BACKGROUND:Cardiorenal-protective sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) lack selection guidance. We aimed to build a SGLT-2i/GLP-1RA Decision Score (TiP DecScore) to tailor selection between them. METHODS:We developed the TiP DecScore in type 2 diabetes (T2D) patients receiving either therapy from the China Metabolic Analytics Project (derivation dataset: n = 24,322; validation dataset: n = 1,459), using gradient boosting decision tree and 15 features. The primary outcomes were glycated haemoglobin (HbA1c) control (<7%) and HbA1c levels at 6 and 12 months. The model's clinical effectiveness was evaluated by comparing HbA1c control between concordant (receiving the predicted optimal therapy) and discordant groups (receiving the predicted non-optimal therapy). RESULTS:Here we show the derivation cohort has mean (SD) age 53.7 (11.5) years, 63.0% males. Model validation shows good predictive performance (the receiver operating characteristic curve 0.71-0.78). GLP-1RA is favored over SGLT-2i (57.6% vs. 24.2% at 6 months; 57.9% vs. 28.6% at 12 months). At 6 months, compared with SGLT-2i, GLP-1RA is prioritized for patients with a shorter diabetes duration and higher fasting C-peptide, alanine aminotransferase, body mass index (BMI), and low-density lipoprotein cholesterol levels. At 12 months, patients with higher baseline HbA1c and BMI levels are more likely to be recommended GLP-1RA than SGLT-2i. Higher rates of HbA1c control are observed in concordant versus discordant groups, especially in younger patients (<55 years; 64.1% vs. 46.2%, P = 0.001) and males (58.6% vs. 45.6%, P = 0.018) at 12 months. CONCLUSIONS:The TiP DecScore effectively guides personalized selection between SGLT-2i and GLP-1RA therapies for T2D patients.

Long non-coding RNA (lncRNA) holds considerable promise in mitigating the onset and progression of diabetic cardiomyopathy (DCM). FENDRR was selected due to its reported involvement in cardiac apoptosis and inflammatory regulation, key pathways in DCM pathogenesis. This study investigated role and underlying mechanisms of FENDRR in DCM. Type 2 diabetes mellitus (T2DM) patients were included and stratified by DCM status. One group was T2DM patients without DCM (n = 49), and the other was T2DM patients with DCM (n = 47).. Clinical data from both groups were compared. qRT-PCR was utilized to quantify serum FENDRR expression, with ROC analysis assessing its diagnostic value. A DCM cell model was established using high glucose-treated H9c2 cells. Flow cytometry and ELISA assays measured apoptosis, myocardial enzyme levels, antioxidant enzyme levels, and inflammatory. Dual-luciferase assays confirmed FENDRR-miR-296-5p and miR-296-5p-HMGA1 interactions. FENDRR was upregulated in DCM patients and high glucose-treated H9c2s (AUC = 0.888). si-FENDRR mitigated apoptosis in high glucose-stimulated H9c2 cells by inhibiting Bax and promoting Bcl-2 expression. si-FENDRR reduced myocardial enzymes release and inflammatory, and restored antioxidant enzyme levels. miR-296-5p was validated as a target of FENDRR, exhibiting an expression pattern opposite to that of FENDRR. miR-296-5p knockdown negated the positive effects of si-FENDRR on cardiomyocytes. HMGA1, a target gene of miR-296-5p, was upregulated in DCM patients and high glucose environments. This preliminary study uncovers the potential diagnostic value of FENDRR in DCM and explores its molecular mechanisms regulating myocardial cell injury via the miR-296-5p/HMGA1 axis.

Purpose: Elevated urine albumin-to-creatinine ratio (UACR) is an established risk factor for microvascular disease in the general population. However, it is unclear whether UACR is associated with arterial stiffness in diabetes. We aimed to assess the relationship between UACR levels and the risk of arterial stiffness in patients with diabetes. Methods: From July 2021 to February 2023, a total of 1039 participants were assessed for the risk of arterial stiffness, which was evaluated by brachial-ankle pulse wave velocity (baPWV). The value of UACR >= 30 mg/g was defined as high UACR. The UACR level had an abnormal distribution and was log2-transformed for analyses to reduce skewness and volatility. High baPWV was evaluated as categorical variables divided by the highest quartile of the values by sex. The relationship between UACR and arterial stiffness was analyzed by linear curve fitting analyses. Multiple logistic regression models were used to analyze the crude and adjusted odds ratio (OR) of UACR for high baPWV with 95% confidence interval (CI). In addition to applying non-adjusted and multivariate-adjusted models, interaction and stratified analyses were also carried out. Results: The baPWV level was significantly higher in the high UACR group compared with that in the normal UACR group (1861.84 +/- 439.12 cm/s vs 1723.13 +/- 399.63 cm/s, p< 0.001). Adjusted smoothed plots suggested that there are linear relationships between log2-transformed UACR and high baPWV, and Spearman correlation coefficient was 0.226 (0.176- 0.276, p< 0.001). The OR (95% CI) between log2-transformed UACR and high baPWV were 1.26 (1.19- 1.33, p< 0.001), and 1.16 (1.08- 1.25, p< 0.001) respectively in diabetic patients before and after adjusting for potential confounders. Conclusion: The elevated UACR was associated with arterial stiffness in Chinese patients with diabetes.

This research was done to find out how liraglutide affected the growth and movement of two human thyroid cancer cell lines overexpressing GLP-1 receptor (migration of medullary thyroid cancer TT/GLP-1R and papillary thyroid carcinoma TCP-1/GLP-1R). Flow cytometer and cAMP assays were used to identify the expression and activation of GLP-1R in two stable cell lines. Counting Kit-8 for Cells was applied to examine the proliferative ability of cells in two stable cell lines after treatment with different concentrations of liraglutide at indicated time points. To track the capacity for cell migration, the Transwell test was utilized. We found that liralutide-activated GLP-1R could significantly reduce the growth and metastasis of two kinds of thyroid tumor cells, and the inhibitory effect was dose- and time- dependent. The phosphorylatios of Akt, S6K1, and 70SK declined after receiving liraglutide therapy In our previous studies, we found that the GLP-1 receptor agonist Liraglutide inhibited the proliferation and migration of thyroid cancer cells through the PI3K/Akt/mTOR pathway. This finding provides a theoretical basis for the treatment of diabetes mellitus complicated with medullary thyroid cancer, and is relatively safe.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

目的 探讨胆囊收缩素(cholecystokinin,CCK)、间隙连接蛋白43(connexin 43,Cx43)、胰高血糖素样肽1(glucagon-like peptide-1,GLP-1)对2型糖尿病胃轻瘫患者胃排空的预测价值及其相关性.方法 选择2型糖尿病胃功能异常患者127例,其中功能性消化不良49例设为消化不良组,糖尿病胃轻瘫患者78例设为胃轻瘫组,另选择同期体检的胃功能正常的健康者50例设为对照组,所有受试对象均进行胃半排空时间测定.酶联免疫吸附法检测CCK、Cx43、GLP-1水平,放射性核素法检测固体胃排空功能.分析CCK、Cx43、GLP-1对2型糖尿病胃轻瘫患者胃排空的预测价值,并分析CCK、Cx43、GLP-1的相关性.结果 消化不良组和胃轻瘫组CCK、Cx43水平低于对照组,GLP-1水平高于对照组,胃半排空时间长于对照组;胃轻瘫组CCK、Cx43水平低于消化不良组,GLP-1水平高于消化不良组,胃半排空时间长于消化不良组(P<0.05).CCK、Cx43、GLP-1联合检测对2型糖尿病胃轻瘫患者胃排空的预测价值较高.CCK、Cx43呈正相关(r=0.482;P<0.001);CCK、GLP-1呈负相关(r=-0.356;P<0.001);Cx43、GLP-1呈负相关(r=-0.619;P<0.001).结论 CCK、Cx43、GLP-1在2型糖尿病胃轻瘫疾病中异常表达,对预测2型糖尿病胃轻瘫患者有一定的价值.

Objective:To investigate the effects of once-weekly dulaglutide 1.5 mg treatment on glucose variability and glucose control in type 2 diabetes patients using 24 h continuous glucose monitoring (CGM) technology.Methods:A multi-center, prospective study was carried out. A total of 149 type 2 diabetes patients were recruited, who were treated with dulaglutide for 2 to 4 weeks, wearing CGM devices to monitor the glucose level. The primary evaluation indicators included mean amplitude of glycemic excursions (MAGE), mean daily glucose (MDG), time in target glucose range (TIR), time above range and time below range (TAR, TBR). Secondary indicators included change of concomitant medication dosages, treatment-related adverse events and change of blood pressure. Mixed effects model (MEM) of repeated measurement data or paired Mann-Whitney rank-sum test was used to analysis the differences between CGM parameters in each week during the treatment period.Results:MDG and MAGE of patients decreased by (0.76±0.31) and (0.50±0.13) mmol/L ( P<0.05), respectively, after the 4-week dulaglutide treatment. When compared with the first week, time in range (TIR) in week 2 increased from 73.91% (IQR 25.20%) to 7.49% (IQR 24.89%), and the mean difference was 3.58% ( P<0.01). Time in hyperglycemia decreased from 2.95% (IQR 10.76%) to 1.94% (IQR 7.24%), and the median difference was 1.01% ( P<0.001), while the time in hypoglycemia did not change ( P>0.05). Mean systolic pressure of patients decreased by (5.2±1.5) mmHg (1 mmHg=0.133 kPa) after the first-week treatment. Furthermore, 14 patients reported treatment-related adverse events including gastrointestinal reaction and hypoglycemia. Conclusions:Treatment with dulaglutide 1.5 mg weekly for 2 to 4 weeks could significantly reduce glycemic variability, improve short-term glucose control and lower blood pressure in type 2 diabetes patients without significantly increasing the risk of hypoglycemic events.

Metformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma glucose levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both the pancreas and liver glucokinase, decreases postprandial glucose in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, the efficacy and safety of dorzagliatin as an add-on therapy to metformin were assessed in patients with T2D who had inadequate glycemic control using metformin alone. Eligible patients with T2D (n = 767) were randomly assigned to receive dorzagliatin or placebo (1:1 ratio) as an add-on to metformin (1,500 mg per day) for 24-weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin (HbA1c) levels from baseline to week 24, and safety was assessed throughout the trial. At week 24, the least-squares mean change from baseline in HbA1c (95% confidence interval (CI)) was -1.02% (-1.11, -0.93) in the dorzagliatin group and -0.36% (-0.45, -0.26) in the placebo group (estimated treatment difference, -0.66%; 95% CI: -0.79, -0.53; P < 0.0001). The incidence of adverse events was similar between groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin and metformin combined therapy group. In patients with T2D who experienced inadequate glycemic control with metformin alone, dorzagliatin resulted in effective glycemic control with good tolerability and safety profile (NCT03141073).

Chiglitazar (Carfloglitazar) is a novel non-thiazolidinedione (TZD) structured peroxisome proliferator-activated receptor (PPAR) pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes in previous clinical studies. This randomized phase 3 trial aimed to compare the efficacy and safety of chiglitazar with placebo in patients with type 2 diabetes with insufficient glycemic control by strict diet and exercise alone. Eligible patients were randomly assigned to receive chiglitazar 32 mg (n = 167), chiglitazar 48 mg (n = 166), or placebo (n = 202) once daily. The primary endpoint was the change in glycosylated hemoglobin A1c (HbA1c) at week 24 with superiority of chiglitazar over placebo. The results showed that both chiglitazar 32 and 48 mg resulted in significant and clinically meaningful reductions in HbA1c, and placebo-adjusted estimated treatment differences at week 24 for chiglitazar 32 and 48 mg were -0.87% (95% confidential interval (CI): -1.10 to -0.65; P < 0.0001) and -1.05% (95% CI: -1.29 to -0.81; P < 0.0001), respectively. Secondary efficacy parameters including glycemic control, insulin sensitivity and triglyceride reduction were also significantly improved in the chiglitazar groups. The overall frequency of adverse events and study discontinuation attributable to adverse events were similar among the groups. Low incidences of mild edema and body weight gain were reported in the chiglitazar dose groups. The results from this phase 3 trial demonstrated that the PPAR pan-agonist chiglitazar possesses an overall good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions, thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.

糖尿病患者发生冠心病的风险较非糖尿病患者明显升高,且心血管疾病是2型糖尿病患者最主要的致死原因.传统降糖药物尽管降糖疗效显著,但缺乏对心血管结局的良好评估.新型降糖药物经过大型临床试验确保了疗效和对心血管结局的安全性.本文从降糖药物对心血管结局影响的角度,介绍传统降糖药物及新型降糖药物在糖尿病治疗中的心血管安全性,指出某些新型降糖药物如钠-葡萄糖共转运蛋白2抑制剂(SGLT-2i)和胰高血糖素样肽1受体激动剂(GLP-1RAs)在2型糖尿病患者中具有良好心血管保护作用,其治疗地位在多项指南中得到提升,成为2型糖尿病合并心血管疾病患者的重要选择.本文结合多项国内外最新临床证据对糖尿病治疗药物对心血管结局的影响进行分析、总结,以期为临床医疗工作者制定糖尿病治疗策略提供参考.

BACKGROUND:FOXO3a is a widely studied transcription factor and plays an important role in a variety of biology. The purpose of this study was to explore the role and potential mechanism of FOXO3a on lipid accumulation and adipocyte inflammation in adipocytes through regulation of autophagy.METHODS:The obese mouse model was successfully induced by high-fat diet. SiRNA targeting FOXO3a was transfected into differentiation of 3T3-L1 adipocytes to reduce the expression of FOXO3a. The culture medium of RAW264.7 cells was added to the differentiated 3T3-L1 adipocytes to form a co-culture system. Subsequently, ELISA or AdipoRed assay was performed to measure the expression of triglyceride (TG) and cholesterol (TC) in mouse adipose tissue or differentiation of 3T3-L1 adipocytes. Adipocyte differentiation was detected by Oil Red O-staining. Ad-mCherry-GFP-LC3II was used to detect the level of autophagy in differentiation of 3T3-L1 adipocytes. Western blotting or qRT-PCR was used to detect the expression of FOXO3a, autophagy-related proteins (beclin 1, CEBPβ, PPARγ, ACC1 and KLF4), inflammatory cytokines (TNF-α, IL-1β, IL-6 and MCP1), NF-κB signal pathway-related proteins or adipokines (Adiponectin, AdipoR1 and resistin) in differentiated 3T3-L1 or RAW264.7 cells.RESULTS:The expression of FOXO3a and autophagy levels were significantly increased in visceral adipose tissue of obese mice and differentiation of 3T3-L1 adipocytes. Downregulation of FOXO3a significantly inhibited the autophagy and lipid accumulation in differentiation of 3T3-L1 adipocytes. In addition, FOXO3a knockdown significantly reduced Lipopolysaccharide (LPS)-induced inflammation and adipokines release in RAW264.7 cells treated with the culture medium of 3T3-L1 adipocytes. These above activity changes could be reversed by autophagy inducer rapamycin.CONCLUSION:FOXO3a could promote lipid accumulation and inflammation in differentiated 3T3-L1 adipocytes by targeting autophagy. Our results provide a new theoretical basis for FOXO3a to regulate obesity.

目的 探讨男性2型糖尿病伴胰岛素抵抗患者的临床特点及其影响因素.方法 收集男性2型糖尿病患者576例,根据稳态模型胰岛素抵抗指数分为非胰岛素抵抗组248例,胰岛素抵抗组328例.比较两组一般临床资料及实验室数据和两组其他疾病构成比的差异,两变量相关分析胰岛素抵抗与一般临床指标的相关性,并用二元Logistic回归方法分析胰岛素抵抗与影响因素的相关性.结果 男性2型糖尿病伴胰岛素抵抗患者年龄较轻,血压较高,体重、体重指数、腰围、臀围、腰臀比、内脏脂肪、皮下脂肪及总脂肪均高于非胰岛素抵抗组(均P＜0.001),实验室数据结果提示,胰岛素抵抗组糖化血红蛋白、空腹、餐后2h血糖、胰岛素、C肽均高于非胰岛素抵抗组(均P＜0.001),转氨酶、尿酸、总胆固醇、三酰甘油较非胰岛素抵抗组高,差异有统计学意义(P＜0.01、P＜0.01、P＜0.05、P＜0.01).在其他疾病构成上,胰岛素抵抗组肥胖症、高血压病、高脂血症,高尿酸血症比例高于非胰岛素抵抗组(P＜0.01、P＜0.01、P＜0.01、P＜0.05).相关分析提示,胰岛素抵抗指数与腰围(r=0.119,P=0.004)、腰臀比(r=0.117,P=0.005)、内脏脂肪(r=0.089,P=0.044)和总脂肪(r=0.095,P=0.032)呈正相关关系.二元Logistic回归分析显示,内脏脂肪(OR=1.007,P=0.028)、皮下脂肪(OR=1.009,P=0.014)、三酰甘油(OR=1.147,P=0.046)与胰岛素抵抗有关.结论 男性2型糖尿病伴胰岛素抵抗患者肥胖症、高血压、高脂血症、高尿酸血症发生比例高于非胰岛素抵抗组.内脏脂肪、皮下脂肪、三酰甘油与胰岛素抵抗有关.

目的 研究阿卡波糖、沙格列汀联合甘精胰岛素对初发2型糖尿病患者血糖波动的影响.方法 将60例初发的2型糖尿病患者随机分为沙格列汀和甘精胰岛素组及阿卡波糖和甘精胰岛素组,在治疗前和治疗后3个月分别行72h动态血糖监测,比较空腹、餐后血糖,糖化血红蛋白及血糖波动指标.结果 两组患者治疗后空腹、餐后血糖,糖化血红蛋白均明显降低(均P＜0.01);72h动态血糖监测提示,除低血糖发生外,其他血糖参数均明显改善(均P＜0.01);72 h动态血糖监测提示,两组治疗后均有2例患者有低血糖发生;与沙格列汀组比较,阿卡波糖组在餐后血糖(P＜0.01)、糖化血红蛋白(P＜0.01)、血糖标准差(P＜0.05)、平均血糖水平(P＜0.01)、早餐后平均血糖(P＜0.01)、中餐后平均血糖(P＜0.05)、血糖百分比(＞7.8 mmol/L,P＜0.01)方面明显降低,差异有统计学意义.结论 阿卡波糖、沙格列汀联合甘精胰岛素均能明显降低初发2型糖尿病患者血糖指标,减少血糖波动,阿卡波糖联合甘精胰岛素在降低糖化血红蛋白水平,尤其是餐后血糖方面更有优势.

目的 探讨内脏脂肪指数(visceral adiposity index,VAI)、脂质蓄积指数(lipid accumulation product,LAP)与血尿酸(serum uric acid,SUA)水平的关系,评估其对高尿酸血症(hyperuricemia,HUA)预测的有效性.方法 选取2016年4月-2016年7月在上海市杨浦区进行流行病学调查观察人群868人为研究对象.根据SUA水平四分位进行分组,比较组间BMI、腰围(WC)、臀围(HC)、腰臀比(WHR)、收缩压(SBP)、舒张压(DBP)、空腹血糖(FPG)、餐后2h血糖(2hPG)、空腹胰岛素(FINS)、餐后2h胰岛素(2hINS)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、血肌酐(Cr)、HOMA胰岛素抵抗指数(HOMA-IR)、HOMA胰岛素敏感性指数(HOMA-ISI)、LAP和VAI等指标的差异.采用多因素Logistic回归分析方法筛选与HUA关系密切的变量.以受试者工作曲线(ROC)分析体脂指标VAI、LAP对HUA风险预测有效性.结果 随着SUA水平的升高,HOMA-IR逐渐增加(P＜0.05),HOMA-ISI降低(P＜0.001),LAP和VAI逐渐升高(P均＜0.01).SUA水平与体重、BMI、WC、HC、WHR、DBP、SBP、FINS、2hINS、HOMA-IR、TG、Cr、LAP、VAI呈显著正相关(P均＜0.01),与TC、HDL-C、HOMA-ISI呈显著负相关(P均＜0.05).根据LAP和VAI的四分位将研究对象分组,在校正性别、年龄、吸烟、饮酒、血压、血糖、胰岛素水平、血脂、血Cr等因素后,LAP第3和第4分位组发生HUA的风险分别为3.164(95％CI:1.62～6.18)、4.131(95％CI: 1.913～8.921)(P均＜0.01);VAI第3和第4分位组发生HUA的风险分别为2.22(95％CI:1.197～4.115)、3.955(95％CI:2.159～7.245)(P均＜0.05).ROC分析显示,LAP和VAI评估HUA的曲线下面积(AUC)分别为0.673 (95％ CI:0.630～0.716,P＜0.001)和0.645 (95％CI: 0.599～0.691,P＜0.001),VAI、LAP及HOMA-IR三个指标联合可较好地在女性人群中识别HUA的风险.结论 新型体脂指标LAP、VAI和SUA水平密切相关,LAP和VAI可作为HUA的独立预测因子.

背景 我国糖尿病患病率逐年激增,给患者、家庭、社会带来沉重经济负担.但目前我国糖尿病患者的管理模式仍存在许多不足,尚有很大的进步空间.近年来,随着社区卫生服务中心的不断发展和国家构建分级诊疗制度的建立,探索一种适合我国国情的糖尿病管理模式十分必要.目的 探讨糖尿病区域卫生协同发展管理模式在糖尿病患者管理中的应用效果.方法 选取2017年1—12月在同济大学附属杨浦医院及上海市杨浦区长白、江浦社区卫生服务中心就诊的符合纳入标准的198例糖尿病患者为研究对象,进行前瞻性随访研究.依据患者意愿分为两组,即采取糖尿病区域卫生协同发展管理模式的试验组(n=70)及继续保持目前就医方式、以社区管理为主的对照组(n=128).两组患者均干预12个月.比较两组患者干预前后体质指数(BMI)、腰臀比(WHR)、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),健康行为情况(包括健康知识掌握、规律饮食、定期监测血糖、坚持运动).结果 试验组患者干预前HbA1c高于对照组(P<0.05).试验组患者干预后BMI、FBG、TG、LDL-C低于对照组,HDL-C高于对照组(P<0.05);试验组与对照组患者干预后WHR、HbA1c、TC比较,差异无统计学意义(P>0.05).干预后对照组FBG、HbA1c、TG、TC、LDL-C低于同组干预前,HDL-C高于同组干预前(P<0.05).干预后试验组BMI、FBG、HbA1c、TG、TC、LDL-C低于同组干预前,HDL-C高于同组干预前(P<0.05).试验组干预后健康知识掌握、规律饮食、定期监测血糖、坚持运动患者的比例(依次为67.1％、78.6％、71.4％、55.7％)均高于对照组(依次为52.3％、44.5％、46.1％、32.8％)(χ2值分别为4.058、21.342、11.738、9.818,P<0.05).结论 糖尿病区域卫生协同发展管理模式在糖尿病管理中的初步疗效确切,主要体现在体质量、血糖及血脂的控制效果及健康行为的依从性提高,是基于分级诊疗的糖尿病管理道路上的一项有益尝试.

目的 探讨西格列汀对初诊2型糖尿病患者短期胰岛素泵强化治疗后胰岛细胞功能的影响.方法 选取我院初诊2型糖尿病患者96例,随机分为对照组和观察组,各48例.两组均行胰岛素泵强化治疗,后续治疗时,对照组采用盐酸二甲双胍缓释片治疗,观察组采用西格列汀治疗,对比两组血糖水平、胰岛功能及不良反应.结果 随访1年,两组FPG、2 h PBG及HbA1c水平均较后续治疗前降低,且观察组更低(P＜0.05);随访1年,两组FINS、HOMA-β及HOMA-IR水平均较后续治疗前改善,较对照组,观察组FINS、HOMA-B水平更高,HOMA-IR水平更低(P＜0.05);两组不良反应差异无统计学意义(P＞0.05).结论 西格列汀用于初诊2型糖尿病患者短期胰岛素泵强化治疗后可有效降低患者的血糖水平,改善其胰岛细胞功能.

Chiglitazar showed favorable effect on glycemic control and lipid modulation with well tolerated safety profile in phase 2 trials. This trial aimed to further compare the efficacy and safety of chiglitazar with placebo in patients with type 2 diabetes inadequately controlled with lifestyle interventions (ClinicalTrials.gov NCT02121717). Patients were randomly assigned to receive chiglitazar 32 mg or 48 mg, or placebo once daily. After 24-week treatment, patients in placebo group were randomly assigned to receive chiglitazar 32 mg or 48 mg, while others remained on the planned treatment till to 52 weeks. The primary endpoint was change in HbA1c at week 24 with superiority of each chiglitazar dose versus placebo. Analysis was done in all randomized patients who received at least one dose of study drug (n= 535). Chiglitazar was superior to placebo in HbA1c reduction at 24 weeks (LS mean difference -0.87% [95% CI -1.10 to -0.65] and -1.05% [95% CI -1.29 to -0.81] for 32 mg and 48 mg, respectively) and achieved sustainable effect till to 52 weeks. Overall adverse events were comparable across groups. The incidences of weight gain, edema, and hypoglycemia were relatively higher in chiglitazar groups. Chiglitazar showed superior and sustainable HbA1c lowering effect with well tolerated safety profile in patients with type 2 diabetes. Disclosure L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi. W. Song: None. H. Fang: None. W. Li: None. J. Geng: None. Y. Xu: None. Y. Wang: None. L. Guo: None. H. Cai: None. T. Yang: None. H. Li: None. G. Yang: None. Q. Li: None. K. Liu: None. S. Li: None. Y. Liu: None. F. Shi: None. X. Li: None. X. Gao: None. Q. Ji: None. H. Tian: None. Q. Su: None. Z. Zhou: None. W. Wang: None. Z. Zhou: None. X. Li: None. Y. Xu: None. Z. Ning: None. X. Lu: None. W. Jia: None. Funding Ministry of Science and Technology of the People´s Republic of China (2013ZX09401301)

Background: Chiglitazar is a novel PPARα/γ/δ pan-agonist with moderate transcriptional activities. Phase 2 studies demonstrated that chiglitazar had significant effects on glycemic control and lipid modulation in patients with type 2 diabetes. The current CMAP study aimed to assess the efficacy and safety of chiglitazar compared with placebo in type 2 diabetes patients who had not previously received anti-diabetic treatment.Methods: This study was a double-blind and placebo-controlled phase 3 trial conducted at 26 centres in China. Eligible patients were 18-70 years old, type 2 diabetes with HbA1c ≥7*5% and ≤10*0% and without previous anti-diabetic treatment. Patients were randomly assigned to receive chiglitazar 32 mg or 48 mg, or placebo once daily. The primary endpoint was change in HbA1c at week 24 with superiority of chiglitazar to placebo.Findings: Between June 17, 2014, and Oct 13, 2016, 535 patients were randomly assigned to receive chiglitazar 32 mg (n=167), 48 mg (n=166), or placebo (n=202). In the primary LOCF analysis in the full-analysispopulation, both chiglitazar doses were superior to placebo for HbA1c reduction at week 24, with the mean differences between chiglitazar 32 mg or 48 mg versus placebo were -0*87% [95% CI -1*10 to -0*65] or -1*05% [- 1*29 to -0*81], respectively. Overall frequency of adverse events and study discontinuation attributable to adverse events were similar among groups. Serious adverse events were reported for seven (3%) in the placebo group, four (2%) in the chiglitazar 32 mg group, and eight (5%) in the chiglitazar 48 mg group. A small increased mild edema events and body weight gain was reported in the chiglitazar dose groups.Interpretation: The PPAR pan-agonist chiglitazar had significant and clinically relevant improvements in glycaemic control in patients with type 2 diabetes, with no unexpected safety findings.Trial Registration: This study is registered with clinicaltrials.gov number NCT02121717.Funding Statement: Chipscreen Biosciences. This study was partly supported by grants from Chinese National and Provincial Major Project for New Drug Innovation (National: 2008ZX09101-002, 2013ZX09401301; Provincial: 2011A080501010) and Shenzhen Municipal Major Project (2010-1746). Declaration of Interests: ZN, HC, DP, HY and XL are employees of Chipscreen Biosciences Ltd. The other authors declare no competing interests.Ethics Approval Statement: The study complied with the Declaration of Helsinki and Good Clinical Practice guidelines, and was approved by institutional review boards and independent ethics committees for participating centers. All participants provided written informed consent.

目的 探讨2型糖尿病患者糖尿病视网膜病变的相关危险因素.方法 社区2型糖尿病患者326例,根据眼底照相结果分为正常(NDR)组和视网膜病变(DR)组.分析两组之间一般资料及相关临床资料的差异,并运用多因素Logistic回归分析DR的危险因素.结果 和NDR组比较,DR组患者的年龄更大,糖尿病病程更长,吸烟的比例更高,空腹血糖(FPG)、2 h血糖(2hPG)、糖化血红蛋白(HbA1C)、尿微量白蛋白显著升高,差异均具有统计学意义.Logistic回归分析表明:HbA1C和尿微量白蛋白是DR发生的独立危险因素.结论 糖化血红蛋白(HbA1C)、尿微量白蛋白是糖尿病视网膜病变的主要危险因素.