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Background: SHORT syndrome is a rare inherited multisystem disease that includes characteristic facial features, growth retardation, and metabolic anomalies and is related to heterozygous mutations in the PIK3R1 gene. However, it is difficult to ascertain the relationship between the phenotype and the genotype quickly and efficiently. Methods: We report two Chinese girls with SHORT syndrome who presented with growth retardation, dysmorphic features, insulin resistance, and diabetes. Comprehensive medical evaluations were collected, including anthropometric measurements, laboratory measurements, and imaging examinations. Whole exome and Sanger sequencing was performed to detect and confirm the underlying genetic mutations in these patients. We prescribed metformin for the patients. Results: The patients both presented diabetes, insulin resistance, short stature, lipodystrophy, and characteristic facial dysmorphic features. A heterozygous mutation was detected in the PIK3R1 gene (c.1615_1617del) of Patient 1. The analysis of patient 2 revealed another PIK3R1 mutation (c.1945C>T). After family validation, neither their parents nor their brothers had similar clinical presentations or carried the same mutation. Conclusion: We identified two de novo heterozygous mutations in PIK3R1 as the cause of SHORT syndrome in two Chinese girls. Additionally, in terms of diabetes control, metformin works well in the early treatment stage. [ABSTRACT FROM AUTHOR]

Objective. Delays in skeletal maturity are related to bone mass and fracture risk in children, but the factors that determine it are unknown. We aimed to identify the association between insulin-like growth factor-1 (IGF-1) and skeletal maturation before and after growth hormone (GH) treatment. Methods. In this retrospective cohort study, we observed 783 short children and adolescents, 229 of whom received GH therapy. Skeletal maturation was assessed based on the difference between bone age (BA) and chronological age (CA) (noted as BA-CA). Anthropometric data and laboratory values were measured, and BA was evaluated using the Greulich and Pyle method. Results. The delayed BA group was defined as BA ‐ CA < − 2 SD (n = 457), and the occurrence rate of BA delay was 58.37%. A nonlinear relationship was observed between the IGF-1 standard deviation score (IGF-1 SDS) and BA-CA before and after GH therapy. Before GH therapy, there was a significant positive association between the IGF-1 SDS and BA-CA when the IGF-1 level was greater than -2 SDS (β 0.17, 95% CI 0.08, 027; P < 0.001). However, we did not observe a significant relationship between the IGF-1 SDS and BA-CA when the IGF-1 level was lower than -2 SDS (β 0.07, 95% CI -0.12, 0.26; P = 0.454). After GH therapy, there was a significant positive association between the IGF-1 SDS and BA-CA when the IGF-1 level was lower than 2 SDS (β 0.20, 95% CI 0.12, 028; P < 0.001). However, we did not observe a significant relationship between the IGF-1 SDS and BA-CA when the IGF-1 level was greater than 2 SDS (β -0.03, 95% CI -0.33, 0.27; P = 0.866). Conclusion. BA is more delayed in short children and adolescents. There is a nonlinear relationship between IGF-1 and BA maturation in short children before and after GH treatment. These findings suggest that a low level of IGF-1 may contribute to BA delay in short children and adolescents. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The purpose of the present study was to observe the relationship between serum α‐klotho (KL) protein level and diabetic retinopathy (DR), and to further examine the effects of KL protein on apoptosis induced by palmitic acid (PA) in human retinal endothelial cells. Materials and Methods: A total of 17 healthy people and 60 type 2 diabetes patients were included. According to the results from fundus fluorescein angiography, the diabetes patients were divided into three subgroups: without DR, non‐proliferative DR and proliferative DR. Serum KL level was measured by enzyme‐linked immunosorbent assay. In vitro, human retinal endothelial cells were exposed to PA with or without KL protein. Apoptosis rates were analyzed by flow cytometry analysis. Apoptotic‐related protein expressions were detected by western blotting analysis. Results: Serum KL level was lower in diabetes patients than that in healthy participants (P = 0.007), and was gradually decreased among the without DR, non‐proliferative DR and proliferative DR subgroups (P = 0.045). A logistic regression analysis showed that after adjusting for the other confounding factors, serum KL level was independently and negatively related with DR (P = 0.049). Furthermore, the increased apoptosis rates induced by PA were inhibited with the addition of KL protein. Consistently, KL protein reversed the expression levels of the increased pro‐apoptotic protein Bax and the decreased anti‐apoptotic protein Bcl‐2 induced by PA. However, the anti‐apoptotic effect of KL protein was attenuated by LY294002 through the phosphatidylinositol 3 kinase‐serine∕threonine kinase pathway. Conclusions: The data suggested that KL protein was probably a potential protective factor against retinopathy in type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

Objective. This study aimed to examine the relationship between serum alanine aminotransferase (ALT) and growth hormone (GH) in children and adolescents with short stature. Methods. In this retrospective cohort study, 670 Chinese children and adolescents with short stature were included, and 253 of them received recombinant human GH (rhGH) therapy. Anthropometric and biochemical indicators were measured. GH peak levels were assessed after provocation tests with L-dopa and insulin. The subjects were divided into 3 groups according to the GH peak level. The association between the GH peak and ALT was analyzed. The change of ALT during rhGH therapy was assessed by a generalized additive mixed model. Results. Serum ALT and incidence of ALT elevation were both decreased across the GH tertiles (P = 0.002, 0.012, respectively). A univariate analysis showed that the GH peak was negatively associated with ALT (β: -0.12; 95%CI: -0.22, -0.02; P = 0.023). Furthermore, multiple linear stepwise regression analysis demonstrated that the GH peak was independently related to ALT after adjusting for other confounding variables (β: -0.12; 95%CI: -0.24, -0.00; P = 0.042). Besides, mean values of the change in ALT from baseline displayed that, during the early stages of rhGH treatment, serum ALT level indicated a temporary upward trend, but it subsequently gradually decreased (β: -0.16; 95%CI: -0.23, -0.09; P < 0.001). Conclusions. GH secretion level was strongly negatively correlated with ALT in short children and adolescents. And rhGH therapy could reduce ALT level over time. [ABSTRACT FROM AUTHOR]

Objective. This study was designed to analyze the association between the growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis gene polymorphisms and short stature in Chinese children. Methods. 181 growth hormone deficiency (GHD) patients and 206 normal stature controls were enrolled to attend this study. Five single-nucleotide polymorphisms in the GH receptor (GHR) and 5 SNPs within the GH-signaling pathway were genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry. We conducted an association study between these SNPs and the risk of developing short stature. Linkage disequilibrium analysis was performed using Haploview software and the associations of the SNPs frequencies with short stature were analyzed using X2 tests. Results. No significant difference was found in gender, weight, height, and BMI between the GHD and control groups, except that the age of GHD group was older than the control one. Allele and genotype frequencies were consistent with those expected from Hardy-Weinberg equilibrium. Compared with the controls, heterozygous genotype frequencies (CT) of rs12515480 and rs6873545 of GHR gene were significantly lower. Genotype frequencies of the other 8 SNPs did not show significant difference between these two groups. Considering a dominant model, an OR < 1 was observed for genotypes rs12515480 (OR = 0.532, P=0.019) and rs6873545 (OR = 0.587, P=0.017). Conclusions. The heterozygous genotypes of rs12515480 and rs6873545 of GHR gene were associated with decreased risk of GHD in Chinese children. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to examine the relationship between insulin-like growth factor-1 (IGF-1) and serum uric acid (UA) in Chinese children and adolescents with idiopathic short stature (ISS). Methods. A cross-sectional study of 91 Chinese children and adolescents with ISS was performed. Anthropometric measurements and biochemical parameters were tested. The standard deviation score of IGF-1 (IGF-1 SDS) was calculated. Results. A univariate analysis displayed a significant positive correlation between IGF-1 SDS and UA (P=0.004). In multivariate piecewise linear regression, the levels of IGF-1 SDS increased with the elevation of UA when UA was between 168 μmol/L and 301 μmol/L (β 0.010, 95% CI 0.004–0.017; P=0.002). The levels of IGF-1 SDS decreased with the elevation of UA when UA was either less than 168 μmol/L (β  −0.055, 95% CI −0.081–−0.028; P<0.001) or more than 301 μmol/L (β  −0.005, 95% CI −0.013–0.002; P=0.174). Conclusions. This study demonstrated a nonlinear relationship between IGF-1 and UA levels in Chinese children and adolescents with ISS. This finding suggests that either high or low levels of UA may have an adverse effect on IGF-1, whereas appropriate UA levels have a beneficial effect. [ABSTRACT FROM AUTHOR]

Background The aims of the present study were to detect serum brain-derived neurotrophic factor (BDNF) protein concentrations in healthy and diabetic subjects with sleep disorders and to explore correlations among serum BDNF concentrations, metabolic parameters and inflammation. Methods In all, 377 eligible subjects were recruited to the study and underwent a 75-g oral glucose tolerance test. Various clinical parameters of metabolic disorders and cytokines were measured. Sleep disorders were assessed using the Pittsburgh Sleep Quality Index (PSQI). Subjects were grouped into those with normal glucose tolerance (NGT), those with NGT and sleep disorders (NGT-SDi), those with newly diagnosed type 2 diabetes mellitus (T2DM), and those with newly diagnosed T2DM and sleep disorders (T2DM-SDi). Results Serum BDNF levels were higher in the NGT-SDi and T2DM-SDi subgroups than in the NGT and T2DM groups, respectively. Multiple linear regression analysis revealed that serum BDNF concentrations were independently correlated with PSQI scores, homeostasis model assessment of insulin resistance, and HbA1c, interleukin 6 and tumor necrosis factor-α concentrations ( P < 0.05 for all). Binary logistic regression analysis revealed that significant associations remained between serum BDNF concentrations and sleep disorders after adjustment for glucose- and metabolic-related factors in both the NGT-SDi and T2DM-SDi subgroups. Conclusions Serum BDNF concentrations were higher in patients with sleep disorders and were associated with various metabolic parameters and inflammatory cytokines. [ABSTRACT FROM AUTHOR]