Characterization of insulin resistance syndrome in children and young adults. When to screen for prediabetes?

CONTEXT: Insulin resistance syndrome (IRS) is associated with the development of type 2 diabetes mellitus (DM2). However, it is unclear which individuals with insulin resistance will develop DM2. AIM: To study the prevalence of IRS in childhood and to identify the group with the highest risk of further progression to DM2. METHODS: In a cross-sectional study, 86 obese individuals underwent an intravenous glucose tolerance test (IVGTT). Insulin resistance index (Si(IVGTT)), acute insulin response (AIR) and disposition index (DI) were calculated from IVGTT. RESULTS: For analysis the participants were divided into insulin-sensitive (IS) (n = 25, 13.3 +/- 5.9 yr) and insulin-resistant (IR) groups on the basis of having an Si(IVGTT) greater or lesser than 4.5 x 10(-4) mU/ml/min, respectively. The IR group was then subdivided according to DI, with the standard cut-off value of 0.13 min(-1), into compensated IR (CIR) (n = 37, 13.0 +/- 3.5 yr) and decompensated IR (DIR) (n = 24, 21.9 +/- 12.6 yr) groups. The frequency of IRS was 43% in children, 78% in adolescents and 83.6% in adults. Decompensated insulin response first appeared during adolescence. The frequency of decompensation increased from 22% in adolescence to 67% in adulthood. The DIR group had increased triglycerides (TG) and urinary free cortisol levels. CONCLUSIONS: The frequency and severity of IR increases with age. Decompensation first presents in adolescence with low AIR and elevated TG. Decompensated adolescents are the group at highest risk for further progression to DM2.     

Ghrelin--an indicator for fat oxidation in obese children and adolescents during a weight reduction program

The aim of this study was to investigate the effect of short-term energy restriction combined with physical activity on changes in substrate oxidation and changes in plasma concentrations of ghrelin. We designed a longitudinal intervention study of 4.2 MJ (= 1,000 kcal) daily with exercise. Eighteen obese children and adolescents (age: 13.1 +/- 1.6 years, 13 girls, 5 boys, 17 White, 1 Black) participated. We measured body mass index (BMI), plasma ghrelin, resting energy expenditure (REE), VCO2, VO2 and respiratory quotient (RQ) at baseline and after 10 days. There was a significant decrease of BMI during the 10 day program (28.6 +/- 4.3 vs 27.5 +/- 4.2; p < 0.001). Ghrelin and RQ showed a tendency to increase, but the difference did not reach significance (ghrelin: 83.4 +/- 37.1 vs 99.5 +/- 41.2, p = 0067; RQ: 0.83 +/- 0.06 vs 0.85 +/- 0.08, p = 0.433). The changes in RQ were significantly and independently correlated with the changes in plasma ghrelin (p = 0.029). The increase in RQ suggests a shift from fat oxidation towards carbohydrate oxidation. Ghrelin reflects the same sensitivity as RQ to changes in energy balance. Therefore, ghrelin seems to be a sensitive indicator for changes in substrate oxidation.     

Relationship between plasma leptin, insulin and tumor necrosis factor alpha in obese children

OBJECTIVES: 1. To evaluate the relationship between plasma leptin and TNFalpha concentrations in obese children and to assess the differences between hyperinsulinemic and normoinsulinemic groups. 2. To evaluate the relationship between plasma leptin and insulin levels in obese children. 3. To investigate the TNFalpha G308A mutation in obese children. METHODS: Body mass index (BMI), fasting plasma glucose and insulin levels, oral glucose tolerance test results, homeostasis model assessment of insulin resistance (HOMA-IR) results, and plasma leptin and TNFalpha concentrations were evaluated in obese children (n = 45) and age- and gender-matched, lean healthy controls (n = 40). RESULTS: In obese children the fasting insulin, HOMA-IR results, plasma leptin and TNFalpha concentrations were significantly higher than in controls (p <0.05). Furthermore, obese females showed higher plasma leptin and insulin resistance compared to obese males. While plasma leptin, TNFalpha levels and HOMA-IR results were similar in the prepubertal and pubertal groups, insulin levels were significantly higher in the pubertal group. Plasma leptin and TNFalpha concentrations were similar in hyperinsulinemic and normoinsulinemic obese children. In control children, plasma leptin concentrations showed a positive correlation with BMI, age, fasting insulin and HOMA-IR results. In obese children, plasma leptin levels did not correlate with BMI, fasting insulin or TNFalpha. CONCLUSION: Plasma leptin concentrations did not show any correlation with TNFalpha levels in obese children. Furthermore, plasma leptin and TNFalpha concentrations were similar in hyperinsulinemic and normoinsulinemic obese children.     

肥胖儿童伴良性黑棘皮病与胰岛素抵抗19例分析

目的　探讨肥胖儿童伴良性黑棘皮病与胰岛素抵抗及 2型糖尿病的关系。方法2 0 0 3年 6月～ 2 0 0 3年 9月 ,在我院内分泌门诊及病房就诊的体重指数 (BMI)≥ 2 5的肥胖儿童共 76例 ,对其中伴黑棘皮病皮肤改变的 19例 ( 2 5 % )均行皮肤病理活检以明确诊断 ,同时对这些患儿行空腹血糖、空腹血胰岛素水平、空腹血糖 /胰岛素比值 (FGIR)及人体测量学参数 [腰围 /臀围比值(WHR) ,全身体脂含量 (FM)、体脂百分数 (BF % )、体重指数 (BMI) ]等的检测 ,并行葡萄糖耐量试验(OGTT试验 ) ,以探讨肥胖儿童伴良性黑棘皮病与胰岛素抵抗及 2型糖尿病的关系。结果　 19例良性黑棘皮病患儿人体测量学参数包括腰围 /臀围比值 ,全身体脂含量 (FM)、体脂百分数 (BF % )、体重指数 (BMI)及空腹血胰岛素水平明显高于正常对照组 (P <0 0 1) ,空腹血糖 /胰岛素比值 (FGIR) ( 4 2 7± 0 5 3)小于 7,存在明显的胰岛素抵抗 ,其中 1例诊断为 2型糖尿病 ,10例有糖耐量异常。结论　儿童良性黑棘皮病与肥胖、高胰岛素血症 ,胰岛素抵抗及 2型糖尿病密切相关 ,是临床胰岛素抵抗的皮肤标志     

Serum levels of soluble tumor necrosis factor-alpha receptor 2 are linked to insulin resistance and glucose intolerance in children

BACKGROUND: 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). OBJECTIVE: To investigate the relationship between insulin resistance and the TNF-alpha system in childhood obesity. CHILDREN AND METHODS: 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). RESULTS: 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. CONCLUSION: sTNFR2 is a candidate marker of insulin resistance and glucose intolerance.     

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.     

52例肥胖和超重儿童糖耐量及胰岛素释放试验分析

目的 了解肥胖和超重儿童糖代谢及胰岛细胞功能状况。方法 对52例单纯性肥胖与超重儿童进行口服糖耐量试验,并测定其血糖及胰岛素水平。计算胰岛素抵抗指数(IR),胰岛素敏感指数(IS),服糖后30min胰岛素增加值与血糖增加值的比值。并查甘油三酯、肝脏B超。体重指数(BMI)与IR之间、不同BMI组之间、糖耐量减低组与对照组之间进行比较。结果 发现糖尿病1例(1．9％),IGT者5例(9．6％)。IR≥2．8为胰岛素抵抗,占76．9％。BMI与IR之间无相关关系。不同BMI组之间IR、IS、服糖后30min胰岛素增加值与血糖增加值的比值差异均无统计学意义。糖耐量减低组与对照组之间IR、IS差异无统计学意义,服糖后30min胰岛素增加值与血糖增加值的比值之间差异有统计学意义。甘油三酯升高19例(37％),脂肪肝16例(53％)。结论 肥胖与超重儿童普遍存在胰岛素抵抗和敏感性下降,其与BMI程度无关。肥胖伴糖耐量减低儿童除胰岛素抵抗外存在明显的B细胞功能减退。许多肥胖和超重儿童同时存在脂代谢紊乱。     

Leptin levels in children with insulin dependent diabetes mellitus

Leptin, a product of the ob gene, is a polypeptide hormone produced in adipose tissue that informs the brain about the amount of energy storage of body fat. It has very important effects on neuroendocrine functions and energy expenditure. The aim of our study was to determine leptin levels of children with insulin dependent diabetes mellitus (IDDM), which is known to affect body metabolism, and to investigate the relationship between duration of the disease, insulin dosage, HbA1c levels, body mass index (BMI), serum lipids and IGF-1 levels. Sixteen patients with IDDM (chronological age 13.8 +/- 2.6 years) whose HbAlc levels were 10.2 +/- 1.9 %, BMI 21.2. +/- 2.7 kg/m2, insulin dosage 0.9 +/- 0.4 U/kg/day and duration of the disease 6.7 +/- 2.6 years, and 12 healthy controls (13.4 +/- 2.6 years) were included in the study. Fasting plasma leptin levels were measured by radioimmunoassay method. The mean plasma leptin levels of the patient and the control groups were 19.1 +/- 7.6 ng/ml and 6.1 +/- 2.9 ng/ml, respectively, and significant difference was found between the two groups (p < 0.05). No correlation was found between leptin values and IGF-1, cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride levels, atherogenic index, insulin dosage or HbA1c levels in the patient group. A weak statistical correlation was determined between BMI and leptin levels in the IDDM group (r = 0.28, p < 0.05). A positive correlation was also found between leptin levels and the duration of the disease (r = 49, p < 0.05). As a result, it seems that leptin levels of children with IDDM differed from the levels of the control group significantly, and that the duration of insulin therapy was responsible for this difference.     

Deterioration of insulin sensitivity and beta-cell function in overweight Hispanic children during pubertal transition: a longitudinal assessment.

PURPOSE: To examine 1-year changes in insulin dynamics in overweight Hispanic children at high-risk of type 2 diabetes as a function of body composition and pubertal transition. EXPERIMENTAL DESIGN: Longitudinal changes in insulin dynamics, body composition and maturation were determined in 132 Hispanic children (70 boys/62 girls; aged 10.9 +/- 1.8 years). METHODS: Body composition was determined by dual energy x-ray absorptiometry and Tanner stage by physical examination. Insulin sensitivity (SI), the acute insulin response to glucose (AIR) and the disposition index (DI; an index of beta-cell function) were determined using an insulin modified intravenous glucose tolerance test. These measures were conducted at baseline and 1-year later. RESULTS: Fat mass increased by 13% (3.0 kg) and SI declined by 24%. In repeated measures analysis of variance, the fall in insulin sensitivity over 1 year remained highly significant even after adjusting for baseline fat mass, age, gender and change in fat mass. The fall in SI was not significantly influenced by Tanner stage. However, subjects in earlier maturation showed a compensatory increase in AIR (i.e. appropriate beta-cell compensation), whereas subjects in the latter stages of maturation did not (i.e. poor compensation). CONCLUSIONS: These results indicate that failure to increase AIR in response to the fall in SI may be one factor in the pathogenesis of the progression of pediatric type 2 diabetes in this at risk population.     

Association of Trp64Arg polymorphism of beta3-adrenergic receptor with insulin resistance in Polish children with obesity

AIM: To establish the influence of the Trp64Arg variant of the beta3-adrenergic receptor (Trp64Arg- beta3AR) on body mass index (BMI) and insulin resistance (IR) in obese children. METHODS: BMI, presence of the Trp64Arg mutation, plasma glucose and insulin concentrations during an oral glucose tolerance test (OGTT) and IR were determined in 60 obese and 33 normal weight children. RESULTS: The frequency of Trp64Arg was similar in normal weight and obese children. BMI, glucose and insulin concentrations during an OGTT in children with Trp64Argbeta3AR were not different from those with Trp64Trpbeta3AR. IR was confirmed in 42.8% of children with Trp64Argbeta3AR and in 45.6% of children with Trp64Trpbeta3AR (NS). CONCLUSIONS: 1. The similar frequency of the Trp64Argbeta3AR variant in normal weight and obese children suggests that it is not a susceptibility gene for obesity in Polish children. 2. The presence of the Trp64Argbeta3AR variant does not have an unfavourable influence on BMI, glucose or insulin concentrations during OGTT or on IR frequency in Polish obese children.     

Relation of circulating oxidized LDL to obesity and insulin resistance in children

Kelly AS, Jacobs DR Jr, Sinaiko AR, Moran A, Steffen LM, Steinberger J. Relation of circulating oxidized LDL to obesity and insulin resistance in children. Introduction: Circulating oxidized low‐density lipoprotein (LDL), a marker of oxidative stress, is associated with obesity, insulin resistance, metabolic syndrome, and cardiovascular disease in adults. However, little is known about its relation to insulin resistance and cardiovascular risk factors in children. The purpose of this study was to assess the relation of oxidative stress, measured by circulating oxidized LDL, with measures of adiposity and insulin resistance in children. Methods: Oxidized LDL, measures of body fatness (body mass index: BMI, percent body fat, waist circumference, percent trunk fat, abdominal visceral and subcutaneous fat), insulin resistance with euglycemic insulin clamp (Mlbm), blood pressure, and blood lipids were obtained in 78 children. Oxidized LDL was compared between normal weight children (BMI < 85th percentile) and overweight/obese children (BMI ≥ 85th percentile) and levels were evaluated for associations with body fatness and insulin resistance. Results: Oxidized LDL levels were significantly higher in overweight/obese vs. normal weight children (p < 0.0001). Oxidized LDL was significantly correlated with BMI, percent body fat, waist circumference, percent trunk fat, abdominal visceral fat, and abdominal subcutaneous fat (all p‐values <0.0001). Moreover, oxidized LDL was negatively correlated with Mlbm, even after adjustment for adiposity (p < 0.01). Conclusions: Oxidized LDL is significantly associated with adiposity and with insulin resistance, independent of body fatness, in children. Oxidative stress may be independently related to the development of insulin resistance early in life, especially in obese youth.     

罗格列酮对肥胖大鼠外周血瘦素抵抗的影响

目的观察高脂喂养的肥胖大鼠模型瘦素抵抗出现的时间、程度、在肥胖形成过程中的动态变化及与胰岛素抵抗的关系;探讨罗格列酮对商脂肥胖大鼠瘦素抵抗的影响。方法清洁级雄性Wistar大鼠30只按体质量随机分成正常对照组、肥胖组和治疗组。肥胖组和治疗组以高脂饮食喂养20周,制备肥胖模型。治疗组于20周后予以罗格列酮2 mg/(kg·d)灌胃。于实验过程第10、20、24周分别取血检测空腹血糖、空腹胰岛素和血清瘦素。结果肥胖组大鼠血清瘦素水平明显高于正常组、治疗组(P均<0.05);正常组与治疗组无显著差异。肥胖组血清瘦紊水平逐渐升高,第20周显著高于第10周(P<0.01)。血清瘦素与血清胰岛素水平(r=0.427 P<0.05)、三酰甘油(r=0.515 P<0.01)呈显著正相关。结论肥胖存在瘦素抵抗。瘦素抵抗与胰岛素抵抗密切相关,血清瘦素水平是代谢综合征和心血管疾病发展的预报器。罗格列酮治疗在改善胰岛素抵抗的同时,也降低瘦素抵抗的水平。     

Waist circumference is an independent predictor of insulin resistance in black and white youths

OBJECTIVES: We examined how well waist circumference (WC) reflects total and abdominal fat and whether WC predicts insulin resistance independent of body mass index (BMI) percentile in youths. STUDY DESIGN: Body composition was measured by dual-energy x-ray absorptiometry and abdominal adiposity by computed tomography. Insulin sensitivity was measured by the hyperinsulinemic-euglycemic clamp. RESULTS: Both BMI percentile and WC were significantly associated (P < .01) with total and abdominal fat and insulin sensitivity. WC remained a significant (P < .01) correlate of total and abdominal fat and insulin sensitivity after controlling for BMI percentile. By contrast, BMI percentile did not remain a significant correlate of visceral fat and markers of insulin resistance after controlling for WC. Without exception, WC explained a greater variance in abdominal fat and metabolic profiles than did BMI percentile. CONCLUSIONS: Our findings suggest that the prediction of health risks associated with obesity in youths is improved by the additional inclusion of WC measure to the BMI percentile. Such observations would reinforce the importance of including WC in the assessment of childhood obesity to identify those at increased metabolic risk due to excess abdominal fat.     

Carbohydrate and lipid metabolism following infliximab therapy in pediatric Crohn's disease

Improvements in insulin resistance after anti-TNF-alpha therapy have been reported in inflammatory conditions, although no changes were noted in adult patients with Crohn's disease. There is no information concerning insulin resistance and substrate metabolism in children with Crohn's disease after anti-TNF-alpha therapy. Our aim was to describe changes in carbohydrate and lipid metabolism in children with active Crohn's disease after their initial dose of infliximab. Children with active Crohn's disease underwent measurement of plasma insulin and glucose just before and 2 wk after their initial infusion of infliximab, an anti-TNF-alpha antibody. In addition, resting energy expenditure, with determination of both carbohydrate and lipid oxidation rates, was determined. Measurements were conducted in both fasting and parenterally fed states. Despite no changes in resting energy expenditure, a significant reduction (p < 0.05) in RQ (5%) and carbohydrate oxidation rate (24%), with a corresponding increase in lipid oxidation rate (42%) was found during parenteral nutrition infusion. No differences in plasma insulin, glucose, and insulin resistance were noted when comparing pre- and postinfliximab measurements.     

The role of leptin, soluble leptin receptor, resistin, and insulin secretory dynamics in the pathogenesis of hypothalamic obesity in children

Introduction  In this study, we have investigated the role of leptin, soluble leptin receptor(sOb-R), resistin, and insulin secretory dynamics in the development of hypothalamic obesity. Materials and methods  Children who had hypothalamo-pituitary tumor were divided into two groups. First group included obese-overweight (hypothalamic obese = HOB group, n = 23) and second group included non-obese children (hypothalamic non-obese = HNOB group, n = 16). Exogenously obese-overweight children (OB group, n = 22) were included as controls. Basal and second-hour serum glucose and insulin in oral glucose tolerance test (OGTT), basal serum leptin, sOb-R, resistin levels, and homeostasis model assessment (HOMA) indexes were compared between the groups. Results  Age, sex, and pubertal status were similar in study groups. Median and interquartile ranges of body mass index (BMI) z scores were similar in HOB and OB groups (2.0 (1.5–2.1) and 2.1 (1.8–2.3), respectively). Serum leptin levels corrected for BMI were highest and total leptin/sOb-R ratios (free leptin index (FLI)) tended to be higher in HOB than HNOB and OB groups, indicating leptin resistance (leptin/BMI, 4.0 (1.6–5.2), 1.5 (0.8–3.1), and 2.5 (1.8–3.5); FLI, 2.0 (0.8–3.5), 0.6 (0.3–1.2), and 1.5 (1–2.3) in HOB, HNOB, and OB groups; respectively). Serum resistin levels were similar in groups (2.6 (1.9–3.1), 2.8 (1.7–3.4), and 3.0 (2.2–3.5) ng/ml in HOB, HNOB, and OB groups, respectively). Basal serum glucose, basal and second-hour insulin levels in OGTT, and HOMA index were higher in OB group than the HOB and HNOB groups, indicating insulin resistance in simple obesity; however, increment of insulin to same glycemic load in OGTT was highest in the HOB group indicating insulin dysregulation (p < 0.05). Conclusion  Hypothalamic obesity seems to be related to both dysregulated afferent (leptin) and efferent (insulin) neural outputs through the autonomic nervous system resulting in energy storage as fat. This work has been presented in part in the free communication session of ESPE 2007 meeting (Helsinki-Finland, 2007).     

The metabolic response to intravenous medium-chain triglycerides in infants after surgery

OBJECTIVE: The aim of this study was to determine if administration of mixed medium-chain triglycerides (MCT)/long chain triglycerides (LCT) fat emulsion would increase net fat oxidation and if carbohydrate intake would influence net fat oxidation. STUDY DESIGN: Stable infants receiving total parenteral nutrition were studied after surgery. Respiratory gas exchange was measured by indirect calorimetry and urinary nitrogen excretion by the micro-Kjeldahl method. Intravenous fat (4 g/kg/day) was given as either pure LCT fat emulsion or 50/50 MCT/LCT fat emulsion. Carbohydrate intake was either "high" (15 g/kg/day) or "low" (10 g/kg/day). Four groups of patients were studied: group 1 = LCT and high-carbohydrate; group 2 = LCT and low-carbohydrate; group 3 = MCT/LCT and high-carbohydrate; group 4 = MCT/LCT and low-carbohydrate. RESULTS: At a carbohydrate intake of 15 g/kg/day, the calories available from glucose exceeded the measured resting energy expenditure (REE), and no differences were seen in either energy expenditure or net fat oxidation between patients receiving LCT and MCT/LCT fat emulsions. However, at a carbohydrate intake of 10 g/kg/day, when glucose calories were less than REE, net fat oxidation was significantly higher in patients receiving MCT/LCT (median, 1.94; range, 1.05-2.24 g/kg/day) compared with patients receiving LCT (median, 0.60; range, -0.09 to 1.35; P =.03). CONCLUSION: Providing that carbohydrate calories do not exceed REE, partial replacement of LCT by MCT in intravenous fat emulsions can increase net fat oxidation in infants after surgery.     

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目的探讨丙戊酸治疗对癫癎患儿血浆胰岛素和瘦素水平的影响。方法测定2003-04—2004-02在山东大学齐鲁医院儿科癫癎治疗中心就诊且服用丙戊酸的32例癫癎患儿和33例对照组(儿外患儿)血浆胰岛素、瘦素水平并计算胰岛素抵抗值、体重指数,并对服用丙戊酸的癫癎患儿胰岛素抵抗值、瘦素与丙戊酸的剂量、疗程、体重指数进行相关分析。结果丙戊酸治疗组体重指数、胰岛素、胰岛素抵抗值、瘦素水平高于对照组;胰岛素抵抗值、瘦素水平与体重指数、丙戊酸疗程显著正相关,与剂量无相关性;偏相关分析示对照组胰岛素、胰岛素抵抗值与瘦素显著负相关,而丙戊酸治疗组胰岛素、胰岛素抵抗值与瘦素显著正相关。结论丙戊酸治疗可引起肥胖程度增加、胰岛素抵抗及瘦素抵抗;胰岛素抵抗、瘦素抵抗与肥胖程度增加有关,与丙戊酸疗程正相关;胰岛素抵抗与瘦素水平显著正相关。     

Characterization of alterations in carbohydrate metabolism in children with Prader-Willi syndrome

OBJECTIVE: To study carbohydrate metabolism and insulin sensitivity and secretion in children and adolescents with Prader-Willi syndrome (PWS) compared with multifactorial obesity (MO) controls. PATIENTS AND METHODS: Seventy-five patients with PWS and 395 controls with MO were studied by oral glucose tolerance test. Insulin resistance (IR) and beta-cell function were assessed by homeostasis model assessment (HOMA), insulin glucose index, fasting insulin and insulin sensitivity index. RESULTS: The incidence of diabetes mellitus was 0% in PWS and 1.5% in MO, while carbohydrate intolerance was 9.3% in the former group and 7.6% in the latter (NS); basal insulin level (12 +/- 8.2 vs 22.3 +/- 25 mU/ml) and HOMA-IR (2.47 +/- 1.6 vs 4.18 +/- 5.05) were lower in PWS (p = 0.004 and 0.04, respectively), whereas HOMA beta-cell index was lower in PWS than in MO (59 +/- 42 vs 102 +/- 119, p = 0.03). ISI Composite was higher in PWS compared to MO (6 +/- 5.7 vs 4.18 +/- 5.05, p = 0.04). CONCLUSION: Patients with PWS presented lower insulin resistance and a dissociation between beta-cell secretion and the degree of obesity.     

Use of markers of dyslipidemia to identify overweight youth with insulin resistance

CONTEXT: Markers to identify overweight youth with insulin resistance are of clinical importance. OBJECTIVE: To determine if markers of dyslipidemia could identify overweight adolescents with insulin resistance. SETTING, PARTICIPANTS, AND STUDY DESIGN: We retrospectively examined the association between markers of dyslipidemia and insulin resistance in 35 overweight [body mass index (BMI) of > or =95th percentile], white adolescents [mean age 13.5 +/- (SD) 1.6 yr] who had participated in hyperinsulinemic-euglycemic clamp studies to evaluate insulin action. Total body fat was measured by dual-energy X-ray absorptiometry and abdominal fat with computed tomography. Using receiver-operating curves, cut-points for triglyceride (TG)/high-density lipoprotein (HDL) and TG level to identify overweight individuals in the lowest tertile for insulin sensitivity were determined. MAIN OUTCOME MEASURE: Difference in the values for insulin sensitivity among the groups. RESULTS: Of the markers examined (TG, TG/HDL, adiponectin, measures of adiposity and fasting insulin), fasting insulin was the strongest correlate of insulin sensitivity (r = 0.87, p < 0.001). Youth with TG/HDL level > or =3 had lower insulin sensitivity (50% lower median values, p < 0.01) and higher visceral fat (p < 0.05) despite BMI comparable to that of youth with TG/HDL level <3. Youth with TG/HDL > or =3 had a sensitivity of 61% and specificity of 82% for identifying participants with the greatest degree of insulin resistance. CONCLUSIONS: TG and TG/HDL are easily obtained markers associated with insulin resistance. Further research is needed to determine if a constellation of clinical findings, such as components of the metabolic syndrome along with other metabolic markers including adiponectin, better predicts insulin resistance in overweight youth.     

Associations of several anthropometric indices with insulin resistance in children: The Children Study

AIM: To compare the associations of several anthropometric indices (i.e. waist circumference [WC], waist-to-height ratio, body mass index (BMI) and waist-to-hip ratio) with the insulin resistance (IR) proxy measures in Greek schoolchildren. METHODS: A random sample of 248 children was used. Fasting plasma glucose and serum insulin levels were measured. IR was estimated through homeostasis model assessment (HOMA), glucose-to-insulin ratio and quantitative insulin sensitivity check index. RESULTS: Insulin levels and IR indices were significantly related to BMI, WC and waist-to-height ratio. Glucose-to-insulin ratio and quantitative insulin sensitivity check index were inversely correlated with all anthropometric indices, while insulin levels and HOMA were positively associated with these indices. Generally, all significant correlations were weak to moderate (0.217 相似文献