Role of METTL3 in homocysteine-induced autophagy in mouse islet beta cells / 中国组织工程研究

BACKGROUND:Hyperhomocysteinemia is closely related to the function of islet β cells,but its specific molecular mechanism is not fully understood. OBJECTIVE:To investigate the role of N6 methyltransferase-like 3(METTL3)in homocysteine(Hcy)-induced autophagy of mouse islet β cells. METHODS:The 3rd and 4th generation mouse islet β cells were taken for the experiment.(1)Cell modeling and grouping:cells in control group were not treated with Hcy,while those in homocysteine group were treated with 100 μmol/L Hcy for 48 hours.(2)The mouse islet β-cells were transfected with the plasmids overexpressing Ad-METTL3 and si-METTL3 according to the instructions of LipofectamineTM 2000.Three different interfering fragments were designed,and the one with the best interfering efficiency was verified and screened by PCR.(3)After transfection,the cells were divided into control group,Hcy group,Ad-NC(negative control)+Hcy group,Ad-METTL3+Hcy group,si-NC(negative control)+Hcy group and si-METTL3+Hcy group.(4)qRT-PCR and western blot were used to detect the expression levels of METTL3 and autophagy-related proteins LC3Ⅱ/Ⅰ and p62 in cells.Insulin level was determined by ELISA to evaluate insulin secretion capacity of islet cells.Autophagy-related proteins and insulin level were detected after overexpression and interference with METTL3. RESULTS AND CONCLUSION:Compared with the control group,the expression level of LC3Ⅱ/Ⅰ was increased(P＜0.05),the expression of p62 was significantly reduced(P＜0.05),and the insulin secretion capacity was significantly decreased(P＜0.05)in the Hcy group.Compared with the control group,the protein and mRNA levels of METTL3 were reduced in the Hcy group(P＜0.05).After METTL3 silencing in islet β cells,Hcy further upregulated the expression of LC3Ⅱ/Ⅰ(P＜0.05),significantly dowregulated the expression of p62(P＜0.05),and increased the insulin level(P＜0.05).After overexpression of METTL3,Hcy significantly decreased the LC3Ⅱ/Ⅰ expression and increased the p62 expression in islet β cells(P＜0.05).To conclude,METTL3 is involved in the Hcy-induced autophagy regulation of islet β cells and plays a role in the regulation of insulin secretion.

Study on the mechanism of improving islet β-cell function in patients with type 2 diabetes mellitus by Alogliptin benzoate / 中国糖尿病杂志

Objective To investigate the effect of Alogliptin benzoate on the serum autophagy markers in type 2 diabetes mellitus(T2DM)patients.Methods Eighty newly diagnosed T2DM patients who visited the Department of Endocrinology in Baoding No.1 Central Hospital from December 2021 to October 2022 were randomly divided into a group treated with Metformin(Met group,n=40)and a group treated with Met and Alog(Met+Alog group,n=40).The differences in BMI,WHR,FPG,HbA1c,Atg7 and Beclin-1 between two groups before and after 12 weeks of treatment were compared.Results After treatment,the levels of Atg7 and Beclin-1 increased in both groups(P<0.05),while FPG,HbA1c and HOMA-IR decreased(P<0.05).After treatment,Atg7,Beclin-1 and HDL-C in Met+Alog group were higher than those in Met group(P<0.05).Pearson correlation analysis showed that Atg7 was negatively correlated with BMI,FPG and HbA1c(P<0.05);Beclin-1 was positively correlated with HDL-C(P<0.05),and negatively correlated with BMI,FPG,HbA1c,and TG(P<0.05).Meta linear regression analysis showed that BMI was the influencing factor of Atg7,while BMI and HDL-C were the influencing factors of Beclin-1.Conclusion Alogliptin benzoate may improve islet β cell function by up-regulating the expression of autophagy related factors Atg7 and Beclin-1 in patients with T2DM.

Research progress in the mechanism of stimulator of interferon genes in type 2 diabetes mellitus and its microvascular complication / 中国糖尿病杂志

Type 2 diabetes mellitus(T2DM)is a chronic metabolic disease that can lead to the damage of multiple tissues and organs throughout the body.Stimulator of interferon genes(STING)is an endoplasmic reticulum membrane protein that acts as an indirect cytoplasmic DNA sensor.The activation of the STING signaling pathway may be involved in T2DM and its microvascular complications through various mechanisms.This article reviews the research progress in the mechanism of STING in T2DM and its microvascular complications.

Mechanism of compound Fufangteng mixture-containing serum in promoting proliferation of bone marrow mesenchymal stem cell / 器官移植

Objective To investigate the effect of compound Fufangteng mixture-containing serum on the proliferation of bone marrow mesenchymal stem cell (BMSC) and its mechanism. Methods Rat BMSC were isolated, cultured and purified in vitro by direct adherence method. Cell morphology was observed. Surface markers were identified by flow cytometry. The rats were treated with compound Fufangteng mixture at a dose of 3 mL/(kg·d) by gavage for 14 d, and then the drug-containing serum was collected. BMSC were divided into the blank control group, drug-containing serum group, Notch1 small interfering ribonucleic acid (siRNA) group and Notch1 siRNA+drug-containing serum group. The proliferation rate of BMSC was detected and the relative expression levels of Notch1 signaling pathway-associated messenger ribonucleic acid (mRNA) and proteins were measured in each group. Results Microscopic observation showed that the first generation BMSC were seen in the long spindle shape, and grown in the parallel or spiral pattern. The third generation BMSC positively expressed CD90 and CD44, whereas were negative for CD45. Compared with the blank control group, the proliferation rate of BMSC in the drug-containing serum group and Notch1 siRNA+ drug-containing serum group was significantly increased, whereas that of BMSC was significantly decreased in the Notch1 siRNA group (all P < 0.05). Compared with the Notch1 siRNA group, the proliferation rate of BMSC was significantly increased in the Notch1 siRNA+drug-containing serum group (P < 0.05). Compared with the blank control group, the relative expression levels of Hey1 and Delta-like ligand (DLL)1 mRNA and proteins were significantly up-regulated in the drug-containing serum group, whereas those were significantly down-regulated in the Notch1 siRNA group and Notch1 siRNA+drug-containing serum group (all P < 0.05). Compared with the Notch1 siRNA group, the relative expression levels of Hey1 and DLL1 mRNA and proteins were significantly up-regulated in the Notch1 siRNA+drug-containing serum group (all P < 0.05). Conclusions Compound Fufangteng mixture-containing serum may promote the proliferation of rat BMSC, and its mechanism is probably associated with the activation of Notch1 signaling pathway.

Investigation on the mechanism of acupuncture in treatment of diabetes mellitus type 2 based on the network of islet macrophages-pancreatic adipose cells-islet β cells / 中国针灸

To explore the possible new mechanism of acupuncture in the treatment of diabetes mellitus type 2 (T2DM) based on the islet inflammatory response. Islet macrophages, pancreatic adipose cells and islet β cells all participate in the pathogenesis of T2DM, and the three could form a network interaction. Acupuncture could regulate the functional phenotype of islet macrophages, improve the ectopic deposition of pancreatic adipose and repair the function of islet β cells, and play a unique advantage of overall regulation. It is suggested that acupuncture can be a potential treatment strategy for T2DM.

Progress on Hypoglycemic Effect and Mechanism of Momordica charantia / 中国实验方剂学杂志

Momordica charantia has been a traditional Chinese medicine （TCM） and food since ancient times. The discussions on its nature， taste and efficacy in ancient books of TCM are almost the same. With a high nutritional value， M. charantia is rich in a variety of vitamins and minerals， and has been widely used in the production of a wide range of dietary supplements and functional foods. At the same time， M. charantia is one of the most deeply studied natural medicines in traditional alternative medicine， with a wide range of pharmacological effects， especially in the treatment of metabolic diseases. Clinical trials have confirmed that M. charantia has a hypoglycemic effect， and could reduce blood lipids and weight loss， so as to improve metabolism in a comprehensive manner. According to the study on the mechanism of M. charantia in the treatment of diabetes， M. charantia could reduce blood sugar by improving islet β-cell function， improving insulin resistance， inhibiting intestinal glucose absorption and resisting inflammation and oxidative stress. However， at present， there is a lack of unified standards for the hypoglycemic effects and various mechanisms of action of M. charantia， and the safety has not been fully confirmed. Further studies shall be conducted to investigate the hypoglycemic effect and mechanisms of M. charantia， explore active components of M. charantia， define the pharmacodynamics material basis， extract monomer compounds with a clear structure and confirm its effectiveness and safety， which is helpful to develop and utilize the homologous value of medicine and food of M. charantia and further apply it in clinic. The application of the hypoglycemic effect of M. charantia in clinic has important economic benefits and a social significance.

Study on the correlation between serum vitamin D level, parathyroid hormone and type 2 diabetes mellitus in Inner Mongolia / 中华临床营养杂志

Objective:To evaluate the correlation of serum vitamin D (VitD) and parathyroid hormone (PTH) with insulin resistance and islet β-cell function in patients with type 2 diabetes mellitus (T2DM), and to analyze the role of serum VitD and PTH in the progression of T2DM.Methods:A total of 376 T2DM patients hospitalized in endocrinology department from January 2018 to January 2021 were selected. The baseline data were collected and the biochemical indexes were determined. Patients were divided into 3 groups according to serum VitD level, including 220 cases in deficiency group [25-(OH)D ≤ 20 μg/L], 107 cases in insufficiency group [25-(OH)D>20 and ≤ 30 μg/L] and 49 cases in sufficiency group [25-(OH)D > 30 μg/L]. Meanwhile, 31 of the patients were classified into PTH decreased group (PTH < 25.16 ng/L), 137 into normal PTH group (PTH ≥ 25.16 and < 38.35 ng/L) and 208 into PTH elevated group ( PTH ≥ 38.35 ng/L). According to body mass index (BMI), patients were divided into normal weight group (18.5 kg/m 2 ≤ BMI ≤ 23.9 kg/m 2), overweight group (BMI ≥24 and ≤ 27.9 kg/m 2) and obese group (BMI ≥ 28 kg/m 2). Results:Among the three groups defined by serum VitD level, comparisons of glucose metabolism and calcium and phosphorus metabolism indicators showed no significant differences in BMI, fasting insulin (FINS), fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance index (HOMA-IR), serum calcium and phosphorus (all P > 0.05). The levels of glycated hemoglobin (HbA1c) and PTH in vitamin D deficiency group and sufficiency group were significantly lower compared with vitamin D deficiency group (both P < 0.05). Among the three groups defined by PTH level, there were no significant differences in BMI, FINS, FPG, HbAlc, HOMA-IR, and serum calcium (all P > 0.05). Serum phosphorus in the PTH elevated group was significantly lower compared with PTH decreased and normal PTH group ( P = 0.000), and VitD in the PTH elevated group was significantly lower compared with PTH decreased group ( P = 0.002). There were significant differences in age and blood phosphorus among the three groups defined by BMI level (all P<0.05). According to the analysis of clinical indexes of different nationalities, the level of VitD in Mongolians was significantly higher than that in Han nationality patients ( P <0.034). Spearman correlation analysis showed that VitD was negatively correlated with PTH and HOMA-IR and positively correlated with serum calcium. PTH was negatively correlated with serum calcium and phosphorus, and positively correlated with HOMA-IR. There was a significant negative correlation between normal PTH and VitD. Multiple linear regression analysis showed that HOMA-IR and homeostasis model assessment of β-cell function (HOMA-β) were protective factors, and FPG and FINS were risk factors for HOMA-IR and HOMA- β. Conclusion:There is a negative correlation between VitD and insulin resistance, and a positive correlation between PTH and insulin resistance, suggesting that VitD and PTH are possibly two impacting factors for T2DM pathogenesis.

Acupuncture combined with western medication in treatment of type 2 diabetes mellitus with angina pectoris of coronary heart disease: a randomized controlled study / 中国针灸

OBJECTIVE@#To compare the therapeutic effect on type 2 diabetes mellitus (T2DM) complicated with angina pectoris of coronary heart disease between the combined therapy of acupuncture and western medication and the simple administration of western medication.@*METHODS@#A total of 134 patients with T2DM and angina pectoris of coronary heart disease were randomly divided into two groups, i.e. an acupuncture plus medication group (67 cases, 3 cases dropped off) and a medication group (67 cases, 4 cases dropped off). The routine western medication was used according to symptoms in the patients of both groups. In the acupuncture plus medication group, on the base of medication, acupuncture was applied to Jianshi (PC 5), Quchi (LI 11), Neiguan (PC 6), etc. The needles were retained for 20 min in each treatment and 3 treatments of acupuncture were required weekly. The treatment was given consecutively for 8 weeks in the two groups. Separately, before and after treatment, the symptom scores of TCM were observed and the indexes were detected, including glycolipid metabolism [fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), glucosylated hemoglobin (HbA1c), triacylglycerol (TG) and total cholesterol (TC)], islet β cell function [homeostasis model assessment-β (HOMA-β), homeostasis model assessment-IR (HOMA-IR), fasting insulin (FINS) and insulin sensitivity index (ISI)], cardiac function indexes [cardiac output (CO), early diastolic peak velocity/late diastolic peak velocity (E/A), left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF)], as well as electrocardiogram QT dispersion (QTd). Besides, the clinical therapeutic effects were compared between the two groups.@*RESULTS@#After treatment, the TCM symptom scores and the values of FPG, 2hPG, HbA1c, TG, TC, HOMA-IR, FINS, E/A and LVEDD as well as QTd were all lower than those before treatment in the two groups (@*CONCLUSION@#The combined therapy of acupuncture and medication is effective in treatment of T2DM complicated with angina pectoris of coronary heart disease. Such therapy effectively improves glucolipid metabolism, islet β cell function, cardiac function and myocardial blood supply. Its curative effect is better than the simple administration of western medicine.

Role of autophagy in islet β cells: A novel target for diabetes’ therapy / 中国临床药理学与治疗学

Autophagy is a catabolism process in which lysosomes degrade damaged organelles, protein aggregates and recover nutrients. Studies have shown that autophagy could protect the structure and function of islet β cell and maintaining normal secretion of insulin. In addition, autophagy plays important roles in the occurrence and development of diabetes mellitus by reducing oxidative stress, preventing apoptosis and removing ubiquitination protein aggregates. Therefore, autophagy may be a new target for the prevention and treatment of diabetes. At present, hypoglycemic drugs have been proved to play positive roles by regulating autophagy including thiazolidine dione and guanidine. Therefore, this paper will review autophagy definition, the role of autophagy in diabetes mellitus and autophagy-related hypoglycemic drugs, providing a new direction for clinical treatment of diabetes.

Identification of differentially expressed genes and pathways in lipoprotein lipase gene heterozygous knockout mice through gene microarray analysis / 上海交通大学学报（医学版）

Objective • To screen the differentially expressed genes (DEGs) and pathways in the islet tissues of lipoprotein lipase (Lpl) gene heterozygous knockout (Lpl+/-) mice and wild type (WT) mice, and explore the molecular mechanism of pathogenesis of type 2 diabetes mellitus (T2DM) mediated by lipotoxicity. Methods • The islets of Lpl+/- mice and WT mice were isolated and purified. DEGs were screened by gene microarray analysis. Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were performed. The expressions of key genes were verified by quantitative real-time PCR (qPCR). Results • A total of 187 DEGs were identified. GO functional analysis and KEGG pathway analysis showed that DEGs were mainly involved in the biological processes such as immune cell proliferation and differentiation, inflammatory signaling pathways and cell adhesion. Among the top 10 DEGs screened from Lpl+- mice and WT mice, gremlin 1 (Grem1) gene was closely related to the function of islet β cells, while the result of qPCR was consistent with that of gene microarray analysis. Conclusion • Multiple signaling pathways are involved in the process of T2DM mediated by lipotoxicity, which may lead to the dysfunction of islet β cells by inhibiting Grem1 expression.

Progress in betatrophin research / 医学研究生学报

Betatrophin is a new kind of secretory glycoprotein,which belongs to the angiopoietin like protein family.It ex-pressed in liver and adipose tissue,and their expression level are affected by age,gender and thyroid hormone. The active mechanism of Betatrophin mechanism is still unclear. It plays an important role in the islet beta cell proliferation and in the lipid metabolism. In this paper,we mainly focus on the structure of betatrophin and the related research on blood glucose and lipid,metabolic syndrome and nonalcoholic fatty liver in recent years.

Clinical characteristics and analysis of five cases of fulminant type 1 diabetes mellitus / 中国糖尿病杂志

Clinical and laboratory data of 5 cases of fulmiant type 1 diabetes mellitus (FTlDM) hospitalized in our department of endocrinology and metabolism from February 2014 to December 2016 were collected analyzed.All these patients characterized by acute onset and severe ketoacidosis,with course of 1-3 d.At admission,the blood glucose level was 31.8 ～ 58.9 mmol/L,HbA1c 6.0％ ～ 7.5％,F-CP 0.01～0.05 nmol/L and 2 hC-P 0.02～0.05 nmol/L The pancreatic βcell function had no significant improvement after 1year.FTlDM patients have clinical features of abrupt onset,often with severe metabolic disorders,poor prognosis and seriously damaged islet β cell function.

Effect of baicalein on pancreas insulin secretion in rats and its mechanism / 中国药理学通报

Aim To investigate the effect of baicalein on insulin secretion from rat islets and the underlying mechanism. Methods Pancreatic islets were obtained from the pancreas of male Wistar rats by collagenase P digestion and histopaque-1077 density gradient separa-tion. Single islet cells were dispersed from pancreatic islets by Dispase II digestion. Insulin secretion experi-ment was applied to observe insulin release after baica-lein stimulation. To study the potential mechanism, calcium imaging technique and patch-clamp experiment were applied to measure intracellular Ca2+ concentra-tion and voltage-dependent potassium channel currents (Kv). Results In 16. 7mmol·L-1 glucose, baica-lein accelerated insulin secretion in a dose-dependent manner. Baicalein promoted the intracellular Ca2+ con-centration. The patch-clamp experiment showed that baicalein inhibited Kv current in a dose-dependent manner. Conclusion Baicalein can increase the in-tracellular Ca2+ concentration by inhibiting Kv chan-nels and eventually promoting insulin secretion.

Association between fibroblast growth factor 21 and islet β cell function in pregnant women with different glucose tolerance status / 中国糖尿病杂志

Objective To explore the relationship between fibroblast growth factor 21(FGF21) and islet β cell function in pregnant women with different glucose tolerance status.Methods A total of 441 pregnant women were selected in this study from our hospital.Their 50 g GCT at 24~28 gestational weeks were all positive.One week later,all the subjects were treated with 75 g OGTT,and divided into three groups according to their test results:GDM group (n=228),GIGT group (n=112) and GNGT group (n=91).Serum FGF21 level was tested by ELISA.Islet β cell function was evaluated by HOMA-IR,ISI-Matsuda,HOMA-IS,Stumvoll first,second phase secretion and ISSI.The correlation between FGF21 and islet β cell function was evaluated by Pearson correlation analysis.Results (1) BMI,0 h,1 h,2 h,3 hPG and 1 h,2 h,3 hIns were higher in GDM group and GIGT group than in GNGT group,and highest in GDM group (P0.05).(3)Pearson correlation analysis showed that FGF21 was positively correlated with HOMA-IR(r=0.255,P=0.030) and was negatively correlated with ISI-Matsuda,HOMA-β,Stumvoll first,second phase secretion and ISSI(r=-0.289,-0.256,-0.224,-0.230,-0.277,P=0.019,0.037,0.045,0.040,0.023).Conclusion Along with the worsening of glucose metabolic damage,the FGF21 level is increased gradually.FGF21 is related to islet β cell function,and may enroll in the occurrence and development of GDM.

Effect of DA on insulin secretion fromrat pancreatic cells and possible mechanism / 中国药理学通报

Aim To investigate the effects of dopamine(DA)on insulin secretion from rat islets and the possible mechanism.Methods Pancreatic islets were obtained from the pancreatic of male SD rats by collagenase P digestion and histopaque-1077 density gradient separation.Insulin secretion experiment was used to observe the change of insulin release after DA treatments.As to study the potential mechanisms of the effects of DA,patch-clamp experiment and calcuim image technique were applied to test the depolarization-evoked Ca2+ currents,action potential duration and intracellular Ca2+ concentration.Results In 2.8 mmol·L-1 glucose,DA had no effect on insulin secretion;in 16.7 mmol·L-1 glucose,dopamine inhibited insulin secretion in a dose-dependent manner.DA inhibited the inward calcium current,shorten the action potential duration,and reduced the intracellular Ca2+ concentration.Conclusion DA inhibits insulin secretion maybe by decreasing the inward calcium current leading to shorten the action potential duration and reduce the intracellular Ca2+ concentration.

Jiawei Erzhiwan improves menopausal metabolic syndrome by enhancing insulin secretion in pancreatic β cells / 中国天然药物

Menopausal metabolic syndrome (MMS) is a series of syndrome caused by ovarian function decline and hormone insufficiency, and is a high risk factor for cardiovascular diseases (CVD) and type II diabetes mellitus (T2DM). Erzhiwan (EZW), composed of Herba Ecliptae and Fructus Ligustri Lucidi, is a traditional Chinese herbal formula that has been used to treat menopausal syndrome for many years. We added Herba Epimedii, Radix Rehmanniae, and Fructus Corni into EZW, to prepare a new formula, termed Jiawei Erzhiwan (JE). The present study was designed to determine the anti-MMS effects of JE using ovariectomized (OVX) adult female rats that were treated with JE for 4 weeks, and β-tc-6 cells and INS cells were used to detected the protect effectiveness of JE. Our results showed JE could increase insulin sensitivity and ameliorated hyperlipidemia. Metabolomics analysis showed that the serum levels of branched and aromatic amino acids were down-regulated in serum by JE administration. Moreover, JE enhanced the function of islet β cells INS-1 and β-tc-6, through increasing the glucose stimulated insulin secretion (GSIS), which was abolished by estrogen receptor (ER) antagonist, indicating that JE functions were mediated by ER signaling. Additionally, JE did not induce tumorigenesis in rat mammary tissue or promoted proliferation of MCF-7 and Hela cells. In conclusion, our work demonstrated that JE ameliorated OVX-induced glucose and lipid metabolism disorder through activating estrogen receptor pathway and promoting GSIS in islet β cells, thus indicating that JE could be a safe and effective medication for MMS therapy.

Progress of the test and assessment of islet β cell function / 国际儿科学杂志

Islet β cell secretion deficiency and( or) the decreased insulin sensitivity of target tissue are the important pathophysiological mechanisms of diabetes. So,detection and assessment of isletβcell function in the early stages,could be of great significance for disease severity evaluation,early intervention and prognosis of the disease. At present,the main methods of the testing and assessment ofβcell function includeβcell function evaluating indexes,pulsatile insulin secretion,insulin secretion by glucose or non-glucose secretagogues and func-tion testing by other secretions of isletβcells. Among of them,βcell functional assessment methods by detecting C-peptide( especially aspects such as 90 minutes of C-peptide testing in mixed-meal tolerance test,urinary C-pep-tide creatinine ratio) have experienced some progress in recent years.

Efficacy of Acarbose in combination with life style modification on waist circumference in patients with impaired glucose tolerance / 中国糖尿病杂志

Objective To investigate the effect of acarbose on waist circumference (WC) in patients with IGR. Methods A total of 46 subjects with IGT (2 hPG>7.8 mmol/L) were selected in this study. All the subjects were given diet and exercise treatment for half a month and then treated with acarbose for 3 months in combination with life style modification. Self-paired method was adopted to compare islet βcell function and WC before and after the treatment. Results After acarbose treatment for 3 months ,islet βcell function were markedly improved. Insulin secretion of Fins and 2 hIns decreased ,early insulin secretion index (ΔI30/ΔG30 ) significantly increased ,and BMI and WC were reduced significantly (P<0.05) . Multiple regression analysis showed that there was correlation between WC and TG ,insulin resistance index (HOMA-IR) and islet β-cell function index (HOMA-β) (P< 0.05). Conclusion Acarbose in combination with life style modification can improve islet β-cell function in patients with IGR and reduce WC and abdominal fat accumulation as well.

Analysis of risk factors for adverse pregnancy outcomes in women with gestational diabetes mellitus / 中华临床营养杂志

Objective To evaluate clinical features,insulin sensitivity and β-cell function of pregnant women with different glucose tolerance status,so as to identify the possible risk factors for adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM).Methods We retrospectively analyzed the clinical data of 360 pregnant women with positive results of 50 g glucose challenge test who received antenatal care and admitted for delivery in the period from January 2009 to June 2012 in Peking Union Medical College Hospital.According to the result of 100 g oral glucose tolerance test (OGTT),the 360 women were divided into GDM group (n =83),impaired glucose tolerance (IGT) group (n =75),and normal glucose tolerance (NGT) group (n =202).The blood glucose level in all those women was controlled in normal range for gestational period.We compared the general clinical data,biochemical indexes,insulin resistance index,insulin sensitivity index,function index of islet β-cell,first-and second-phase insulin secretion,insulin secretion-sensitivity index as well as the pregnancy outcomes of the 3 groups,analyzing the possible risk factors for adverse pregnancy outcomes in women with GDM.Results Compared with the NGT group,the pregnant women in GDM group were older [(33.1 ± 3.7) years vs.(31.7 ± 3.4) years,P =0.008],had higher systolic blood pressure [(115.8 ± 9.7) mmHg vs.(111.4 ± 13.5) mmHg (1 mmHg =0.133 kPa),P =0.031] and diastolic blood pressure in first trimester [(75.4 ±9.0) mmHg vs.(71.8 ±8.8) mmHg,P =0.010],higher positive rate of family history of diabetes in first-degree relatives (37.3％ vs.22.3％,P =0.012),positive rate of insulin therapy (10.8％ vs.0％,P =0.001),serum triglyceride level [(2.8 ±0.9) mmol/L vs.(2.3 ±0.9) mmol/L,P =0.001],free fatty acid level [(486.7 ± 137.6) μmol/L vs.(438.1 ± 140.7) μmol/L,P =0.033],and C-reactive protein level [(5.7 ± 4.3) mg/L vs.(3.6 ± 3.0) mg/L,P =0.001].The GDM group had a larger pre-pregnancy body mass index [(22.6 ± 2.9) kg/m2] than that in IGT group [(21.3 ± 2.7) kg/m2] (P =0.049) and NGT group [(21.2 ±2.8) kg/m2] (P =0.003).In the order from NGT to IGT to GDM group,the hemoglobin A1c [(5.2 ± 0.3) ％ vs.(5.3 ± 0.3) ％ vs.(5.4 ± 0.3) ％,P =0.001,P =0.007],the areas under curve of glucose [(20.4±2.0) mmol · h/L vs.(22.9 ± 1.5) mmol · h/L vs.(26.9 ±2.1) mmol · h/L,both P=0.001] and the areas under curve of insulin [(1.7 ±0.9) × 103 pmol · h/L vs.(2.1 ± 1.1) × 103 pmol · h/L vs.(2.7±1.3) ×103 pmol · h/L,P=0.001,P=0.007] increased gradually,while insulin sensitivity index (88.1 ± 52.1 vs.80.0 ± 30.6 vs.50.0 ± 24.1,P =0.001,P =0.014) and insulin secretion-sensitivity index (134 507.0 ± 43 291.0 vs.102 542.0 ± 15 291.0 vs.77 582.0 ± 20 764.0,both P =0.001) decreased gradually.The insulin resistance index in the GDM group (3.3 ± 2.2) was significantly higher than that in IGT (2.2 ± 1.0) and NGT groups (3.0 ± 1.1) (both P =0.001).The function of β-cell,first-and second-phase insulin secretion were not significantly different among the 3 groups.Compared with the NGT group,pregnant women with GDM had shorter gestational age [(38.8 ± 1.1) weeks vs.(39.4 ± 1.1) weeks,P=0.004] and higher incidence of adverse pregnancy outcomes (44.6％ vs.21.8％,P =0.001).Seven risk factors predicting adverse pregnancy outcomes in women with GDM were identified,including pre-pregnancy body mass index (P=0.017),0-,1-,and 2-hour blood glucose in 100 g OGTT (P=0.036,P=0.009,P=0.004),3-hour insulin (P =0.014),and hemoglobin A1 c (P =0.002) and C-reactive protein (P =0.005) in second trimester,among which 1-hour blood glucose displayed the highest coefficient (OR =2.767).Conclusions Pregnant women with GDM have elevated blood pressure,dyslipidemia and increased inflammatory cytokine C-reactive protein.Women with GDM and IGT both show insulin resistance and β-cell dysfunction,and these impairments are more severe in women with GDM.Higher pre-pregnancy body mass index and blood glucose levels during pregnancy are associated with adverse pregnancy outcomes in women with GDM.

Restoration of β-cell function: New hope in the treatment of type 2 diabetes mellitus / 中华内分泌代谢杂志

Type 2 diabetes mellitus is a chronic progressing disease.In some recent studies,hyper glycemic patients get fine control of blood glucose without any hypoglycemic agents after a period of treatment.These results suggest the possibility of remission of islet β-cell function,at least in some diabetic patients.Restoration of β-cell function brings a new hope in the treatment for type 2 diabetes mellitus.