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Objective We assessed the efficacy and safety of a weekly pegylated human growth hormone (PEG-rhGH) (Jintrolong) vs daily rhGH for children with growth hormone deficiency (GHD). Design Phase II and III, multicenter, open-label, randomized controlled trials. Methods 108 and 343 children with treatment-naive GHD from 6 hospitals in China were enrolled in the phase II and III studies respectively. Patients in the phase II study were randomized 1:1:1 to weekly Jintrolong (0.1 mg/kg/week PEG-rhGH complex), weekly Jintrolong (0.2 mg/kg/week PEG-rhGH complex) or daily rhGH (0.25 mg/kg/week) for 25 weeks. Patients in the phase III study were randomized in a 2:1 ratio to weekly Jintrolong (0.2 mg/kg/week) or daily rhGH (0.25 mg/kg/week) for 25 weeks. The primary endpoint for both studies was height velocity (HV) increase at the end of treatment. Other growth-related parameters, safety and compliance were also monitored. Results The phase II study established the preliminary efficacy, safety and recommended dose of Jintrolong PEG-rhGH. In the phase III study, we demonstrated significantly greater HV increases in patients receiving Jintrolong treatment (from 2.26 ± 0.87 cm/year to 13.41 ± 3.72 cm/year) vs daily rhGH (from 2.25 ± 0.82 cm/year to 12.55 ± 2.99 cm/year) at the end of treatment (P P Conclusion Jintrolong PEG-rhGH at a dose of 0.2 mg/kg/week for 25 weeks is effective and safe for GHD treatment and is non-inferior to daily rhGH.

The gene SLC2A2 encodes GLUT2, which is found predominantly in pancreas, liver, kidney and intestine. In mice, GLUT2 is the major glucose transporter into pancreatic beta cells, and biallelic Slc2a2 inactivation causes lethal neonatal diabetes. The role of GLUT2 in human beta cells is controversial, and biallelic SLC2A2 mutations cause Fanconi-Bickel syndrome (FBS), with diabetes rarely reported. We investigated the potential role of GLUT2 in the neonatal period by testing whether SLC2A2 mutations can present with neonatal diabetes before the clinical features of FBS appear.We studied SLC2A2 in patients with transient neonatal diabetes mellitus (TNDM; n = 25) or permanent neonatal diabetes mellitus (PNDM; n = 79) in whom we had excluded the common genetic causes of neonatal diabetes, using a combined approach of sequencing and homozygosity mapping.Of 104 patients, five (5%) were found to have homozygous SLC2A2 mutations, including four novel mutations (S203R, M376R, c.963+1GA, F114LfsX16). Four out of five patients with SLC2A2 mutations presented with isolated diabetes and later developed features of FBS. Four out of five patients had TNDM (16% of our TNDM cohort of unknown aetiology). One patient with PNDM remains on insulin at 28 months.SLC2A2 mutations are an autosomal recessive cause of neonatal diabetes that should be considered in consanguineous families or those with TNDM, after excluding common causes, even in the absence of features of FBS. The finding that patients with homozygous SLC2A2 mutations can have neonatal diabetes supports a role for GLUT2 in the human beta cell.

Methods This phase IV open-label interventional study was performed on samples from 205 GHD children (175 subjects born AGA and 30 subjects SGA) of Chinese Han origin, recruited at 8 centers. All the subjects were given r-hGH for 4 weeks (0.033mg/kg/d).1536 SNPs were selected from 100 Candidate Genes involved in the GHIGFI axes, growth plate and other short stature-related diseases. We genotyped Single nucleotide polymorphism (SNP) using Illumina GoldenGateTM Assays. Linear regression was used to identify single SNPs significantly associated with changes, from baseline to week 4, in serum IGF-I SDS and IGFBP3 SDS. Gestational age (GA) was also included in the model. The significance threshold was set as a corrected P-value

Results: The standardized prevalence of overweight significantly increased from 12.75 to 14.2% (p < 0.01), and the prevalence of obesity significantly increased from 3.35 to 3.94% (p < 0.01) during the study period. In contrast to data from developed countries, the prevalence of obesity decreased with age in both boys and girls. The prevalence of obesity and overweight in boys was significantly higher than that in girls (p < 0.01). Interestingly, the prevalence of overweight and obesity in the urban area was also significantly higher than that in suburb area (p < 0.01). Conclusion: Over a 5-yr period, there was a significant increase in the prevalence of obesity in children and adolescents in Shanghai. The high percentage of overweight and obesity in the young age groups is of particular concern. Urbanization might be a causative factor for the increase in obesity prevalence in Chinese children in the Shanghai area.

Objectives: To compare the response between Chinese children with growth hormone deficiency (GHD) born either small for gestational age (SGA) or appropriate for gestational age (AGA) after 4 weeks of recombinant human growth hormone (r-hGH) therapy. Methods: This was a phase IV, open-label, multicenter, interventional study (NCT01187550). Prepubertal children with GHD received open-label treatment with daily r-hGH (0.033 mg/kg) for 4 weeks. Serum levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 (IGFBP3), and metabolic markers (including fasting glucose, insulin, total cholesterol, and homeostasis model assessment of insulin resistance) were assessed at baseline and after 4 weeks of treatment, and were analyzed according to patient subgroup (SGA or AGA). Results: A total of 205 children with GHD (mean age 10.4 years; 175 AGA, 30 SGA) were included in the analysis. Mean baseline serum IGF-I and IGFBP3 standard deviation scores (SDS) across the whole patient population were lower than the population norms (mean values: -2.1 SDS for IGF-I and -1.2 SDS for IGFBP3), with no significant differences between the two patient subgroups. After 4 weeks, IGF-I and IGFBP3 levels increased by 1.0 SDS ( p < 0.001) and 0.34 SDS ( p < 0.001), respectively, but no significant differences were found between the two patient subgroups for growth-related or metabolic markers. Conclusions: For children with GHD born SGA, IGF-I and IGFBP3 are short-term biomarkers of responsiveness to treatment with growth hormone, as for children with GHD born AGA.

ContextCongenital generalized lipodystrophy (CGL) is a rare and heterogeneous disease of autosomal recessive inheritance. Until now, no genetic findings had been reported in Chinese patients with CGL.ObjectiveTo analyze Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) and 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) gene variation in a Chinese boy with CGL and his family.Design, setting, and participantsAll exons of BSCL2 and AGPAT2 with adjacent intron–exon junctions were analyzed using direct sequencing.Main outcome measuresSequences of each exon and nearby intron of the BSCL2 and AGPAT2 genes of the family members were compared with the gene bank genomic sequences.ResultsDNA sequence analysis of the entire coding regions and surrounding uncoding regions disclosed a novel homozygous G→T mutation at nucleotide 909 in exon 5 of the BSCL2 gene in the affected child. A heterozygous state of the G→T mutation of the BSCL2 gene was also found in other family members. This mutation predicts the substitution of glutamic acid at codon 189 by the stop codon (Glu189X or E189X). No variation was found in the AGPAT2 gene.ConclusionE189X is a novel BSCL2 gene mutation that contributes to CGL formation in a family of Chinese origin.

Subjects and methods We reviewed the records for all patients undergoing GHRT at our hospital over the study period. Patients were included if they had received CP resection, GHRT for at least 12 months, and records of serial magnetic resonance imaging data and data for treatment, pituitary hormone profiles and growth chart were available. GHnaive control patients were selected from our hospital database of patients carried out the same surgery. Patients were matched for date of surgery, age, site of primary diagnosis and sex.

Objective Toll-like receptors (TLRs) recognize a wide range of pathogen-associated molecular patterns (PAMP) and mount the initiation of immune response. Single nucleotide polymorphisms (SNPs) in exons of genes encoding TLRs might be responsible for the generation of an abnormal immune response which could lead to autoimmune diseases. In this study, we investigated the SNPs in TLRs in a Chinese population, and we hypothesized that SNPs in TLRs are associated with type 1 diabetes (T1D), an autoimmune disease caused by destruction of insulin producing pancreatic β-cells, in the studied population. Research design and methods We selected 28 SNPs in exons of TLRs with an aim to identify those that might have a direct correlation with T1D etiology and many have not been included in previous GWAS studies. Genotyping of those SNPs in TLRs was performed in 429 T1D patients and 300 age and gender-matched healthy controls in Chinese Han population which was not included in the earlier GWAS studies. Results Among the SNPs genotyped, the T allele of TLR1–626 was positively associated with T1D (OR = 1.98, Pc = 0.01). We identified another T1D association locus in TLR6: the homozygous AA genotype of TLR6-1329 was negatively and heterozygous GA was positively associated with T1D (OR = 0.54, Pc = 0.02 and OR = 1.70, Pc = 0.03, respectively). We also identified the haplotype T-G-A in TLR1 gene to be positively associated with T1D (OR = 2.22, Pc = 0.03). Additional haplotypes in TLR-6 also showed significant positive and negative association. In addition, our haplotype analysis and conditional analysis showed that these two SNPs are the primary T1D associated loci among the SNPs tested in our cohort in each TLR gene. Conclusion SNPs and haplotypes in TLR1 and TLR6 gene were associated with T1D in Chinese Han population. Our study, for the first time, indicates that TLR1 and TLR6 gene might play important roles in the etiology of T1D.