黑棘皮病与青少年肥胖

黑棘皮病是青少年肥胖患者中常见的皮肤病变,是青少年肥胖患者体内严重胰岛素抵抗的皮肤标志.在肥胖患者中,高胰岛素血症、炎性反应因子、异常分泌的脂肪细胞因子可促进皮肤组织内的成纤维细胞及角蛋白细胞的增殖,从而促进黑棘皮病的发生.另外,基因多态性同样在这一过程中发挥重要作用.然而青少年肥胖患者黑棘皮病的治疗尚无特效方法,通过饮食、运动及药物改善内胰岛素敏感性可能有效.     

肥胖相关黑棘皮病的发病机制

黑棘皮病是肥胖患者常见的皮肤过度角化伴局部肤色加深的特征性改变,是高胰岛素血症和胰岛素抵抗的可靠皮肤标志.该病是由于循环中过量的胰岛素通过直接或间接途径激活胰岛素样生长因子-1受体(IGF-1R),促进角化细胞和成纤维细胞生长所致.近年来的研究发现,肥胖患者皮肤的慢性炎性反应、维生素D浓度减低、瘦素分泌增加、色素上皮衍生因子(PEDF)水平升高、哺乳动物雷帕霉素靶蛋白(mTOR)通路过度活化与皮肤稳态受损等,也参与了黑棘皮病的发生和发展.探讨肥胖相关黑棘皮病的发病机制可以为临床诊断和治疗提供依据.     

二甲双胍对高胰岛素血症儿童假性黑棘皮病的疗效观察

对88例高胰岛素血症假性黑棘皮病(AN)肥胖儿童给予二甲双胍治疗3个月和6个月后,对空腹胰岛素、葡萄糖耐量试验2 h胰岛素和AN评分等进行评价,结果表明二甲双胍可改善假性AN肥胖患儿高胰岛素血症状态,AN分级方法可作为病情变化的无创监测手段.     

二甲双胍对假性黑棘皮病胰岛素抵抗及高胰岛素血症的作用

假性黑棘皮病 (ａｃａｎｔｈｏｓｉｓｎｉｇｒｉｃａｎｓ,ＡＮ)是一种胰岛素抵抗、高胰岛素血症、高雄激素血症的皮肤特征性改变 ,在不同的胰岛素抵抗综合征中常常伴有假性ＡＮ。胰岛素抵抗和代偿性高胰岛素血症已被证明对糖尿病、肥胖、高血压、高脂血症等疾病的发生起着重要的促进作用。及早发现和识别高胰岛素血症并给予早期干预治疗是目前临床研究的重点。二甲双胍除降低血糖外 ,可改善机体对胰岛素的敏感性 ,增加细胞的胰岛素受体数目 ,从而改善高胰岛素血症。本研究旨在观察二甲双胍对假性ＡＮ中胰岛素抵抗及高胰岛素血症、高雄激素血…     

儿童高胰岛素血症发生的相关因素及危害

儿童高胰岛素血症的发生与肥胖、低出生体重、青春期、遗传及种族等多种因素有关。高胰岛素血症对儿童机体可能造成多种损害，如黑棘皮病，日后亦可能发展成为2型糖尿病；高胰岛素血症还是心血管疾病发生的危险因子等。针对儿童高胰岛素血症，可通过改善胎儿营养状态，控制体重或口服药物进行治疗，以期能控制和减少儿童高胰岛素血症造成的危害。     

肥胖儿童胰岛素抵抗和代谢糖尿病综合症的临床分析

目的分析肥胖儿童胰岛素抵抗和代谢综合症的之间的关系。方法回顾性分析2014年1月—2015年12月在该院住院治疗的76例肥胖儿童临床病例资料,分析肥胖儿童胰岛素抵抗和代谢综合症的之间的关系。结果 76例患儿中糖代谢异常者24例、血压增加者12例、血脂代谢紊乱者46例、被确诊为代谢综合症患者26例;胰岛素抵抗患儿与非胰岛素患儿相比,糖代谢异常率、血脂代谢异常和代谢综合症发生率比较差异具有统计学意义(P0.05)。结论肥胖儿童具有一定程度的代谢异常,较易发生代谢综合症。     

二甲双胍对IGT伴黑棘皮病肥胖青少年体重、血糖、血脂及胰岛素水平的影响

二甲双胍是已经有 6 0年应用历史的降血糖药物 ,近年来英国糖尿病前瞻性研究 (ＵＫＰＤＳ)证明其除降血糖外 ,还是改善 2型糖尿病患者长期临床转归的药物。本研究利用该药不增加体重 ,不发生低血糖的特点 ,观察二甲双胍对ＩＧＴ伴黑棘皮病肥胖青少年体重、血糖、血脂及胰岛素水平和黑棘皮病本身的影响。一、对象和方法1.1996年 8月至 1998年 12月间在我院门诊就诊、体重指数 (ＢＭＩ)≥ 30的肥胖青少年共 87例 ,其中伴不同程度的黑棘皮病者 32例 (男性 17例 ,女性 15例 ) ,占 36 .8% ,黑棘皮病诊断按标准〔1〕。本研究把仅有腋窝部轻度色素…     

北京地区儿童青少年胰岛素抵抗分布及其与瘦素／脂联素比值的关系

目的研究北京儿童青少年胰岛素抵抗指数的分布,探讨血液瘦素／月旨联素比值（LEP／APN）对儿童胰岛素抵抗状态的诊断价值。方法选取北京地区6—18岁儿童青少年代谢综合征研究队列的3506名儿童青少年,以中国肥胖问题工作组2004年制定的中国学龄儿童青少年超重、肥胖筛查体质指数（BMI）分类标准将研究对象分为正常体重人群（1628人）、超重人群（659人）和肥胖人群（1219人）,进行体量指标和青春发育程度的评价以及测定空腹血糖、血脂、真胰岛素、LEP和APN等。以稳态模型胰岛素抵抗指数（HOMA—IR）评价胰岛素抵抗状态。在健康儿童青少年中,按HOMA—IR百分位分布确定评价儿童青少年胰岛素抵抗界值。采用相关和回归分析评价LEP／APN与HOMA—IR的相关性,受试者工作特征曲线（ROC曲线）探讨LEP／APN对儿童胰岛素抵抗状态的诊断价值。结果尝试建立北京地区健康儿童青少年胰岛素抵抗界值：青春发育前期HOMA—IR≥2．6;青春发育期HOMA—IR≥3．4。超重和肥胖儿童胰岛素抵抗检出率分别为22．2％和42．9％。相关分析显示LEP／APN与HOMA—IR相关（相关系数为0．51,偏相关系数为0．40,P〈0．01）。多元线性回归分析提示LEP／APN独立于其他因素对HOMA—IR的影响最大（偏回归系数0．273,标准化偏回归系数为0．467,P〈0．01）。ROC曲线分析显示LEP／APN对胰岛素抵抗预测能力高于LEP、APN和评价肥胖的体量指标（如腰围、BMI和体脂率）。结论评价儿童青少年胰岛素抵抗需考虑青春发育状况,超重和肥胖儿童存在明显胰岛素抵抗。LEP／APN可作为一项反映儿童青少年胰岛素抵抗的新指标,对肥胖相关代谢紊乱的预测具有参考价值。     

罗格列酮联合枸橼酸氯米芬对多囊卵巢综合征伴假性黑棘皮病患者的疗效研究

多囊卵巢综合征（PCOS）是一种常见的内分泌紊乱性疾病，发病率约占育龄妇女的5％～10％。PCOS患者普遍存在胰岛素抵抗和高雄激素血症，由此导致糖、脂代谢异常。假性黑棘皮病（AN）是一种胰岛素抵抗、高胰岛素血症、高雄激素血症的皮肤特征性改变。在不同的胰岛素抵抗综合征中常常伴有假性黑棘皮病。本研究观察新型胰岛素增敏剂罗格列酮联合枸橼酸氯米芬治疗PCOS伴假性黑棘皮病的疗效，及其对胰岛素抵抗的影响。     

儿童高胰岛素血症发生的相关因素及危害

儿童高胰岛素血症的发生与肥胖、低出生体重、青春期、遗传及种族等多种因素有关。高胰岛素血症对儿童机体可能造成多种损害 ,如黑棘皮病 ,日后亦可能发展成为 2型糖尿病 ;高胰岛素血症还是心血管疾病发生的危险因子等。针对儿童高胰岛素血症 ,可通过改善胎儿营养状态 ,控制体重或口服药物进行治疗 ,以期能控制和减少儿童高胰岛素血症造成的危害。     

Prevalence of obesity and metabolic syndrome in Indigenous Australian youths

We conducted a cross-sectional study of Indigenous youths residing in the Torres Strait region of Australia to assess the prevalence of obesity and the metabolic syndrome. Data on body mass index (BMI), waist circumference, blood pressure, presence of acanthosis nigricans and blood glucose were collected. Fasting glucose, insulin, C-Peptide, HbA1c and lipids were measured, and an oral glucose tolerance test was performed in those with a BMI greater than 25 (childhood-equivalent cut-points) or fasting glucometer reading >5.5 mmol/L. Of 158 youths, 31% were overweight and 15% were obese, 38% had enlarged waist circumference consistent with central obesity, 43% had acanthosis nigricans and 27% were hypertensive. More females than males had enlarged waist circumferences (59% vs. 13%, P  < 0.001). Among overweight or obese youth, 56% had significantly elevated insulin ( P  = 0.021); they also had higher HOMA-IR ( P  = 0.002). The metabolic syndrome was present in 17% of all youths (mostly females) and in 33% of the overweight or obese subgroup. Type 2 diabetes was diagnosed in two youths. These very high proportions of overweight or obese Torres Strait youth with metabolic risk factors have major public health implications.     

Relationship between insulin resistance and serum alanine aminotransferase as a surrogate of NAFLD (nonalcoholic fatty liver disease) in obese Korean children

There has been increasing number of obese children who accompany obesity-related comorbidities. It has been known that nonalcoholic fatty liver disease (NAFLD) as one of obesity-related comorbidities is related with insulin resistance. So, we investigated the relation between insulin resistance and NAFLD, using serum alanine aminotransferase (ALT) as a surrogate of NAFLD among obese children in Korea. The study subjects were 909 obese children aged 9–12 years (boys 613, girls 296). Body mass index (BMI), waist circumference (WC), blood pressure, fasting blood glucose, fasting insulin, lipid profile were measured. ALT, liver enzyme was used as a surrogate of NAFLD and homeostasis model assessment of insulin resistance (HOMA-IR) was used as the index of insulin resistance. The prevalence of elevated serum ALT (≥40 mg/dl) was 33.4% in boys, and 19.6% in girls respectively. In boys, ALT was correlated with BMI, waist circumference, total cholesterol, triglyceride, HDL-cholesterol, systolic and diastolic blood pressure, HOMA-IR, fasting serum insulin. Odds ratio for HOMA-IR against the elevated ALT (≥40 mg/dl) was 1.061 (95% confidence interval, 1.020–1.103, P = 0.003). In girls, ALT was correlated with BMI, waist circumference, total cholesterol, triglyceride, glucose, systolic and diastolic blood pressure, HOMA-IR, fasting serum insulin. Odds ratio for HOMA-IR against the elevated ALT (≥40 mg/dl) was 1.042 (95% confidence interval, 0.998–1.088, P = 0.063). Among obese Korean children, insulin resistance and ALT, lipid profile, BMI, WC, blood pressure showed significant correlation. Especially, in boys, higher ALT is founded to be independently associated with insulin resistance.     

Elevated total and central adiposity and low physical activity are associated with insulin resistance in children

The aim of this study was 2-fold: (1) to examine insulin resistance, blood lipid levels, and inflammatory markers in 9- to 11.5-year-old obese and lean children and (2) to identify factors that influence insulin resistance in this cohort of youths. Body mass index, skinfold thickness, waist circumference, physical activity (4-day triaxial accelerometer), cardiorespiratory fitness (submaximal bicycle ergometer test), and dietary intake (3-day food records) were evaluated in 27 obese and 27 lean boys and girls. Fasting blood samples were analyzed for insulin, glucose, lipids and lipoproteins, C-reactive protein (CRP), interleukin 6, soluble intercellular adhesion molecule, and soluble vascular cell adhesion molecule. Homeostasis model assessment (HOMA) was used to evaluate insulin resistance (HOMA-IR). Obese children presented higher HOMA-IR, CRP, and blood lipid levels (all P < .01) compared with lean children. Total body fat and waist circumference were positively associated with fasting insulin (r > or = 0.51), HOMA-IR (r > or = 0.56), CRP (r > or = 0.51), and blood triacylglycerol (r > or = 0.38), and were inversely correlated with high-density lipoprotein cholesterol (r > or = -0.39; all P < .01). Cardiorespiratory fitness was inversely associated with HOMA-IR (r = -0.24; P < .05), but this association disappeared when adjusted for age, sex, and fat mass. Waist circumference and total daily physical activity explained 49% of the variance in HOMA-IR in these children. In conclusion, these findings suggest that total and central adiposity are positively associated and physical activity is negatively associated with insulin resistance in children. Interventions to improve glucose metabolism in youth should target at reducing total body and abdominal fat and increasing physical activity. The lack of association between inflammatory markers and HOMA-IR suggests that obesity may precede the elevation of these markers in the evolution of insulin resistance in youth.     

Serum 25-hydroxyvitamin D is associated with insulin resistance independently of obesity in children ages 5–17

AimTo determine the association of vitamin D with insulin resistance and obesity in children.MethodsA total of 92 obese and 58 non-obese children aged 5–17 years were evaluated. Data were collected related to anthropometric (weight, height), and biochemical parameters (fasting plasma glucose, serum insulin, serum 25-hydroxyvitamin D, lipid profile, vitamin B12, parathormone) and physical examination (blood pressure, acanthosis nigricans, stria, lipomastia). Insulin resistance (IR) was calculated using the homeostasis model assessment (HOMA). HOMA-IR = fasting insulin level (μU/ml) × fasting glucose (mg/dL)/405. A HOMA-IR value >2.5 was defined as insulin resistance.ResultsAccording to the US Endocrine Society classification, vitamin D deficiency (0−20 ng/ml) was determined at significantly higher rates in the obese group than in the control group (p < 0.001). The rate of subjects with a vitamin D level of 20−30 ng/ml was significantly lower in the obese group than in the control group (p < 0.001) Within the obese group a statistically significant difference was determined between the insulin resistant and non-insulin resistant groups in respect of serum 25-hydroxyvitamin D levels (p = 0.001) and vitamin B12 levels (p = 0.001). A significant negative correlation was determined between serum 25-hydroxyvitamin D and HOMA-IR (r=−0.256, p = 0.016) and insulin (r = −0.258, p = 0.015). The systolic blood pressure (p = 0.001) and diastolic blood pressure (p = 0.003) values were significantly different in the control and obese groups. A statistically significant difference was determined between the control and obese groups in terms of the levels of insulin, HOMA-IR, HbA1c, cortisol, LDL, total cholesterol, HDL, triglyceride, hemoglobin, MCV, MPV, and calcium.ConclusionThe prevalence of vitamin D deficiency was higher in obese children compared to normal-weight and overweight children. Serum 25(OH)D levels showed a negative correlation with insulin and HOMA-IR. Serum 25(OH)D is associated with insulin resistance independently of obesity.     

Insulin resistance and impaired glucose tolerance in obese children and adolescents referred to a tertiary-care center in Israel

OBJECTIVE: To establish the prevalence of insulin resistance and impaired glucose tolerance (IGT) and their determinants in a cohort of obese children and adolescents. METHODS: A retrospective design was used. The study group included 234 patients with a body mass index (BMI) greater than the 95th percentile for age and gender and 22 patients with a BMI between the 85th and 95th percentile for age and gender referred for evaluation to a major tertiary-care center in Israel. Ages ranged from 5 to 22 y. Estimates of insulin resistance (homeostatic model assessment (HOMA-IR)); insulin sensitivity (ratio of fasting glucose (GF) to fasting insulin (IF) (GF/IF), the quantitative insulin sensitivity check index (QUICKI)), and pancreatic beta-cell function (HOMA-derived beta-cell function (HOMA %B)) were derived from fasting measurements. An oral glucose tolerance test (OGTT) was performed in 192 patients to determine the presence of IGT. RESULTS: Insulin resistance was detected in 81.2% of the patients, IGT in 13.5%, and silent diabetes in one adolescent girl. Only two patients with IGT also had impaired fasting glucose (IFG). The prevalence of IGT was higher in adolescents than prepubertal children (14.7 vs 8.6%). GF/IF and QUICKI decreased significantly during puberty (P<0.005), whereas HOMA-IR and HOMA %B did not. Insulin resistance and insulin sensitivity indexes were not associated with ethnicity, presence of acanthosis nigricans or family history of type 2 diabetes. Patients with obesity complications had lower insulin sensitivity indexes than those without (P=0.05). Compared with subjects with normal glucose tolerance (NGT), patients with IGT had significantly higher fasting blood glucose (85.9+/-6.5 vs 89.2+/-10.6 mg/dl, P<0.05), higher 2-h post-OGGT insulin levels (101.2+/-74.0 vs 207.6+/-129.7 microU/ml, P<0.001), a lower QUICKI (0.323+/-0.031 vs 0.309+/-0.022, P<0.05), and higher fasting triglyceride levels (117.4+/-53.1 vs 156.9+/-68.9, P=0.002). However, several of the fasting indexes except QUICKI failed to predict IGT. There was no difference between the group with IGT and the group with NGT in fasting insulin, HOMA-IR, HOMA %B or the male-to-female ratio, age, BMI-SDS, presence of acanthosis nigricans, ethnicity, and family history of type 2 diabetes.CONCLUSIONS:Insulin resistance is highly prevalent in obese children and adolescents. The onset of IGT is associated with the development of severe hyperinsulinemia as there are no predictive cutpoint values of insulin resistance or insulin sensitivity indexes for IGT, and neither fasting blood glucose nor insulin levels nor HOMA-IR or HOMA %B are effective screening tools; an OGTT is required in all subjects at high risk. Longitudinal studies are needed to identify the metabolic precursors and the natural history of the development of type 2 diabetes in these patients.     

不同体质指数的2型糖尿病患者血管性血友病因子水平和胰岛素抵抗的临床研究

目的了解不同体质指数（BMI）的2型糖尿病（T2DM）患者的血管性血友病闪子（vWF）水平以及胰岛素抵抗（IR）程度。方法依据BMI将134例T2DM患者分为正常体重组（50例）、超重组（50例）与肥胖组（34例）,分别测定血浆vWF水平,并评估、比较各组IR程度。结果肥胖组的vWF水平、HOMAIR高于正常体重组（P〈0．05）;各组间胰岛素作用指数（IAI）及定量胰岛素敏感性指数（QUICKI）有统计学差异（P〈0．05）;HOMAIR、IAI及QUICKI各指标间呈正相关。结论肥胖的T2DM患者血浆vWF水平升高、IR程度明最加重。     

Adipose tissue and liver lipid metabolism in obese children: role of the body mass index and the presence of acanthosis nigricans.

AIMS: The aims of our study were to determine if insulin resistance is associated with increased plasma levels of non-esterified fatty acids (NEFA), glycerol, 3-hydroxybutyrate and triglycerides in obese children. We also studied whether the presence of acanthosis nigricans (AN) led to further alterations in the above parameters. METHODS: A total of 101 children were studied on their first visit to the paediatric endocrine clinic. Seventy-four were obese, 30 of them with AN. The remaining 27 were non-obese healthy children (control group). NEFAs, glycerol, triglycerides, 3-hydroxybutyrate, insulin, leptin, adiponectin and glucose were determined in blood samples obtained after overnight fasting. The insulin resistance index (IRI) was calculated following the homeostasis model assessment (HOMA). Data from the three groups were compared using appropriate statistical tests. RESULTS: No differences in age, sex ratio and pubertal stage were observed among the three groups. The group of children with the highest body mass index (BMI) showed higher plasma levels of insulin and leptin, higher IRI and lower plasma levels of adiponectin. As insulin and IRI increased, NEFA and 3-hydroxybutyrate decreased and triglycerides increased. When obese children were categorized by BMI, the presence of AN further exacerbated these differences. CONCLUSIONS: In obese children, insulin resistance is associated with plasma lipid alterations suggestive of both decreased adipose tissue lipolysis and hepatic beta-oxidation and increased hepatic synthesis of triglycerides. Such a metabolic condition may facilitate fat storage and hinder weight loss.     

体重指数和腰围与代谢综合征发生风险的比较研究

目的 比较体重指数、腰围与代谢综合征发生风险的相关性.方法 554例人选者(男316例,女238例),按照体重指数和腰围被分为周围肥胖组192例、腹部肥胖组135例和混合肥胖组237例,7年后进行随访.结果 共随访到520例.周围肥胖组代谢综合征累积发生率26.3%(49/186),腹部肥胖组代谢综合征累积发生率41.7%(50/120),混合肥胖组代谢综合征累积发生率43.0%(92/214).腹部肥胖组和混和肥胖组代谢综合征累积发生率显著高于周围肥胖组(X2分别为7.825和12.082,均P＜0.01),且基线时舒张压、甘油三酯、空腹血糖、空腹胰岛素及稳态模型评估法胰岛素抵抗指数(HOMA-IR)也显著高于前者(均P＜0.05).以有或无代谢综合征分组后基线资料比较,代谢综合征组无论男女,腰围和腰臀比均高于非代谢综合征组(P＜0.01和P＜0.05),体重指数在两组无统计学差异,并且代谢综合征组空腹血糖、空腹胰岛素和HOMA-IR显著高于非代谢综合征组(均P＜0.05).Logistic回归显示,与代谢综合征发生风险相关的因素主要为腰围(P=0.021)、腰臀比(P=0.009)、HOMA-IR(P=0.004).结论 腹部脂肪堆积及胰岛素抵抗是代谢综合征发生的两个重要因素,腰围比体重指数与代谢综合征的发生风险关系更密切.     

Reduced insulin requirements during participation in the DAFNE (dose adjustment for normal eating) structured education programme

Acanthosis nigricans is a hyperkeratotic lesion of the epidermis associated with insulin resistance. We present a diabetic patient with acanthosis nigricans at the insulin injection site on the abdominal wall. Neglecting rotation of sites for insulin injections and local hyperinsulinemia may play a role in the development of acanthosis nigricans.