic ketoacidosis (DKA) at onset, and severity of DKA. Data were compared before and during the pandemic. Results: We registered 1444 new cases of type 1 diabetes in children: 1085 in the pre-pandemic period (2015-2019) and 359 during the pandemic (2020-March 2021). There was a significant increase in the group aged ≤4 years in the pandemic period (chi-squared = 10.986, df 2, p = 0.0041). In 2020-2021, cases of DKA increased significantly by 12% (95% CI: 7.2-20.4%), with a higher percentage of moderate and severe DKA, although this increase was not significant. In 2020, there was a sharp decrease in the number of cases in March, with a progressive increase from May through November, higher than in the same months of the period 2015-2019, highlighting the increase in the number of cases in June, September, and November. The first three months of 2021 showed a different trend to that observed both in the years 2015-2019 and in 2020, with a marked increase in the number of cases. Conclusions: A change in monthly distribution was described, with an increase in DKA at onset of type 1 diabetes. No differences were found in severity, although there were differences in the age distribution, with an increase in the number of cases in children under 4 years of age.

High prevalence of variants in skeletal dysplasia associated genes in individuals with short stature and minor skeletal anomalies.

OBJECTIVE: Next generation sequencing (NGS) has expanded the diagnostic paradigm turning the focus to the growth plate. The aim of the study was to determine the prevalence of variants in genes implicated in skeletal dysplasias in probands with short stature and mild skeletal anomalies. DESIGN: Clinical and radiological data were collected from 108 probands with short stature and mild skeletal anomalies. METHODS: A customized skeletal dysplasia NGS panel was performed. Variants were classified using ACMG recommendations and Sherloc. Anthropometric measurements and skeletal anomalies were subsequently compared in those with or without an identified genetic defect. RESULTS: Heterozygous variants were identified in 21/108 probands (19.4%). Variants were most frequently identified in ACAN (n = 10) and IHH (n = 7) whilst one variant was detected in COL2A1, CREBBP, EXT1, and PTPN11. Statistically significant differences (P < 0.05) were observed for sitting height/height (SH/H) ratio, SH/H ratio standard deviation score (SDS), and the SH/H ratio SDS >1 in those with an identified variant compared to those without. CONCLUSIONS: A molecular defect was elucidated in a fifth of patients. Thus, the prevalence of mild forms of skeletal dysplasias is relatively high in individuals with short stature and mild skeletal anomalies, with variants in ACAN and IHH accounting for 81% of the cases. An elevated SH/H ratio appears to be associated with a greater probability in detecting a variant, but no other clinical or radiological feature has been found determinant to finding a genetic cause. Currently, we cannot perform extensive molecular studies in all short stature individuals so detailed clinical and radiological phenotyping may orientate which are the candidate patients to obtain worthwhile results. In addition, detailed phenotyping of probands and family members will often aid variant classification.

Falso negativo en el primer cribado neonatal de hipotiroidismo congénito en recién nacido gemelo / False negative in the first neonatal screening for congenital hypothyroidism in a newborn twin

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