Insulin Secretion In Children Research Articles

Obstructive sleep apnea (OSA) is associated with the impairment of beta-cell response to glucose in children and adolescents with obesity

BackgroundThe main purpose of the study is to assess the association between obstructive sleep apnea (OSA) and insulin secretion in children with obesity.MethodsWe enrolled children and adolescents who attended our pediatric clinic because of obesity and OSA. Glucose homeostasis was assessed through standard 2-h oral glucose tolerance test (OGTT). Nocturnal cardio-respiratory polygraphy was performed for OSA diagnosis. Twenty-two patients underwent a 3-h OGTT to investigate insulin secretion and sensitivity through the oral-minimal model.Resultsseventy-seven children and adolescents were included in the study. Based on OSA severity, the cohort was divided into three groups (29 mild, 29 moderate, and 19 severe OSA). The group with mild OSA showed lower levels of 30-min glucose (p = 0.01) and 60-min glucose (p = 0.03), and lower prevalence of elevated 1-h glucose (10.4% versus 44.8% in moderate and 31.6% in severe OSA, p = 0.01). The odds for elevated 1-h plasma glucose was 6.2-fold (95%CI 1.6–23.4) higher in subjects with moderate and severe OSA compared to mild OSA (p = 0.007) independent of confounders. Spearman correlation test revealed a positive correlation between 30-min plasma glucose and apnea-hypopnea index (AHI, r = 0.31, p = 0.01), oxygen desaturation index (ODI, r = 0.31, p = 0.009), and mean desaturation (r = 0.25, p = 0.04). The 3-h OGTT study included 22 participants (7 mild, 9 moderate, and 6 severe OSA). The group with mild OSA showed a higher dynamic, static, and total insulin secretion compared to those with moderate and severe OSA (p < 0.0001, p = 0.007, p = 0.007, respectively). AHI was significantly correlated to dynamic insulin secretion (r = −0.48, p = 0.02).ConclusionsOSA might impair beta-cell function reducing the pool of promptly releasable insulin in children and adolescents with obesity, in the absence of an effect on insulin sensitivity.

Surrogate markers and predictors of endogenous insulin secretion in children and adolescents with type 1 diabetes.

No studies have examined endogenous insulin secretion in pediatric patients with type 1 diabetes in China using the gold-standard mixed-meal tolerance test. Because the latter is labor-intensive, we examined simpler surrogate markers of endogenous insulin secretion in Chinese youth, as previously reported for a European population. Participants were 57 children and adolescents with type 1 diabetes aged 4.4-16.8years (56% females). We performed 120-minute mixed-meal tolerance tests with serum C-peptide (CP) measurements every 30minutes. Severe insulin deficiency (SID) was defined as CP peak < 0.2nmol/L. Urine CP and creatinine levels were measured at 0 and 120minutes. Twenty-five (44%) patients had SID. Fasting CP levels missed one case (96% sensitivity) with no false positives (100% specificity). While the 120-minute urine CP/creatinine had 100% sensitivity, it yielded markedly lower specificity (63%). Every 1-year increase in diabetes duration and 1-year decrease in age at diagnosis were associated with 37% (P < 0.001) and 20% (P = 0.005) reductions in serum CP area-under-the-curve, respectively. Thus, 86% of children aged < 5years had SID compared to none among patients aged ≥ 11years. Simple fasting CP measurements could be used to detect most SID cases in Chinese youth with type 1 diabetes. Fasting CP is a far more reliable measure of endogenous insulin secretion than the more commonly used insulin dose. Therefore, it could more precisely determine insulin secretory capacity to target those who could benefit, if treatments to preserve residual insulin secretion are developed.

Metabolic bone markers can be related to preserved insulin secretion in children with newly diagnosed type 1 diabetes.

Type 1 diabetes (T1D) may be associated with numerous complications including bone metabolism disorders. The aim of the study was to evaluate the bone metabolism markers twice in children with a newly diagnosed T1D and after an average of seven months of its duration in relation to parameters of the clinical course of diabetes. In 100 T1D patients and 52 control subjects, the following bone turnover markers were evaluated: osteocalcin - OC, osteoprotegerin - OPG, sRANKL, and deoxypyridoline in urine - DPD and DXA examination was also performed. Lower OC concentration at T1D onset in comparison to controls (p < 0.001) and its increase during follow-up (p < 0.001) was ob-served. The OPG concentration was elevated at T1D onset as compared to the control group (p = 0.024) and decreased thereafter (p < 0.001). The s-RANKL level increased during follow-up (p < 0.001) and was lower than in controls (p < 0.001). Urine DPD con-centration also increased during follow-up in the T1D patient group (p < 0.001) and was higher in comparison to the control group (p = 0.021). BMD-TBLH was higher in the control group as compared to patients both at T1D onset (p = 0.025) and in follow-up ob-servation (p = 0.034). Moreover, OPG correlated positively with glycated haemoglobin (HbA1c) (p = 0.004) and negatively with fasting C-peptide level (p = 0.046) and BMI Z-score (p = 0.003), whereas s-RANKL correlated positively with both fasting (p < 0.001) and stimulated C-peptide levels (p < 0.001). Bone metabolism disorders observed at T1D onset in children and modified after reaching the metabolic control of the disease seem to be most strongly associated with preserved insulin secretion.

Early development of decreased β‐cell insulin secretion in children and adolescents with hemoglobin H disease and its relationship with levels of anemia

Diabetes mellitus (DM) associated with iron overload has been reported among adults with transfusion-dependent thalassemia and those with non-transfusion-dependent thalassemia (NTDT), especially in β-thalassemia disease. However, little is known about glucose metabolism and how early its dysregulation can develop in α-thalassemia hemoglobin H (Hb H) disease, which is one of the most common types of NTDT worldwide. We prospectively calculated glucose metabolism index in 40 patients (aged 10-25 years) with Hb H disease. Glucose metabolism data were compared between patients with deletional versus nondeletional Hb H, and between patients with normal versus abnormal insulin secretion/sensitivity. Despite normal glucose tolerance in all patients, 52.5% had abnormal insulinogenic index indicating decreased β-cell insulin secretion. Patients with functional hemoglobin < 8 g/dL had significantly higher percentages of abnormal insulinogenic index. There was no significant difference in abnormal insulinogenic index between deletional and nondeletional Hb H. Decreased β-cell insulin secretion is highly prevalent among children and adolescents with Hb H disease, and it is associated with levels of functional anemia at baseline, but not with the type of Hb H disease. This result warrants heightened awareness among hematologists due to potentially increased risk of DM later in life.

Utility of C-peptide for a reliable estimate of insulin secretion in children with growth hormone deficiency

ObjectiveGH treatment (GHT) can lead to glucose metabolism impairment through decreased insulin sensitivity and impaired pancreatic β-cell function, which are the two key components of the pathogenesis of diabetes. Therefore, in addition to insulin sensitivity, during GHT it is very important to perform a reliable evaluation of insulin secretion. However, conflicting data exist regarding the insulin secretion in children during GHT. C-peptide provides a more reliable estimate of β-cell function than insulin, but few studies evaluated it during GHT. Our aim was to assess the usefulness of C-peptide in the evaluation of insulin secretion in GH deficiency (GHD) children. DesignIn 48 GHD children, at baseline and after 12 and 24months of GHT, and in 56 healthy subjects we evaluated fasting and glucagon-stimulated (AUCCpep) C-peptide levels in addition to other commonly used secretion indexes, such as fasting and oral glucose tolerance test-stimulated insulin levels (AUCINS), Homa-β, and insulinogenic index. The main outcomes were the change in C-peptide during GHT and its correlation with the auxological and hormonal parameters. ResultsAt baseline GHD children showed a significant lower AUCCpep (p=0.006), while no difference was found for the other indexes. Both fasting C-peptide (beta 0.307, p=0.016) and AUCCpep (beta 0.379, p=0.002) were independently correlated with IGF-I SDS, while no correlation was found for all other indexes. After 12months an increase in Homa-β (p<0.001), fasting C-peptide (p=0.002) and AUCCpep (p<0.001) was found. At multivariate analysis, only fasting C-peptide (beta 0.783, p=0.001) and AUCCpep (beta 0.880, p<0.001) were independently correlated with IGF-I SDS. ConclusionsC-peptide, rather than the insulin-derived indexes, has proved to be the most useful marker of insulin secretion correlated to IGF-I levels in GHD children. Therefore, we suggest the use of glucagon test both as diagnostic test for the GH assessment and as a useful tool for the evaluation of insulin secretion during GHT in children.

Association among Fibrinolytic Proteins, Metabolic Syndrome Components, Insulin Secretion, and Resistance in Schoolchildren.

We investigated the role of urokinase plasminogen activator (uPA) and its soluble receptors (suPAR) and plasminogen activator inhibitor-1 (PAI-1) in metabolic syndrome (MetS) components, insulin secretion, and resistance in schoolchildren. We enrolled 387 children, aged 10.3 ± 1.5 years, in Taipei. Anthropometry, fibrinolytic proteins, MetS components, insulin secretion, and resistance were measured. Subjects were divided into normal, overweight, and obese groups. Finally, the relationship between fibrinolytic proteins and metabolic syndrome in boys and girls was analyzed. In boys, PAI-1 was positively associated with body mass index (BMI) percentile, hypertriglyceride, insulin secretion, and resistance. In girls, PAI-1 was positively associated with obesity, hypertriglyceridemia, and insulin secretion. In girls, uPA was positively associated with insulin secretion. suPAR was positively associated with high-sensitivity C-reactive protein in both boys and girls, and with BMI percentile and body fat in girls. The obese boys had higher suPAR and PAI-1 levels than the normal group. The obese girls had higher uPA, suPAR, and PAI-1 than the normal group. Boys and girls with MetS had higher PAI-1. Fibrinolytic proteins, especially PAI-1, are associated with MetS components and insulin secretion in children. Fibrinolytic proteins changes were more likely to occur in girls than in boys.

Effects of correction of vitamin D insufficiency on serum osteocalcin and glucose metabolism in obese children

Osteocalcin (OCN) and vitamin D insufficiency (VDI) have been shown to be associated with abnormal glucose metabolism (GluMet). Whether correction of VDI affects serum OCN is unknown. This study evaluated the effects of correction of VDI on OCN and GluMet, and determined the associations of OCN with 25-hydroxyvitamin D (25-OHD) and GluMet. This study involved 230 obese children in a cross-sectional part and 72 participants in a prospective part in which children with VDI were treated with vitamin D2 at a dose of 20 000 IU daily for 28 days. All 230 children underwent an oral glucose tolerance test and had their serum total and undercarboxylated OCNs and 25-OHD measured. Forty of 72 children were reassessed for the GluMet and serum total and undercarboxylated OCNs and 25-OHD after the vitamin D2 treatment. In the prospective part, correction of VDI by raising mean (SD) 25-OHD of 51·5 (12·3) to 141·8 (40·8) nmol/l resulted in an improvement of their GluMet and increase in their whole-body insulin sensitivity index with no changes in their OCN measures. In the cross-sectional part, after adjustments for age, sex and puberty, the total (β = 0·322) and undercarboxylated OCNs (β = 0·315) were positively associated with insulinogenic index, which is an index of insulin secretion (P = 0·034 and 0·037, respectively) in the group of prediabetic and diabetic children. Correction of VDI increased insulin sensitivity and improved GluMet, but had no effect on serum OCN measures. OCN was associated with increased insulin secretion in children with abnormal GluMet.

Insulin secretion and its association with physical activity, fitness and screen time in children

To determine the independent associations of moderate to vigorous physical activity (MVPA), fitness, screen time, and adiposity with insulin secretion in children. Caucasian youth (n = 423/630), 8-10 years old, with at least one obese biological parent, were studied (QUALITY cohort). Insulin secretion was measured using HOMA2-%B, area under the curve (AUC) of insulin to glucose over the first 30 minutes (AUC I/G(t30min)) of the OGTT and AUC I/G(t120min) over 2 hours. Fitness was measured by VO₂peak ; percent fat mass (PFM) by DXA; 7-day MVPA by accelerometry; self-reported screen time included television, video game, or computer use. Models were adjusted for age, sex, season, puberty, PFM, and insulin sensitivity [IS] (HOMA2-IS, Matsuda-ISI). PFM was strongly associated with insulin secretion, even after adjustment for IS: for every 1% increase in PFM, insulin secretion increased from 0.3% to 0.8% across indices. MVPA was negatively associated with HOMA2-%B (P < 0.05), but not with OGTT-derived measures. Fitness was negatively associated with AUC I/G(t120min) (P < 0.05). Screen time showed a trend toward higher HOMA2-%B in girls (P = 0.060). In children with an obese parent, lower insulin secretion is associated with lower adiposity, higher MVPA, better fitness, and possibly reduced screen time.

Infliximab in the Treatment of Crohn Disease and Type 1 Diabetes

Inhibition of tumor necrosis factor (TNF)-α is an effective treatment for Crohn disease. It is recommended as a second-line therapy in steroid-dependent or -refractory disease, although first-line treatment may improve chances of intestinal mucosal healing (1). In the context of diabetes, TNF-α has been implicated in the development of insulin resistance during obesity (2) and in autoimmune destruction of pancreatic β-cells in an animal model of type 1 diabetes (3), and a recent study demonstrated some preservation of insulin secretion in children with new-onset type 1 diabetes upon TNF-α inhibition (4). Here, we report a case of a 29-year-old Caucasian man who was diagnosed with type 1 diabetes at the age of 27 years on the basis of rapid onset of hyperglycemia, a lean BMI of 22.7 kg/m2, signs of β-cell autoimmunity (autoantibodies to GAD 476 IU/mL [normal value <10] and islet-cell autoantibodies 125 units/mL [normal value <1.5]), and a negative family history of diabetes. Upon treatment with insulin glargine …

Higher Fasting Plasma Free Fatty Acid Levels Are Associated with Lower Insulin Secretion in Children and Adults and a Higher Incidence of Type 2 Diabetes

There are limited data in humans on the association between fasting free fatty acid (FFA) levels and pancreatic β-cell function. Our objective was to examine this association in children and adults with normal glucose tolerance and to explore fasting FFA levels in relation to subsequent risk of impaired glucose tolerance (IGT) and type 2 diabetes (T2D). We measured FFA, glucose, and insulin levels after an overnight fast and 30 min after an oral glucose load in 797 children aged 8 yr in the Avon Longitudinal Study of Parents and Children and 770 adults aged 44-71 yr in the Medical Research Council Ely Study. We calculated the homeostasis model assessment to estimate fasting insulin sensitivity, the insulinogenic index to estimate insulin secretion, and the disposition index to assess insulin secretion corrected for insulin sensitivity. Higher fasting FFA levels were associated with lower insulin secretion in children (boys, P = 0.03; girls, P = 0.001) and adults (men, P = 0.03, women, P = 0.04). Associations with insulin sensitivity were more variable, but after adjustment for insulin sensitivity, higher fasting FFA levels remained associated with lower insulin secretion (disposition index). Compared with adults in the lowest tertile of fasting FFA levels, those in the middle and highest tertiles had a 3-fold higher incidence of IGT or T2D over the following 5-8 yr. Higher fasting FFA levels were consistently associated with lower insulin secretion in children and adults with normal glucose tolerance. Furthermore, higher fasting FFA levels were prospectively associated with a greater risk of subsequent IGT and T2D.

Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes

A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). We have performed a 4-year follow-up study of 59 of the original 70 patients to investigate long-term cellular and humoral immune responses after GAD-alum-treatment. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD65. Frequencies of naïve, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD65 autoantibody (GADA) levels. We here show that GAD-alum-treated patients display increased memory T-cell frequencies and prompt T-cell activation upon in vitro stimulation with GAD65, but not with control antigens, compared with placebo subjects. GAD65-induced T-cell activation was accompanied by secretion of T helper (Th) 1, Th2 and T regulatory cytokines and by induction of T-cell inhibitory pathways. Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD65 enzymatic activity. In conclusion, memory T- and B-cell responses persist 4 years after GAD-alum-treatment. In parallel to a GAD65-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD65 immunity.

GAD autoantibody epitope pattern after GAD-alum treatment in children and adolescents with type 1 diabetes

We have previously shown that two injections of glutamic acid decarboxylase formulated in alum (GAD-alum) preserved residual insulin secretion in children and adolescents with recent onset type 1 diabetes (T1D), and was accompanied by increased GAD autoantibody (GADA) titers. The aim of this study was to investigate whether GAD-alum treatment affected the GADA epitope pattern. Serum samples from patients treated with GAD-alum (n = 33) or placebo (n = 27), at baseline, 1, 3, 9, and 15 months after the initial injection, were tested for their binding capacity to specific GADA epitopes in an epitope-specific radioligand binding assay with six recombinant Fab (rFab) (b96.11, DPA, DPD, MICA3, b78, and N-GAD(65) mAb). No significant differences in variability of binding to any of the tested rFab were observed from baseline to 15 months. There was a sustained low binding of GADA to the b78- and N-GAD(65) mAb-defined epitopes, often recognized by GADA in patients with stiff person syndrome (SPS) and seldom in T1D patients. However, binding of GADA to the T1D-associated b96.11-defined epitope increased between baseline and 3 months in GAD-alum (-8.1%, min -72.4%, max 39.6%) compared to placebo patients (1.5%, min -28.3%, max 28.6%) (p = 0.02). Subsequently, the b96.11-defined epitope recognition returned to levels similar to that observed at baseline. GAD-alum injections did not affect binding of GADA to SPS-related epitopes, further supporting the safety of the treatment. There were no changes in GADA epitope specificity to the T1D-related epitopes, except for a temporarily increased binding to one of the tested epitopes.

Too Much Glucagon, Too Little Insulin

OBJECTIVE—To determine the time course of changes in glucagon and insulin secretion in children with recently diagnosed type 1 diabetes.RESEARCH DESIGN AND METHODS—Glucagon and C-peptide concentrations were determined in response to standard mixed meals in 23 patients with type 1 diabetes aged 9.4 ± 4.6 years, beginning within 6 weeks of diagnosis, and every 3 months thereafter for 1 year.RESULTS—Glucagon secretion in response to a physiologic stimulus (mixed meal) increased by 37% over 12 months, while C-peptide secretion declined by 45%. Fasting glucagon concentrations remained within the normal (nondiabetic) reference range.CONCLUSIONS—Postprandial hyperglucagonemia worsens significantly during the first year after diagnosis of type 1 diabetes and may represent a distinct therapeutic target. Fasting glucagon values may underestimate the severity of hyperglucagonemia. The opposing directions of abnormal glucagon and C-peptide secretion over time support the link between dysregulated glucagon secretion and declining β-cell function.

Changes in Insulin Sensitivity and Glucose Metabolism During Therapy with Recombinant Human Growth Hormone in Short Children Born Small For Gestational Age show a Negative Correlation with Baseline Measurements

Recombinant human growth hormone (rhGH) is an effective therapy for children with short stature born small for gestational age (SGA); however, insulin resistance can develop during treatment. This retrospective analysis assessed the effect of rhGH treatment (0.067 mg/kg/day) on glucose metabolism and insulin secretion in children with short stature born SGA, and measured whether baseline characteristics correlated with changes in insulin resistance or glucose sensitivity during treatment. Baseline glucose area under the concentration-time curve (AUC) was negatively correlated with the change in glucose AUC (p<0.001). Similar negative correlations were seen between baseline insulin AUC and the change in insulin AUC during treatment (p<0.001); and between baseline HOMA-IR (homeostatic model of insulin resistance) and the change in HOMA-IR during treatment (p<0.001). Small but significant changes, not thought to be clinically significant, were seen in indicators of insulin sensitivity during rhGH treatment. Glucose levels remained within the normal range during oral glucose tolerance testing.

Questioning INS VNTR role in obesity and diabetes: subclasses tag IGF2-INS-TH haplotypes; and -23HphI as a STEP (splicing and translational efficiency polymorphism)

Le Fur et al. ([4][1]) claim that INS VNTR subclass ID is responsible for the higher insulin secretion in children previously attributed to the whole class I group. This VNTR (variable number tandem repeat) is a minisatellite locus in the promoter region of INS. For European ancestry, there are long

Validation of surrogate estimates of insulin sensitivity and insulin secretion in children and adolescents

ObjectivesTo compare insulin sensitivity and pancreatic β-cell function measured by the euglycemic and the hyperglycemic clamp, with simple estimates of insulin sensitivity and pancreatic β-cell function in youth. Study designWe measured insulin sensitivity with a euglycemic clamp and first- and second-phase insulin secretion with a hyperglycemic clamp in 156 AA and white youths. Estimates of insulin sensitivity (fasting insulin level [IF], the ratio of fasting glucose [GF] to IF [GF/IF], homeostasis model assessment estimate of insulin sensitivity [HOMA IS], and quantitative insulin sensitivity check index [QUICKI]) and estimates of pancreatic β-cell function (IF, the ratio of IF to GF [IF/GF], and homeostasis model assessment estimate of pancreatic β-cell function [HOMA %B]) were derived from fasting measurements. ResultsIn the total group, ISEu correlated strongly with IF (r=−0.92), GF/IF (r=0.92), HOMA IS (r=0.91), and QUICKI (r=0.91) (P<.01). First-phase and second-phase insulin secretion correlated with IF, IF/GF, and HOMA %B (first-phase insulin secretion: r=0.76, 0.79, 0.82; second-phase insulin secretion: r=0.83, 0.86, 0.86, respectively; P<.01). ConclusionsSimple estimates of insulin sensitivity and pancreatic β-cell function using fasting insulin and glucose levels serve as surrogate measures of insulin sensitivity and secretion in nondiabetic youths. The validity of these conclusions in children with impaired glucose tolerance and type 2 diabetes mellitus remains to be determined.

Specific features of leptin secretion in children and adolescents with obesity

The purpose of the study was to examine baseline leptin secretion and its association with insulin secretion in children and adolescents with obesity and in those having normal body weight. Sixty- six children and adolescents aged 11-16years, including 48 individuals with obesity, were examined. Anthropometric indices, fasting serum leptin concentrations, and the time course of changes during a three-hour oral glucose test were assessed. In obese children and adolescents, the baseline level of leptin was significantly higher than in normally weighing children and adolescents of the same age. Abdominovisceral obesity showed a higher level of leptin than gluteofemoral obesity. Age- and gender-specific features of leptin production were revealed in obese children and adolescents. There was an association of leptin production with anthropometric indices. Children and adolescents with obesity showed a positive correlation of the baseline level of leptin with overall insulin secretion during the oral test and a negative correlation of the baseline level of leptin with the insulin sensitivity index.

Limitations of first-phase insulin response to evaluate insulin secretion in children.

The first-phase insulin response (FPIR) is a widely used method to evaluate beta-cell function during the prediabetic phase of evolving type 1 diabetes mellitus (DM). The aim of the present study was to evaluate the influence of clinical and methodological variables on FPIR in normal children and adolescents. Children and adolescents who were first-degree relatives of those with type 1 DM and healthy young adults were studied. All subjects were islet cell antibody-negative. A FPIR test was performed on all subjects while fasting. Insulin samples were drawn at 0, 1, 2, 3, 4, 5, 6, 8, and 10 min after 0.3 g/kg of dextrose. FPIR(1-10) was calculated as the area under the FPIR curve corrected for baseline. Eighty-five subjects aged 4-22 yr were studied, 43 of whom were pre-pubertal, 24 pubertal, and 18 post-pubertal. FPIR(1-10) values were lower in the pre-pubertal group when compared to either the pubertal and post-pubertal groups (415 [179-965, 2SD], 756 [256-2 223] and 684 [235-1 180] mU/L, respectively; p<0.05). Obese subjects had a higher FPIR than non-obese subjects (856 vs. 520 mU/L; p<0.005). Despite correcting for the influence of puberty and obesity, there remained considerable unaccounted variability in FPIR(1-10) (R=0.46). Further variables found to influence FPIR(1-10) were: fasting insulin level (r(2)=0.49); weight for length index (r(2)=0.38); peak blood glucose level (r(2)=0.38, all p<0.001); and pre-pubertal age (r(2)=0.20, p<0.05). FPIR exhibited wide inter-subject variability and was influenced by a number of clinical and methodological factors that make interpretation more difficult without more specifically defined standards.

Insulin Pulsatility in Obese and Normal Prepubertal Children

Objective: To assess whether in prepubertal children insulin secretion is pulsatile as in adults and to study the influence of body weight on the pattern of insulin secretion. Design and Patients: Insulin profiles were obtained by 4-min sampling for 2 h, starting at 08.00 a.m. after an overnight fast in 10 prepubertal obese children (BMI-SDS 4.9 ± 1.6) and in 6 healthy age-matched controls. Five of the obese children were also studied after weight reduction (Δ BMI-SDS 1.6 ± 0.4). The data have been analyzed by the Pulsar program. Results: Obese children had higher mean insulin levels, insulin secretory areas under the curve above 0 (AUC₀), and AUC above baseline (AUC_b), with more frequent peaks of larger amplitude and duration compared to controls. Following weight reduction there was a normalization of AUC₀ and mean insulin levels while AUC_b, peak frequency, amplitude and duration did not change significantly. Correlation analysis revealed that BMI-SDS was strictly related to the parameters of pulsatile insulin secretion such as AUC₀, AUC_b, mean insulin level, peak amplitude and peak frequency. Conclusions: Insulin secretion in children is pulsatile and its secretory pattern is influenced by body weight.

Glucose Tolerance and Insulin Secretion in Children before and during Recombinant Growth Hormone Treatment

This study evaluates glucose metabolism and insulin secretion in children with Ullrich-Turner syndrome (UTS), chronic renal failure (CRF) and kidney transplantation (KTx) with rh GH therapy using an intravenous glucose infusion test. Before treatment, glucose AUC was significantly increased in all patient groups when compared to normal controls. Both the early and second phases of insulin secretion were not altered. During treatment, elevated glucose AUC showed a further increase in patients with KTx but not in patients with CRF or UTS. Both the early and second insulin secretion phases rose significantly in UTS and were transiently elevated after 6 and 12 months of therapy in patients with CRF and KTx. We conclude that growth hormone therapy aggravates alteration of glucose metabolism in patients with KTx and not in children with CRF and UTS. Progressive hyperinsulinemia occurred only in patients with UTS.