Insulin resistance in obese children and adolescents

ObjectiveTo evaluate the presence of insulin resistance and its association with other metabolic abnormalities in obese children and adolescents.MethodsRetrospective study of 220 children and adolescents aged 5-14 years. Anthropometric measurements were performed (weight, height, and waist circumference) and clinical (gender, age, pubertal stage, and degree of obesity) and biochemical (glucose, insulin, total cholesterol, and fractions, triglycerides) data were analyzed. Insulin resistance was identified by the homeostasis model assessment for insulin resistance (HOMA-IR) index. The analysis of the differences between the variables of interest and the HOMA-IR quartiles was performed by ANOVA or Kruskal-Wallis tests.ResultsInsulin resistance was diagnosed in 33.20% of the sample. It was associated with low levels of high-density lipoprotein cholesterol (HDL-C; p = 0.044), waist circumference measurement (p = 0.030), and the set of clinical and metabolic (p = 0.000) alterations. Insulin-resistant individuals had higher mean age (p = 0.000), body mass index (BMI; p = 0.000), abdominal circumference (p = 0.000), median triglycerides (p = 0.001), total cholesterol (p ≤ 0.042), and low-density lipoprotein cholesterol (LDL–C; p ≤ 0.027); and lower HDL-C levels (p = 0.005). There was an increase in mean BMI (p = 0.000), abdominal circumference (p = 0.000), and median triglycerides (p = 0.002) as the values of HOMA -IR increased, with the exception of HDL-C, which decreased (p = 0.001). Those with the highest number of simultaneous alterations were between the second and third quartiles of the HOMA–IR index (p = 0.000).ConclusionThe results confirmed that insulin resistance is present in many obese children and adolescents, and that this condition is associated with alterations that represent an increased risk for developing metabolic disorders in adulthood.     

Insulin resistance in healthy prepubertal twins

OBJECTIVES: To evaluate insulin sensitivity (S(I)) in prepubertal twins and to examine the relation to reduced birth weight, prematurity, and peroxisome proliferator-activated receptor-gamma (PPAR gamma) polymorphism. STUDY DESIGN: Fifty twins (birth weight SDS, -0.7 +/- 0.2; gestation, 33.5 +/- 0.5 weeks; and body mass index SDS, -0.04 +/- 0.2) were studied at 8.2 +/- 0.3 years. S(I) was measured by Bergman's minimal model from a 90 minutes frequently sampled intravenous glucose test. Twenty control children (height SDS, -1.7 +/- 0.3; birth weight SDS, -0.3 +/- 0.2; and gestation of 39.2 +/- 0.7 weeks) were also evaluated at 7.0 +/- 0.4 years. The PPAR gamma T-variant polymorphism was evaluated in 41 twins. Values are expressed as mean +/- SEM, or 95% confidence intervals. RESULTS: S(I) was reduced in twins compared with control subjects, (12.7 [11-15] versus 23.0 [16.8-31.4] 10(-4) min(-1) microU/mL, respectively, P=.005). The reduction in S(I) was independent of prematurity and birth weight and zygosity (P<.0001). There was no difference in S(I), even in twin pairs with >20% difference in birth weight (P=.9). The PPAR gamma heterozygote T-variant polymorphism was present in 7 of 41, with a further reduction in S(I) (P=.03) and a later gestation (P=.03). These twins also had increased fat mass (P=.02) but with similar fat free mass (P=.14). CONCLUSIONS: Twin children, independent of prematurity or birth weight, had a marked reduction in S(I). To use twins as a model to study the fetal origins of adult diseases for glucose homeostasis is not valid.     

Ghrelin serum levels during oral glucose tolerance test in prepubertal obese children with insulin resistance

BACKGROUND: An involvement of ghrelin in glucose metabolism has been suggested; nevertheless, the relationship between ghrelin and insulin resistance (IR) remains unclear. AIMS: 1. To investigate the effect of glucose loading on ghrelin in prepubertal obese children with IR. 2. To assess possible correlations between IR and changes in circulating ghrelin. PATIENTS AND METHODS: Twenty prepubertal obese, insulin-resistant and 18 age- and sex-matched lean children were studied. Fasting glucose, insulin and ghrelin levels were measured. In the obese group, measurements were repeated during an OGTT. RESULTS: Ghrelin levels were decreased at 60 min, but thereafter increased to baseline values. The fall in circulating ghrelin was negatively correlated with IR and the respective rise in insulin levels. CONCLUSIONS: In prepubertal, insulin-resistant obese children, ghrelin is significantly suppressed shortly after glucose intake. It is possible that the above effect is attenuated by IR and the resultant increase in insulin levels.     

Insulin resistance in children

Insulin resistance is characterized by decreased tissue sensitivity to insulin. The hallmark of insulin resistance is decreased tissue glucose uptake despite normal or elevated insulin concentration. There has been an upward trend in the incidence of insulin resistance in developed countries, although in pediatric population it is difficult to assess. Both genetic and environmental factors play an important role in the etiology of insulin resistance, namely increased diet caloricity and decreased physical activity. Gradually, this leads to adipose tissue build-up. The role of visceral adipose tissue is of particular importance, mainly due to its significant endocrine activity, leading to adverse metabolic effects. The most important consequences of insulin resistance in children include increased incidence of type 2 diabetes, atherogenic dyslipidemia and arterial hypertension, which lead to increased cardiovascular risk. Children with insulin resistance can develop nonalcoholic steatohepatitis and sleep apnea syndrome. In case of female pediatric patients a higher incidence of polycystic ovary syndrome (PCOS) is observed. Furthermore, the authors reviewed opinions on risk factors for insulin resistance, as well as direct and indirect insulin resistance assessment methods. The article presents the principles of primary and secondary prevention of insulin resistance in children, with particular allowance for dietary recommendations and recommendations to increase physical activity, and, in selected cases, current guidelines on pharmacological treatment.     

Insulin resistance and metabolic syndrome in prepubertal boys with Klinefelter syndrome

Aims: To investigate risk factors for metabolic syndrome in prepubertal boys with Klinefelter syndrome. Methods: Eighty‐nine boys with Klinefelter syndrome, ages 4–12.9 years, and 34 age‐matched control boys had height, weight, waist circumference and blood pressure measured and their parents completed a questionnaire about physical activity. The boys with Klinefelter syndrome also had measurement of lipids, fasting glucose and insulin. Insulin‐glucose homeostasis model assessment was calculated, and the boys were evaluated for childhood metabolic syndrome. Results: The Klinefelter syndrome and control groups were similar ages (7.5 ± 2.4 vs. 8.1 ± 2.3 years). Body mass index measurements were similar, but waist circumference was >90 percentile in 30% of boys with Klinefelter syndrome versus 21% of controls. The mean daily time spent running was 42 min less in the Klinefelter syndrome versus control groups (p < 0.01). About 37% of the boys with Klinefelter syndrome had elevated LDL cholesterol, 24% had insulin resistance, and 7% met the three criteria for diagnosis of metabolic syndrome. Conclusions: Truncal obesity, insulin resistance and metabolic syndrome are present in boys as young as 4–12 years with Klinefelter syndrome, and these occur in association with reduced running‐type activity.     

Insulin resistance and ferritin as major determinants of abnormal serum aminotransferase in severely obese children.

OBJECTIVES: Liver involvement is a common complication of obesity related in part to insulin resistance. The role of ferritin has not been investigated in children. The aim was to determine the prevalence of liver enzyme abnormalities in severely obese children and to look for relationships between fat mass distribution, insulin resistance, and plasma ferritin. METHODS: 197 children with severe obesity (defined as a body mass index Z-score (BMI-Z) > 3.0) were studied prospectively from 2001 to 2004. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values were measured, as well as anthropometric characteristics: blood pressure; body composition by dual energy X-ray absorptiometry, and plasma fasting glucose, insulin, leptin, lipid, and ferritin concentrations. RESULTS: Serum ALT and AST values were abnormal in 23 (11.7%) and 13 (6.6%) children, respectively. By univariate analysis, serum ALT and AST values were positively correlated with android fat mass distribution (P < 0.0001 and P = 0.005, respectively) after adjustment for age, sex, ethnicity, and Tanner stage. Using the same model, a positive correlation and a positive trend linked plasma ferritin to serum AST (P = 0.02) and serum ALT (P = 0.06), respectively. Serum ALTwas positively correlated to insulin resistance (P = 0.03). Using a multivariate model, with the android/gynoid fat mass ratio as an additional independent variable, ferritin remained correlated with serum AST and ALT (P = 0.001 and P = 0.008, respectively). CONCLUSIONS: Abnormal serum aminotransferase values are uncommon in severely obese children in France. Android fat mass distribution, insulin resistance, and higher ferritin concentrations are significantly associated with liver abnormalities in our cohort.     

Insulin resistance in obese boys with acanthosis nigricans.

Insulin resistance was investigated in three obese boys with acanthosis nigricans and their results were compared to those obtained in non-acanthotic obese patients. Blood glucose immune reactive serum insulin and C-peptide during oral glucose tolerance test and 125I-insulin binding investigated. Obese patients with acanthosis nigricans were more insulin resistant than simple obese controls. Insulin binding studies performed in two acanthotic patients suggested that one of them had insulin resistance type A, and the second patient had insulin resistance type B. According to the results acanthosis nigricans can serve as a marker for severe insulin resistance in obesity.     

肥胖男童骨密度变化与骨代谢指标及胰岛素抵抗的关系探讨

目的 探讨单纯性肥胖男童骨密度变化与骨代谢生化指标及胰岛素抵抗之间的关系,以了解肥胖男童骨代谢异常可能的发病机制.方法 应用定量骨密度超声仪测定70例7～14岁小同体质指数(BMI≥23)的肥胖男童及20例年龄、性别匹配的健康男童的桡骨远端的超声传播速度(SOS),对其骨骼矿物质密度(BMD)进行评价.并对其空腹血钙(Ca)、磷(P)、碱性磷酸酶(ALP)、血糖(FBG)、胰岛素(FINS)、骨钙素(OC)、甲状旁腺素(PTH)进行监测.用稳态模式(HOMA)计算胰岛素抵抗指数(IR=FBG×FINS/22.5)、胰岛β细胞分泌指数[IS=20×FINs/(FBG-3.5)1.结果 BMI≥25的肥胖男童BMD、OC明显低于正常对照组(P<0.01),而FBG、FINS、HOMA-IR、DTH、ALP均显著高于正常对照组(P<0.01);经双变量相关分析,BMD分别与BMI、FINS及HOMA-IR呈负相关(r=-0.50,r5=-0.58、-0.60,P均<0.01),与OC呈正相关(r=0.63,P<0.01).结论 严重肥胖男童存在明显的骨代谢异常,且与肥胖程度、高胰岛素血症和胰岛素抵抗密切相关.     

Insulin and insulin resistance index are not independent determinants for the variation in leptin in obese children and adolescents

Recent findings have questioned the independent influence of insulin on leptin. We studied whether insulin contributes to leptin in obese children, independent of confounding parameters, such as total adiposity, fasting insulin resistance index, and fat free mass. In 100 obese boys and 103 obese girls, blood levels of leptin, insulin, glucose, and triglycerides were determined. The fasting insulin resistance index (FIRI) was calculated, and body composition was assessed by means of impedance. Leptin and glucose were higher in girls, and all estimates of adiposity were significantly associated with leptin. However, when adjusted for adiposity, the relationship between insulin and leptin, and also between FIRI and leptin, remained significant in boys and girls (p<0.05). Although several regression models were tested, neither insulin nor FIRI were found to contribute significantly and independently to leptin. BMI together with triglycerides and FFM were the main determinants for the variation in leptin in boys (adj. R2=0.46, p<0.0001). In girls, BMI explained a great magnitude of the variation in leptin (adj. R2=0.60, p<0.0001). These findings indicate that in the state of childhood and adolescent obesity, total adiposity but not insulin or insulin resistance index is the main determinant for leptin. In contrast to obese girls, the fat free mass and triglycerides contribute significantly to the variation in leptin in obese boys. The biological significance for these findings should be elucidated in longitudinal studies.     

Evaluation of adipocytokines in obese children with insulin resistance

Obesity and overweight are among the most serious health problems in western societies and an increasing problem in developing countries. Recent studies indicate an important role of adipose tissue hormones, or "adipokines", in obesity-associated complications. To investigate the relation of two circulating adipokines (visfatin, adiponectin) with markers of insulin sensitivity and obesity in children, 40 obese children and 40 control children were recruited. Homeostasis model assessment for insulin resistance (HOMA-IR) and visfatin levels (4.99 +/- 2.08 vs. 1.47 vs. 0.7, p < 0.001; 31.3 +/- 11.1 vs. 18.5 +/- 10.7, p < 0.001, respectively) were significantly elevated and adiponectin levels (2.01 +/- 1.02 vs. 12.5 +/- 6.2, p < 0.001) were significantly lower in the obese group. Comparisons of the clinical and metabolic characteristics between insulin-resistant and noninsulin-resistant groups in obese children are summarized. The insulin-resistant group had higher visfatin levels (36 +/- 9.7 vs. 22.9 +/- 7.6, p < 0.001) and lower adiponectin levels (1.7 +/- 1.05 vs. 2.5 +/- 0.77, p: 0.016). Visfatin was correlated positively and adiponectin was correlated negatively with body mass index standard deviation score (BMI-SDS) and HOMA-IR. The role of various adipokines as connectors between obesity and diabetes mellitus has been better elucidated in recent years. Based on the findings of this study, visfatin and adiponectin levels can be used as specific markers for insulin sensitivity.     

Insulin resistance in short children with intrauterine growth retardation

Chiarelli F, di Ricco L, Mohn A, De Martino M, Verrotti A. Insulin resistance in short children with intrauterine growth retardation. Acta Pædiatr 1999; Suppl 428: 62–5. Stockholm. ISSN 0803–5326
Scientific evidence is accumulating for an association between intrauterine growth retardation (IUGR) and an increased risk of developing adult degenerative diseases, such as essential hypertension, non-insulin-dependent diabetes mellitus and ischaemic heart disease. A possible underlying mechanism for these conditions is insulin resistance. In this paper, mechanisms and methods of measurement of insulin resistance are briefly reviewed, and recent studies on the evaluation of insulin resistance in short children with IUGR are summarized. In our experience, short prepubertal children with IUGR show consistent insulin resistance, which becomes particularly evident during pubertal development. □ Intrauterine growth retardation, insulin resistance, short children     

Glucose alteration and insulin resistance in asymptomatic obese children and adolescents

Objective

Obesity is associated with the abnormal glucose metabolism preceding type 2 diabetes mellitus. Thus, further investigation on the prediction of this lethal outcome must be sought. The objective was the profile glycemic assessment of asymptomatic obese children and adolescents from Salvador, Brazil.

Racial and etiopathologic dichotomies in insulin hypersecretion and resistance in obese children

OBJECTIVES: To assess insulin dynamics to oral glucose tolerance testing in obese children, denoting individual contributions of insulin hypersecretion versus resistance to racial and etiopathogenetic specificity. STUDY DESIGN: We performed 3-hour oral glucose tolerance testing in 113 nondiabetic obese children (age 13.6 +/- 3.1 years; 41 male, 78 female; 37 black, 41 white; 35 with central nervous system [CNS] insult). The corrected insulin response (CIRgp; measuring beta-cell secretion) and the composite insulin sensitivity index (CISI) were computed and log-transformed, and each was modeled in terms of the other, plus race/etiology, age, sex, body mass index z score, glucose tolerance, pubertal status, and geographic location. RESULTS: A scatterplot of logCIRgp versus logCISI showed that racial and etiopathogenetic groups plotted in different areas. CISI (controlled for CIRgp and other variables) was only 13% lower in blacks than in whites ( P = .32). Conversely, CIRgp (controlled for CISI and other variables) was 49% higher in blacks ( P = .028). CNS insult exhibited a 40% higher CIRgp ( P = .054) and 11% higher CISI ( P = .42) than intact white subjects. CONCLUSIONS: Insulin hypersecretion and resistance are distinct phenomena in childhood obesity. Insulin hypersecretion appears to be the more relevant insulin abnormality both in obese blacks and in CNS insult.