Efficacy and safety of human chorionic gonadotropin combined with human menopausal gonadotropin and a gonadotropin-releasing hormone pump for male adolescents with congenital hypogonadotropic hypogonadism / 中华医学杂志(英文版)

BACKGROUND@#Compared to adult studies, studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism (CHH) are limited and no universal treatment regimen is available. The aim of this study was to evaluate the feasibility of human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) therapy for treating male adolescents with CHH.@*METHODS@#Male adolescent CHH patients were treated with hCG/hMG (n = 20) or a gonadotropin-releasing hormone (GnRH) pump (n = 21). The treatment was divided into a study phase (0-3 months) and a follow-up phase (3-12 months). The testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were compared between the two groups. The TV and other indicators between the groups were analyzed using a t-test (equal variance) or a rank sum test (unequal variance).@*RESULTS@#Before treatment, there was no statistical difference between the two groups in terms of the biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV of the hCG/hMG and GnRH groups increased to 5.1 ± 2.3 mL and 4.1 ± 1.8 mL, respectively; however, the difference was not statistically significant (P > 0.05, t = 1.394). The PL reached 6.9 ± 1.8 cm and 5.1 ± 1.6 cm (P  0.05, t = 0.314). After 9 to 12 months of treatment, the T level was higher in the hCG/hMG group. Other parameters did not exhibit a statistical difference.@*CONCLUSIONS@#The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy. Furthermore, results from the extended time-period showed positive outcomes at the 1-year mark; however, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further research.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT02880280; https://clinicaltrials.gov/ct2/show/NCT02880280.

Interleukin-1β and C-reactive protein level in plasma and gingival crevicular fluid in adolescents with diabetes mellitus / 北京大学学报(医学版)

OBJECTIVE@#Cytokines produced by various cells are strong local mediators of inflammation. Interleukin-1beta (IL-1β) and C-reactive protein (CRP) play essential roles in the development and progression of diabetes mellitus (DM). Thus periodontal diseases could be related to DM via the same mediators of inflammation. To evaluate plasma and gingival crevicular fluid (GCF) levels of IL-1β and CRP in adolescents with DM to further investigate whether DM has an impact on the levels of inflammation factors at an early stage, and to analyze the risk of developing periodontal diseases in adolescents with DM.@*METHODS@#A total of 121 adolescents aged from ten to sixteen years were enrolled, 41 adolescents diagnosed with diabetes mellitus were collected in the DM group, and 80 nondiabetic adolescents as the control group. The periodontal indices of each individual were recorded, including plaque index (PLI), modified bleeding index (mBI), probing depth (PD) and attachment loss (AL). GCF and intravenous blood samples were collected, and CRP and IL-1β levels were detected by enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#(1) PLI of DM group and control group were 1.23±0.05 and 0.95±0.04 separately, with significant difference (P=0.001). DM group and control group had mBI of 0.80±0.08 and 0.51±0.06 separately, with significant difference (P=0.003). Attachment loss was found in none of the subjects. PDs of DM group and control group were (2.37±0.51) mm and (2.31±0.05) mm separately, and there was no significant difference. (2) CRP in GCF was only detectable in partial of the individuals, with a detectable rate of 22.9% (11/48) in total. The detectable rate of CRP in GCF was significantly higher in DM group (38.5%) than that in control group (4.5%, P=0.006). The plasma level of CRP in DM group [0.23 (0.15, 1.89) mg/L] was higher than that in control group [0.19 (0.12, 4.18) mg/L], but without significance (P=0.776). (3) The plasma levels of IL-1β in DM group and control group were (14.11±0.57) ng/L and (14.71±0.50) ng/L separately, but there was no significance (P=0.456). GCF levels of IL-1β in DM group and control group were (12.91±1.95) μg/L and (17.68±3.07) μg/L, without significant difference (P=0.185).@*CONCLUSION@#Periodontitis was not observed in adolescents with DM at an early stage. However, the rising levels of periodontal indices and CRP in GCF, might indicate that adolescents with DM have a higher risk of developing periodontal diseases in the future.

Efficacy and safety of domestic leuprorelin in girls with idiopathic central precocious puberty: a multicenter, randomized, parallel, controlled trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In central precocious puberty (CPP), the pulse secretion and release of gonadotropin-releasing hormone (GnRH) are increased due to early activation of the hypothalamic-pituitary-gonadal axis, resulting in developmental abnormalities with gonadal development and appearance of secondary sexual characteristics. The CPP without organic disease is known as idiopathic CPP (ICPP). The objective of the study was to evaluate the clinical efficacy and safety of domestic leuprorelin (GnRH analog) in girls with ICPP.</p><p><b>METHODS</b>A total of 236 girls with ICPP diagnosed from April 2012 to January 2014 were selected and were randomized into two groups. One hundred fifty-seven girls in the test group were treated with domestic leuprorelin acetate, 79 girls in the control group were treated with imported leuprorelin acetate. They all were treated and observed for 6 months. After 6-month treatment, the percentage of children with peak luteinizing hormone (LH) ≤3.3 U/L, the percentage of children with peak LH/peak follicle stimulating hormone (FSH) ratio <0.6, the improvements of secondary sexual characteristics, gonadal development and sex hormone levels, the change of growth rate of bone age (BA) and growth velocity, and drug adverse effects between two groups were compared.</p><p><b>RESULTS</b>After the treatment, the percentage of children with a suppressed LH response to GnRH, defined as a peak LH ≤3.3 U/L, at 6 months in test and control groups were 96.80% and 96.20%, respectively, and the percentage of children with peak LH/FSH ratio ≤0.6 at 6 months in test and control groups were 93.60% and 93.70%, respectively. The sizes of breast, uterus and ovary of children and the levels of estradiol (E 2 ) were significantly reduced, and the growth rate of BA was also reduced. All the differences between pre- and post-treatment in each group were statistically significant (P < 0. 05), but the differences of the parameters between two groups were not significant (P > 0.05).</p><p><b>CONCLUSIONS</b>Domestic leuprorelin is effective and safe in the treatment of Chinese girls with ICPP. Its effectiveness and safety are comparable with imported leuprorelin.</p>

Analysis of clinical and genetic characteristics of 20 cases of children with Silver Russell syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>To improve the accuracy of the diagnosis of the disease on the basis of the clinical features and genetic characteristics of patients with Silver Russell syndrome (SRS).</p><p><b>METHOD</b>Patients diagnosed with SRS by Price criteria in 2006 to 2011 were reviewed for their clinical manifestations, physical signs, laboratory examinations and treatments.</p><p><b>RESULT</b>Twenty cases with SRS were 0.08-12.17 yr old. Fifteen were male and 5 were female. The clinical characteristics included more than 80% of cases had postnatal growth retardation 100% (20/20), craniofacial dysmorphism 100% (20/20), small for gestation age 95% (19/20), asymmetry and thinning of the face and/or limbs 90% (18/20), fifth finger clinodactyly 80% (16/20), BMI < -2 SDS 80% (16/20). Their height was obviously lagging behind in the bone age. HD SDS/average of bone retardation was 3.08. The two patients with the chief complaint of external genital abnormalities would have aggressive surgical treatment and they did not use the growth hormone (GH) treatment. Only six patients had used the GH treatment. GH treatment at a dose of 0.1 IU/(kg·d) used in 2 cases achieved a growth velocity (GV) 8 - 11 cm/yr but in another 2 cases < 5 cm/yr. In genetic study, 6 patients were found to have 11p15 low methylation, 1 had low and high methylation, 1 had duplication, no relation between clinical and methylation of 11p15 was found.</p><p><b>CONCLUSION</b>There were great variations of clinical features in SRS characterized by small for gestation age and/or postnatal growth retardation, craniofacial dysmorphism, asymmetry of the face and/or limbs or ultrafine limbs, fifth finger clinodactyly. Severely low BMI was seen and height was obviously lagging behind in the bone age. The findings of laboratory tests and imaging of SRS were not specific. Some of SRS had 11p15 imprinting defects. The treatment of SRS is mainly symptomatic.</p>

Glycemic control and management of type 1 diabetes mellitus children in Beijing during 10 years / 中华实用儿科临床杂志

Objective To compare the anterior-posterior decade glycemic control with improvement of diabetes management and evaluate the influence of socioeconomic factors on glycemic control.Methods This cross-sectional clinical-based survey enrolled 158 with type 1 diabetes mellitus (T1DM) children from Sep.2011 to May 2012 (group A) in Beijing Children's Hospital of more than 1 year management and compared with 123 children with T1DM who were recruited in Asia and the West Pacific Region T1DM Study from Sep.2001 to May 2002 (Group B) in Beijing Children's Hospital.Normally distributed data were reported,linear correlation and regression analysis were performed for glycemic control.Results There was no complication in the both groups.The average of hemoglobin A1C(HbA1C) in group A was (8.50 ± 1.53) ％,better than that of group B [(9.90 ± 1.85) ％,P =0.000].The ratio of optimal and suboptimal HbA1C in group A and group B were 15.0 ％ vs 10.6％,while the ratio of suboptimal HbA1C in group A and group B were 52.5 ％ vs 25.2％,respectively,there were significantly statistical differences (all P =0.000).The ratio of insulin injection twice daily in group A and group B were 43.0％ vs 92.6％,respectively and the ratio of multiple daily injection and continuous subcutaneous insulin injection were increasing significantly 10 years after.The frequency of self-monitoring blood glucose(SMBG) between 60-120 times per month and over 120 times per month in group A was 45.5％ and 37.8％,while 0.8％,0 in group B,respectively,there was significant statistical difference (P =0.000).HbA 1C was positively correlated with age,duration,insulin dosage per day while inversely correlated with frequency of SMBG in liner correlation and regression analysis.It was showed that duration was the most important factor for HbA1C.Conclusions There were younger with T1DM in Beijing Children's Hospital.The frequency of SMBG and the ratio of multiple daily injection and continuous subcutaneous insulin injection were increasing significantly after 10 years.Duration was the most important factor for glycemic control.There was no complication in children with T1DM.Glycemic control would be better due to improvement of SMBG and increase of the frequency of insulin injection.

Correlation between blood glucose fluctuations and activation of oxidative stress in type 1 diabetic children during the acute metabolic disturbance period / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Studies have shown that complications in type 1 diabetes mellitus (T1DM) in children are mainly due to oxidative stress (OS). Lipid peroxidation is the main marker of OS and iso-prostaglandin is a reliable biomarker of lipid peroxidation in type 2 diabetes mellitus (T2DM). However, there have been few studies on OS in T1DM children with hyperglycemia and glucose fluctuations.</p><p><b>METHODS</b>We prospectively enrolled 23 newly diagnosed T1DM patients and 23 age and sex matched healthy controls in Beijing Children's Hospital from May 2010 to January 2011. They were treated with continuous subcutaneous insulin injection (CSII) and monitored by continuous glucose monitoring system (CGMS). Twenty-four-hour urine samples were collected to measure the concentration of 8-iso prostaglandin F2a (8-isoPGF2α). Samples taken from diabetic children were collected at days 8 to 10 after insulin treatment. Intraday glucose fluctuations were assessed by mean amplitude of glucose excursions (MAGE), largest amplitude of glycemic excursions (LAGE), standard deviation of blood glucose (SDBG) and number of glycemic excursions (NGE). The correlations between glucose parameters and the index of oxidative stress were analyzed.</p><p><b>RESULTS</b>Urine 8-isoPGF2α in the T1DM group was higher than that in the control group ((967.70±412.68) ng vs. (675.23±354.59) ng, P = 0.019). There was a correlation between urine 8-isoPGF2a level and MAGE (r = 0.321, P = 0.039), a significant correlation between low-density lipoprotein and urine 8-isoPGF2a level (r = 0.419, P = 0.03). There was no significant correlation between urine 8-isoPGF2α level and blood pressure, glycosylated hemoglobin (HbA1c), fasting C-peptide or other lipid indices.</p><p><b>CONCLUSION</b>A correlation between urine 8-isoPGF2a levels and MAGE and low-density lipoprotein was found in children newly diagnosed with T1DM.</p>

Study on physique index set for Chinese children and adolescents / 中华流行病学杂志

Objective To provide data as age-gender dependent mean,standard deviation and percentile on height,weight.waist circumference (WC),hip circumference (HC).body mass index (BMI),waist hip ratio (WHR),waist to height ratio (WHtR) among 7-16 year-olds Chinese children and adolescents,towards setting up diagnostic criteria on metabolic syndrome for them.Methods A representative sample involvng 22 197 children and adolescence aged 7 to 16 years were randomly surveyed and they were from 6 representative geographical areas,including Beijing.Tianjin? Hangzhou,Shanghai,Chongqing and Nanning.A total of 21858 had available data,with male/female ratio as:11460/10 398.Using the standard methods,we measured height,weight.WC,HC,BMI.WHtR and other data in all age groups.Physique indexes among different geographic regions (North.Mid-west and East) were compared.Results (1) Both male and female showed an inaeasing trend of height.weight,waist circumference,hip circumference and BMI along with the increase of age.WHR of girls decreased gradually from 0.84 to 0.76 went from 7 to 16 years old while WHR of boys changed from 0.87 to 0.81 accordingly.(2) WHtR was rarely affected by age.It fluctuated between 0.42-0.43 in all girls and 0.44-0.45 in boys less than 11 years.WHtR of boys older than 12 years showed a slight decline from 0.45 to 0.42 of WHtR.(3) The average height,weight,BMI of children and adolescents from the northem regions (Beijing,Tianjin) were significantly higher than that of the mid-western (Chongqing,Nanning) and the eastem regions (Shanghai,Hangzhou) (P＜0.001 ),while those from the mid-western region were slightly higher than that of the eastern region (P＜0.05) in each of the age group.Conclusion Reference values and percentile curves for WC and WHtR of Chinese children and adolescents were provided.For the assessment of central obesity.WHtR had the advantages of relative stability and small degree of variation and rarely affected by age and gender,when compared with WC.and could be used as an simple index to reflect the central obesity of children and adolescents.

Survey on the levels of lipids in school-aged children of Beijing, Tianjin, Hangzhou, Shanghai,Chongqing and Nanning cities / 中华流行病学杂志

Objective To investigate the lipid levels of Han ethnicity Chinese children at school-age,to provide objective data for the formulation of prevention and management strategy regarding dyslipidemia among children and adolescents.Methods 20 191 children (with 10 669 boys and 9522 girls) aged 7 to 16 years old from 6 representative geographical areas,including Beijing,Tianjin,Hangzhou,Shanghai,Chongqing and Nanning,were surveyed in a randomly selected clustered sample in China.Data on fasting blood triglyceride (TG),total cholesterol (TC),lowdensity lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were measured.Non-high-density lipoprotein cholesterol (non-HDL-C) levels were calculated with data collection,entry,and collation were under the same criteria.Results (1) In the 7-16 year-old group,TG (P95) fluctuated between 1.26 mmol/L and 1.88 mmol/L,while TC (P95) was between 4.80 mmol/L and 5.46 mmol/L.LDL-C(P95) was between 2.67 mmol/L and 3.27 mmol/L while non-HDL-C (P95) was between 3.36 mmol/L and 3.91mmol/L,sugesting that age did not seem to be an affecting factor for the lipid level (P＞0.05).The level of HDL-C (P5) fluctuated bctwcen 1.08 mmol/L and 0.83 mmol/L,and the dependability analysis on HDL-C and age showed statistically significant difference (P＜0.01,r=-0.274).(2) In the 7-9 year-old group,the levels ofTG,TC,LDL-C and non-HDL-C of boys were lower but the HDL-C level was higher than in girls.However,in the 10-16 year-old group,the levels of five lipids of boys were all lower than in girls,with all the differences statistically significant (P＜0.05).(3) The levels of TG,TC,LDL-C and non-HDL-C in the obese group were significantly higher than those in non-obesity group,as HDL-C was significantly lower than in non-obese group(P＜0.01).Incidence rates of single and multiple dyslipidemia in obese group were significantly higher than in non-obese group (P＜0.01).(4) Grouped by region,the abnormal rates of TG were descending,with the ranking as North (10.4％),Midwest (9.7％) and East (8.3％),while the abnormal rates of TC were descending with the ranking as Midwest (6.0％),North (5.2％)and East (4.8％).The abnormal rates of LDL-C were descending as the ranking of North (3.1％),East (2.6％) and Midwest (0.9％),with the abnormal rates of non-HDL-C were descending as Midwest (6.5％),North(4.2％)and East (3.6％).The abnormal rates of HDL-C were descending as Midwess (14.2％),North(5.7％) and East(5.5％).All the differences in the above-said items were statistically significant (P＜0.05).(5) According to the standards of hyperlipidemia formulated by the American Academy of Pediatrics,the incidence rates of abnormal TG,TC,LDL-C,non-HDL-C,HDL-C were 9.4％,5.4％,2.2％,4.8％,8.6％ respectively.Conclusion (1) Levels of lipids were affected by many factors,but age was not one of them in children and adolescents.However,HDL-C was declining along with the increase of age,to some extent.(2)Girls had a relatively protective tendency through the increasing HDL-C level when they entered the puberty years.(3)Lipids levels in non-obese group were significantly better than the obese group.(4)The lipids levels of children and adolescents in the Eastern region of the country were better than that in the northern and mid-western areas.

A new mutation in the thyroid hormone receptor gene of a Chinese family with resistance to thyroid hormone / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Resistance to thyroid hormone (RTH) is a dominant inherited syndrome of reduced tissue responsiveness to thyroid hormone. It is usually due to mutations located at the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor β (TRβ). We report the clinical and laboratory characteristics and the genetic analysis of a patient with this rare disorder and his family members.</p><p><b>METHODS</b>The clinical presentations and changes of thyroid function tests (TFTs) including magnetic resonance imaging (MRI) of pituitary and other laboratory tests were analysed. TFTs of his family's members were detected as well. Direct DNA sequencing of the TRβ gene was done for those with abnormal TFTs.</p><p><b>RESULTS</b>The RTH child had goiter, irritability, aggressiveness, and sudoresis. His TFTs showed high levels of circulating free thyroid hormones (FT(4) and FT(3)) and normal thyroid-stimulating hormone (TSH) concentrations. He felt worse when treated as hyperthyroidism (Grave disease) with thiamazole and his clinical presentations got improved obviously when treated as RTH with bromocriptine without obvious advert effect. We identified a novel missense mutation, A317D, located in exon 9 of the gene of this boy and his mother. His mother had not any clinical presentation, but having abnormal TFTs results.</p><p><b>CONCLUSIONS</b>This patient reported here was concordant with the criteria of RTH. The feature is dysfunction of hypothalamus-pituitary-thyroid axis. A novel mutation was found in the TRβ, A317D, of this family. This research verified the phenomena that there is a clinical heterogeneity within the same mutation of different RTH patients.</p>

Efficacy and safety of recombinant human growth hormone solution in children with growth hormone deficiency in China: a multicenter trial / 中华儿科杂志

<p><b>OBJECTIVE</b>Human growth hormone (hGH) is an essential therapeutic drug for the treatment of growth hormone (GH) deficiency (GHD). However, the process of dissolving hGH of the powder form is complicated and potentially hazardous. In the present study, we evaluated the efficacy and safety of preparation in the replacement therapy for children with GH deficiency.</p><p><b>METHODS</b>A 12-month randomized, open-label, multicenter trial was conducted in 31 previously untreated children with growth failure secondary to GH deficiency [20 boys and 11 girls, mean age (10.5 +/- 4.1) years]. An recombined human growth hormone (rhGH) solution (Iintropin AQ) was given via subcutaneous injection daily in every evening at a weekly dose of 0.25 mg/kg. The patients were followed up at 3, 6, 9, and 12 months of the treatment, and the course of treatment was 12 months. Body height was measured 3-monthly and height velocity (HV) and mean height standard deviation score (HT SDS) were calculated. Serum Insulin-like growth factor I (IGF-1), Insulin-like growth factor binding protein 3 (IGFBP-3), GH antibodies and safety parameters were assessed at the baseline and at 3-month intervals. Bone age (BA) was assessed at the baseline and the rate of skeletal maturation (DeltaBA/DeltaCA) was calculated after 6 and 12 months of rhGH treatment by a central bone age reader. Moreover, the safety of rhGH solution treatment was assessed.</p><p><b>RESULTS</b>After 12 months of liquid rhGH therapy, growth parameters were significantly increased over baseline. (1) The mean (+/- SD) height increment DeltaHT (cm) was 4.0 +/- 1.3, 7.0 +/- 2.0, 10.3 +/- 2.6 and 12.9 +/- 3.3 after 3, 6, 9, and 12 months of treatment, respectively (P < 0.01), which indicated linear growth after treatment. The GV (cm/years) was 2.7 +/- 0.9 before treatment and increased to 16.0 +/- 5.1, 14.1 +/- 4.0, 13.7 +/- 3.5, and 12.9 +/- 3.3 after treatment, suggesting that catch-up growth was significant after treatment as compared to the pre-treatment status (P < 0.01). Accordingly, post-treatment catch-up growth was obvious, significant differences were observed in HT SDS, which was -4.62 +/- 1.46 at the onset of therapy and increased significantly after the treatment to -3.80 +/- 1.53, -3.28 +/- 1.60, -2.86 +/- 1.75 and -2.47 +/- 1.86, respectively (P < 0.01). The height difference between GH deficient children and unimpaired children of the same age and gender gradually decreased after treatment, which was significantly different from that seen before treatment (P < 0.01). (2) The levels of serum IGF-1 and IGFBP-3 were increased comparably for the treatment. IGF-1 level (microg/L) was 41 +/- 64 at baseline and increased to 179 +/- 155, 202 +/- 141, 156 +/- 155 and 159 +/- 167 after 3, 6, 9, 12 months of treatment. IGFBP-3 level (mg/L) was 1540 +/- 1325 at baseline, and increased to 3891 +/- 1815, 4051 +/- 1308, 3408 +/- 1435 and 3533 +/- 1413, respectively, suggesting that with the increases in height, IGF-1, and IGFBP-3 were significantly activated to relatively high levels by the medication and reached peak values between 3 and 6 months of treatment. The levels of IGF-1 and IGFBP-3 were significantly different before and after treatment (P < 0.01). The IGF-1/IGFBP-3 molar ratio significantly increased during GH therapy (0.143 +/- 0.013 pre-therapy up to 0.240 +/- 0.055 post-therapy, P < 0.01). The IGF-1/IGFBP-3 molar ratio tended to stabilize after 3-month GH therapy. (3) The bone age assessment carried out 6 and 12 months after treatment showed that the bone maturity (DeltaBA/DeltaCA) was 1.01 +/- 0.57 and 1.07 +/- 0.75, respectively, suggesting that there was no speed-up development in the bone age. No severe adverse events were observed during the trial and the most frequent accompanying event was mild hypothyroidism.</p><p><b>CONCLUSIONS</b>rhGH solution (Iintropin AQ) is a safe and effective preparation in the replacement therapy for children with GH deficiency.</p>

Blood glucose profile in children and adolescents in Beijing area / 中华儿科杂志

<p><b>OBJECTIVE</b>There are scant data about normal reference values of blood glucose (BG) in children. This study was conducted to learn the BG profile of children and adolescents in Beijing area.</p><p><b>METHOD</b>The population for survey was selected as a stratified cluster sample from 8 urban and 10 rural areas in Beijing. Fasting capillary blood glucose (FCBG) was determined in 19,593 children and adolescents aged 6 to 18 years in 4 urban and 3 rural areas using haemosaccharometer model II [Roche Diagnostic, (Shanghai) Ltd].</p><p><b>RESULTS</b>There were 1 9112 (97.5%) individuals with complete records, the mean age was 12.1 +/- 3.3 years (ranged from 6 to 18.9 years); 9514 (49.8%) were boys, 9598 (50.2%) were girls, 9792 were (51.2%) from urban areas and 9320 (48.8%) from rural areas. The average level of FCBG in boys was higher than that in girls (4.7 +/- 0.5 vs. 4.5 +/- 0.5, u = 28.0, P < 0.01). Among urban children, the trend of variation of FCBG was similar between boys and girls, the levels of FCBG increased with age, the peak of FCBG was reached at 12-13 years in urban girls, and from the age of 15 years, the level of FCBG declined. In boys, the FCBG level increased slowly from 13 years of age, there was no significant variation until 17 years old, and declined at the age of 18. Among suburban children, the trend of variation of FCBG was similar between boys and girls, both of them had two peaks, from 6 to 11 years old, FCBG of both boys and girls increased with age, and both reached the first peak at the age of 11 years. While at 13 years of age, there was an obvious drop in FCBG level. From 14 years of age on, there was a rise of FCBG in both boys and girls, and the second peak of FCBG was reached at 15 and 16 years of age in girls and boys respectively. The FCBG level of urban children was higher than that of rural children (4.7 +/- 0.5 vs. 4.6 +/- 0.5, u = 13.8, P < 0.01). The level of FCBG in overweight and obese children was higher than that of normal children. More boys, more obese and more urban children had abnormal FCBG.</p><p><b>CONCLUSIONS</b>The blood glucose level of children was associated with age, gender, obesity and district.</p>

Metabolic syndrome in overweight and obese schoolchildren in Beijing / 中华儿科杂志

<p><b>OBJECTIVE</b>To determine the prevalence and clinical phenotype of metabolic syndrome among overweight and obese schoolchildren in Beijing, and to compare the rates of diagnosis made according to the criteria of the National Cholesterol Education Program (NCEP) of the United States and International Diabetes Federation (IDF).</p><p><b>METHODS</b>Based on Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study with body mass index (BMI), waist circumference (WC) and blood pressure measured, the overweight and obese children were screened among nearly 20 000 children 6-18 years of age in Beijing by Chinese BMI cutoffs for schoolchildren (7-18 years) and the US 2000 CDC Growth Charts--the 85th and 95th percentile (6 years) and were enrolled as the study population. Simultaneously a group of children with normal BMI were selected as the control group and based on the international method of age grouping, each of the above groups was divided further into 4 sub-groups in terms of age: 6-9, 10-12, 13-15 and 16-18 years old, respectively. Fasting plasma glucose (FPG) and insulin (FINS), serum high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) were examined. HOMA-IR index was calculated for estimating individual insulin resistance. A child who met any three or more of the following five criteria, according to NCEP definition, was diagnosed as MS. A diagnosis of MS using IDF definition required abdominal obesity plus any two or more of the other four criteria: (1) abnormal obesity: WC > or = P(90); (2) elevated BPs: SBP/DBP > or = P(90); (3) low HDL-C: HDL-C < 1.03 mmol/L (40 mg/dl); (4) high TG: TG > or = 1.24 mmol/L (110 mg/dl); (5) impaired fasting glucose (IFG): FPG > or = 5.6 mmol/L (100 mg/dl).</p><p><b>RESULTS</b>The prevalence rates of MS by NCEP definition were: 0.9%, 7.6% and 29.8% in the normal weight (control group), overweight and obese children, respectively, which were higher than the rates diagnosed by IDF definition with 0.1%, 5.2% and 28.6% in the three groups. The prevalence rates of individual MS component among obese children were: 81.6% for abnormal obesity, 47.7% for elevated BPs, 35.6% for high TG, 16.9% for low HDL-C, and 13.4% for IFG. Elevated BPs (29.8%), abnormal obesity (27.4%) and high TG (26.0%) were the leading three abnormalities among overweight children. With the increase of BMI, the clustering of MS components and insulin resistance (HOMA-IR) were remarkably increased. HOMA-IR significantly increased as the number of MS component increased.</p><p><b>CONCLUSIONS</b>MS has been in an epidemic status among the obese schoolchildren in Beijing. Abnormal obesity, elevated BPs and high TG were the three most common metabolic abnormalities for overweight and obese children. The prevalence rates of MS by NCEP definition in the present study was higher than those diagnosed by using IDF definition.</p>

Allgrove syndrome in the mainland of China: clinical report and mutation analysis / 中华儿科杂志

<p><b>OBJECTIVE</b>Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of adrenal insufficiency, achalasia and alacrima and many cases have multi-systems disorder: endocrine, gastrointestinal tract, eyes and nervous system. This syndrome is also known as achalasia-addisonianism-alacrima syndrome or triple A syndrome. Allgrove syndrome is now known to be caused by mutations of AAAS gene encoding the aladin protein. In the present paper, we report a Chinese mainland girl with Allgrove syndrome with mutations in the AAAS gene.</p><p><b>METHOD</b>The patient was a 7-year-old girl complained of coma and dark skin; she was treated as Addison disease for 2 years and had vomiting for 9 months before the second admission. Gene analysis was performed after extracting genomic DNA by amplification and sequencing of the specific fragments of AAA gene.</p><p><b>RESULTS</b>The patient was confirmed to have adrenal insufficiency at the age of 5 years and 6 months. During the second hospitalization, she was found to have a remarkable brisk reflexion, bilateral optic nerve atrophy, alacrima and achalasia besides ACTH resistance. The girl was born to consanguineous parents. Based on these findings, she was diagnosed as having Allgrove syndrome. Mutation analysis revealed a novel homozygous deletion of a single G, c.771delG, in exon 8 of the AAAS gene. This frame shift mutation was predicted to create a premature stop codon at locus 290, p.R258GfsX33, leading to a truncated and non-functioning aladin protein. Both the parents were heterozygous for the mutation.</p><p><b>CONCLUSION</b>The clinical manifestations and AAAS gene mutations analysis confirmed the diagnosis of Allgrove syndrome. Gene analysis indicated that this syndrome is an autosomal recessive inherent disorder. ALADIN is significant for the normal cell function. When compared with reported cases, it seems that there are no remarkable relation between gene mutation loci and clinical manifestations in Allgrove syndrome.</p>

The prevalence of diabetes in children and adolescents of Beijing / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the prevalence of Diabetes mellitus (DM) in children and adolescents and to describe the characteristics on age, gender and district distribution of schoolchildren, in Beijing.</p><p><b>METHODS</b>A cross-sectional screening program the fasting capillary blood glucose (FCBG) was carried out in 19,593 schoolchildren in 7 areas of Beijing from March to October, 2004. According to the WHO diagnostic criteria: DM was set as FCBG < or = 6.1 mmol/L, impaired fasting glucose (IFG) was set as 5.6 mmol/L < or = FCBG < 6.1 mmol/L.</p><p><b>RESULTS</b>The total aggregate age-adjusted prevalence rates of DM and IFG were 5.7 per thousand and 13.5 per thousand, respectively. The prevalence rates of DM and IFG in males were significantly higher than that in females (7.7 per thousand vs. 3.6 per thousand and 26.8 per thousand vs. 11.3 per thousand. DM X2 = 12.27, P = 0.0005; IFG X2 =47.29, P = 0.0000). Among seven districts, East District had the highest prevalence rates of DM and IFG, 8.9 per thousand and 27.4 per thousand (companied high obesity 28.68%) while Ping-Gu District having the lowest ones as 2.0 per thousand and 7.5 per thousand (obese 12.75%) respectively (X2 = 13.75, and X2 = 32.65, P = 0.0002 and P < 0.0001). The DM prevalence rates between districts ranged from 2.0 per thousand to 8.9 per thousand, X2 = 18.94, P = 0.004 and the IFG prevalence of districts ranged from 7.5 per thousand to 27.4 per thousand (X2 = 52.05, P < 0.0001). The prevalence rates of DM among different age groups increased with age, with the highest prevalence of IFG on the 10-14 age group. Among boys, the highest prevalence rates of DM and IFG fell in the 15-18 and 10-14 age groups respectively while the highest prevalence rates on both DM and IFG among girls were in the same age group 10-14.</p><p><b>CONCLUSION</b>The high prevalence rates on DM and IFG were seen in Beijing and showed significant discrimination on age, gender and district distribution. More developed urban district and males had a higher prevalence, companied by higher obesity prevalence. Age seemed to be a high risk factor on DM for boys while the puberty development seemed a high risk factor for girls.</p>

Relationship between serum high-sensitivity C-reactive protein and obesity and impaired glycose metabolism in children and adolescents / 中华儿科杂志

<p><b>OBJECTIVE</b>High-sensitivity C-reactive protein (hs-CRP) may predict the development of type 2 diabetes mellitus (T2DM), metabolic syndrome (MS) and cardiovascular diseases (CVD) in adult, but few reports on relevant studies in children are available. The present study aimed to understand possible correlation between serum hs-CRP levels and some factors of obese children and adolescents with or without impaired glycometabolism.</p><p><b>METHODS</b>Seventy obese children and adolescents (age 8 - 17 years) and 30 non-obese healthy controls (group 1, 20 boys and 10 girls, mean age 12.6 years) were enrolled into this study. The obese individuals were subdivided into two groups according to the results of oral glucose tolerance test: the obese subjects without IGR (group 2, 54 cases, 43 boys and 11 girls, mean age 11.3 years) and the obese subjects with impaired glycometabolism (group 3, 16 cases, 8 boys and 8 girls, mean age 12.8 years). The levels of serum parameters including hs-CRP, glucose, lipid, insulin, C-peptide and whole blood HbA1c were determined. SPSS 10.0 was used for statistical analysis.</p><p><b>RESULTS</b>(1) There was significant increase of serum hs-CRP level in obese children and adolescents, the median was 2.44 (0.01 - 14.6) mg/L; the level of control group was 0.1 (0.01 - 2.1) mg/L. (2) Some of the following parameters, such as fasting plasma glucose (FPG), triglyceride (TG), fasting insulin (FINS), C-peptide (Cp) and insulin resistance index (IRI), were found increased in group 2 and 3 as compared to group 1. When FPG and TG were still in normal range in group 2, the levels of hs-CRP and IRI were significantly higher than those in group 1, the level of hs-CRP was 2.4 (0.01 - 9.0) mg/L. While FPG and TG were abnormal in group 3, the level of hs-CRP was 2.6 (0.1 - 14.6) mg/L, but the difference had no statistical significance. (3) Pearson correlation analysis showed that there was a moderate correlation between serum hs-CRP and BMI (r = 0.414, P = 0.000). There was a low correlation between hs-CRP and waist circumference, hip circumference and waist to hip ratio (WHR). The correlation of serum hs-CRP with blood pressure, TG, cholesterol, high density lipoprotein-cholesterol (HDL-C), HbA1c, FPG, FINS and Cp had no significant deviation. (4) Multiple linear regression analysis showed that body mass index (BMI) was the only indicator which had correlation with hs-CRP.</p><p><b>CONCLUSION</b>(1) There may be a chronic low-grade inflammation and insulin resistance in obese children. (2) The level of hs-CRP might be independently correlated with BMI in children. (3) Hs-CRP and IRI elevated before FPG and TG did, which may suggest that the low-grade inflammation and insulin resistance may be a pathogenic base of DM rather than the outcome of it. (4) The elevation of hs-CRP may help predict impaired glucose and lipid metabolism.</p>

Correlative Analysis on Human Leukocyte Antigen-DQ Gene Susceptibility for Autoimmune Polyglandular Syndrome,Type 1 Diabetic Mellitus and Autoimmune Thyroid Disease / 实用儿科临床杂志

Objective To evaluate the associations of human leukocyte antigen(HLA)-DQ gene with autoimmune polyglandular syndrome(APS),type 1 diabetic mellitus(T1DM) and autoimmune thyroid disease(AITD).Methods Fifteen cases of APS,29 cases of T1DM and 40 cases of AITD were selected as research subjects,while 27 healthy children were selected as controls.The DQA1 and DQB1 alleles were determined by polymerase chain reaction(PCR) and sequence-based typing method.The difference of their frequency in children and adolescents was analyzed.Results Compared with controls,APS and T1DM patients had increased frequency of subjects with DQA1*0301,0501(all P

Survey of type 1 diabetes incidence in children from 1997 to 2000 in Beijing area / 中华儿科杂志

<p><b>OBJECTIVE</b>The incidence of type 1 diabetes varied in different countries, different nations and different regions. This survey was conducted to clarify the incidence of type 1 diabetes of children in Beijing area between 1997 and 2000, to compare and analyze the difference in incidence of type 1 diabetes between the 2 periods of 1988 - 1996 and 1997 - 2000.</p><p><b>METHOD</b>According to the criteria of WHO Diabetes Mondial (DIAMOND), data were collected from all the children younger than 15 years of age in Beijing area who had the onset of type 1 diabetes during Jan. 1st, 1997 to Dec. 31st, 2000. Using the capture-recapture methods, 95% confidence intervals of incidence were calculated with Poisson's distribution formula. The significance of differences was tested with Chi-square method.</p><p><b>RESULTS</b>The incidences of type 1 diabetes during 1997 - 2000 were around 0.76/100 000 to 1.21/100 000. The average yearly incidence was 1.014/100 000 (95% confidence interval was 0.98/100 000 - 1.16/100 000). There was no significant difference in the incidence between 1988 - 1996 and 1997 - 2000, and it showed the same result when the incidences were adjusted by age according to the Chinese population census in 2000 (The incidence was 0.83/100 000 in 1988 - 1996 and 0.86/100 000 in 1997 - 2000, respectively). The incidence was higher in 10 - 14 year-old group than the younger groups (P = 0.002). There was no significant difference between male and female groups, either.</p><p><b>CONCLUSIONS</b>No significant difference was found between the periods 1988 - 1996 and 1997 - 2000 when the average yearly incidence of type 1 diabetes of children in Beijing was compared. These results were different from the other countries' reports that the incidence of type 1 diabetes was increasing by 3% - 5% per annum. There was no significant difference between male and female groups either and there was a higher incidence of type 1 diabetes in 10 - 14 yr group than the other groups in 1997 - 2000. Although the life-style of Beijing people changed a lot, it didn't affect the incidence of type 1 diabetes in children in this area. But since many people migrated to Beijing from other parts of the country, the changes in constitutive proportions of population might have some impacts on the results of the survey.</p>

Etiology of recurrent diabetes ketoacidosis in children with type 1 diabetes / 实用儿科临床杂志

Objective To analyze the etiology of diabetes ketoacidosis(DKA) in children with type 1 diabetes.Methods Totally 850 person-time of type 1 diabetes children in recent 20 years in our hospital were selected as studied subjects. Two hundred and twenty-five person-time of them were hospitalized because of DKA.Fifty-six cases (131 person-time) were due to recurrent DKA.These patients were classified into 2 groups according to onset time: group 1(diagnosed from 1982 to 1991) and group 2(diagnosed from 1992 to 2001).Results The analysis of recurrent DKA suggested that 71.8 % of them was due to infection, 20.4 % of them did not obey diabetic diet and 9.2 % of them discontinued insulin injection. The etiology of DKA showed no difference in two groups. The number of recurrent DKA in two groups was significantly different (P