西格列汀联合二甲双胍治疗肥胖型2型糖尿病的疗效及对体脂含量情况分析

目的研究肥胖型2型糖尿病患者联合采用西格列汀、二甲双胍治疗的临床效果。方法选择2018年10月—2020年4月该院100例肥胖型2型糖尿病患者为研究对象,采用随机数表法分成常规组和治疗组,每组50例。常规组予二甲双胍治疗,治疗组予二甲双胍+西格列汀治疗。比较两组治疗效果、血糖指标、体脂含量、胰岛功能指标及不良反应。。结果两组治疗效果比较,差异有统计学意义(P<0.05)。治疗后常规组血糖指标高于治疗组,差异有统计学意义(t=8.183、4.828、18.158,P<0.05)。治疗后常规组体脂含量高于治疗组,差异有统计学意义(t=5.993、7.657、4.420,P<0.05)。治疗后两组胰岛功能比较,差异有统计学意义(t=5.898、5.283、16.033,P<0.05)。常规组不良反应总发生率低于治疗组,但差异无统计学意义(χ²=0.136,P=0.712)。结论西格列汀、二甲双胍联合治疗肥胖型2型糖尿病效果确切。     

二甲双胍和西格列汀对绝经后2型糖尿病患者骨代谢的影响

目的探讨二甲双胍和西格列汀对绝经后2型糖尿病合并骨量减少或骨质疏松患者骨代谢及骨密度的影响。方法选择接受治疗的绝经后2型糖尿病合并骨量减少或骨质疏松患者129例,采用随机数字表法分为磺脲类促泌剂治疗组（格列吡嗪组,G组）、二肽基肽酶-4抑制剂联合磺脲类促泌剂治疗组（西格列汀+格列吡嗪组,S+G组）、双胍类联合磺脲类促泌剂治疗组（二甲双胍+格列吡嗪组,M+G组）3组,随访48周,治疗前后测定患者空腹血糖（FBG）、糖化血红蛋白（HbA1C）、LDL-C、碱性磷酸酶（ALP）、骨钙素（OC）、Ⅰ型胶原羧基端肽β特殊序列(β-CTX),采用双能X线骨密度仪测定所有患者股骨颈和髋关节骨密度,对比治疗前后一般生化指标、骨转换指标及骨密度变化。结果129例中有122例完成48周随访,其中G组40例,S+G组41例,M+G组41例。3组患者治疗后BMI、OC、β-CTX、股骨颈和髋关节骨密度比较差异均有统计学意义（均P＜0.05）。3组患者治疗后FBG、HbA1C均较治疗前显著下降（均P＜0.01）。M+G组治疗后BMI较治疗前显著下降（P＜0.01）,G组和S+G组治疗后OC均较治疗前显著下降（均P＜0.01）,S+G组治疗后β-CTX较治疗前显著下降（P＜0.01）,G组治疗后股骨颈和髋关节骨密度均较治疗前显著下降（均P＜0.01）。结论西格列汀主要通过抑制骨吸收,并可能有部分促进成骨发挥其减少骨丢失的作用,二甲双胍可能通过促进成骨发挥其减少骨丢失的作用,两者均可作为绝经后女性2型糖尿病合并骨量减少或骨质疏松患者降糖的一线用药选择。     

西格列汀对妊娠期糖尿病患者餐后血糖异常的控制效果

目的 研究西格列汀对妊娠期糖尿病患者餐后血糖(2hPG)异常的控制效果.方法 选取本院2013年6月至2015年6月80例妊娠期糖尿病患者为研究对象,抽签随机分为观察组与对照组,每组40例.观察组采用西格列汀治疗,对照组单用胰岛素治疗,比较两组治疗前后空腹血糖(FPG)、餐后血糖水平及治疗期间的不良反应发生率.结果 观察组与对照组治疗前FPG、2 hPG比较差异无统计学意义(P＞0.05),治疗后2、4、6周观察组2 hPG分别为(10.16±1.58) mmol/L、(9.23±1.78)mmol/L、(8.86±1.25)mmol/L,显著低于对照组的(12.25±1.66)mmol/L、(11.44±1.79)mmol/L、(10.13±1.44)mmol/L (P＜0.05).治疗后2、4、6周观察组FPG分别为(8.06±0.85) mmol/L、(7.63±0.59) mmol/L、(6.78±0.43) rnmol/L,显著低于对照组的(9.81±0.36) mmol/L、(8.02±0.49) mmol/L、(7.01±0.37)mmol/L (P＜0.05).治疗过程观察组低血糖2例,恶心1例;对照组低血糖1例,眩晕1例,两组比较差异无统计学意义(P＞0.05).结论 西格列汀可以有效地控制妊娠期糖尿病患者的餐后血糖水平,不良反应率低,值得临床应用和推广.     

Sitagliptin rescues memory deficits in Parkinsonian rats via upregulating BDNF to prevent neuron and dendritic spine loss

Objectives: Parkinson’s disease (PD) is a neurodegenerative disease with high morbidity among adults worldwide that causes tremendous trouble to people’s lives. The purpose of this study was to investigate the impact of sitagliptin on PD and its potential mechanism.

Methods: First, the memory of rats in each group was evaluated with the Morris water maze (MWM) test and the passive avoidance test. Then, both brain-derived neurotrophic factor (BDNF) protein and mRNA levels were detected by ELISA and qPCR assays, respectively. Then, rapid Golgi impregnation was used to observe the density of dendritic spines in the hippocampal CA1 area. Finally, k252a, an antagonist of Trk receptors, was used to block the binding of BDNF with its receptors, and the effects of sitagliptin on PD improvement were detected.

Results: Our study showed that sitagliptin improved memory deficits in PD rats. Meanwhile, the expression level of BDNF and tyrosine hydroxylase (TH) was upregulated, and the density of dendritic spine was increased by sitagliptin administration. Moreover, K252a administration blocked the positive effects of sitagliptin on memory in PD rats.

Discussion: Sitagliptin rescued the memory deficits, which was achieved by upregulating BDNF to prevent neuronal death and dendritic spine loss. Our findings indicate that sitagliptin might be a promising potential drug for PD treatment in the future.     

Simultaneous Determination of Sitagliptin Phosphate Monohydrate and Metformin Hydrochloride in Tablets by a Validated UPLC Method

A novel approach was used to develop and validate a rapid, specific, accurate and precise reverse phase ultra performance liquid chromatographic (UPLC) method for the simultaneous determination of Sitagliptin phosphate monohydrate and Metformin hydrochloride in pharmaceutical dosage forms. The chromatographic separation was achieved on Aquity UPLC BEH C8 100 × 2.1 mm, 1.7 μm, column using a buffer consisting of 10 mM potassium dihydrogen phosphate and 2 mM hexane-1-sulfonic acid sodium salt (pH adjusted to 5.50 with diluted phosphoric acid) and acetonitrile as organic solvent in a gradient program. The flow rate was 0.2 mL min(-1) and the detection wavelength was 210 nm. The limit of detection (LOD) for Sitagliptin phosphate monohydrate and Metformin hydrochloride was 0.2 and 0.06 μg mL(-1), respectively. The limit of quantification (LOQ) for Sitagliptin phosphate monohydrate and Metformin hydrochloride was 0.7 and 0.2 μg mL(-1), respectively. This method was validated with respect to linearity, accuracy, precision, specificity and robustness. The method was also found to be stability-indicating.     

Effects of DPP-4 inhibition on cardiac metabolism and function in mice

Type 2 diabetes is associated with an increased risk of cardiac complications. Inhibitors of dipeptidylpeptidase 4 (DPP-4) are novel drugs for the treatment of patients with type 2 diabetes. The effect of DPP-4 inhibitors on myocardial metabolism has not been studied in detail. In wild-type C57Bl6-mice, 3 weeks of treatment with sitagliptin had no effect on body weight and glucose tolerance nor on phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoAcarboxylase (ACC), phosphofructokinase-2 (PFK2) or tuberin-2 (TSC2) in the left ventricular myocardium. However, in 10 week old db/db−/− mice, a model of diabetes and obesity, sitagliptin potently reduced plasma glucose rise in peritoneal glucose tolerance tests and reduced weight increase. The myocardium of untreated db/db−/− mice exhibited a marked increase of the phosphorylation of AMPK, ACC, TSC2, expression of p53 and fatty acid translocase (FAT/CD36) membrane expression. These changes were reduced by DPP-4 inhibition. Sitagliptin showed no effect on cardiomyocyte size but prevented myocardial fibrosis in the 10 week old db/db−/− mice and reduced expression of TGF-β1, markers of oxidative stress and the accumulation of advanced glycation end products in cardiomyocytes. Working heart analyses did not show an effect of sitagliptin on parameters of systolic cardiac function. In animals with diabetes and obesity, sitagliptin improved glucose tolerance, reduced weight gain, myocardial fibrosis and oxidative stress. Furthermore the study provides evidence that treatment with sitagliptin decreases elevated myocardial fatty acid uptake and oxidation in the diabetic heart. These observations show beneficial myocardial metabolic effect of DPP-4 inhibition in this mouse model of diabetes and obesity.     

Dipeptidyl peptidase-4 inhibitor for steroid-induced diabetes

The addition of the dipeptidyl peptidase-4 (DDP-4) inhibitor has been reported to achieve greater improvements in glucose metabolism with fewer adverse events compared to increasing the metformin dose in type 2 diabetic patients. We present a patient with steroid-induced diabetes whose blood glucose levels were ameliorated by the use of the DPP-4 inhibitor, showing that the DPP-4 inhibitors may be an effective and safe oral anti-diabetic drug for steroid-induced diabetes.     

Dipeptidyl peptidase-4: A key player in chronic liver disease

Dipeptidyl peptidase-4 (DPP-4) is a membrane-associated peptidase, also known as CD26. DPP-4 has widespread organ distribution throughout the body and exerts pleiotropic effects via its peptidase activity. A representative target peptide is glucagon-like peptide-1, and inactivation of glucagon-like peptide-1 results in the development of glucose intolerance/diabetes mellitus and hepatic steatosis. In addition to its peptidase activity, DPP-4 is known to be associated with immune stimulation, binding to and degradation of extracellular matrix, resistance to anti-cancer agents, and lipid accumulation. The liver expresses DPP-4 to a high degree, and recent accumulating data suggest that DPP-4 is involved in the development of various chronic liver diseases such as hepatitis C virus infection, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Furthermore, DPP-4 occurs in hepatic stem cells and plays a crucial role in hepatic regeneration. In this review, we described the tissue distribution and various biological effects of DPP-4. Then, we discussed the impact of DPP-4 in chronic liver disease and the possible therapeutic effects of a DPP-4 inhibitor.     

利拉鲁肽、西他列汀和吡格列酮治疗NAFLD合并2型糖尿病患者疗效初步比较研究

目的 探讨利拉鲁肽、西他列汀和吡格列酮治疗非酒精性脂肪性肝病（NAFLD）合并2型糖尿病患者的疗效。方法 2013年1月～2015年12月我院收治的150例NAFLD合并2型糖尿病患者被随机分成胰高糖素样肽-1、西他列汀和吡格列酮治疗组,每组50例,分别接受相应药物治疗3 m。结果 胰高糖素样肽-1治疗组患者治疗后体质量、BMI、AST、ALT、空腹血糖、HbA1c和AST/血小板计数比值分别为【（67.3±5.2） kg、（27.3±3.1） kg/m2、（52.6±11.5） U/ml、（75.5±10.8） U/ml、（9.4±1.7） mmol/L、（8.4±1.2） mmol/L、何（0.75±0.21）】,西他列汀组患者治疗后ALT、空腹血糖和HbA1c水平分别为【（78.8±14.2） U/ml、（9.8±1.4） mmol/L、（8.7±1.5） mmol/L、）】,吡格列酮组患者治疗后AST、HbA1c和甘油三酸脂水平分别为【（48.4±8.9） U/ml、（8.0±1.6） mmol/L、和（2.8±0.8） mmol/L、】。结论 相比之下,胰高糖素样肽-1能够显著降低NAFLD合并2型糖尿病患者体质量,改善肝功能和血脂水平。