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.     

Glucose metabolism disorder in obese children assessed by continuous glucose monitoring system

Background  Continuous glucose monitoring system (CGMS) can measure glucose levels at 5-minute intervals over a few days, and may be used to detect hypoglycemia, guide insulin therapy, and control glucose levels. This study was undertaken to assess the glucose metabolism disorder by CGMS in obese children. Methods  Eighty-four obese children were studied. Interstitial fluid (ISF) glucose levels were measured by CGMS for 24 hours covering the time for oral glucose tolerance test (OGTT). Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), type 2 diabetic mellitus (T2DM) and hypoglycemia were assessed by CGMS. Results  Five children failed to complete CGMS test. The glucose levels in ISF measured by CGMS were highly correlated with those in capillary samples (r=0.775, P<0.001). However, the correlation between ISF and capillary glucose levels was lower during the first hour than that in the later time period (r=0.722 vs r=0.830), and the ISF glucose levels in 69.62% of children were higher than baseline levels in the initial 1–3 hours. In 79 obese children who finished the CGMS, 2 children had IFG, 2 had IGT, 3 had IFG + IGT, and 2 had T2DM. Nocturnal hypoglycemia was noted during the overnight fasting in 11 children (13.92%). Conclusions  Our data suggest that glucose metabolism disorder including hyperglycemia and hypoglycemia is very common in obese children. Further studies are required to improve the precision of the CGMS in children.     

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     

Elevated fasting triglycerides predict impaired glucose tolerance in adolescents at risk for type 2 diabetes

OBJECTIVE: The aim of this study was to evaluate whether fasting laboratory values can predict impaired glucose tolerance (IGT) in adolescents who are at risk for developing type 2 diabetes mellitus (T2DM). HYPOTHESIS: Elevated fasting triglycerides, a marker for worsening insulin resistance, predict risk for IGT. DESIGN: Following a fast of at least 9 h, laboratory measures, body mass index (BMI), and demographic information were obtained. The subjects then underwent a 75-g oral glucose challenge with a 2-h postchallenge glucose determination. SUBJECTS: Eighty-four adolescents aged 12-20 yr with at least two risk factors for developing T2DM (obesity, family history of T2DM, or acanthosis nigricans) and with either a fasting insulin level > or =25 microU/mL or a homeostasis model assessment of insulin resistance (HOMA-IR) > or =3.5 were recruited for the study. RESULTS: Ten subjects (12%) had IGT [2-h glucose > or =140 mg/dL (7.77 mmol/L)], and 10 subjects (12%) had impaired fasting glucose [IFG; fasting glucose > or =100 mg/dL (5.55 mmol/L)]. However, only three (30%) subjects with IGT had IFG, though all subjects with IGT had a fasting triglyceride level > or =150 mg/dL (1.70 mmol/L). Of those subjects with elevated triglycerides, 29% had IGT. As a screening test to predict risk for IGT, elevated triglycerides >150 mg/dL had a sensitivity of 100% and a specificity of 68%. The positive predictive value was 29%, and the negative predictive value was 100%. CONCLUSIONS: Screening with fasting glucose alone would have missed 70% of subjects with IGT in this population of insulin-resistant adolescents. However, a fasting triglyceride level > or =150 mg/dL was strongly associated with IGT and may help to identify at-risk adolescents who should undergo formal glucose tolerance testing.     

The prevalence of impaired fasting glucose and type 2 diabetes in a population‐based sample of overweight/obese children in the Middle East

Moadab MH, Kelishadi R, Hashemipour M, Amini M, Poursafa P. The prevalence of impaired fasting glucose and type 2 diabetes in a population‐based sample of overweight/obese children in the Middle East. Background: Type 2 diabetes mellitus (T2DM) and impaired fasting glucose (IFG) are increasing in young population who are facing an escalating trend of overweight. The aim of this study was to determine the prevalence of IFG and T2DM for the first time in a population‐based sample of Iranian obese children. Methods: This cross‐sectional, population‐based study was conducted in Isfahan, the second large city of Iran. Overall, 672 overweight and obese school students, selected from 7554 students, aged 6–19 yr, were screened for IFG and T2DM. Fasting plasma glucose (FPG) and lipid profile were measured in all participants. Oral glucose tolerance test and insulin level were measured in those children with IFG. Insulin resistance was defined as homeostasis model assessment for insulin resistance (HOMA‐IR) > 3.10. Results: Among the7554 students (48.7% boys and 51.3% girls) studied, 9.34% (n = 706) were overweight and 5.3% (n = 403) were obese. A number of 672 overweight and obese students including 302 (44.9%) boys and 370 (55.1%) girls, with a mean age of 12.8 ± 3.10 yr underwent biochemical work up. Overall, the prevalence of IFG was 4.61% (n = 31), the corresponding figure was 2% (n = 4) in the 6–10 yr age group, and 5% (n = 27) in those aged 10.1–19 yr. The prevalence of T2DM was 0.1% (n = 1; age, 18.00 yr). Impaired glucose tolerance and insulin resistance were detected in three and six participants with IFG, who consisted 0.4 and 0.8% of total obese and overweight students, respectively. Conclusions: Although the prevalence of T2DM is low in Iranian obese children, IFG is not uncommon. Preventive measures and screening of FPG should be considered for these children.     

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.     

Insulin resistance and hyperinsulinemia in prepubertal obese children

BACKGROUND: Tissue resistance to insulin has been demonstrated in obese individuals. Pancreatic beta-cells respond to the reduced tissue sensitivity with increased insulin secretion so that glucose homeostasis is maintained. OBJECTIVE: The purpose of this prospective study was to investigate the presence of hyperinsulinemia and insulin resistance in obese children and adolescents. SUBJECTS AND METHODS: Fasting glucose (FG) and insulin (FI) levels and fasting glucose to insulin ratio (FGIR) were measured in 26 obese prepubertal children and 20 obese adolescents, as compared to 20 non-obese prepupertal children and 20 adolescents with normal body weight. Furthermore, obese children and adolescents underwent an oral glucose tolerance test with measurements of glucose and insulin 2 hours post glucose load. RESULTS: In 14/26 (54%) obese prepubertal children and in 16/20 (80%) obese adolescents FI was >24 microU/ml. FGIR was <6 in 23/26 (88%) prepubertal obese children and in all obese adolescents. All non-obese prepubertal children and adolescents had normal FI. However, FGIR was <6 in 6/20 (30%) non-obese prepubertal children and in 15/20 (75%) non-obese adolescents. CONCLUSION: Hyperinsulinemia and insulin resistance are already present in prepubertal obese children. As hyperinsulinemia is a potentially reversible condition and the complications related to it may be prevented, early measurements should be undertaken so that obese children lose body weight before the onset of puberty which may enhance the problem of insulin insensitivity.     

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.     

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     

Prevalence of glucose intolerance in school age children. Population based cross-sectional study

AIM: The aim of the study was to determine the prevalence of glucose intolerance among school children in south-eastern Poland. METHODS: Schools were randomly selected in the area and the entire school population was studied. We examined 1083 children (510 boys and 573 girls) in the mean age 14.49 years (age range: 7.9-19 years). Their weight and height were measured and body mass index (BMI) was calculated. Patients were classified as overweight or obese based on International Obesity Task Force (IOTF) criteria. We tested fasting glucose level in randomly selected children with normal weight (N=83) in all overweight and obese subjects (N=229). In children with fasting blood glucose level higher than 5.5 mmol/L (100 mg/dL) oral glucose tolerance test (OGTT) was performed. RESULTS: About 17.8% of children were overweight and 4.6% obese. Fasting hyperglycemia was found in 16.7% obese children. The calculated prevalence of fasting hyperglycemia for entire population was 6.7/1000. Impaired glucose tolerance (IGT) was found only in obese children. The prevalence of glucose intolerance in obese children was 7.1%, in contrast the calculated prevalence of glucose intolerance for the entire population was 3.0/1000 (95% confidence interval: 0-8.4/1000). CONCLUSION: Despite relatively high number of obese children, the prevalence of IGT among schoolchildren of south-eastern Poland remains low.     

二甲双胍治疗肥胖伴高胰岛素血症非糖尿病儿童疗效

目的探讨二甲双胍治疗肥胖伴高胰岛素血症非糖尿病儿童的有效性和安全性。方法将22例肥胖伴高胰岛素血症的非糖尿病患儿分为治疗组（二甲双胍＋饮食控制＋锻炼）和对照组（饮食控制＋锻炼）。观察二组治疗前和治疗6个月后体质量指数（BMI）、胰岛素抵抗指数（HOMA-IR）、空腹血糖（FPG）和空腹胰岛素（FINS）、餐后2 h血糖和胰岛素（2 h PG和INS）,及血浆总胆固醇（TC）和三酰甘油（TG）的变化,观察治疗组治疗期间不良反应。结果治疗组治疗前后BMI、TC、FINS、HOMA-IR比较差异有显著性（P〈0.05,0.001）;对照组治疗前后BMI比较差异有显著性（P〈0.05）,其余各项指标比较均无显著差异（Pa〉0.05）。治疗组和对照组治疗前各项指标比较差异均无显著性（Pa〉0.05）,治疗6个月后FINS、HOMA-IR比较差异有显著性（Pa〈0.001）。治疗组治疗初期有腹部不适、腹泻3例（27%）,无其他不适症状,治疗3、6个月随访肝肾功能均正常。结论二甲双胍用于治疗肥胖伴高胰岛素血症非糖尿病儿童可明显降低空腹胰岛素,改善胰岛素抵抗。     

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。     

Repetitiveness of the oral glucose tolerance test in children and adolescents

BACKGROUNDData regarding the most suitable diagnostic method for the diagnosis of glucose impairment in asymptomatic children and adolescents are inconclusive. Furthermore, limited data are available on the reproducibility of the oral glucose tolerance test (OGTT) in children and adolescents who are obese (OB).AIMTo investigate the usefulness of the OGTT as a screening method for glucose dysregulation in children and adolescents.METHODSEighty-one children and adolescents, 41 females, either overweight (OW), OB or normal weight (NW) but with a strong positive family history of type 2 diabetes mellitus (T2DM), were enrolled in the present observational study from the Outpatient Clinic of Paediatric Endocrinology of the University Hospital of Patras in Greece. One or two 3-h OGTTs were performed and glucose, insulin and C-peptide concentrations were measured at several time points (t = 0 min, t = 15 min, t = 30 min, t = 60 min, t = 90 min, t = 120 min, t = 180 min).RESULTSGood repetitiveness was observed in the OGTT response with regard to T2DM, while low repetitiveness was noted in the OGTT response with regard to impaired glucose tolerance (IGT) and no repetitiveness with regard to impaired fasting glucose (IFG). In addition, no concordance was observed between IFG and IGT. During the 1^st and 2^nd OGTTs, no significant difference was found in the glucose concentrations between NW, OW and OB patients, whereas insulin and C-peptide concentrations were higher in OW and OB compared to NW patients at several time points during the OGTTs. Also, OW and OB patients showed a worsening insulin and C-peptide response during the 2^nd OGTT as compared to the 1^st OGTT.CONCLUSIONIn mild or moderate disorders of glucose metabolism, such as IFG and IGT, a diagnosis may not be reached using only one OGTT, and a second test or additional investigations may be needed. When glucose metabolism is profoundly impaired, as in T2DM, one OGTT is probably more reliable and adequate for establishing the diagnosis. Excessive weight and/or a positive family history of T2DM possibly affect the insulin and C-peptide response in the OGTT from a young age.     

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     

Characterisation of morbidity in a UK, hospital based, obesity clinic.

AIM: To identify clinical features which predict those most at risk of co-morbidities within an obesity clinic. METHODS: Children attending an obesity clinic had fasting glucose, insulin, and lipids measured prior to a standard oral glucose tolerance test (OGTT). History and examination established birth weight, family history of type 2 diabetes/obesity, pubertal status, and presence of acanthosis nigricans. Central and total fat mass was estimated by bio-impedance. RESULTS: Of the 126 children evaluated, 10.3% (n = 13) had impaired glucose tolerance (IGT); the majority (n = 11) of these would not have been identified on fasting glucose alone. Those with IGT were more likely to have a parental history of type 2 diabetes (relative risk 3.5). IGT was not associated with acanthosis nigricans. Twenty five per cent (n = 19) of those evaluated (n = 75) had evidence of the "metabolic syndrome" (MS). HDL cholesterol and triglyceride levels were related to insulin sensitivity (HOMA-R); HDL cholesterol was also related to birth weight SDS. We observed a trend for those with MS to have a lower birth weight SDS. The severity of obesity did not influence the likelihood of IGT or MS. CONCLUSIONS: Significant numbers of obese children have associated co-morbidities. Analysis of fasting blood glucose samples alone is not satisfactory to adequately evaluate glucose homoeostasis. The overall level of obesity does not predict co-morbidities. Special attention should be given to those with parental diabetes and a history of low birth weight who are more likely to have IGT and abnormal lipid profiles respectively.     

Differential impact of impaired fasting glucose versus impaired glucose tolerance on cardiometabolic risk factors in multi-ethnic overweight/obese children

We aimed to investigate the prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and their associations with cardiometabolic risk factors, according to ethnicity in a large obese paediatric cohort. A 75-g oral glucose tolerance test was performed in 1,007 overweight/obese Dutch children of multi-ethnic origin, referred to the obesity outpatient clinics of two Dutch hospitals in Amsterdam (mean age, 11.4 ± 3.2 years; 50.7% boys). Anthropometric parameters and blood samples were collected, and cardiometabolic risk factors were assessed. The cohort consisted of Dutch native (26.0%), Turkish (23.7%), Moroccan (18.8%) and children of ‘other’ (31.5%) ethnicity. The prevalence of IFG was significantly higher in Moroccan and Turkish children as compared to Dutch native children (25.4% and 19.7% vs. 11.8%, respectively, P < 0.05). IGT was most frequently present in Turkish and Dutch native children, relative to Moroccan children (6.3% and 5.3% vs. 1.6%, P < 0.05). Besides pubertal status and ethnicity, components of ‘metabolic syndrome’ (MetS) which were associated with IGT, independent of hyperinsulinaemia, were hypertension [odds ratio (OR), 2.3; 95% CI, 1.1–4.9] while a trend was seen for high triglycerides (OR, 2.0; 95% CI, 0.9–4.3). When analyzing components of MetS which were associated with IFG, only low high-density lipoprotein cholesterol was significantly associated (OR, 1.7; 95% CI, 1.2–2.5) independent of hyperinsulinaemia. In conclusion, in a Dutch multi-ethnic cohort of overweight/obese children, a high prevalence of IFG was found against a low prevalence of IGT, which differed in their associations with cardiometabolic risk factors.     

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.     

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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。     

The absence of insulin resistance in metabolic syndrome definition leads to underdiagnosing of metabolic risk in obese patients

This study explores in a group of obese children and adolescents aged 10 to 16 years, the prevalence of metabolic syndrome (MS) according to the criteria of International Diabetes Federation (IDF). In addition, the prevalence of insulin resistance (IR) was investigated to find correlations between MS and IR. IDF definition was compared to a modified WHO definition. A total of 159 obese patients (74 male and 85 female; median age 12.7 years) were included in the study. Anthropometric measurements, blood pressure, and serum fasting lipids were evaluated. An oral glucose tolerance test (OGTT) was performed, and serum glucose and insulin levels were measured at 0, 30, 60, 90, and 120 min. Homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), fasting glucose/insulin ratio (FGIR), Matsuda index, and total insulin levels during OGTT were calculated. For the IR diagnosis, we used cutoff values described in previous publications (HOMA-IR of >3.16, QUICKI of <0.357, FGIR of <7, and/or the sum of insulin levels during OGTT of >300 mIU/mL). MS prevalence, defined according to IDF criteria, was 34.6 %. Using the IDF definition, there was no statistically significant difference for the surrogate IR indices between patients with or without MS (QUICKI, 94.5 vs. 83.7 %), FGIR (81.1 vs. 78.8 %), HOMA-IR (70.9 vs. 63.5 %), and total insulin levels during OGTT (61.8 vs. 51.9 %). The Matsuda index values, the prevalence of fasting hyperinsulinemia, and impaired glucose tolerance were also similar in these two groups. In conclusion, IR was prominent in obese patients with and without MS. IDF definition of MS fails to discover individuals with IR, unless it is specifically investigated.     

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.