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     

肥胖伴黑色棘皮病儿童胰岛分泌功能的临床研究

目的　研究肥胖伴黑棘皮病儿童胰岛素分泌功能的改变 ,探讨其临床意义。方法　对35例肥胖伴黑色棘皮病患儿、38例单纯肥胖患儿及 39例正常儿童进行胰岛 β细胞功能指标的测定。结果　肥胖伴黑色棘皮病组空腹胰岛素、C肽、胰岛素原、真胰岛素、胰岛素原与胰岛素、C肽比值、胰岛素抵抗指数和胰岛 β细胞分泌指数 (中位数及范围 )分别为 18 5 (5 0～ 6 0 5 )pmol/L、3 9(1 3～14 0 ) μg/L、2 8 84 (9 9～ 6 4 2 )pmol/L、32 96 (6 2～ 6 6 0 )pmol/L、1 2 (0 4～ 8 9)、6 9(2 5～ 36 6 )、5 0(0 8～ 14 1)和 30 3 3(5 2 2～ 116 3 8) ,均显著高于单纯肥胖组和正常组 (P <0 0 0 1)。结论　肥胖伴黑色棘皮病已经存在严重的胰岛 β细胞分泌亢进和胰岛素抵抗 ,是儿童患 2型糖尿病的高危 信号     

儿童良性黑棘皮病与代谢异常

目的：观察儿童良性黑棘皮病与人体测量指标参数及代谢指标的关系,探讨儿童良性黑棘皮病与代谢性疾病的关系。方法：回顾性分析2007年2月至 2011年10月于我院诊治的29例良性黑棘皮病患儿的临床资料,以同年龄同性别同民族相匹配的32例正常儿童为对照组。比较两组儿童人体肥胖指标（体重指数、腰臀围比、体脂含量及体脂百分比）及代谢指标（血糖、胰岛素水平、血脂系列）等的不同。结果：29例良性黑棘皮病患儿体重指数、体脂含量、体脂百分数、腰臀围比、空腹血糖及胰岛素水平、甘油三酯均高于对照组（P<0.05）,而高密度脂蛋白低于对照组（P<0.05）。29例良性黑棘皮病患儿中,16例存在糖耐量异常,3例确诊为糖尿病（1例1型,2例2型）。结论：儿童良性黑棘皮病与肥胖、胰岛素抵抗及血脂异常密切相关。     

Insulin resistance and acanthosis nigricans, type A: case report

A 9-year-old Somali girl was referred to the Paediatric Diabetic Clinic, Al-Amiri Hospital for control of her diabetes. On physical examination, she was found to have several somatic abnormalities and acanthosis nigricans. Biochemical and hormonal investigations revealed no major abnormalities apart from that of glucose metabolism. Insulin resistance was detected early on initiating treatment and, even with high doses, it was impossible to achieve normoglycaemia. This case is similar to other cases described in the literature with insulin resistance and acanthosis nigricans type A.     

Obesity, acanthosis nigricans, insulin resistance, and hyperandrogenemia: pediatric perspective and natural history

We studied the syndrome of acanthosis nigricans, obesity, insulin resistance, and hyperandrogenemia in 22 patients. Although isolated case reports in adolescents have appeared, this syndrome has not received full recognition as a pediatric entity. Our patients (17 girls, five boys) had a mean weight 5.7 SD above the mean for age, although mean height was only 0.5 SD above the mean for age. All patients had acanthosis nigricans. Their insulin resistance was significantly greater than that in a control group with comparable obesity. Fasting insulin concentration was 5.25 microU/ml in lean controls, 19.6 microU/ml in obese controls, and 49.8 microU/ml in study patients (P less than 0.002). Mean glucose disappearance rate during an insulin tolerance test was 6.7%/min in lean controls, 5.19%/min in obese controls, and 2.35%/min in study patients (P less than 0.02). After menarche, mean plasma testosterone concentration was 106 ng/dl, compared with less than 50 ng/dl in all lean and obese control patients. Data derived from our series of patients lead us to conclude that (1) this is a genetic syndrome, although the exact mode of inheritance is unclear; (2) the natural history of the syndrome invariably begins with the onset of obesity, followed by acanthosis nigricans that worsens with progressive weight gain; (3) acanthosis nigricans is thus a marker for hyperinsulinemia, which occurs before hyperandrogenemia; (4) hyperandrogenemia occurs only after menarche. Identification of this syndrome should permit monitoring for the development of hyperandrogenemia during puberty and determination of other affected family members.     

Familial insulin resistance and acanthosis nigricans

Insulin resistance exists in 0.1% of diabetics having insulin treatment. In addition to diabetics, insulin resistance can also be seen in association with acanthosis nigricans. Both conditions become a syndrome that may happen in a family. This is a report of two siblings, a brother and a sister, 14 and 10 years of age, whose parents are cousins, who suffered from diabetes mellitus, acanthosis nigricans, and growth retardation. The insulin therapy until 54 units per day given to the boy and 174 units per day to the girl, did not give response to the plasma glucose level. Plasma C-peptide and prolactin values of the girl were normal. The plasma fasting insulin level of both was high. Measurement of insulin binding to erythrocytes and monocytes was not performed. The GTT observations of their parents did not represent glucose intolerance.     

单纯性肥胖儿童黑色棘皮症与胰岛素抵抗性及细胞因子的关系

目的 探讨单纯性肥胖儿童的黑色棘皮症(AN)和体质量指数、胰岛素抵抗性、瘦素、血浆酶原纤维蛋白溶解原活化抑制剂(PAI-1)的关系。方法 单纯性肥胖儿童38例,其中AN阳性17例,测量身高、体质量、腹围、臀围,同时测血胰岛素、瘦素、空腹血糖、PAI-1。结果 AN阳性者肥胖度、腹围、空腹胰岛素、自动动态平衡标准评价胰岛素抵抗指数(HOMA-R)关系有显著差异,AN与体脂肪率间无关。AN阳性肥胖儿中均升高,PAI-1 40μg／L以上,瘦素30 μg／L以上者均为AN阳性。结论　单纯性肥胖儿童,特别是伴AN阳性肥胖儿,要特别注意随访观察2型糖尿病和冠状动脉疾病的发生和发展。     

Prevalence and clinical features of type 1.5 diabetes mellitus in children

AIM: To classify children with diabetes mellitus as type 1, 1.5 or 2, based on strict criteria, and then compare their features and treatment. METHODS: In this retrospective study, all children with diabetes mellitus in our clinic with antibody status available (n = 120) were reclassified as type 1, 1.5 or type 2 based on status of antibodies to the pancreas and presence of obesity and/or acanthosis nigricans, and their features compared. RESULTS: Sixty-four percent of type 2 patients were reclassified as type 1.5. Type 1.5 patients had significantly lower BMI SDS, blood pressure and acanthosis nigricans than type 2 patients. They had a higher insulin requirement (0.82 +/- 0.44 U/kg/day) than type 1 (0.72 +/- 0.35 U/kg/day) or type 2 (0.28 +/- 0.3 U/kg/day) patients. Total cholesterol, HDL-cholesterol, ALT and AST significantly worsened from type 1 to 1.5 to type 2 patients. CONCLUSIONS: Type 1.5 diabetes mellitus should be considered among obese adolescents presenting as type 2, as their clinical course is more aggressive and insulin requirement higher.     

Premature adrenarche: findings in prepubertal African-American and Caribbean-Hispanic girls

Premature adrenarche was previously thought to be a benign condition. However, the authors and several other research groups have noted hyperinsulinism and insulin resistance in many girls with premature adrenarche. African-American and Caribbean-Hispanic girls with premature adrenarche are frequently obese with marked hyperandrogenism, signs which correlate with the degree of insulin resistance (i.e., those girls who are obese and insulin resistant tend to have higher levels of adrenocorticotropic hormone-stimulated androgens). Also, girls with premature adrenarche and reduced insulin sensitivity can have subtle decreases in their high-density lipoprotein (HDL) profile. Many of these girls have a strong family history of type 2 diabetes mellitus. Preliminary data regarding long-term follow-up of girls with premature adrenarche indicate that those girls who remain obese are at risk of developing polycystic ovary syndrome (PCOS). The term 'syndrome X'refers to the constellation of laboratory and clinical findings associated with hyperinsulinism stemming from insulin resistance. These findings include obesity, acanthosis nigricans, glucose intolerance, type 2 diabetes mellitus, dyslipidaemia with reduced HDL and elevated low-density lipoprotein, cardiovascular disease and PCOS. Hence, for certain girls, premature adrenarche may be a part of the clinical spectrum of syndrome X.     

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.     

Acanthosis nigricans is a reliable cutaneous marker of insulin resistance in obese Japanese children

BACKGROUND: Acanthosis nigricans (AN) is a skin condition characterized by darkening and thickening of skin with formation of irregular folds, usually limited to a few specific areas of the body. Recently, AN has been reported to be linked to hyperinsulinemia and obesity. The aim of the present study was to determine whether or not the presence of AN in obese Japanese children is a reliable cutaneous marker. METHODS: The authors analyzed the clinical characteristics of 439 obese Japanese children (260 boys, 179 girls; mean age 10.1 years; mean percentage overweight 51.9%), who had visited Tsuruoka City Shonai Hospital in 1990-2000. Eighty-two of the 439 children were examined using an oral glucose tolerance test (OGTT). Of these children, the authors retrospectively studied 16 subjects: eight with AN and eight without AN (age range: 10.8-13.9 years; percentage overweight range: 54.3-97.0%). They were age and percentage obesity-matched males with normal glucose tolerance during OGTT. Females with normal glucose tolerance during OGTT were excluded from the 16 subjects because the number was too small and children with impaired glucose tolerance or type 2 diabetes during OGTT were also excluded because of glucose toxicity. Eighty-two children including the 16 subjects were analyzed at their first visit for the presence or absence of AN on the posterior of the neck, and for characteristics including age, birthweight, body height, bodyweight, percentage overweight, blood pressure, liver function markers serum lipid concentrations, fasting plasma glucose concentrations and insulin concentrations shown by the results of OGTT. RESULTS: (1) Children with AN showed significantly more glucose intolerance including impaired glucose tolerance and type 2 diabetes compared with those children without AN, and fasting plasma insulin concentrations were most significantly correlated with the presence of AN. (2) Insulin resistance based on fasting plasma insulin concentrations was seen in significantly more children with AN than in children without AN, even in age and percentage obesity-matched subjects with normal glucose tolerance during OGTT. CONCLUSIONS: Acanthosis nigricans could be a reliable cutaneous marker of insulin resistance in obese Japanese children.     

Premature adrenarche: findings in prepubertal African-American and Caribbean-Hispanic girls

Premature adrenarche was previously thought to be a benign condition. However, the authors and several other research groups have noted hyperinsulinism and insulin resistance in many girls with premature adrenarche. African-American and Caribbean-Hispanic girls with premature adrenarche are frequently obese with marked hyperandrogenism, signs which correlate with the degree of insulin resistance (i.e., those girls who are obese and insulin resistant tend to have higher levels of adrenocorticotropic hormone-stimulated androgens). Also, girls with premature adrenarche and reduced insulin sensitivity can have subtle decreases in their high-density lipoprotein (HDL) profile. Many of these girls have a strong family history of type 2 diabetes mellitus. Preliminary data regarding long-term follow-up of girls with premature adrenarche indicate that those girls who remain obese are at risk of developing polycystic ovary syndrome (PCOS). The term 'syndrome X' refers to the constellation of laboratory and clinical findings associated with hyperinsulinism stemming from insulin resistance. These findings include obesity, acanthosis nigricans, glucose intolerance, type 2 diabetes mellitus, dyslipidaemia with reduced HDL and elevated low-density lipoprotein, cardiovascular disease and PCOS. Hence, for certain girls, premature adrenarche may be a part of the clinical spectrum of syndrome X.     

INSULIN RESISTANCE IN A CHILD WITH ACANTHOSIS NIGRICANS TYPE A*

ABSTRACT. The patient, a female 6 years 4 months old, diagnosed as affected by Acanthosis nigricans and diabetes mellitus was referred to our Clinic for further investigation of her glucose metabolism. She had a typical face with hypertelorism, prognathism, macroglossia and large auricles. The skin was hyperpigmented, verrucous, hyperkeratotic especially in the folds and flexural areas with small papillomatous or nodular growth; diffused hypertrichosis and hypertrophic clitoris were also present. Biochemical and hormonal investigations revealed no major abnormalities apart from glucose metabolism. After an unsuccessful trial with conventional insulin therapy, endovenous continuous insulin infusion was started: even with 32 U/kg/h it was not possible to achieve normoglycemia. Insulin receptors were studied on erythrocytes: ¹²⁵I-insulin binding (specific) was clearly lower than normal. The concentration of insulin receptors was reduced, while the average affinity profile was normal. The study of erythrocyte insulin receptors has demonstrated that insulin resistance in this patient is due to a decrease in the number of receptors, i. e. Acanthosis nigricans type A.     

Acanthosis nigricans as a clinical marker to detect insulin resistance in Caucasian children from West Virginia

The accuracy of acanthosis nigrcans (AN) as a dermatological clinical marker to predict insulin resistance (IR) has not been well established in children. A cohort of obese Caucasian children was prospectively recruited. Demographic data, body mass index values, and laboratory data were compared for the presence or absence of AN. A total of 76 children participated. In all, 46 (60.5%) children had AN, and 34 (44.7%) children were positive for IR (>3.16); 25 (32.9%) children were positive for both AN and IR. Sensitivity, specificity, positive and negative predictive values, and accuracy level for AN to detect IR in the obese children who participated in this study were 73.5%, 50%, 54.3%, 70%, and 49%, respectively. The correlation between insulin and fasting glucose levels in AN-negative or AN-positive patients was low (R (2) = 13% to 17%). Acanthosis nigricans was only a surrogate marker for IR. It is concluded that IR should be examined in every obese West Virginian child irrespective of his or her AN status.     

Familial Insulin-Resistant Diabetes Mellitus without Acanthosis Nigricans or Androgenization

A 12-year-old Japanese girl and her mother showed insulin-resistant diabetes mellitus which was confmed by the response to an oral glucose load in both patients and by the small decrease in blood glucose after intravenous insulin in the daughter. Anti-insulin antibodies and anti-insulin-receptor antibodies were not detected in either patient. The circulating erythrocytes were found to have reduced insulin binding capacity, which, to judge from ID₅₀, was probably caused by decreased binding affhty of insulin receptors. The patients did not have acanthosis nigricans or signs of androgenization such as hirsutism, dysmenorrhea or polycystic ovaries. Endocrinological studies in the daughter showed elevated basal serum levels of luteinizing hormone (LH), dehydroepiandrosterone, testos terone and estrone, and an exaggerated LH response to LH-RH. It is possible that hyper-insulinemia caused by insulin resistance contributed to the increased secretion of LH and androgens, but it was unclear why signs of androgenization were absent in spite of increased secretion of LH and androgens.     

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.     

Type 2 diabetes mellitus in children--an increasing health problem in Mexico

The incidence of type 2 diabetes mellitus (DM2) in children has increased worldwide and is commonly associated with overweight. Forty-four children with DM2 were studied by clinical histories, anthropometric measurements, and biochemical analysis. Homeostasis model assessment (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were determined to evaluate insulin resistance. Only five patients presented normal body mass index (BMI); the remainder were overweight, and 76% had acanthosis nigricans. Laboratory results yielded hyperglycemia, elevated glycosylated hemoglobin, insulin and C-peptide. Elevated HOMA-IR and decreased QUICKI values suggest insulin resistance. No significant difference was found between sexes, although overweight in girls had more influence over blood pressure and lipid levels (p <0.05). Time from diagnosis and HOMA-IR yielded relevant values (p = 0.010). Laboratory results, QUICKI, and HOMA-IR values suggested that these patients present DM2 and decreased insulin sensitivity. We recommend prevention of overweight and sedentary life-style.     

Is this patient insulin resistant? How much does it matter?

Alex was an obese 10-year-old girl with a family history of type 2 diabetes, hypertension, and perhaps polycystic ovarian syndrome. Her physical examination was significant for a central accumulation of body fat and acanthosis nigricans. Although the laboratory studies indicated that Alex was not diabetic and probably not glucose intolerant, she could be insulin resistant (IR). Should any further evaluation be done? If Alex is IR, what kind of treatment should be offered? The following discussion addresses these questions by reviewing the pathophysiology, diagnosis, and consequences of isolated IR.     

Glucose alteration and insulin resistance in asymptomatic obese children and adolescents

Objective

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

Anthropometric and metabolic characteristics in children with clinically diagnosed nonalcoholic fatty liver disease

BACKGROUND

Childhood obesity is currently approaching epidemic proportions worldwide. Various chronic diseases are associated with obesity, but nonalcoholic fatty liver disease (NAFLD) has received little attention from paediatricians.

AIM

To examine anthropometric and metabolic variables relevant to NAFLD disease mechanism and severity.

METHODS

A retrospective review of 53 consecutive paediatric patients clinically diagnosed with NAFLD was performed between 1997 and 2004. Variables studied included ethnicity, body mass index, acanthosis nigricans, aspartate aminotransferase and alanine amino-transferase levels, and fasting levels of glucose, insulin and lipids. Insulin resistance was quantified by validated models (the homeostasis model of insulin resistance [HOMA-IR] and the quantitative insulin-sensitivity check index [QUICKI]).

RESULTS

The cohort was comprised of 34 boys and 19 girls; there was a 2:1 male predominance. The mean age of the children was 13.5 years (median 14.2 years; range 5.6 to 18.9 years), and 13 were 11 years of age or younger. Forty-five per cent were Caucasian, 30% Asian and 21% Hispanic. Thirty-eight children (72%) were classified as obese and 11 children (21%) were classified as overweight, with a mean ideal body weight percentage of 150.9±4.2 (range 67% to 226%) and a BMI Z score of 1.9±0.1 (range −1.2 to 3.2). Hyperinsulinemia was present in 35 children (66%). Insulin resistance (HOMA-IR 9.8±2.6, abnormal if greater than 3) was associated with increased plasma triglyceride (P=0.03) and total cholesterol (P=0.04) levels. These parameters were significant irrespective of alanine aminotransferase or aspartate aminotransferase levels.

CONCLUSIONS

Hyperlipidemia with hyperinsulinemia and insulin resistance in overweight and obese children with fatty liver may be important signs of liver dysfunction in childhood NAFLD, irrespective of serum aminotransferases. In overweight or obese children with hyperlipidemia or insulin resistance, evaluation for NAFLD is warranted.