Association of time in range with metabolic associated fatty liver disease and liver fibrosis in patients with type 2 diabetes / 中华内分泌代谢杂志

Objective:To investigate the association of time in range with metabolic associated fatty liver disease(MAFLD) and advanced liver fibrosis in patients with type 2 diabetes.Methods:This study was a retrospective study. A total of 494 type 2 diabetic patients were recruited in the Department of Endocrinololgy of Henan Provincial People′s Hospital from November 2019 to April 2022. Time in range(TIR) was calculated with continuous glucose monitoring data. Abdominal ultrasound scan was used to diagnose fatty liver. Liver stiffness measurement(LSM) by transient elastography was used to evaluate liver fibrosis. Pearson and multivariate linear regression analysis was used to evaluate the association between TIR and LSM. Multivariate logistic regression analysis was used to analyze the association of TIR with risk of MAFLD and advanced liver fibrosis.Results:Pearson correlation analysis showed that LSM was negatively correlated with TIR( r=-0.86, P<0.001) and was positively correlated with homeostasis model assessment for insulin resistance(HOMA-IR; r=0.48, P<0.001). After adjusting for confounding factors, multivariate linear regression analysis showed that TIR significantly negatively predicted LSM( β=-0.75, P<0.001), and HOMA-IR significantly positively predicted LSM( β=0.21, P=0.025). After adjusting for confounding factors, logistic regression analysis showed that compared with TIR Q4 patients, TIR Q1 patients had an increased risk of MAFLD( OR=1.96, 95% CI 1.07-3.62, P=0.027), advanced liver fibrosis( OR=3.82, 95% CI 1.17-12.50, P=0.027), and HOMA-IR was an independent risk factor for MAFLD( OR=1.22, 95% CI 1.04-1.43, P=0.005) and advanced liver fibrosis( OR=1.26, 95% CI 1.03-1.54, P=0.025). Conclusions:TIR and insulin resistance are independent risk factors for MAFLD and advanced liver fibrosis in patients with type 2 diabetes. TIR has a significant predictive value for MAFLD and advanced liver fibrosis.

Gut microbiota and immune mechanism of type 1 diabetes mellitus / 中华内分泌代谢杂志

Type 1 diabetes mellitus is a T-cell-mediated autoimmune disease that commonly affects adolescents, characterized by progressive destruction of pancreatic β-cells, absolute insulin deficiency, and hyperglycemia. The pathogenesis of type 1 diabetes mellitus is complex and is believed to be mainly associated with immunity, environment, and genetics. There is increasing evidence that gut microbiota is closely related to the occurrence of type 1 diabetes mellitus. This article focuses on the immune mechanisms and roles of gut microbiota and its derivatives in the development of type 1 diabetes mellitus from the perspectives of innate and adaptive immunity. Additionally, it introduces therapeutic approaches targeting gut microbiota for the treatment of type 1 diabetes mellitus.

Association between time in target range and risk of vertebral fracture in patients with type 2 diabetes / 中华内分泌代谢杂志

Objective:To investigate the association between time in target range and risk of vertebral fracture in patients with type 2 diabetes.Methods:The clinical data of 1 032 patients with type 2 diabetes who were hospitalized in endocrine department of Henan Provincial People′s Hospital from June 2017 to July 2021 were collected. Among which 632 patients were included into final analysis. The diabetes-specific risk score for vertebral fracture was used to assess the risk of vertebral fracture. Multivariate linear regression analysis was used to test the association between time in target range and risk score of vertebral fracture. Risk score≥9 was defined as increased risk of vertebral fracture. Multivariate logistic regression was used to estimate the association between time in target range and risk of vertebral fracture. Results:Among the included patients, mean age was(55.0±12.4) years and the percent of male was 72.5%. The mean course of diabetes was(9.4±8.0) years, and mean score of risk of vertebral fracture was 5.6±4.3. Time in target range was negatively correlated with risk score of vertebral fracture( P for trend <0.001), which was independent of potential confounders and continuous glucose monitoring parameters. The included patients were divided into four groups based on quartiles of time in target range. Multivariate logistic regression indicated that the risk of vertebral fracture in the first quartile of time in target range was 4.6 times higherthanthatinthe4thquartile, and the significance remained adjusted for potential confounders, s, CV, or meanamplitudeofglycemicexcursions(MAGE), respectively. Conclusion:Timein target rangewasnegativelycorrelatedwithriskscoreofvertebralfracturein patient with type 2 diabetes. Low time in range level was an independent risk factor for increased risk of vertebral fracture.

Advance in diabetic kidney disease and gut microbiota / 中华内分泌代谢杂志

Diabetic kidney disease is a severe microvascular complication of diabetes characterized by complex etiology, diverse mechanisms, long course, and poor prognosis, posing a significant threat to patients′ quality of life. In recent years, research on gut microbiota has progressed deeper, and the concept of the gut-kidney axis emerges, introducing novel therapeutic concepts. This article provides an overview of the role of gut microbiota in the development of diabetic kidney disease and explores potential therapeutic strategies involving gut microbiota for the treatment of this condition.

The composition of gut microbiota in patients with subclinical hypothyroidism and euthyroid Hashimoto′s thyroiditis / 中华内分泌代谢杂志

Objective:To investigate the gut microbiota composition in subclinical hypothyroidism and euthyroidism patients with Hashimoto′s thyroiditis, and its relationship with clinical indicators and inflammatory factors.Methods:A total of 48 patients diagnosed with Hashimoto′s thyroiditis and 28 healthy controls(HC group) were enrolled from Henan Provincial People′s Hospital from July 2019 to March 2022 in this cross-sectional study. According to thyroid function, 18 patients with Hashimoto′s thyroiditis were divided into subclinical hypothyroidism group(SH group) and 30 patients in euthyroidism function group(Eu group). Fecal microbial composition was detected by 16S rRNA sequencing technology, and peripheral blood was collected to test clinical indicators and inflammatory factors.Results:Compared with HC group, there were significant differences in α and β diversity of gut microbiota in SH and Eu group( P=0.045, P=0.037). At the phylum level, Firmicutes, Bacteroidota, and Proteobacteria were the dominant phylum in the three groups. At the genus level, the abundance of 4 bacterial genera increased gradually in HC group, Eu group, and SH group, including Streptococcus, Comamonas, Elizabethkingia, Achromobacter. However, the abundance of the other 9 genera decreased gradually, such as Subdoligranulum, Coprococcus, Oscillospirales_ UCG-010, Clostridia_ UCG-014, Oscillospiraceae_ UCG-002, Alistipes et al. In addition, the level of serum B-cell activating factor was positively correlated with several bacterial genera such as Achromobacter, Streptococcus, Intestinibacter et al. Conclusion:There are differences in the gut microbiota structure of patients with Hashimoto′s thyroiditis in different thyroid functional states, which is correlated with inflammatory factors.

Time in range of glucose and sarcopenia in elderly patients with type 2 diabetes / 中华内分泌代谢杂志

Objective:To investigate the relationship between time in range(TIR) of glucose and sarcopenia in elderly patients with type 2 diabetes mellitus.Methods:A total of 673 patients with type 2 diabetes aged 65 years and above who were admitted to Henan Provincial People′s Hospital from March 2018 to July 2020 were selected. All patients completed questionnaire, physical and laboratory examination. Sensor-based flash continuous glucose monitoring(CGM) systems was used to monitor glucose levels, and the TIR was computed. Dual energy X-ray was used to assess total muscle mass and appendicular skeletal muscle mass index(ASMI) was calculated, the muscle strength was assessed with testing handgrip strength, and physical function was assessed by testing gait speed. Sarcopenia was diagnosed and graded according to the 2019 Asian Working Group on Sarcopenia(AWGSOP) standard. Patients with less than 3 days of CGM were excluded and a total of 658 subjects were included in the analysis.Results:The total prevalence of sarcopenia was 28.72%. Compared with non-sarcopenia group, TIR levels in the sarcopenia and severe sarcopenia groups were significantly decreased [55.0%(36.5%, 68.0%), 49.0%(31.0%, 70.5%) vs 66.0%(44.8%, 79.0%), both P<0.01]. The level of ASMI increased in line with TIR quartiles and topped in the fourth quartile group( P<0.05). Pearson correlation analysis showed that TIR was significantly positively correlated with ASMI, gait speed, and handgrip strength in male patients( P<0.05 or P<0.001), and TIR was significantly positively associated with ASMI and gait speed in female patients( P<0.05 or P<0.01). After logistic regression adjusted for gender, age, body mass index, blood pressure, disease duration, HbA 1C, fasting blood glucose, total cholesterol, triglyceride, low density lipoprotein-choresterol, high density lipoprotein-choresterol, estimated glomerular filtration rate, protein intake, exercise intensity, smoking and alcohol consumption, an increase in TIR levels was associated with a decrease in the prevalence of severe sarcopenia( OR=0.923, 95% CI 0.878-0.970, P=0.002). The lowest quartile TIR significantly increased the risk of sarcopenia compared with the highest quartile TIR( OR=3.733, 95% CI 1.129-12.342, P=0.031). Conclusion:Decline in TIR is significantly associated with an increased risk of sarcopenia in older patients with type 2 diabetes.

Ocular surface flora in obese patients before and after dietary intervention / 中华内分泌代谢杂志

Objective:To investigate the changes of ocular surface microbiota in obese patients before and after dietary intervention.Methods:From November 1, 2020 to May 1, 2021, 35 obese patients in the obesity management center of the Department of Endocrinology and Metabolic Diseases of Henan Provincial People′s Hospital were selected for a 4-week low-calorie dietary intervention of 1 600-1 800 kcal/day. The body weight, body mass index(BMI), body composition(body fat, body fat percentage, visceral fat grade, total body water, and skeletal muscle) were observed before and after dietary intervention. The characteristics of ocular surface flora in obese patients before and after intervention were analyzed by 16S rRNA sequencing.Results:The body weight, BMI, body fat, percentage of body fat, visceral fat grade and total body water decreased significantly after 4 weeks( P<0.05), while there was no significant difference in skeletal muscle( P>0.05). There was no significant difference of ocular surface flora α and β in diversity( P>0.05). Opportunistic pathogens Pseudomonas and Cutibacterium decreased significantly, while Faecalibacterium, Lachnospiraceae NK4A136 group, Oscillospiraceae UCG 002, and Blautia, which producing short chain fatty acids, increased significantly( P<0.05). Functional prediction analysis showed that the metabolic pathways such as degradation related pathways and insulin signaling pathways of volatile organic compounds(VOCs) were significantly enriched. Conclusion:After dietary intervention, opportunistic pathogenic bacteria decreased and short chain fatty acid producing bacteria increased in obese patients. The altered ocular surface flora may be related to the degradation of VOCs and the improvement of insulin sensitivity.

Analysis of PROKR2 gene mutation in patients with hypogonadotropic hypogonadism / 中华内科杂志

To investigate the clinical and genetic characteristics of patients with idiopathic hypogonadotropic hypogonadism (IHH), the clinical data of 23 patients with IHH were retrospectively analyzed. Gene analyses were accomplished with whole-exome sequencing (WES) and Sanger sequencing. Functional prediction of mutation sites was conducted using two bioinformatics platforms, SIFT and Polyphen. Among the 23 patients with IHH, 9 patients carried prokinin 2 (PROKR2) gene mutations including 4 missense mutations (p.W178S, p.Y113H, p.A103V, p.R164Q), and 1 frameshift mutation (p.D42delinsDED), the remaining 14 cases were found negative in gene sequencing. Functional prediction showed that the above mutations may affect protein function suggestive of a pathogenic role of PROKR2 mutation in the patients. There were no significant differences in the levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol between the IHH patients with PROKR2 gene mutation and those without. PROKR2 gene mutation might associated with IHH, and the mutations reported in the present study could enrich the pathogenic spectrum of genes.

Correlation between single nucleotide polymorphism and protein expression of FcγRⅡb in Hashimoto′s thyroiditis / 中华内分泌代谢杂志

Objective:To investigate whether FcγRⅡb rs775 single nucleotide polymorphism confers susceptibility to Hashimoto′s thyroiditis and its impact on expression of FcγRⅡb protein on B cell surface.Methods:A total of 187 Hashimoto′s thyroiditis patients(HT group) were enrolled, including 46 males(24.60%) and 141 females(75.40%), with a median age of 43(32, 53) years, and 187 healthy controls(conrol group), including 62 males(33.16%) and 125 females(66.84%), with a median age of 41(31, 51) years. The peripheral blood of two groups were sequenced, genotype and allele frequencies distribution of FcγRⅡb rs775 T>C were compared with clinical parameters as strata between the two groups. At the same time, the expression of inhibitory receptor FcγRⅡb on B cell surface was detected using flow cytometry.Results:Compared with control group, the mutant homozygous CC genotype was obviously enrichment in HT group( OR=3.321, 95% CI 1.175-9.386, P=0.018), and the proportion of CC genotype increased in male of HT group( P=0.076). However, there is no significant difference in genotype and allele frequencies between control group and HT group after stratification by sex. In addition, the percentage of FcγRⅡb on B cell surface decreased significantly in HT group( P=0.029). Conclusion:There was no significant correlation between FcγRⅡb polymorphism and the down-regulation of FcγRⅡb protein on B cell surface in Hashimoto′s thyroiditis patients, and FcγRⅡb can be a predisposed factor for Hashimoto′s thyroiditis.

Correlation between corneal neuropathy and ocular surface flora in type 2 diabetes / 中华内分泌代谢杂志

Objective:To explore the changes of corneal neuropathy and ocular surface flora in patients with type 2 diabetes, and the correlation between corneal neuropathy and ocular surface flora changes.Methods:According to the results of fundus fluorescein angiography, 65 patients with type 2 diabetes (130 eyes in total) who were treated with insulin alone and without comorbid retinopathy in the Department of Endocrinology, Henan People′s Hospital from March to June 2019 were selected. Sixty-five age-matched normal glucose tolerance subjects (130 eyes in total) were also enrolled. Confocal microscopy was performed and conjunctival sac secretions were collected. Through 16S rRNA analysis and sequencing and PICRUSt bacterial gene function prediction, the relationship between patients with type 2 diabetes and the difference in the degree of corneal neuropathy and the composition of ocular surface flora and function prediction in healthy people were explored, and the correlation between corneal neuropathy and ocular surface flora was analyzed as well.Results:Compared with healthy people, patients with type 2 diabetes have more severe corneal neuropathy, and it was related to the changes in ocular surface flora. Brevibacillus and paenibacillus were significantly positively correlated with the degree of corneal neuropathy ( P<0.05), and enhydrobacter and proteobacteria were significantly negatively correlated with the degree of corneal neuropathy ( P<0.05). PICRUSt analysis showed that the degree of enrichment of metabolism-related genes in the ocular surface flora of patients with type 2 diabetes was significantly changed compared with healthy people. Conclusion:Patients with type 2 diabetes present with more severe corneal neuropathy. The diversity of ocular surface flora and metabolic function have significant changes. The degree of severity corneal neuropathy is related to brevibacillus, paenibacillus, enhydrobacter, and proteobacteria.

Association of time in range with the severity of coronary artery disease in type 2 diabetic patients / 中华内分泌代谢杂志

Objective:To investigate the association of time in range(TIR) with the severity of coronary artery disease and acute coronary syndrome in patients with type 2 diabetes mellitus.Methods:A total of 216 patients with type 2 diabetes mellitus and coronary heart disease were recruited and undergone anthropometric and biochemical measurements, continuous glucose monitoring, and calculation of SYNTAX score. TIR was defined as the percentage of time within the glucose range of 3.9-10.0 mmol/L during 24 h. Spearman correlation analysis and multivariate linear regression analysis were used to evaluate the correlation factors of SYNTAX score. Multivariate logistic regression analysis was used to analyze the association of TIR with the severity of coronary artery disease and acute coronary syndrome. Results:Compared with patients with mild coronary artery disease, TIR in patients with moderate to severe coronary artery disease was lower[(69.4±17.3)% vs (60.8±17.8)%, t=3.0, P=0.003], and HbA 1C of patients with moderate to severe coronary artery disease was higher [(9.6±1.7)% vs (8.8±1.6)%, t=3.3, P=0.001]. SYNTAX score was negatively correlated with TIR ( r=-0.251, P<0.01) and positively correlated with HbA 1C ( r=0.249, P<0.01). Moreover, compared with HbA 1C (standardized coefficients=0.181, P=0.007), TIR (standardized coefficients=-0.192, P=0.004) had a greater influence on SYNTAX score. Multivariate linear regression analysis showed that TIR, HbA 1C, duration of diabetes and smoking were independently correlated with SYNTAX score. Multivariate logistic regression analysis revealed that compared with TIR Q1, Q3 and Q4 were independent protective factors for moderate to severe coronary artery disease (respectively, OR=0.61 and 0.59, 95% CI 0.39-0.96 and 0.38-0.94, P=0.014 and 0.009) and acute coronary syndrome (respectively, OR=0.51 and 0.39, 95% CI 0.32-0.95 and 0.26-0.75, P=0.022 and 0.008). Conclusion:TIR was significantly and independently correlated with the severity of coronary artery disease and acute coronary syndrome in type 2 diabetes mellitus after controlling confounding factors. When TIR level was decreased, the severity of coronary artery disease was aggravated, and SYNTAX score and the risk of acute coronary syndrome was increased.

Glucagon-like peptide-1 and gastrin synergistically promote the differentiation of insulin-producing cells / 中华内分泌代谢杂志

Objective@#Glucagon-like peptide-1(GLP-1) and gastrin synergistically promote the differentiation of insulin-producing cells which differentiated from rat bone marrow mesenchymal stem cells (BMSCs).@*Methods@#(1)Prepare IPCs model: pancreatic duodenal homeobox 1 (Pdx-1), neurogenin 3 (Ngn3) combined with V-type tendon fibrosarcoma oncogene homolog A (MafA) co-transfected BMSCs differentiation into IPCs; (2)IPCs were divided into 4 groups: Group A(uninduced group), group B(GLP-1 induction group), group C(gastrin induction group), and group D(GLP-1 combined with gastrin induction group). Cultured in high glucose medium for 7 days, the expression levels of insulin2, Pdx-1, GK, nestin, and glucagon mRNA were detected by RT-PCR. The insulin secretion of each group was detected by ELISA.@*Results@#After cultured for 7 days under high glucose conditions, the morphology of IPCs in each induction group changed significantly, gradually aggregated and formed scattered cell masses, and the combined induction group formed large cell masses. The staining of disulfide brown was reddish brown; The levels of insulin secretion increased gradually on the 0, 3rd, 5th, 7th, and 9th day after induction, and the increase was the most significant in the combined induction group (P<0.05). Compared with group A, the expression of insulin2 and GK in group B and D was significantly up-regulated, the expression of glucagon was down-regulated in group D, the expression of Pdx-1 was down-regulated in group C, and the expression of glucagon was up-regulated (P<0.05). Compared with group B, The expression of insulin2 was down-regulated in group C, and the expression level of glucagon was up-regulated. The expression levels of Pdx-1 and Insulin2 were significantly up-regulated in group D, and the expression level of glucagon was down-regulated (P<0.05). Compared with group C, the expression level of Pdx-1, insulin2 and GK was significantly up-regulated in group D, and the expression level of glucagon was down-regulated (P<0.05).@*Conclusion@#GLP-1 and gastrin synergistically promote the differentiation of IPCs into islet β cells by up-regulating GK and insulin2 and down-regulating glucagon.

Inhibitory effect of small interfering RNA-TLR9 on high glucose-induced retinal ganglion cell apoptosis / 中华实验眼科杂志

Objective To investigate the effect of Toll-like receptor 9 (TLR9) on high glucose-induced retinal ganglion cells-5 (RGC-5) apoptosis and the inhibitory effects of small interfering RNA-TLR9 (si-TLR9) on apoptosis.Methods RGC-5 cells were divided into normal control group,high glucose group,high glucose+ negative control group and high glucose + si-TLR9 group which cells were respectively dealt with normal culture medium,high glucose medium,transfection of non-specific siRNA under high glucose and transfection of siRNA-TLR9 under high glucose.The expression of TLR9 mRNA was detected by real time PCR;the survival rate of the cells was evaluated by MTT assay;the apoptotic rate of the cells was detected by flow cytometry;the caspase-3 activity in the cells was detected by related kit,and the expressions of TLR9,B cell lymphoma (bcl-2),bcl-2 associated X protein (bax),p38 mitogen-activated protein kinases (p38MAPK) and phosphorylated (p)-p38MAPK proteins were detected by Western blot.Results The expressions of TLR9 mRNA and protein in the high glucose+si-TLR9 group were significantly decreased in comparison with the high glucose+negative control group (both at P＜0.05).The cell survival rate of the high glucose group and high glucose+negative control group was (78.36±5.13)％ and (75.12± 4.25) ％,respectively,which was significantly lower than (95.48± 7.25) ％ in the normal control group,and that in the high glucose+si-TLR9 group was (86.58±5.32)％,which was significantly reduced in comparison with the high glucose+negative control group (all at P＜0.05).The apoptotic rate of the cells in the high glucose group and high glucose+negative control group was (13.23 ± 1.22) ％ and (12.52± 1.38) ％,respectively,which was significantly higher than (2.26±0.15)％ of the normal control group,and apoptotic rate in the high glucose+si-TLR9 group was (7.15±0.24) ％,which was significantly lower than that in high glucose+negative control group (all at P＜0.05).The expression of bax in the cells of the high glucose+si-TLR9 group was significantly decreased,and the expression of bcl-2 in the cells of the high glucose+si-TLR9 group was significantly increased in comparison with the high glucose+ negative control group (both at P＜ 0.05).Caspase-3 activity in the cells was significantly decreased in the high glucose+si-TLR9 group compared with the high glucose+negative control group (P＜0.05).The relative expression of p-p38MAPK in the cells was significantly decreased in the high glucose+ si-TLR9 group compared with the high glucose+negative control group (P＜0.05).Conclusions Down-regulation of TLR9 expression in the RGC-5 cells can inhibit the apoptosis induced by high glucose probablely by suppressing p38MAPK signaling pathway.

Predictive value of peripheral blood platelet to lymphocyte ratio for the survival in elderly patients with diabetic ketoacidosis / 中华老年医学杂志

Objective:To investigate the predictive value of peripheral blood platelet to lymphocyte ratio(PLR)for the survival of elderly type 2 diabetes mellitus(T2DM)patients with diabetic ketoacidosis(DKA).Methods:Clinical data of 137 elderly T2DM patients with DKA admitted to our hospital between January 2014 and December 2018 were divided into the survival group(n=109)and the death group(n=28)and retrospectively analyzed.Another 137 elderly T2DM inpatients without DKA during the same period were enrolled as the control group.Clinical data of all patients were recorded to analyze predisposing factors of DKA.Multivariate Logistic regression analysis was used to analyze the related factors for the death in elderly T2DM patients with DKA.The best cut-off value for PLR to predict the survival status of patients was determined.Results:The main predisposing factors for DKA were pulmonary infections and insufficient insulin. Logistic multivariate analysis showed that diastolic blood pressure, Glasgow coma score, the coexisted other organ failure, PLR( OR: 3.576, 95% CI2.225~5.472)and mechanical ventilation were risk factors for the survival in elderly T2DM patients with DKA( P<0.05). ROC curve analysis indicated that the area under the curve(AUC)of PLR was 0.803( P=0.002, 95% CI: 0.758-0.886). The optimal cut-off value of PLR for prognosis(survival/death)was 224.29, with a sensitivity of 81.7% and a specificity of 70.1%. Conclusions:PLR is easy to obtain and can be used as a sensitive indicator to predict the survival of elderly T2DM patients with DKA.

Glucagon-like peptide-1 and gastrin synergistically promote the differentiation of insulin-producing cells / 中华内分泌代谢杂志

Objective:Glucagon-like peptide-1(GLP-1) and gastrin synergistically promote the differentiation of insulin-producing cells which differentiated from rat bone marrow mesenchymal stem cells (BMSCs).Methods:(1)Prepare IPCs model: pancreatic duodenal homeobox 1 (Pdx-1), neurogenin 3 (Ngn3) combined with V-type tendon fibrosarcoma oncogene homolog A (MafA) co-transfected BMSCs differentiation into IPCs; (2)IPCs were divided into 4 groups: Group A(uninduced group), group B(GLP-1 induction group), group C(gastrin induction group), and group D(GLP-1 combined with gastrin induction group). Cultured in high glucose medium for 7 days, the expression levels of insulin2, Pdx-1, GK, nestin, and glucagon mRNA were detected by RT-PCR. The insulin secretion of each group was detected by ELISA.Results:After cultured for 7 days under high glucose conditions, the morphology of IPCs in each induction group changed significantly, gradually aggregated and formed scattered cell masses, and the combined induction group formed large cell masses. The staining of disulfide brown was reddish brown; The levels of insulin secretion increased gradually on the 0, 3rd, 5th, 7th, and 9th day after induction, and the increase was the most significant in the combined induction group ( P<0.05). Compared with group A, the expression of insulin2 and GK in group B and D was significantly up-regulated, the expression of glucagon was down-regulated in group D, the expression of Pdx-1 was down-regulated in group C, and the expression of glucagon was up-regulated ( P<0.05). Compared with group B, The expression of insulin2 was down-regulated in group C, and the expression level of glucagon was up-regulated. The expression levels of Pdx-1 and Insulin2 were significantly up-regulated in group D, and the expression level of glucagon was down-regulated ( P<0.05). Compared with group C, the expression level of Pdx-1, insulin2 and GK was significantly up-regulated in group D, and the expression level of glucagon was down-regulated ( P<0.05). Conclusion:GLP-1 and gastrin synergistically promote the differentiation of IPCs into islet β cells by up-regulating GK and insulin2 and down-regulating glucagon.

Genetic analysis of Gitelman syndrome in a patient with recurrent spontaneous abortion / 中华内分泌代谢杂志

Sanger sequencing was applied to analyze the SLC12A3 gene of a patient with suspected Gitelman syndrome(GS) and recurrent spontaneous abortions, as well as for her parents. The results showed that a compound heterozygous mutation(c.1077C>G, c.2890C>T) was found in the proband, which led to the change of amino acid sequence(p.N359K, p.R964W). Among the family members, her mother was a single heterozygotes mutation carrier of c. 1077C>G(p.N359K) and her father had c. 2890C>T(p.R964W) heterozygotes.These results suggest that the GS may cause adverse pregnancy outcomes due to imbalance of internal environment, complex hormonal changes, and electrolyte abnormalities. The pregnancy management should be strengthened.

Association of serum uric acid with risk of vertebral fracture in patients with type 2 diabetes / 中华内分泌代谢杂志

The clinical data of 239 inpatients with type 2 diabetes in Endocrinology Department of Henan Provincial People′s Hospital from January to February 2017 were collected. A total of 170 subjects were included in the final analysis. One diabetes-specific vertebral facture risk estimation called risk score for vertebral fracture was used to estimate the risk of vertebral fracture. Multivariate linear regression analysis was used to calculate the association of serum uric acid with risk of vertebral fracture. The mean age of subjects in final analysis was 56.5±26.4 years old, with the duration of diabetes 8.6±7.1 years and the vertebral fracture risk score 5.6±4.0. Additionally, there was a negative linear correlation between serum uric acid and vertebral fracture risk score in patients with type 2 diabetes( Ptrend=0.021) independent of age, gender, systolic blood pressure, HbA 1C, course of diabetes, obesity status, total cholesterol, and estimated glomerular filtration rate( P=0.033). Multivariate linear regression indicated that age, course of diabetes, blood pressure, total cholesterol, serum albumin, T score at femoral neck were related to the vertebral fracture risk score.

Study on the composition of ocular surface bacteria in patients with type 2 diabetes mellitus / 中华内分泌代谢杂志

Objective:To analyze the differences of ocular surface bacteria between patients with type 2 diabetes and healthy subjects, and to explore the relationship between ocular surface bacteria and type 2 diabetic keratopathy.Methods:Fifty subjects were selected and divided into type 2 diabetes group and healthy control group. Bacterial culture of conjunctival sac secretion was conducted and 16S rRNA sequencing was performed to analyze the difference in the composition of ocular surface bacteria between patients with type 2 diabetes and healthy subjects.Results:There were significant differences in the diversity of ocular surface bacteria between patients with type 2 diabetes and healthy subjects. The species of bacillus brevis and paenibacillus in type 2 diabetes group were significantly higher than those of the healthy control group, while the species of aquatic bacteria were lower.Conclusion:The differences in the composition of ocular surface bacteria may be related to type 2 diabetes mellitus.

Correlation between serum calcium levels and disease severity in patients with COVID-19 / 中华内分泌代谢杂志

Objective:To investigate the correlation between serum calcium levels and severity of novel coronavirus pneumonia(COVID-19).Methods:The clinical data of 165 COVID-19 patients diagnosed from January to February 2020 were analyzed retrospectively. Combined with clinical classification, the differences of various indexes between the critically ill group and the control group were compared, and the influencing factors of disease severity were analyzed by multivariate logistic regression. According to the corrected serum total calcium levels, patients were divided into low calcium group and normal calcium group, and the related indexes of the 2 groups were compared for further analyzing the causes of hypocalcemia. Results:Compared with the control group, the age, diabetes, basic respiratory disease, and cardiovascular disease ratio, C-reactive protein(CRP), fasting blood glucose(FPG), interferon γ(IFN-γ), and interleukin 17(IL-17) levels increased while the lymphocyte percentage, serum albumin(ALB), corrected calcium levels, CD4 + T cells percentage, CD8 + T cell percentage decreased, the difference was statistically significant( P<0.05). There was no significant statistical difference in gender between the two groups, hypertension ratio, alanine aminotransferase(ALT), glomerular filtration rate(eGFR), CD4 +/CD8 + ratio and interleukin 4(IL-4) levels( P>0.05). The decrease of calcium level, age and eGFR were all risk factors for COVID-19 patients. Compared with the normal calcium group of COVID-19 patients, the level of ALB, CD4 + T cells percentage, CD8 + T cell percentage in low calcium group decreased and age, proportion of critically ill patients, diabetes, basic respiratory disease and cardiovascular disease ratio and CRP level all increased, the differences were statistically significant( P<0.05), and there was no statistical difference in the other biochemical indexes( P<0.05). Conclusion:There are obvious hypocalcemia and immune dysfunction in critically ill patients of COVID-19, and close monitoring of blood calcium levels may predict the severity of the disease more effectively

Relationship between mild cognitive impairment and time in the range of blood glucose targets and time below the target range in elderly patients with type 2 diabetes by a cognitive assessment / 中华内分泌代谢杂志

Objective:To investigate the relationship between mild cognitive impairment (MCI) and time in target range (TIR) and time below target glucose range (TBR) in elderly patients with type 2 diabetes.Methods:Ninety-five elderly patients with type 2 diabetes who were admitted to the Henan Provincial People′s Hospital from November 2017 to November 2018 were selected. Patients were assessed for cognitive function using the Montreal cognitive assessment (MoCA), and were classified into mild cognitive impairment group (MCI group) and non-mild cognitive impairment group (non-MCI group) according to the scores; all enrolled patients were scanned with a glucose monitoring system to record TIR and TBR within the first 24 hours of admission.Results:The MoCA score of the patients in the MCI group was (21.3±3.7)point, which was significantly lower than that in the non-MCI group (28.2±1.2)point, P<0.01); the TIR of the patients in the MCI group was significantly lower than that in non-MCI group [(50.6±24.5)% vs (65.8±28.7)%, P<0.01], the TBR of patients in the MCI group was significantly higher than that in the non-MCI group [(6.6±3.2)% vs (1.2±1.9)%, P<0.01]. Correlation analysis showed that MoCA score was negatively correlated with TBR ( r=-0.892, P<0.01) and positively correlated with TIR ( r=0.816, P=0.001). Multivariate linear regression analysis showed that when adjusted for diabetic duration and HbA 1C, TIR and TBR were independent risk factors for MoCA scores. Conclusion:The cognitive level of elderly patients with type 2 diabetes is closely related to TIR and TBR. At the same time, we must pay attention to TBR while increasing TIR.