The association between non-alcoholic fatty liver disease and insulin resistance in 20 obese children and adolescents

AIM: To investigate whether there are correlations between non-alcoholic fatty liver disease (NAFLD) and insulin resistance in obese children. For the first time, we present clinical data of 20 obese children with NAFLD, including an oral glucose tolerance test. METHODS: Twenty obese children were diagnosed as having NAFLD by abdominal ultrasonography. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (gamma-GT) were reported. Insulin sensitivity was evaluated by oral glucose tolerance test, oral glucose insulin sensitivity (OGIS) and homeostasis is model assessment (HOMA) index. All parameters were compared to 20 obese age- and sex-matched patients without NAFLD. RESULTS: With 81% the prevalence of insulin resistance according to HOMA or OGIS criteria was high in the NAFLD-patients compared to the other group with 63%. Statistically significant differences between both groups were found for mean serum ALT levels, mean glucose levels after 30, 60 and 90 minutes and mean insulin levels after 60 minutes of the glucose tolerance test. CONCLUSION: The high prevalence of insulin resistance we found in children with NAFLD confirms the suggestion that there may be an association between insulin resistance and NAFLD in obese children and indicates that markers of insulin sensitivity could be useful screening parameters for NAFLD.     

Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy

Brufani C, Ciampalini P, Grossi A, Fiori R, Fintini D, Tozzi A, Cappa M, Barbetti F. Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy. Childhood obesity is epidemic in developed countries and is accompanied by an increase in the prevalence of type 2 diabetes (T2DM). Aims: Establish prevalence of glucose metabolism alterations in a large sample of overweight/obese children and adolescents from Central Italy. Methods: The study group included 510 overweight/obese subjects (3–18 yr). Oral glucose tolerance test (OGTT) was performed with glucose and insulin determination. Homeostatic model assessment of insulin resistance (HOMA‐IR) and insulin sensitivity index (ISI) were derived from fasting and OGTT measurements. Beta‐cell function was estimated by insulinogenic index. Fat mass was measured by dual‐energy x‐ray absorptiometry. Results: Glucose metabolism alterations were detected in 12.4% of patients. Impaired glucose tolerance (IGT) was the most frequent alteration (11.2%), with a higher prevalence in adolescents than in children (14.8 vs. 4.1%, p < 0.001); silent T2DM was identified in two adolescents (0.4%). HOMA‐IR and glucose‐stimulated insulin levels were higher in patients with IGT than individuals with normal glucose tolerance (HOMA‐IR = 4.4 ± 2.5 vs. 3.4 ± 2.3, p = 0.001). Fat mass percentage and insulinogenic index were not different between the two groups. In multivariate analysis, age, fasting glucose, and insulin resistance influenced independently plasma glucose at 120 min of OGTT. Individuals with combined impaired fasting glucose/IGT (IFG/IGT) and T2DM were older and had reduced plasma insulin values at OGTT when compared to patients with simple IGT. Conclusions: Glucose metabolism alterations are frequently found among children and adolescents with overweight/obesity from Central Italy. Age, fasting glucose, and insulin resistance are main predictors of IGT. We suggest the use of OGTT as a screening tool in obese European adolescents.     

Prevalence of type 2 diabetes mellitus and impaired glucose tolerance in obese Argentinean children and adolescents

The aim of this study was to evaluate the prevalence of type 2 diabetes mellitus (DM2) and impaired glucose tolerance (IGT) in obese children and adolescents and to examine insulin resistance and insulin secretion. We studied 427 asymptomatic obese patients. DM2 and IGT were diagnosed by an oral glucose tolerance test. Insulin resistance and P-cell function were assessed by using homeostasis model assessment (HOMA), insulin/glucose index (I/GI), fasting insulin and insulin sensitivity index (ISI-composite). Thirty patients showed IGT (7%) and seven had DM2 (1.6%). The mean age was 10.7 +/- 3.5 years, the diabetic group being significantly older than the normal group (p < 0.01). The mean body mass index was 30 +/- 5.3 kg/m2 without significant differences between groups. beta-Cell function declined significantly in the patients with IGT and DM2, and insulin resistance increased significantly. Given the rather high prevalence of glucose metabolism impairment, children with obesity should undergo glucose tolerance testing for appropriate therapeutic intervention.     

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。     

Alterations of glucoregulation in childhood obesity--association with insulin resistance and hyperinsulinemia

AIM: To study the prevalence of alterations of glucoregulation in childhood obesity. PARTICIPANTS: 250 obese children. Oral glucose tolerance test was performed, serum glucose and insulin were determined, and HOMA-IR was calculated. RESULTS: Impaired fasting glucose (IFG) was found in 1.2% according to World Health Organisation criteria and 4.4% according to the criteria of the International Diabetes Federation. Impaired glucose tolerance (IGT) was found in 13.6%, type 2 diabetes mellitus (DM2) in 2.4%. Frequency of fasting glucose (FG) above 7.0 mmol/l was 1.2%. Basal hyperinsulinemia was increased in 70%, reactive hyperinsulinemia in 88%, frequency of elevated HOMA-IR was 78%. 120' insulin was increased in all cases with abnormal FG, IGT and DM2, HOMA-IR was elevated in 79% of patients with IGT and all patients with abnormal FG and DM2. Significant positive correlations were demonstrated between body mass index and insulin levels. CONCLUSION: Our data show that hyperinsulinemia can successfully compensate for insulin resistance in the majority of the obese children. Since IFG is less frequent than IGT there is a need for performing OGTT to demonstrate abnormality of glucoregulation in obese children.     

糖耐量减低肥胖儿童胰岛素原和真胰岛素水平测定意义

目的　探讨血清胰岛素原 (PI)及真胰岛素 (TI)测定对肥胖并糖耐量异常患儿的临床意义。方法　选择肥胖并糖耐量减低 (IGT)患儿 2 1例 ,肥胖糖耐量正常 (NGT) 5 2例 ,正常对照组 4 0例。测定各组空腹血清PI、TI、血糖 (G)、胰岛素 (I)和C 肽 (C P) ,并计算PI/I、PI/C P、PI/TI及胰岛素抵抗指数。结果　 1.肥胖并IGT和并NGT两组患儿比较 ,G、PI、C P及胰岛素抵抗指数均明显增加 (P均 <0 .0 1)。 2 .IGT组糖尿病阳性家族史明显高于NGT组 (P =0 .0 2 4 )。结论　高PI、高C P和胰岛素抵抗是肥胖并IGT患儿的突出表现 ,可能是儿童2型糖尿病的预示指标。有糖尿病阳性家族史肥胖儿童更应警惕IGT发生     

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目的探讨血清脂联素水平与高胰岛素血症和(或)胰岛素抵抗的联系。方法采用酶联免疫法测定2004-02—2004-12在天津医科大学总院就诊的34例肥胖儿童和31例正常对照的血清脂联素水平。分析血清脂联素与人体参数、体脂分布及糖代谢中各指标的相关关系。结果(1)肥胖组脂联素水平低于对照组(P<0.001)。(2)脂联素与性别、年龄无相关关系;与收缩压、舒张压呈负相关(相关系数分别为r=-0.369,r=-0.405,P<0.01);与BMI、腰臀比和SF呈负相关(相关系数分别为r=-0.330,r=-0.282和r=-0.350,P<0.01);与空腹血糖、空腹胰岛素水平呈负相关(相关系数r=-0.264和r=-0.357,P<0.01);与HOMA-R呈负相关(P<0.01),与HOMA-β无相关关系。(3)多元回归分析表明,HOMA-R是影响脂联素最为显著的因素,R2=0.122;标准化偏回归系数-0.369(P<0.01)。结论肥胖症儿童血清脂联素水平较正常儿童降低。血清脂联素水平的变化,是影响空腹血糖、空腹胰岛素水平、HOMA-R的重要因素。低脂联素血症可能参与胰岛素抵抗的发生。     

The abnormalities of carbohydrate metabolism in Turner syndrome: analysis of risk factors associated with impaired glucose tolerance

An oral glucose tolerance test (OGTT) was performed in 103 patients with Turner syndrome (TS) who had normal fasting and postprandial glucose levels. The plasma glucose, insulin, C-peptide and proinsulin levels were measured every 30 min during the test. Using a homeostatic model assessment (HOMA) and a quantitative insulin sensitivity check index (QUICKI), the insulin resistance in TS patients was investigated. Diabetes mellitus and impaired glucose tolerance (IGT) were newly diagnosed in two and 18 patients respectively. There was a significant increase in mean plasma glucose, insulin, C-peptide and proinsulin reponse during an OGTT in the IGT group in contrast to the normal glucose tolerance (NGT) group ( P <0.05). There was a significant decrease in the quantitative insulin sensitivity check index (QUICKI) in the IGT group in contrast to the NGT group ( P <0.05). The fasting insulin and triglyceride levels strongly predicted the 2 h glucose level during the OGTT ( P <0.05). Conclusion:The oral glucose tolerance test is superior to the fasting and postprandial plasma glucose test for the early detection of abnormalities of carbohydrate metabolism in patients with Turner syndrome.     

Comparison of several anthropometric indices with insulin resistance proxy measures among European adolescents: The Helena Study

The aim of the current study was to compare the association of several anthropometric indices, with insulin resistance (IR) proxy measures in European adolescents. The present study comprises 1,097 adolescents aged 12.5-17.5 from ten European cities participating in the HELENA study. Weight, height, waist circumference (WC) and hip circumference, skinfolds thickness, fat mass (FM), fasting plasma glucose (G(F)) and serum insulin (I(F)) levels were measured. HOMA (as indicator of IR body mass index (BMI), waist to hip ratio (WHR) and waist to height ratio (WHtR) were calculated. I(F) and HOMA were statistically significantly related to BMI, WC, skinfold sum, WHtR, WHR and FM. BMI, WC, WHtR, skinfold sum and FM displayed similar correlation with I(F) and HOMA as opposed to WHR where lower correlation with IR indices was detected in the overall sample. Similar results were found for boys, girls and underweight/normal weight adolescents. On the other hand, WC and WHtR were found to be more strongly associated with IR proxy measures compared to the rest of anthropometric indices among overweight/obese subjects. Based on the current findings, WC and WHtR could be used, alternatively, to identify the overweight/obese adolescent at risk for developing IR. In addition, all aforementioned anthropometric indices, except WHR, could be used among the underweight/normal weight adolescents.     

Oral glucose tolerance test in children and adolescents: positives and pitfalls

Objectives:   To describe the glycaemic status (assessed by an oral glucose tolerance test (OGTT)) and associated comorbidities in a cohort of Australian children and adolescents at risk of insulin resistance and impaired glucose homeostasis (IGH).
Methods:   Twenty-one children and adolescents (three male, 18 female) (18 Caucasian, one Indigenous, two Asian) (20 obese, one lipodystrophy) referred to the Paediatric Endocrinology and Diabetes Clinic underwent a 2-h OGTT with plasma glucose and insulin measured at baseline, + 60 and + 120 min. If abnormal, the OGTT was repeated.
Results:   The mean (SD) age was 14.2 (1.6) years, BMI 38.8 (7.0) kg/m² and BMI-SDS 3.6 (0.6). Fourteen patients had fasting insulin levels >21 mU/L. Type 2 diabetes mellitus was diagnosed in one patient, impaired glucose tolerance (IGT) in four patients and impaired fasting glycaemia (IFG) in one patient. Despite no weight loss, only one patient had a persistently abnormal OGTT on repeat testing. Three patients with IGH were medicated with risperidone at the time of the initial OGTT. One patient who had persistent IGT had continued risperidone. The other two patients had initial OGTT results of IGT and diabetes mellitus type 2. They both ceased risperidone between tests and repeat OGTT showed normal glycaemic status.
Conclusions:   Use of fasting glucose alone may miss cases of IGH. Diagnosis of IGT should not be made on one test alone. Interpretation of glucose and insulin responses in young people is limited by lack of normative data. Larger studies are needed to generate Australian screening recommendations. Further assessment of the potential adverse effects of atypical antipsychotic medication on glucose homeostasis in this at-risk group is important.     

Abdominal obesity is an independent risk factor for increased carotid intima- media thickness in obese children

We aimed in this study to investigate carotid intima-media thickness (IMT) in obese children and evaluate the relationship of IMT to various cardiovascular risk factors. One-hundred four obese children (9.3 +/- 2.5 years) and 30 healthy age-matched control subjects were enrolled in the study. All children were assessed for fasting levels of glucose, insulin, lipid profile, skinfold thickness (SFT), waist circumference (WC), and blood pressure (BP). Insulin resistance was estimated by the homeostasis model assessment (HOMA) index. Carotid IMT measurements and non-alcoholic fatty liver disease (NAFLD) were diagnosed with ultrasonographic findings. IMT was significantly higher in obese children compared to controls (0.49 +/- 0.05 vs. 0.40 +/- 0.02 mm, p < 0.001). Significant positive correlations were found between increased carotid IMT and body fat percentage (BFP), body mass index (BMI), age, height, systolic BP, WC, SFT, triglyceride and insulin levels, and insulin resistance index. In a linear logistic regression analysis, the only parameter affecting the increase in carotid IMT was WC (beta: 0.589, p < 0.001). Furthermore, IMT was increased significantly in obese children with NAFLD when compared to obese children without NAFLD (0.54 +/- 0.04 vs. 0.48 +/- 0.05 mm, p < 0.001). Children with abdominal obesity are at increased risk for atherosclerosis, and WC can be used to determine the atherosclerosis risk in obese children.     

Glucose tolerance test in morbidly obese children and adolescents

Oral glucose tolerance tests (50 g/m2 body surface) were performed in fifty-two children and adolescents (28 girls and 24 boys) aged 3.1 to 16.8 (mean +/- SD 11.4 +/- 3.28) years. Mean overweight of the patients was calculated to be 69.7 +/- 28.5%. Plasma glucose and immunoreactive insulin were determined before, and 15, 30, 60, 90, 120 and 180 minutes after the oral glucose load. According to the criteria of the National Diabetes Data Group six (11.5%) of the subjects had abnormal glucose test profiles (fasting glucose concentrations over 140 mg/dl or after 120 minutes above 140 mg/dl), and in four of the six probands we could detect elevated fasting insulin levels (above 17 E/ml) as well. In twenty-three out of forty-eight serum samples (47.9%) basal insulin levels were elevated. No correlation between age, sex, duration of overweight with glucose or insulin levels could be found. Our results are in accordance with findings in obese adults reflecting a high prevalence of impaired glucose tolerance and hyperinsulinemia in obese children and adolescents. On the other hand pathophysiologic relevance and clinical importance of these findings in obese children of an impaired glucose tolerance and hyperinsulinemia is questionable in view of the rapid normalization after weight loss.     

Evaluation of glucose intolerance in adolescents relative to adults with type 2 diabetes mellitus

AIM: There is an increasing trend in the prevalence of type 2 diabetes mellitus (DM2) in childhood and adolescence, while positive family history of DM2 and obesity are the most important risk factors. To study the influence of family history and obesity on glucose intolerance in our country was the aim of this study. STUDY DESIGN AND METHODS: A total of 105 children and adolescents aged 10-18 years (mean 13.3 +/- 2.5 years) were included in the study. All children and adolescents were divided into three groups according to positive family history of DM2 and obesity, and an oral glucose tolerance test (OGTT) was performed for all. Prediabetes was defined as impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG). Insulin secretion and insulin resistance were estimated using the insulinogenic index; and the homeostatic model assessment for insulin resistance (HOMA-IR) and Matsuda index, respectively. RESULTS: The prevalence of prediabetes was 15.2% in the whole group, while it was 25.5% in obese children who also had a positive family history of DM2. The frequency of hyperinsulinism was 57.1% in all groups. Prediabetic children had significant insulin resistance (HOMA-IR 11.5 +/- 7.1 and 4.1 +/- 6.4, respectively, p = 0.034). CONCLUSIONS: Obesity and glucose intolerance are also a problem in developing countries. The risk of prediabetes in children is highest in obese children who also have a positive family history of DM2. There is a need for a lifelong preventive program starting in childhood to avoid DM2 and decrease cardiovascular risk factors     

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目的了解不同葡萄糖耐量状态的肥胖儿童血清脂联素水平,探讨其与年龄、体重指数(BMI)、血脂、血糖及胰岛素水平的关系。方法选择2002～2004年于广州市儿童医院初诊并住院诊治的肥胖儿童52例,分为36例糖耐量正常(NGT)肥胖组和16例糖耐量受损(IGT)肥胖组。测定两组肥胖儿童和41例年龄、性别匹配的正常儿童空腹血清脂联素、胆固醇(CHO)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)、血糖和胰岛素(FINS),计算胰岛素抵抗指数(HOMAIR)。肥胖组儿童均做口服葡萄糖耐量试验(OGTT),测定OGTT2h血糖和胰岛素。结果正常对照组、NGT肥胖组及IGT肥胖组血清脂联素水平依次降低,HOMAIR依次升高,且均有统计学意义;相关性分析显示肥胖儿童血清脂联素与TG、LDLC、FINS呈显著负相关(P<0.05)。结论肥胖儿童血清脂联素水平降低,并与血脂、胰岛素抵抗密切相关;与NGT肥胖组相比,IGT肥胖组儿童的血清脂联素水平进一步降低。     

Postprandial hyperlipidemia after a fat loading test in minority adolescents with type 2 diabetes mellitus and obesity

The continuing increase in the incidence of type 2 diabetes mellitus (DM2) and obesity in children and adolescents is attributable to excessive caloric intake. Abnormal lipid metabolism in the postprandial state leads to long exposure of the vasculature to hyperlipidemia. Most children and adolescents with DM2 are obese, and many have fasting hypertriglyceridemia. Clustering of hyperlipidemia, DM2 and obesity increases the risk for cardiovascular disease. We therefore studied lipids, insulin, C-peptide, and glucose in response to an oral fat load simulating the fat content of a high-fat, fast-food meal in 12 type 2 diabetic obese, 15 non-diabetic obese, and 12 non-diabetic non-obese (control) adolescents (aged 10-19 yr; 87% African-Americans). All three groups were age-, sex-, and sexual maturation-matched. Mean body mass indices were similar in the diabetes and obese groups (32.7 +/- 1.1 vs 35.8 +/- 1.6 kg/m2). All patients with DM2 had fasting C-peptide > 0.2 nmol/l (0.7 ng/ml) and negative diabetes-associated autoantibodies. Serum total cholesterol, triglyceride, high- and low-density lipoprotein cholesterol, insulin, C-peptide, and plasma glucose levels were measured at 0, 2, 4, and 6 h after the fat load. The area under the curve (AUC) was calculated by trapezoidal estimation. Triglyceride AUC was significantly greater in the diabetes group than in the other two groups (15.7 +/- 2.9 vs 9.2 +/- 0.7 and 7.5 +/- 0.7 mmol x h/l [1389 +/- 258 vs 819 +/- 60 and 663 +/- 62 mg x h/dl]; p < 0.02 and <0.004, respectively), as were insulin, C-peptide, and glucose AUCs. Incremental triglyceride response (delta triglyceride = peak - fasting) in the diabetes group was significantly higher than that in the control group (2.1 +/- 0.7 vs 0.8 +/- 0.1 mmol/l 189.7 +/- 58.4 vs 71.2 +/- 11.1 mg/dl]; p < 0.04). Insulin resistance was estimated using the homeostasis model assessment (HOMA), which was greater in the diabetes group than in the obese and control groups (14.4 +/- 2.8 vs 5.2 +/- 0.8 and 3.2 +/- 0.4; p < 0.001 and < 0.0001, respectively). The diabetes group was divided into subgroups of high and normal fasting triglycerides on the basis of triglyceride levels above and below the 95th percentile. The delta triglyceride in the subgroup with high fasting triglycerides was substantially greater than in the subgroup with normal fasting triglycerides (3.4 +/- 1.1 vs 0.8 +/- 0.2 mmol/l [305.2 +/- 96.8 vs 74.2 +/- 18.0 mg/dl]; p < 0.001). Total cholesterol and triglyceride AUCs were much greater in the high vs normal fasting triglycerides subgroup (33.0 +/- 2.9 vs 24.2 +/- 1.9 and 23.6 +/- 3.5 vs 7.8 +/- 0.6 mmol x h/l [1274 +/- 113 vs 934 +/- 72 and 2085 +/- 309 vs 692 +/- 49 mg x h/dl]; p < 0.02 and <0.0001, respectively), as were insulin and C-peptide AUCs. HOMA was greater in the high vs normal fasting triglycerides subgroup (20.8 +/- 4.0 vs 8.0 +/- 1.6; p < 0.0001). In addition to elevated plasma glucose levels, there were no significant differences in either insulin or lipid parameters among the diabetes subgroup with normal fasting triglycerides, the obese group, and controls. Our data suggest that postprandial hyperlipidemia in response to a fat loading test is present in adolescents with DM2 who already have fasting hypertriglyceridemia. The degree of insulin resistance as an underlying abnormality--not DM per se--determines the degree of postprandial lipemia.     

Body fat distribution in childhood obesity: association with metabolic risk factors

OBJECTIVES: To evaluate the clinical significance of body fat distribution in childhood obesity, we investigated the associations of subcutaneous and intraabdominal (preperitoneal and visceral) fat, estimated by ultrasonography, with metabolic risk factors. SUBJECTS: Fifty-one obese (age 11.5+/- 2.6 years) and 33 non-obese (age 12.2+/- 2.7 years) children. STUDY DESIGN: Case control study. METHODS: Ultrasonographic measurements of fat thickness [maximum and minimum preperitoneal fat thicknesses (Pmax, Pmin), maximum and minimum subcutaneous fat thicknesses (Smax, Smin), visceral fat thickness (V), triceps (Tr) and subscapular (Ss) skin fold thicknesses] were documented. Blood pressures, lipid profiles, fasting insulin levels, glucose/insulin ratio and HOMA IR (homeostasis model assessment for insulin resistance) were evaluated in both groups and these parameters were correlated with body fat distribution. RESULTS: In the obese group, fasting insulin level was correlated to Smin, Smax, and Pmin. HOMA, accordingly, was also correlated to Smin, Smax, and Pmin. Fasting insulin level and HOMA showed no correlation with either Pmax or visceral fat thickness. ANALYSIS: Abdominal subcutaneous fat thickness measurements were the best predictors of hyperinsulinemia (R2: 0.32). CONCLUSION: We did not observe a significant correlation between blood pressure, lipid parameters and body fat distribution in obese group. Abdominal subcutaneous fat thickness might be a better predictor of the risk for hyperinsulinemia in childhood obesity.     

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目的观察二甲双胍治疗对高胰岛素血症肥胖患儿血清脂源性激素脂联素、抵抗素、瘦素水平的影响。方法2004-01—2005-02将武汉市儿童医院和同济医院54例高胰岛素血症肥胖患儿分为轻、中度肥胖组及重度肥胖组,均以二甲双胍治疗12周,测量治疗前后体重、空腹血糖、空腹胰岛素及脂源性激素脂联素、瘦素、抵抗素的变化。结果治疗前轻、中度肥胖组和重度肥胖组高胰岛素血症患儿空腹血糖水平与健康对照组比较差异无显著性(P>0.05),血清胰岛素、瘦素、抵抗素及胰岛素抵抗指数(HOMA-IR)均高于健康对照组(P<0.01),脂联素水平明显低于健康对照组(P<0.01)。二甲双胍治疗12周后与治疗前相比,血清胰岛素水平、胰岛素抵抗指数明显降低(P<0.01),轻、中度肥胖组及重度肥胖组血清瘦素水平分别由治疗前的(24.3±1.8)μg/L、(30.2±5.1)μg/L降低为治疗后的(19.6±6.3)μg/L、(24.7±5.3)μg/L,差异有统计学意义;抵抗素水平分别由治疗前的(16.5±6.0)μg/L、(22.3±5.2)μg/L升高为(22.0±5.1)μg/L、(30.6±11.7)μg/L,差异有统计学意义;轻、中度肥胖组和重度肥胖组血清脂联素水平治疗前分别为(8.4±3.2)mg/L、(6.5±1.2)mg/L,治疗后分别为(8.9±2.3)mg/L、(7.03±3.0)mg/L,治疗前后相比,P>0.05。体重指数(BMI)下降,但差异无显著性。结论二甲双胍能显著改善肥胖患儿胰岛素抵抗。降低血清瘦素水平可能是其改善胰岛素抵抗机制之一,但在对脂源性激素脂联素、抵抗素水平的改善上,有其局限性。     

Assessment of insulin sensitivity from measurements in fasting state and during an oral glucose tolerance test in obese children

BACKGROUND: Few previous studies have examined the validity of the fasting glucose-to-insulin ratio (FGIR), homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin-sensitivity check index (QUICKI) in pediatric populations. OBJECTIVE: To compare simple indices of insulin resistance calculated from fasting glucose and insulin levels with insulin sensitivity indices (area under the response curve [AUCinsulin], insulin sensitivity index [ISI-compositeL) determined by oral glucose tolerance testing (OGTT) in obese children. METHODS: One hundred and forty-eight obese children and adolescents (86 girls and 62 boys, mean age: 10.86 +/- 3.08 years, mean body mass index (BMI): 27.7 +/- 4.2) participated in the study. OGTT was performed in all participants. After glucose and insulin measurements from OGTT, the children were divided into two groups according to the presence or absence of insulin resistance. Insulin sensitivity indices obtained from the OGTT were compared between the groups. The total plasma glucose response and insulin secretion were evaluated from the AUC estimated by the trapezoid rule. Cut-off points, and sensitivity and specificity calculations were based on insulin resistance with receiver operating characteristic curve (ROC) analysis. RESULTS: The prevalence of insulin resistance, glucose intolerance and dyslipidemia was 37.1%, 24.3% and 54% in obese children, respectively. The groups consisted of 93 children without insulin resistance (54 girls and 39 boys; mean age: 10.5 +/- 3.3 years; mean BMI: 27.0 +/- 4.2) and 55 children with insulin resistance (32 girls and 23 boys; mean age: 11.4 +/- 2.5 years; mean BMI: 27.9 +/- 3.9). There were significant differences in mean FGIR (10.0 +/- 7.2 vs 5.6 +/- 2.8, p < 0.001), HOMA-IR (3.2 +/- 2.3 vs 4.9 +/- 2.3, p < 0.001) and QUICKI (0.33 +/- 0.03 vs 0.30 +/- 0.02, p < 0.001) between the groups. The cut-off points for diagnosis of insulin resistance were < 5.6 for FGIR (sensitivity 61.8, specificity 76.3), > 2.7 for HOMA-IR (sensitivity 80, specificity 59.1), and < 0.328 for QUICKI (sensitivity 80, specificity 60.2). CONCLUSIONS: Indices derived from fasting samples for diagnosis of insulin sensitivity are reliable criteria in obese children and adolescents. HOMA-IR and QUICKI appeared to have similar sensitivity and specificity and to have higher sensitivity than FGIR.     

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.     

不同指标在评价肥胖儿童胰岛素抵抗中的价值

目的探讨单纯性肥胖儿童胰岛素抵抗临床评估的指标。方法对单纯性肥胖和正常对照儿童进行葡萄糖耐量试验和胰岛素释放试验,在试验前及试验后30、60、120、180 min分别测血糖和胰岛素,并计算稳态模型胰岛素抵抗指数(HOMA-IR)、敏感指数(HOMA-IAI)、胰岛素分泌功能(HOMA-IS)、血糖曲线下面积与胰岛素曲线下面积比及空腹血糖和空腹胰岛紊的比值(FBG/FINS)等胰岛素抵抗评价指标。结果肥胖组FINS明显高于对照组,FBG、HOMA-IS与对照组无显著差异。HOMA-IR和HOMA-IAI之间具有显著相关性,r为-1,与FINS的r分别为0.913和-0.913,与FBG/FINS的r分别为-0.889和0.889,与曲线下面积比的r分别为-0.523和-0.523,P均<0.01。结论FINS、HOMA-IR、HOMA-IAI、血糖与胰岛素曲线下面积比、FBG/FINS均适用于肥胖儿童胰岛素抵抗的评估,尤以FINS、HOMA-IR、HOMA-IAI更可取。