Impact of Addition of Metformin to Abiraterone in Metastatic Castration-Resistant Prostate Cancer Patients With Disease Progressing While Receiving Abiraterone Treatment (MetAb-Pro): Phase 2 Pilot Study

Background

There is evidence linking metformin to improved prostate cancer–related outcomes.

Evaluation of the metformin initiation rate in veterans with newly identified type 2 diabetes

BackgroundAn estimated 35 million individuals in the United States have diabetes. The American Diabetes Association recommends metformin as first-line pharmacologic treatment. The primary objective of this study was to evaluate the metformin initiation rate in veterans with recently identified type 2 diabetes.MethodsVeterans with new onset type 2 diabetes were identified using National Veterans Health Administration Data. Retrospective information was obtained from those with a first A1C ≥ 6.5% (48 mmol/mol) between 2013 and 2018. Veterans with at least one additional A1C < 6.5% (48 mmol/mol) documented in the three years prior to the A1C diagnostic for diabetes were included in the analysis.ResultsA total of 144,180 veterans were included. Of those, 45,776 (31.7%) were started on metformin within one year of diabetes diagnosis. The median time to metformin initiation was 12 days and median time to initiation of any anti-hyperglycemic was 11 days. Approximately 16,000 veterans were referred for lifestyle interventions within 90 days.ConclusionMetformin initiation occurred in fewer patients than expected given metformin is a generic, well-tolerated medication recommended as first-line pharmacologic treatment option regardless of A1C. Further studies are needed to assess the barriers of initiating metformin at time of diabetes diagnosis.     

参芪降糖颗粒联合二甲双胍对2型糖尿病患者降糖效果的分析

目的：探析2型糖尿病患者采取参芪降糖颗粒联合二甲双胍进行治疗的降糖效果。方法：选取2016年1月至2019年10月马鞍山市中心医院收治的2型糖尿病患者66例作为研究对象，按照随机数字表法分为对照组与观察组，每组33例，对照组通过二甲双胍进行治疗，观察组通过二甲双胍联合参芪降糖颗粒进行治疗，比较2组患者治疗总有效率、血糖参数、不良反应发生率等指标。结果：对照组、观察组的治疗总有效分别为75.76%、93.94%，与对照组比较，观察组的治疗总有效率明显较高（P<0.05）；观察组的空腹血糖、餐后2 h血糖等血糖参数在治疗后明显低于对照组患者（P<0.05）；对照组、观察组的治疗不良反应发生率分别为21.21%、3.03%，观察组治疗不良反应发生率明显低于对照组（P<0.05）。结论：2型糖尿病患者采取参芪降糖颗粒联合二甲双胍进行治疗能够获得较为理想的效果，可明显改善血糖指标，安全性较高，对改善患者的治疗预后有着促进的作用。     

二甲双胍对甲状腺乳头状癌TPC-1细胞凋亡的影响及其机制研究

目的 探讨二甲双胍对甲状腺乳头状癌TPC-1细胞凋亡的影响及其机制。方法 用不同浓度(0mmol/L、1mmol/L、5mmol/L、10mmol/L、20mmol/L、40mmol/L)二甲双胍分别处理TPC-1细胞24h。采用四甲基偶氮唑蓝（MTT）法检测细胞增殖能力；采用Annexin Ⅴ-FITC/PI流式细胞术检测不同浓度二甲双胍对TPC-1细胞凋亡的影响，同时在40mmol/L组加入腺苷酸活化蛋白激酶(AMPK)抑制剂Compound C，观察其对TPC-1细胞凋亡的影响；采用Western blot法检测磷酸化AMPK（p-AMPK）及Caspase-9蛋白的表达。结果 与0mmol/L组比较，1mmol/L及5mmol/L组的TPC-1细胞增殖能力无明显改变（P＞0.05）；而10mmol/L、20mmol/L、40mmol/L二甲双胍均可明显抑制TPC-1细胞的增殖能力，且呈剂量依赖性（P＜0.05）。与0mmol/L组比较，不同浓度二甲双胍均可明显增加TPC-1细胞凋亡率（P＜0.001）；而加入Compound C后，40mmol/L组TPC-1细胞凋亡率较前明显下降（P＜0.001）。与0mmol/L组比较，1mmol/L、5mmol/L、10mmol/L、20mmol/L、40mmol/L组p-AMPK、Caspase-9表达量增加。结论 二甲双胍可诱导甲状腺乳头状癌TPC-1细胞凋亡，且二甲双胍诱导TPC-1细胞凋亡的过程可能与激活AMPK通路有关，可能由Caspase-9介导。     

Dry eyes in patients with diabetes mellitus

Dry eyes may be caused by impairment in the tear production or excessive tear evaporation and are associated with photophobia, red eyes, vision impairment, local pain and pruritus. It has been described that patients with Diabetes Mellitus (DM) may have a higher prevalence of dry eyes than normal population.This is a case control study of 120 patients with Diabetes Mellitus (DM) and 120 paired controls aiming to compare their prevalence of dry eyes (by the Schirmer test) and its severity (measured by OSDI or Ocular Surface Disease Index) as well as their association with diseases’ clinical variables.We found that 38.3% of DM patients had dry eyes, a prevalence that was higher than controls (p = 0.02). At univariate analysis, they were found to be more common in older individuals (p = 0.001) with type 2 diabetes (p = 0.001) and in those using metformin (p = 0.001). A multivariate linear regression showed that metformin use was the only independent variable associated with dry eyes. When patients with dry eyes with and without DM were compared, no differences in the symptom’s intensity were found.     

二甲双胍增强放射对CT26WT细胞及小鼠移植瘤效应机制研究

目的 探讨二甲双胍(Met)联合放射对结肠癌CT26WT细胞及移植瘤的抑制作用及其机制研究。方法 利用CellTiter-Glo化学发光细胞活性试验检测0.5、1.0、5.0、10.0μmol/L的Met对CT26WT细胞活力影响,克隆形成试验检测对照组、10.0μmol/L的Met、15Gy照射、15Gy+10.0μmol/L的Met组对CT26WT细胞的增殖抑制作用。构建Bablc小鼠皮下移植瘤模型,肿瘤体积>150mm³随机分对照组、单纯15Gy照射、Met组、15Gy+Met组,照射前24h给予小鼠750 mg/kg的Met,定期测量肿瘤体积及小鼠体重绘制肿瘤生长曲线及生存时间曲线。蛋白质印迹法检测上述处理条件下CT26WT细胞及移植瘤组织中P-H2AX、Sting蛋白表达;并利用免疫组化方法检测移植瘤组织中CD8a (+) T细胞的浸润情况。结果 0、0.5、1.0、5.0、10.0μmol/L的Met的相对细胞存活率分别为100%、87.9%、87.8%、87.3%、76.5%(P<0.05),其中10.0μmol/L较5.0μmol/L抑制作用更强(P<0.001)。克隆形成实验结果显示对照组、Met组、15Gy组、15Gy+Met组细胞克隆形成率分别为34.0%、24.0%、22.3%、14.0%(P<0.001)。与对照组比较,Met组、15Gy组、15Gy+Met组细胞内Sting蛋白表达分别增加2.99、1.37、4.41倍(P<0.001、<0.01、<0.001)。15Gy+Met组P-H2AX蛋白表达较15Gy组增加1.43倍(P<0.001)。移植瘤体积15Gy+Met组较对照组生长缓慢,最终结果为(1007.0±388.5)、(2639.0±242.9) mm³,(P<0.05),15Gy+Met组小鼠总生存期较对照组增加(48d︰32d,P<0.001)。移植瘤组织中P-H2AX、Sting蛋白表达量在15Gy+Met组较对照组分别增加8.8、1.6倍(P均<0.001)。15Gy+Met组CD8a (+) T细胞浸润在较对照组明显增高(P<0.01)。结论 Met与放射联合能协同抑制结肠癌细胞增殖、克隆形成,可能作用机制是通过加重DNA损伤、激活Sting信号通路导致肿瘤组织中CD8a (+) T细胞增加加强对肿瘤细胞的杀伤作用。     

rs622342A>C in SLC22A1 is associated with metformin pharmacokinetics and glycemic response

Polymorphisms in SLC22A1 lead to variability in metformin clinical efficacy. Sixty-three Lebanese patients with type 2 diabetes who administered metformin, were followed up for six months and genotyped for rs622342A>C. The area under the plasma concentration-time curve and the maximum concentration of metformin was highest in CC patients (P ≤ 0.03). There was a significant difference between groups in the percentage decrease in fasting blood sugar (FBS) and glycated hemoglobin (HbA₁c). Going into the same direction, rs622342C was associated with decrease in FBS levels after three and six months of treatment (P ≤ 0.02), whereas with HbA₁c, the decrease was noticed after six months (β = −2.78; P = 0.03). In contrast, the serum levels of lactate and creatinine did not vary significantly according to rs622342A>C genotypes.The rs622342A>C in SLC22A1 may be associated with metformin pharmacokinetics and variability in therapeutic efficacy.