Small-for-gestational-age birth is linked to cardiovascular dysfunction in early childhood.

BACKGROUND: The aim of this study was to assess clinical and echographic markers of cardiovascular dysfunction in infants born small for gestational age (SGA) compared to a control group of subjects born adequate for gestational age (AGA). METHODS: This was a single-center cross-sectional case-control study. We recruited 20 SGA and 20 gestational age-matched AGA subjects at 24 months of age. The study population underwent anthropometric and Doppler 2-dimensional echocardiographic assessments, and carotid artery intima-media thickness (cIMT) and endothelium-dependent vasodilation evaluation (FMD). The pressure-volume curve during diastole was calculated using the algorithm for the elastance calculation on 1 single beat. RESULTS: SGA children showed lower stroke volume, lower left ventricle (LV) dimensions and volume, and greater LV thickness. Diastolic function was impaired in SGA with lower capacitance and higher elastance. Birth weight standard deviation score was positively associated with capacitance and negatively associated with E/E' ratio and elastance, and in SGA infants, the end-diastolic pressure-related volume curve was shifted to the left compared to AGA. cIMT and systemic vascular resistance were significantly higher, while FMD was lower, in SGA compared to AGA; birth weight standard deviation score was directly correlated with FMD and inversely correlated with cIMT. Finally, a longer breastfeeding duration was associated to a lower cIMT even after correction for confounding factors. CONCLUSIONS: This study shows that infants born SGA present an early and subtle cardiovascular dysfunction compared to AGA controls. These alterations are strongly related to weight at birth. Finally, breastfeeding exerts an important protective and beneficial cardiovascular effect.

Influence of Ultraviolet Radiation on the Association between 25-Hydroxy Vitamin D Levels and Cardiovascular Risk Factors in Obesity.

OBJECTIVE: To establish if the correction with estimates of ultraviolet (UV) exposure influences the association between 25-OH-vitamin D (25OHD) levels and metabolic variables. STUDY DESIGN: A cross-sectional study was performed in 575 obese children and adolescents (>6 years of age) in a tertiary referral center. Cardiovascular risk factors were measured. The estimate of UV exposure was evaluated by 3 methods: (1) season; (2) mean of UV radiation (UVR); and (3) mean of UV index (UVI). UVR and UVI were considered at 1 (UVR 1 month prior to testing [UVR1], UVI 1 month prior to testing [UVI1]) or 3 (UVR 3 months prior to testing [UVR3], UVI 3 months prior to testing [UVI3]) months prior to testing. All analyses were corrected for confounders (sex, age, puberty, body mass index, waist circumference, the inclusion and exclusion of estimates of UV exposure). RESULTS: The 25OHD levels were associated with seasons, UVR1, UVR3, UVI1, and UVI3, and best associations with UVR3 and UVI3. In all models, total cholesterol, low-density lipoprotein cholesterol and triglycerides were negatively associated with 25OHD levels. The strength of the association increased with no correction, correction for seasons, UVR, and UVI. UVR3 and UVI3 performed better than UVR1 and UVI3. CONCLUSIONS: Higher lipid concentrations were associated with low 25OHD levels in obese children and adolescents with the power of the association dependent on the estimates of UVR. As the mean values 3 months prior to testing for both UVR and UVI determined the best associations, the interval of the steady state time of 25OHD levels could be preferentially used in the metabolic studies. Controlling for an estimate of UVR is important to decrease the heterogeneity of studies.

Case report: Better late than never, but sooner is better: switch from CSII to sulfonylureas in two patients with neonatal diabetes due to KCNJ11 variants.

Neonatal diabetes mellitus (NDM) is a rare genetic disease characterized by severe hyperglycemia requiring insulin therapy with onset mostly within the first 6 months and rarely between 6-12 months of age. The disease can be classified into transient (TNDM) or permanent neonatal diabetes mellitus (PNDM), or it can be a component of a syndrome. The most frequent genetic causes are abnormalities of the 6q24 chromosomal region and mutations of the ABCC8 or KCNJ11 genes coding for the pancreatic beta cell's potassium channel (KATP). After the acute phase, patients with ABCC8 or KCNJ11 mutations treated with insulin therapy can switch to hypoglycemic sulfonylureas (SU). These drugs close the KATP channel binding the SUR1 subunit of the potassium channel and restoring insulin secretion after a meal. The timing of this switch can be different and could affect long-term complications. We describe the different management and clinical outcome over the time of two male patients with NDM due to KCNJ11 pathogenetic variants. In both cases, continuous subcutaneous insulin infusion pumps (CSII) were used to switch therapy from insulin to SU, but at different times after the onset. The two patients kept adequate metabolic control after the introduction of glibenclamide; during the treatment, insulin secretion was evaluated with c-peptide, fructosamine, and glycated hemoglobin (HbA1c), which were within the normal range. In neonates or infants with diabetes mellitus, genetic testing is an indispensable diagnostic tool and KCNJ11 variants should be considered. A trial of oral glibenclamide must be considered, switching from insulin, the first line of NDM treatment. This therapy can improve neurological and neuropsychological outcomes, in particular in the case of earlier treatment initiation. A new modified protocol with glibenclamide administered several times daily according to continuous glucose monitoring profile indications, was used. Patients treated with glibenclamide maintain good metabolic control and prevent hypoglycemia, neurological damage, and apoptosis of beta cells during long-term administration.

High-normal estimated glomerular filtration rate and hyperuricemia positively correlate with metabolic impairment in pediatric obese patients.

BACKGROUND: Childhood obesity represents a major health concern worldwide due to its well established detrimental effect on cardiovascular and its potential negative effect on kidney functions. However, biomarkers that can help diagnose early stages of kidney damage in obese children represent an unmet clinical need. OBJECTIVES: In this study, we asked whether the prevalence of microalbuminuria, estimated glomerular filtration rate (eGFR) or hyperuricemia recorded in a wide cohort of obese children and adolescents would positively correlate with cardiometabolic dysfunction in these subjects. METHODS: We carried out a cross-sectional study on 360 obese children and adolescents between the ages of 3-18 years, enrolled in a tertiary care center. Clinical and biochemical evaluations including oral glucose tolerance tests (OGTTs) were performed on all patients. Microalbuminuria was defined as urinary albumin-to-creatinine ratio (u-ACR) of 30-300 mg/g. All data are expressed as mean ± standard deviation (SD), absolute values or percentages. Sex age-specific and eGFR SDs were used for statistical analyses. Serum uric acid ≥ 5.5 mg/dL was considered abnormal. RESULTS: The prevalence of microalbuminuria was 6.4%. Except for a lower insulinogenic-index, no correlations between microalbuminuria and cardiometabolic risk factors were detected. eGFR was < -1 SD and > 1 SD in 1.4% and 60.8% of subjects, respectively. Subjects with an eGFR > 1 SD had higher systolic blood pressure, liver enzymes, insulin resistance, glucose and insulin during OGTT, lower insulin sensitivity and a more prevalent microalbuminuria. Hyperuricemia (27.5%) increased the odds of hypertension, HDL ≤ 10th percentile and glucose ≥ 155.0 mg/dL after 60 minutes of OGTT. CONCLUSIONS: A worse cardiometabolic profile was observed in subjects with an eGFR > 1 SD compared to other subgroups. Therefore, pediatric obese patients with eGFR > 1 SD or hyperuricemia should be closely monitored for microalbuminuria and post-challenge glucose and insulin secretion, all potential indicators of renal dysfunction in these young patients.

High accuracy of noninvasive tests to diagnose Helicobacter pylori infection in very young children.

OBJECTIVE: To validate the (13)C-urea-breath-test (UBT) and stool antigen test (HpSA) in children aged 5 years or younger, against invasive histologic study and rapid-urease-testing or culture. STUDY DESIGN: On all consecutive children aged 5 years or younger undergoing endoscopy in 1 single center during the last 7.5 years, UBT and HpSA were performed. RESULTS: Of a total of 184 children (median age 2.2 years, range 0.2-5.5), 30 were Helicobacter pylori-positive (16.3%). Sensitivity and specificity of UBT were 93.3% (95%CI 77.9%-99.2%) and 95.5% (90.9-98.2), with a cutoff of 5 per thousand, but specificity increased to 98.1% (94.4%-99.6%) with a cutoff of 8 per thousand. Sensitivity and specificity of HpSA were 93.3% (77.9%-99.2%) and 98.7% (95.4%-99.8%). CONCLUSION: Accuracy of noninvasive tests in our single-center study were satisfactory: specificity of UBT improved with a cutoff at 8%, and sensitivity of HpSA was high when determined locally without transportation after long or inadequate storage that could impair results.