Glucose Tolerance In Children Research Articles

CFTR modulators and glucose tolerance in children

CFTR modulators and glucose tolerance in children

The lncOb rs10487505 polymorphism impairs insulin sensitivity and glucose tolerance in children and adolescents with obesity.

Leptin plays a key role in the regulation of body weight and other endocrine systems. Recently, impairment of leptin gene transcription due to genetic variations in a long noncoding RNA (lncOb) has been described. This retrospective study aims to characterize the clinical and metabolic phenotype of children and adolescents with obesity who were homozygous for the lncOb rs10487505 leptin lowering allele. Enrolled children underwent an anthropometrical evaluation, biochemical assessment, and genotyping for lncOb rs10487505. Plasma leptin levels were assessed in 150 participants. A total of 434 patients were included and divided into two groups according to rs10487505 recessive inheritance (CC vs. GG/GC). Children who were homozygous for the C allele showed higher fasting insulin (p = 0.01), homeostasis model assessment of insulin resistance (p = 0.01), lower whole-body insulin sensitivity index (p = 0.02), and lower disposition index (p = 0.03). Moreover, CC patients presented with a higher prevalence of prediabetes (9.3% vs. 3.4%, p = 0.04) and a 2.9-fold (95% CI: 1.1-7.9, p = 0.04) higher risk of prediabetes compared with G-carriers independently from confounders. Leptin plasma levels were significantly lower in the CC group (p = 0.002). Hormone levels correlated with BMI z score (r = 0.19, p = 0.04), fasting insulin (r = -0.34, p < 0.0001), homeostasis model assessment of insulin resistance (r = -0.33, p < 0.0001), and disposition index (r = 0.20, p = 0.04). The lncOb rs10487505 polymorphism affects leptin circulating levels, worsens insulin resistance, and heightens the risk of prediabetes in children and adolescents with obesity.

Abnormal glucose tolerance in children: oral glucose tolerance test is fit-for-purpose

Aim: Childhood obesity is accompanied by an increased prevalence of abnormal glucose tolerance (AGT) including the prediabetes states. This study aims to investigate and evaluate the use of oral glucose tolerance test (OGTT) for detecting AGT among overweight and obese children. Methods: A retrospective study was conducted on 895 overweight and obese Chinese children (6–18 years) with obesity assessment and analysis of demographic, anthropometric, and biochemical parameters data between January 2006 and December 2015 at Tseung Kwan O Hospital, Hong Kong Special Administrative Region. Results: The proportion of males and older age group was 63.7% and 55.9%, respectively. Girls were more in older age groups (62.7% vs. 52.0%, P = 0.002). AGT occurred in 17.1% of the cohort [impaired glucose tolerance (IGT) was the most frequent morbidity (11.3%)]. After regression analysis, female sex, low-density lipoprotein (LDL), triglyceride (TG), older age group, and homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 4.1 were significantly associated with AGT. Conclusions: AGT is common in overweight and obese Chinese children. Girls, older age, higher LDL, TG and HOMA-IR ≥ 4.1 showed significant association with AGT. OGTT is essential and fit-for-purpose to detect AGT in overweight and obese children.

LBODP085 Effects Of Elexacaftor-tezacaftor-ivacaftor On Glucose Tolerance And Other Metabolic Parameters In Children With Cystic Fibrosis

Abstract Cystic fibrosis related diabetes (CFRD) occurs in up to 20% of teenagers and has detrimental effects on lung function and nutritional status. Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have had positive and mixed effects on glucose tolerance in children. Our study aimed to investigate the effect of elexacaftor-tezacaftor-ivacaftor (ETI) on glucose tolerance, as well as on anthropometric measures and lipids, in children. We hypothesized that glucose tolerance and BMI would improve. We completed a retrospective study of children at a Pediatric Cystic Fibrosis (CF) Center who were started on ETI after December 2019. Our inclusion criteria were children 12 years and older who were on ETI for at least one year. We did not include children on long-term corticosteroids, with type 1, type 2, or other secondary diabetes, or who were post-transplant. Blood glucose at 2 hours after an oral glucose tolerance test (2-hour BG), Hemoglobin A1c (HgbA1c), lipids, and weight and BMI z-scores were assessed after at least one year on ETI. For patients with CFRD, only HgbA1c was performed for monitoring glycemic control. These measures were compared to corresponding measures in control groups of children older than or at 12 years old, heterozygous or homozygous for F508d, who were seen at the CF Center 4 years prior, and therefore were not receiving ETI. Patients with normal and impaired glucose tolerance (NGT/IGT) were compared to controls with similar glucose tolerance and separated by age. Patients with CFRD were compared to controls with CFRD only. Average length of time on ETI was 18.7 months. CFRD was diagnosed in 8.6% of patients and impaired glucose tolerance in 13.8% of patients. Previous CFTR modulators were used in 31.6% of patients. Average 2-hour BG increased by 3.2 mg/dl (n=44, p=0.6) and average HgbA1c decreased by 0. 05% (n=53, p=0.18) after the use of ETI. Weight z-score increased by 0. 07 (n=54, p=0.38) and BMI z-score increased by 0.13 (n=58, p=0.31). Total cholesterol increased significantly by 17.6 mg/dl (n=56, p&amp;lt;0. 0001), but in contrast, triglycerides only increased by 4.75 mg/dl (p=0.46). Change in average 2-hour BG for children in the NGT/IGT control group (total n=30) were similar to children receiving ETI: 12-13 years: 3.6 versus 3.2 mg/dl, 13-14 years: -9. 0 versus -3.5 mg/dl, and 14-18 years: 18.5 versus 8.6 mg/dl (all p&amp;gt;0. 05). In children with CFRD, the control (n=7) and ETI (n=5) groups had similar changes in HgbA1c (-0.56% versus -0.5%, p=0.94). In a retrospective analysis of children, 2-hour BG and HgbA1c changed minimally after at least one year on ETI and did not differ significantly when compared to controls. Minimal changes were also seen for BMI, weight, and triglycerides after use of ETI. However, total cholesterol increased significantly with the use of ETI. Presentation: No date and time listed

Glucose tolerance and insulin sensitivity markers in children and adolescents with excess weight.

Type 2 diabetes mellitus (T2DM) and obesity are alarmingly increasing in children and adolescents. Hence, predictors for early metabolic abnormalities in childhood are urgently needed. We investigated glucose tolerance in children and adolescents with obesity, markers of insulin sensitivity between males and females and the potential association between the parameters measured during an OGTT (glucose, insulin, c-peptide) and prediabetes or stages of puberty. Glucose tolerance in 89 children and adolescents with excess weight, aged 4-19 years, from Western Greece was studied. A 3-hour OGTT was performed and fasting glucose (FG), fasting insulin (FI), 1/FI, FG/FI, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Quantitative insulin sensitivity check index (QUICKI), ISI Matsuda index and Insulinogenic index (IGI30), were also calculated. No significant differences were observed in glucose values between males and females. Insulin and c-peptide concentrations were higher in the girls at several time points. FG/FI was significantly higher in the boys. Girls with obesity may be at higher risk for future insulin resistance. Better surveillance of pubertal girls with obesity is crucial and can be achieved using additional information provided by an OGTT, since they appear to be at a higher risk for beta-cell exhaustion. During the OGTT, not only are the baseline and 2-hour glucose and insulin measurements useful for predicting future metabolic risks and development of T2DM in children and adolescents with obesity, but additional time measurements may also be helpful.

Glycated Hemoglobin as a First-line Screening Test for Cystic Fibrosis‒Related Diabetes and Impaired Glucose Tolerance in Children With Cystic Fibrosis: A Validation Study

ObjectivesOur aims in this study were to document the screening rate for cystic fibrosis‒related diabetes (CFRD) in children followed at a cystic fibrosis (CF) clinic in Canada and to evaluate the accuracy of various glycated hemoglobin (A1C) cutoffs to screen for CFRD and impaired glucose tolerance (IGT) in a pediatric CF population. MethodsThe CFRD screening rate was calculated over a follow-up period of up to 8 years among children who attended the CF clinic between 1993 and 2018. Test performance of A1C at various thresholds ranging from 5.5% to 6.2% was compared with the oral glucose tolerance test (OGTT) as the reference method. Children with CF aged ≥10 years with an OGTT performed within 120 days of A1C measurement were included in the analysis. ResultsThe overall CFRD screening rate was 53.0%. A total of 256 children were included for the A1C performance analysis, of whom 8.6% had an OGTT-confirmed CFRD diagnosis. An A1C threshold of 5.8% demonstrated an optimal balance between sensitivity (90.9%) and specificity (60.7%) for CFRD screening, leading to a potential reduction of 56.3% of the annual required OGTTs. A1C demonstrated poor accuracy for identifying children with IGT. ConclusionsAn A1C threshold ≥5.8% allows for identification of children requiring further CFRD investigations, which may reduce the clinical burden of children with CF without compromising the ability of early CFRD diagnosis.

EPS2.03 Lumacaftor-ivacaftor therapy and its impact on glucose tolerance in children with cystic fibrosis

EPS2.03 Lumacaftor-ivacaftor therapy and its impact on glucose tolerance in children with cystic fibrosis

Effects of aerobic interval training on glucose tolerance in children and adolescents with cystic fibrosis: a randomized trial protocol

BackgroundIndividuals with cystic fibrosis (CF) may develop CF-related diabetes (CFDR). This comorbidity is related to a poorer quality of life, microvascular complications, a decline in lung function, and an increase in exacerbations, as well as delayed growth and puberty. Evidence exists that physical exercise contributes to glycemic control in individuals with non-CF-related diabetes. This exercise is usually continuous with moderate intensity and long duration, which can cause muscle dyspnea and fatigue in CF individuals. Aerobic interval training (AIT) emerges as a safe and effective alternative for treating these individuals. The objective of this study is to evaluate the effects of AIT on glucose tolerance in children and adolescents with CF.MethodsThis study will be a two-arm, prospectively registered, randomized controlled trial with blind assessors and twenty 6- to 18-year-old individuals with cystic fibrosis (CF) from two different Brazilian states. People with CF will be randomly allocated to either the experimental or control group using block randomization, stratified by puberty stage,. Participants from both groups will receive an educational intervention and will be asked to continue their usual daily treatment for the full duration of the study. Those in the experimental group will perform AIT on a cycle ergometer at home three times a week, for 8 consecutive weeks. The sample characterization will include an assessment of puberty stage, socioeconomic status, dyspnea, and anthropometry. The primary outcome will be the change in glucose tolerance, while the secondary outcomes will include lung function, exercise tolerance, respiratory muscle strength, quality of life, and CF exacerbations. All outcomes will be assessed at baseline, week 9, and week 17.DiscussionThis is the first study to evaluate the effects of AIT on glucose tolerance in children and adolescents with CF. This study will serve as a basis for guiding clinical practice and decision-making in treating glucose intolerance and CF-related diabetes (CFRD) in children and adolescents with CF.Trial registrationClinicalTrials.gov Protocol Registration System: NCT03653949. Registered on August 31, 2018.

Impairment of glucose tolerance in children and adolescentstreated for medulloblastoma

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Effects of Interrupting Sedentary Behavior With Short Bouts of Moderate Physical Activity on Glucose Tolerance in Children With Overweight and Obesity: A Randomized Crossover Trial.

OBJECTIVESedentary children have greater risk of developing abnormalities in glucose homeostasis. We investigated whether interrupting sedentary behavior (sitting) with very short periods of walking would improve glucose metabolism without affecting dietary intake in children with overweight or obesity. We hypothesized that interrupting sitting with short bouts of moderate-intensity walking would decrease insulin area under the curve (AUC) during an oral glucose tolerance test (OGTT) compared with uninterrupted sitting.RESEARCH DESIGN AND METHODSOverweight/obese (BMI ≥85th percentile) children 7–11 years of age underwent two experimental conditions in random order: prolonged sitting (3 h of continuous sitting) and interrupted sitting (3 min of moderate-intensity walking at 80% of ventilatory threshold every 30 min for 3 h). Insulin, C-peptide, and glucose were measured every 30 min for 3 h during an OGTT. Each session was followed by a buffet meal. Primary outcomes were differences in OGTT hormones and substrates and in buffet meal intake by condition.RESULTSAmong 35 children with complete data, mixed-model results identified lower insulin and C-peptide in the interrupted condition (P = 0.007 and P = 0.029, respectively); the intervention reduced insulin AUC by 21% (P < 0.001) and C-peptide AUC 18% (P = 0.001) and improved estimated insulin sensitivity (P = 0.013). Neither buffet total energy intake (1,262 ± 480 vs. 1,260 ± 475 kcal; P = 0.89) nor macronutrient composition of the meal (P values >0.38) differed between conditions significantly.CONCLUSIONSInterrupting sitting with brief moderate-intensity walking improved glucose metabolism without significantly increasing energy intake in children with overweight or obesity. Interrupting sedentary behavior may be a promising intervention strategy for reducing metabolic risk in such children.

303 Retrospective and prospective clinical impact of impaired glucose tolerance in children and adolescents with cystic fibrosis

303 Retrospective and prospective clinical impact of impaired glucose tolerance in children and adolescents with cystic fibrosis

Metabolic Risk Factors and Type 2 Diabetes Incidence in American Indian Children.

Data are lacking on how metabolic risk factors during childhood affect the long-term risk of type 2 diabetes. Assess four metabolic risk factors as predictors of type 2 diabetes and determine whether the risk differs between younger and older children. In a prospective cohort study conducted between 1965 and 2007, participants were followed for development of diabetes. Baseline measurements included body mass index (BMI), blood pressure, serum cholesterol, and 2-hour plasma glucose after an oral glucose tolerance test. Additional analyses divided subjects into two groups according to baseline age, 5–11 and 12–19 years. Gila River Indian Community in Arizona. A total of 5532 nondiabetic Pima Indian children 5–19 years old. A total of 1281 children developed diabetes (median follow-up, 12.4 years). Diabetes incidence was higher in overweight children (BMI ≥ 85th percentile) than in nonoverweight children. Nonoverweight children had the lowest risk of diabetes (20-year cumulative incidence, 9.5%), whereas overweight children with impaired glucose tolerance (2-hour glucose ≥ 140 mg/dL) had the highest (79.0%). The relative risk for children with metabolic abnormalities compared with their healthy counterparts was higher in younger children than in older children early in follow-up. BMI and 2-hour glucose were related to incident diabetes in multivariable models (predicted 15-year cumulative incidence for the highest vs lowest quartile was 3.9 and 1.8 times as high for BMI and 2-hour glucose, respectively; P < .001), whereas blood pressure and cholesterol were not. BMI and impaired glucose tolerance in children are strong predictors of type 2 diabetes. Other components of the “metabolic syndrome” are not.

Effects of Interrupting Children's Sedentary Behaviors With Activity on Metabolic Function: A Randomized Trial.

Limited data suggest that interrupting sedentary behaviors with activity improves metabolic parameters in adults. We tested whether interrupting sitting with short, moderate-intensity walking bouts improved glucose tolerance in children. Participants underwent two experimental conditions in random order on different days: continuous sitting for 3 hours or sitting interrupted by walking (3 min of moderate-intensity walking every 30 min). Insulin, C-peptide, glucose, and free fatty acids were measured every 30 minutes for 3 hours during an oral glucose tolerance test. Area under the curve (AUC) was calculated from hormone and substrate measurements. Children were given a buffet meal after each condition. The study was conducted at the National Institutes of Health Hatfield Clinical Research Center. Twenty-eight normal-weight 7-11 year olds participated. Patterns of substrate/hormone secretion and AUC, as well as energy intake, were examined by experimental condition. Interrupting sitting resulted in a 32% lower insulin AUC (P < .001), 17% lower C-peptide AUC (P < .001), and 7% lower glucose AUC (P = .018) vs continuous sitting. Mixed model results indicated that insulin (P = .036) and free fatty acid concentrations (P = .009) were significantly lower in the interrupted vs the continuous sitting condition. Lunchtime buffet meal energy intake did not significantly differ between the conditions (975 ± 387 vs 963 ± 309 kcal; P = .85). Interrupting sedentary time with brief moderate-intensity walking improved short-term metabolic function in non-overweight children without increasing subsequent energy intake. These findings suggest that interrupting sedentary behavior may be a promising prevention strategy for reducing cardiometabolic risk in children.

Association between sleep architecture and glucose tolerance in children and adolescents.

Short sleep duration is a contributing factor for decreased insulin sensitivity and hyperglycemia. Sleep architecture represents a cyclical pattern of sleep that shifts between sleep Stages N1, N2, N3 (slow wave sleep) and Stage R (rapid eye movement sleep). The aim of the present study was to examine the association between sleep architecture and glucose and insulin metabolism in both normal weight and overweight/obese children and adolescents. A total of 118 subjects participated in the study. Subjects under-went overnight polysomnography (PSG) when the percentage of total sleep time (% TST) spent at each sleep stage was recorded and an oral glucose tolerance test together was performed the next morning. We assessed glucose tolerance, insulin sensitivity and pancreatic β-cell function using 2-h glucose levels, the Matsuda index (IS(OGTT)), and insulin secretion-sensitivity index-2 (ISSI-2), respectively. After adjustment for age, gender, body mass index z-score, pubertal status, and obstructive apnea hypopnea index, Stage N3 (% TST) was positively associated with IS(OGTT), whereas Stage N1 (%TST) exerted an opposite effect on IS(OGTT). Higher sleep efficiency and longer TST were independently associated with lower 2-h glucose levels, higher ISSI-2 and/or higher IS(OGTT). Stage N3, sleep efficiency and TST were protective factors in maintaining glucose and insulin homeostasis; however, Stage N1 functioned in the opposite direction.

Kwashiorkor and marasmus are both associated with impaired glucose clearance related to pancreatic β-cell dysfunction

Severe malnutrition is a major health problem in developing countries and can present as kwashiorkor or marasmus. Kwashiorkor is associated with septicaemia, profound metabolic changes including hepatic steatosis, altered protein metabolism and increased oxidative stress. Limited data suggest that children with kwashiorkor have an impaired glucose tolerance and insulin secretion. Our objective was to determine glucose tolerance in children with kwashiorkor compared to marasmus and its relation to insulin secretion and sensitivity. Six children with kwashiorkor and 8 children with marasmus were studied. We were also able to include 3 healthy children for comparison. They received a primed (13mg/kg), constant infusion (0.15mg/kg/min) of [6,6-2H2]glucose for 4h with serial blood sampling. In addition, an oral glucose tolerance test (OGTT) was performed with labeled 10mg/g [U-13C]glucose. Glucose clearance was determined using mathematical modeling. Glucose clearance rates during the OGTT were −392 (range 309) mL/kg in children with kwashiorkor, −156 (426) mL/kg in marasmus and 279 (345) mL/kg in the control group. Glucose clearance rates correlated with plasma albumin concentrations (r=0.67, P=.001). Insulin responses were strongly impaired in both kwashiorkor and marasmus. There was no indication of peripheral or hepatic insulin resistance in the malnourished groups. We show that glucose clearance rates are affected in both children with marasmus as well as kwashiorkor, which correlate with plasma albumin concentrations. The disturbed glucose clearance in malnutrition is related to an impairment in insulin availability.

The Assessment of Glucose Tolerance in Children with Obesity

Introduction: Obesity beggining in childhood is emerging in alarming rates worldwide.Material and methods. The aim of this study was to determine the prevalence of impaired glucose tolerance and type 2 diabetes mellitus in a group of Caucasian children and adolescents with obesity.A total of 102 subjects (54 boys, 48 girls), mean age: 13,12 y (range 7.1-17.9 y) with a BMI> 95 th percentile, who were consecutively admitted to an in-patient Diabetes, Nutrition and Metabolic Disorders Unit participated in this study. A 2-h oral glucose tolerance test (1.75mg of glucose per kilogram of body weight) was performed, with the concomitant determination of glucose and insulin. Insulin resistance was estimated by homeostatic model assessment. (HOMA).Results: Patients were divided into: normal glucose tolerance, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes. Type 2 diabetes was diagnosed in 1 patient (0.98%). IFG was detected in 3 patients(2.94%) and IGT in 2 (1.96%). In 5.88%of the patients, impaired glucose tolerance (IFG, IGT) or diabetes were identified, along with a higher BMI-SDS, higher levels of fasting insulin and a higher insulin resistance index than the patients with normal glucose tolerance.Conclusions: Screening for diabetes in children and adolescents diagnosed with obesity is highly recommended. Patients identified with impaired glucose tolerance could participate earlier in specific treatment programs in order to prevent progression to diabetes.

Nocturnal saturation and glucose tolerance in children with cystic fibrosis

BackgroundGlucose intolerance is common in cystic fibrosis (CF), and is associated with worsening pulmonary function and nutritional status, and increased mortality. As sleep-disordered breathing is associated with disorders of glucose...

Abnormal glucose tolerance in children with cystic fibrosis: the predictive role of continuous glucose monitoring system

A long pre-diabetic phase of abnormal glucose tolerance is described in subjects with cystic fibrosis (CF) since childhood. The aims of the study were to compare oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS) in the diagnosis of altered glucose metabolism, and to longitudinally evaluate the role of CGMS in predicting glucose metabolism deterioration in children with CF. Seventeen children with CF and 14 controls were enrolled (mean age 13.3+/-3.0 years). All subjects underwent OGTT and CGMS registration. On the basis of OGTT, children were classified as normal glucose tolerance, impaired glucose tolerance (IGT), IGT plus at least one glucose value above 200 mg/dl at intermediate OGTT points (IGT+200) and CF-related diabetes (CFRD). HbA1c, glucose area under the curve, insulin sensitivity, and insulinogenic and disposition indexes were also considered. Subjects with CF underwent another OGTT after 2.5 years. Baseline OGTT revealed 3/17 (7.6%) children with CF with at least one glucose value above 200 mg/dl (1 CFRD and 2 IGT+200), while CGMS revealed 6/17 (35.3%) children with glucose excursions above 200 mg/dl (P=0.010). None of the controls showed glucose over 200 mg/dl either at OGTT or at CGMS. At the 2.5-year follow-up OGTT, all the six subjects who had diabetic glucose excursion (i.e. >200 mg/dl) at baseline CGMS presented IGT+200 or CFRD. In logistic regression analysis, CGMS diabetic excursion was the strongest predictor of IGT+200 and CFRD (P<0.001). CGMS could be a useful tool to predict glucose metabolism derangements in children affected by CF.

First phase insulin release and glucose tolerance in children with Fanconi anemia after hematopoietic cell transplantation

Fanconi anemia (FA) is an autosomal and X-linked recessive disease of chromosomal instability, which results in bone marrow failure. Children with FA have been shown to have an increased risk of diabetes mellitus (DM). A cross-sectional study of glucose and insulin metabolism was conducted in 17 children with FA who had undergone hematopoietic cell transplantation (HCT) at the University of Minnesota. First phase insulin release (FPIR) was determined by intravenous glucose tolerance test (IVGTT). Oral glucose tolerance test (OGTT), lipid panel, blood pressure, and medical history were reviewed for additional metabolic abnormalities. Seventeen FA participants, median age 11.3 (range 5.5-17.6) years, were evaluated. IVGTT identified three separate groups: low FPIR, normal FPIR, and high FPIR. Those with low FPIR were more likely to have low BMI, but had normal glucose levels. Those with high FPIR, had high BMI, elevated lipids, and body fat. One patient with normal FPIR had impaired glucose tolerance and another with normal FPIR had impaired fasting glucose. No participant was diagnosed with DM by fasting glucose, 2 hr glucose during OGTT, or hemoglobin A1C. The majority of children with FA had normal glucose tolerance and normal beta-cell function after HCT. Two small subsets of patients had lower than expected and higher than expected FPIR. The clinical significance of these differences is not yet known given the normal glucose tolerance and fasting glucose levels in these two groups.

Letters to the Editor

Letters to the Editor