Glucose Intolerance In Children Research Articles

HbA1c or fructosamine on evaluating glucose intolerance in children with beta- thalassemia

BackgroundBeta-thalassemia major (β-TM) patients are more likely to experience blood glucose intolerance and to date; the blood markers that could evaluate this are debatable. So, this study aimed to assess the roles of glycated hemoglobin A1c (HbA1c) and fructosamine in evaluating glucose intolerance in children with β-TM and figuring out role of insulin resistance in these patients.MethodsOne hundred children diagnosed with β-TM and 100 age and sex-matched controls were enrolled. Fasting plasma glucose (FPG), 2-h post-prandial blood glucose (2-h PG), HbA1c, fructosamine, fasting insulin level (FINS), insulin resistance index (HOMA-IR), and insulin sensitivity index (HOMA-IS) were evaluated.ResultsFPG and 2-h PG revealed glucose intolerance in 51 patients (51%), 19 of them had diabetes mellitus. HbA1c, fructosamine, FINS, and HOMA-IR showed a high statistically significant increase in patients compared to controls, (P < 0.001). Results revealed fructosamine was more specific in detecting prediabetes state and more sensitive in identifying diabetes mellitus in our patients when compared to HbA1c.ConclusionsDespite controversies on HbA1c in children with β-TM, it is still valuable in glucose intolerance detection. Fructosamine showed more sensitivity and specificity. Furthermore, insulin resistance was prevalent in children with β-TM highlighting the necessity of regular glycemic state evaluation.ImpactGlucose intolerance is a common complication in beta thalassemia patients.Conflicting data was reported about the role of HbA1c and fructosamine in evaluating glucose intolerance in thalassemic patients.Fructosamine does not yet have a threshold that may be used to distinguish between patients who have diabetes mellitus and those who do not.Fructosamine was more specific in detecting blood glucose intolerance compared to HbA1c and was more sensitive for diagnosing diabetes mellitus.Insulin resistance was common in patients with beta-thalassemia and often present before the onset of overt diabetes.

Regulatory T cells and bioenergetics of peripheral blood mononuclear cells linked to pediatric obesity.

Obesity-associated inflammation drives the development of insulin resistance and type 2 diabetes. We sought to identify associations of circulating regulatory T cells (Treg) with the degree of obesity (eg, body mass index Z-score [BMIz]), insulin resistance (homeostatic model of insulin resistance [HOMA-IR]), and glycemic control (HbA1c) in children and adolescents. We further sought to examine associations among bioenergetics of peripheral blood mononuclear cells (PBMCs) and CD4 T cells and BMIz, HOMA-IR, and HbA1c. A total of 65 children and adolescents between the ages 5 and 17 years were studied. HbA1c and fasting levels of plasma glucose and insulin were measured. We quantified circulating Tregs (CD3+CD4+CD25+CD127-FoxP3+) by flow cytometry, and measured mitochondrial respiration (oxygen consumption rate [OCR]) and glycolysis (extracellular acidification rate [ECAR]) in PBMCs and isolated CD4 T cells by Seahorse extracellular flux analysis. Tregs (% CD4) are negatively associated with BMIz but positively associated with HOMA-IR. In PBMCs, OCR/ECAR (a ratio of mitochondrial respiration to glycolysis) is positively associated with BMIz but negatively associated with HbA1c. In children, Tregs decrease as body mass index increases; however, the metabolic stress and inflammation associated with insulin resistance may induce a compensatory increase in Tregs. The degree of obesity is also associated with a shift away from glycolysis in PBMCs but as HbA1c declines, metabolism shifts back toward glycolysis. Comprehensive metabolic assessment of the immune system is needed to better understand the implications immune cell metabolic alterations in the progression from a healthy insulin-sensitive state toward glucose intolerance in children. This observational study was registered at the ClinicalTrials.gov (NCT03960333, https://clinicaltrials.gov/study/NCT03960333?term=NCT03960333&rank=1).

Profile of Overweight and Obesity in Children and Adolescents and Frequency of Type 2 Diabetes Mellitus and Glucose Intolerance: A Study in Public School in Brazil.

ObjectiveTo verify if there is an increase in frequency of type 2 diabetes mellitus (DM2) and glucose intolerance in children and adolescents who are overweight and obese.MethodsThis was a cross-sectional survey. The study population consisted of 2757 students of both sexes (1415 girls and 1342 boys) attending public schools in São Paulo state, Brazil,aged 10–19 years, from 2011 to 2012. Students not within this age range and those with type 1 diabetes mellitus were excluded. Upon interview, anthropometry, capillary blood glucose testing, fasting glucosemia (FG) and glucosemia 2 hours after 75 g of dextrose (AD) variables were obtained. We emphasize that, inspite of the 2757 students included in the next stage, only 88 students agreed to participate, and low compliance of those participants is due to the fact that they were children and adolescents who depend on the authorization of their parents or tutors, who have demonstrated deficient knowledge of familial chronic diseases such as obesity and its consequences, and the risk of DM2.ResultsMore often girls, 1415 (51.3%). A total of 27.3% was overweight/obese/severely obese. Capillary blood glucose testing was performed in 88 (3.2%) children and adolescents with low values of glycemic results after the glucose load. There was no statistical significance between sex and glucosemia, with an average FG and AD of 92.8 mg/dL (male), 91.8 mg/dL (female) and 89.1 mg/dL (male) and 88.9 mg/dL (female), respectively.ConclusionThis survey emphasizes that more attention should be paid to diet interventions and practicing of physical activities demanding habit changes and acquisition of special behaviour for self-care, and provision of a better educational health program, suggesting the effective participation of the family.

Glucose intolerance in children with cystic fibrosis: a developing country’s perspective

Background Cystic fibrosis-related diabetes (CFRD) is a common comorbidity reported in patients with cystic fibrosis (CF). There is a dearth of data on glucose intolerance or CFRD in children with CF from developing countries. So, we planned to study the prevalence of abnormal glucose tolerance (AGT) in children with CF and its relation with the duration and severity of CF. Methods We performed an oral glucose tolerance test (OGTT) on children (2-18 years old) having CF for at least 6 months. Two-hour plasma glucose levels on OGTT were correlated with various disease-related factors. Results Out of the 25 children enrolled, there were 18 boys and seven girls. The mean age and duration of CF were 7.9±4.3 and 3.16±2.5 years, respectively. AGT was observed in 16 (64%) children with CF including three (12%) children with CFRD. Children with a duration of CF of 3 years had significantly higher prevalence (81.8%) of AGT when compared with duration ≤3 years (p-value<0.05). Twelve out of 17 (70.6%) children were colonized with Pseudomonas and 12 out of 15 (80%) children >6 years of age had AGT. There was a positive correlation of 2-h glucose value on OGTT with duration of CF and number of hospitalizations with acute pulmonary exacerbations. Conclusions The majority of children having CF for >3 years and/or age >6 years developed AGT. In our clinical setting, an annual screening with OGTT to detect AGT may be required at an early age and duration of CF.

Urinary myo-inositol levels in Japanese schoolchildren with normal glucose tolerance.

Urinary myo-inositol (UMI) level is elevated in adult diabetic patients, and also increases after glucose loading. However, the relationship between UMI and plasma glucose levels in children is unknown. We aimed to assess whether UMI is a practical marker for glucose intolerance in children or not. In Study 1 (328 schoolchildren), fasting and postprandial UMI were measured, with ΔUMI defined as the difference between fasting and postprandial UMI levels. In Study 2, oral glucose tolerance tests and UMI measurements were conducted in 18 children with suspected having diabetes. For Study 1, ΔUMI was observed [-0.65 (-3.9, 1.35) mg/g creatinine]. For Study 2, children with diabetes or impaired glucose tolerance had a significantly higher ΔUMI than children with normal glucose tolerance. These studies demonstrated the normal range of UMI in children and possibility of a novel biomarker for early detection of glucose intolerance in children.

One-time injection of calcitonin induces glucose intolerance in children with the first degree obesity

The effect of calcitonin on the blood glucose level in glucose-tolerance test of children with the first degree obesity was studied. Initial blood glucose level was normal and glucose-tolerance test per os didn’t expose glucose tolerance impairment in children under control. Calcitonin didn’t change initial glucose concentration but evoked impairment of glucose tolerance. The girls with the first degree obesity were more sensitive to hyperglycemic effect of calcitonin than the boys. Sex specificities must be taken into consideration in calcitonin treatment. Besides one ought mean that the increasing secretion of calcitonin occurs in stress-reactions. In these conditions endogenous calcitonin can make the same effect on the regulation of carbohydrate metabolism as exogenous injections of hormone.

Serum Levels of Soluble Tumor Necrosis Factor-α Receptor 2 are Linked to Insulin Resistance and Glucose Intolerance in Children

Obesity and insulin resistance are increasingly common problems in children. Tumor necrosis factor-alpha (TNF-alpha) has important effects on lipid and glucose metabolism. This effect may be mediated through soluble TNF-alpha receptor 2 (sTNFR2). To investigate the relationship between insulin resistance and the TNF-alpha system in childhood obesity. Twenty-one obese and six non-obese children were studied. Body mass index (BMI) z-scores, percent body fat (PBF) and waist to hip ratio (WHR) were determined. Fasting serum levels of total cholesterol, HDL-cholesterol, LDL-cholesterol, TNF-alpha and sTNFR2 were measured. A standard 2-hour oral glucose tolerance test (dose of glucose: 1.75 g/kg, max. 75 g) was done. Insulin resistance (IR) was estimated by fasting plasma insulin, plasma insulin at 120 min, homeostasis model assessment (HOMA) and insulin area under the curve (AUC) from OGTT. Insulin sensitivity was estimated by oral glucose insulin sensitivity (OGIS120). Among the obese participants, one child (5.2%) was found to have diabetes mellitus and four others (21.1%) impaired glucose tolerance (IGT). Obese children had significantly elevated sTNFR2 levels. Furthermore, the group of obese children with IGT and the patient with newly diagnosed diabetes mellitus together (n = 5) had significantly higher levels of serum sTNFR2 (2,865+/-320 pg/ml) than the rest of the obese (2,460+/-352 pg/ml; p = 0.016) or lean (1,969+/-362 pg/ml; p = 0.014) children. Serum sTNFR2 levels correlated positively with insulin AUC, HOMA IR, fasting plasma insulin, plasma insulin at 120 min, total cholesterol and LDL/ HDL ratio, and negatively with OGIS120. Multiple regression analysis revealed that age, WHR, sTNFR2 and LDL predicted 81% of the variability in glucose at 120 min. sTNFR2 is a candidate marker of insulin resistance and glucose intolerance.

Glucose intolerance in children with cystic fibrosis

Objective To evaluate the relations among glucose intolerance, genotype, and exocrine pancreatic status in patients with cystic fibrosis (CF). Study design Data on 335 patients <18 years of age were from the Toronto CF database. A modified oral glucose tolerance test was given to 94 patients 10 to 18 years of age without recognized CF-related diabetes. CF transmembrane conductance regulator mutations and exocrine pancreatic status were determined for all patients. Results CF-related diabetes was clinically recognized in 9 of 335 (2.7%) patients <18 years of age, all of whom were pancreatic insufficient, and 8 of 9 had severe (classes I through III) mutations on both alleles. The ninth patient had unidentified mutations. Although all patients given the oral glucose tolerance test were asymptomatic and had normal fasting blood glucose, 16 of 94 (17%) had impaired glucose tolerance and 4 of 94 (4.3%) had CF-related diabetes without fasting hyperglycemia. Abnormal glucose tolerance was associated exclusively with severe mutations and exocrine pancreatic insufficiency. Glycosylated hemoglobin (HbA1C) levels did not correlate with glucose tolerance results. Conclusions Screening of pancreatic-insufficient, adolescent patients with CF identified more with abnormal oral glucose tolerance than was suspected clinically and is recommended as a routine practice. HbA1C was not useful in screening for CF-related glucose intolerance. (J Pediatr 2003;142:128-32)

Consequences of an Aberrant Intrauterine Milieu: Metabolic Imprinting.• 1429

Diabetes in pregnancy is associated with an increased risk of obesity and glucose intolerance in children and the development of non-insulin dependent diabetes (NIDDM) in young adults. Genetic predisposition may be one factor leading to this increased risk. However, we suggest that an abnormal metabolic intrauterine milieu alone can predispose offspring to develop glucose intolerance. We have developed a rat model of fetal overgrowth (LGA) and mild fetal hyperglycemia and hyperinsulinemia. Maternal rats are not diabetic. We hypothesized that fetuses exposed to this abnormal intrauterine metabolic milieu would develop glucose intolerance as juvenile pups. In addition, as aberrant hepatic metabolism is a feature of NIDDM, we hypothesized that key components of hepatic metabolism such as glucose transport and glucose phosphorylation would be altered in LGA rat pups. We performed selective ablation of alternate fetuses by uterine artery branch ligation on gestational day 15 (term=21.5)(n=15); litters from sham operated mothers served as controls (C) (n=12). Fetuses were allowed to deliver spontaneously. OGTT's, glucokinase and hexokinase activity, and GLUT 2 protein and mRNA, levels were determined in liver of 21d animals. Body, but not liver weights were higher in LGA animals compared to C (Body: 63.39±1.22 v. 52.3±1.64 g; Liver: 2.07±0.17 v.2.09±0.13 g, LGA vs C, respectively)(p<0.05). Basal glucose (10.91 ±1.11 v 11.79±1.2 mM, LGA v C) and insulin (1.79±0.75 v 1.90±0.63 ng/mL, LGA v C) levels were similar in LGA and C. However, after glucose loading, glucose(19.27±2.1 v 14.47±1.8 mM LGA v C) and insulin levels(4.92±0.45 v 3.00±0.21 ng/mL, LGA v C) were higher in LGA compared to C at 1h (p<0.05). Glucokinase activity was lower in LGA liver(10.09±0.54mU/mg protein/min) compared to C (16.99±0.65 mU/mg protein/min), (p<0.05). LGA Glut 2 protein and mRNA levels were also less than C (45% of C for protein and 20% of C for mRNA) (p<0.01). Immunohistochemistry demonstrated that the intensity of staining for Glut 2 was qualitatively less in LGA liver. In summary, LGA pups had increased body weight, glucose intolerance, decreased hepatic GLUT 2 expression, and decreased hepatic glucokinase activity. Decreased glucokinase activity results in an inability of glucose to suppress hepatic glucose production, and its impairment may contribute to the glucose intolerance observed in these animals. The physiologic consequence of diminished hepatic GLUT 2 levels is unclear. Our results support the hypothesis that transient fetal hyperglycemia and hyperinsulinemia can cause permanent metabolic imprinting after birth.