Effectiveness and safety of traditional Chinese medicine decoction for diabetic gastroparesis:A network meta-analysis

BACKGROUND Diabetic gastroparesis(DGP)is a prevalent complication of diabetes that impairs people's quality of life and places a significant financial burden on them.The gastrointestinal symptoms of DGP patients can be improved by several Traditional Chinese Medicine(TCM)decoctions that have been shown to be effective in treating the disease.There are still many unanswered questions regarding the identification of appropriate therapeutic agents for the treatment of DGP in clinical practice.AIM To analyze the efficacy of several TCM decoctions in the treatment of DGP using Bayesian network meta-analysis for reference.METHODS PubMed,EMBASE,Cochrane Library,Web of Science,China National Knowledge Infrastructure,The China Biology Medicine DVD,Wanfang,and CQVIP were searched from inception to September 17,2022,to collect randomized controlled trials(RCTs)about TCM decoctions for DGP.Clinical effects and symptom scores were the primary outcomes.Additionally,we assessed motilin(MOT),somatostatin(SS),gastrin(GAS),gastric emptying rate,gastric emptying time,and adverse drug events as secondary outcomes.RESULTS A total of 67 eligible RCTs involving 4790 DGP patients and 7 TCM decoctions were included.The results of network meta-analysis(NMA)and surface under the cumulative ranking curve showed that with western medicine(WM)as a common control,the Banxia Xiexin Decoction(BXXD)+WM was most effective in clinical effects and enhancing early satiety scores;the Simo decoction(SMD)+WM was most effective in improving nausea and vomiting scores and anorexia scores,bloating scores;the Chaishao Liujunzi Decoction(CSLJD)was most effective in MOT,the Zhishi Xiaopi Decoction(ZSXPD)was most effective in SS and upgrading emptying rate;the Jianpi Xiaozhi Decoction was most effective in GAS;the CSLJD+WM was most effective in improving gastric emptying time.CONCLUSION These NMA results suggest that the BXXD+WM and SMD+WM may be one of the potential optimal treatments.Due to various limitations,further large-sample,double-blind,multi-center randomized RCTs are needed.

Banxia Xiexin Decoction(半夏泻心汤)Treats Diabetic Gastroparesis through PLC-IP3-Ca^2+/NO-cGMP-PKG Signal Pathway

Objective To test the effect of Banxia Xiexin Decoction(半夏泻心汤,BXD)on the contraction and relaxation of gastric smooth muscle(SM)in diabetic gastroparesis(DGP)model rats,and to explore the mechanism of BXD in the prevention and treatment of DGP through experiments of signal pathway both in vivo and in vitro.Methods Sixty Sprague-Dawley rats were divided into 6 groups according to a random number table:control group,model group,high-,medium-and low-dose BXD groups(9.2,4.6 and 1.8 g/(kg·d),respectively),and domperidone group(10 mg/(kg·d)),10 rats per group.DGP model was established initially by a single intraperitoneal injection of streptozotocin(STZ),and was confirmed by recording gastric emptying,intestinal transport velocity and gastric myoelectric activity of rats after 2 months.Each group was treated with a corresponding drug for 4 weeks.The mRNA and protein expressions of phospholipase C(PLC),inositol triphosphate(IP3),neuronal nitric oxide synthase(nNOS),and cyclic guanosine monophosphate(cGMP)dependent protein kinase G(PKG)were detected by reverse transcription-polymerase chain reaction and Western blot,respectively,while nitric oxide(NO)and cGMP expressions were detected by enzyme-linked immunosorbent assay.Gastric tissues were obtained from rats for primary cell culture preparation.Gastric SM cells were treated with 0.8µmol/L of STZ or STZ plus 1,000,500 and 200µg/mL of BXD or STZ plus 2.5µmol/mL of domperidone for 24,48,72 or 96 h,respectively.The length of gastric SM cells and intracellular Ca^2+concentration([Ca^2+]i)before and after BXD treatment was measured.Results Compared with the model group,high-and medium-dose BXD and domperidone significantly increased the expressions of PLC,IP3,NO,nNOS,cGMP and PKG in rat’s gastric tissue(P<0.01).Gastric SM cells treated with BXD showed a time-and dose-dependent increase in cell viability(P<0.01).The treatment with high-and medium-dose BXD and domperidone inhibited the increase in gastric SM cells length and increased[Ca^2+]i compared with the model cells(P<0.01).Conclusions Treatment with high-and medium-dose BXD significantly attenuated STZ-induced experimental DGP in rats.The therapeutic effect of BXD on DGP rats might be associated with the PLC-IP3-Ca^2+/NO-cGMP-PKG signal pathway.

Analysis of the Relationship between Helicobacter pylori Infection and Diabetic Gastroparesis

Background： Whether Helicobacter pylori infection is associated with diabetic gastroparesis （DGP） is unclear. This study aimed to investigate the potential correlation between H. pylori infection and DGP. Methods： In this study, 163 patients with type 2 diabetes mellitus and 175 nondiabetic patients who were treated in our department were divided into DGP, simple diabetes, non-DGP （NDG）, and normal groups based on their conditions. The H. pyh）ri infection rate in each group was calculated. H. pylori eradication therapy was performed for patients with H. pylori infection in each group. The eradication rates were compared between the groups, and the improvements in gastroparesis-associated symptoms were compared before and after treatment in patients with DGP. Results： The tl. pylori infection rate was 74.6% in the DGP group, which was significantly higher than that in the simple diabetes （51.1%, P 〈 0.01）, NDG （57.7%, P 〈 0.05）, and normal groups （48.0%, P 〈 0.01）. With increased disease course, the incidence of DGP and the H. pylori infection rate gradually increased （P 〈 0.05）. In the DGP group, the incidences of upper abdominal pain and distention, early satiety, and anorexia were 75.5%, 66.0%, and 67.9%, respectively, before eradication treatment; and 43.4%, 35.8%, and 39.6%, respectively, after eradication treatment, and the difference was statistically significant （P 〈 0.01）. In patients with DGP with successful H. pylori eradication, the number of barium strips discharged after eradication was 5.9 ± 1.0, which was significantly larger than that before treatment （4.1 ± 0.7, P 〈 0.01）. In addition, the number of barium strips discharged was significantly larger in patients with DGP with successful H. pylori eradication than those with failed H. pylori eradication （P 〈 0.01 ）. Conclusions： DGP development might be associated with H. pylori infection. H. pylori eradication can effectively improve dyspepsia-associated symptoms and delayed gastric emptying in patients with DGP.

Delayed Postprandial Hypertriglyceridemia,Slow Gastrointestinal Transit and Possible Links Between Them in Alloxan-Induced Diabetic Mice

Both postprandial hypertriglyceridemia and diabetic gastroparesis are common dysfunctions af-fecting diabetes mellitus; however, whether diabetic gastroparesis has an influence on postprandial hypertriglyceridemia still remains undetermined. Delayed postprandial hypertriglyceridemia, diabetic gastroparesis, and the possible links between them were investigated using alloxan-induced diabetic mice. After the oral administration of olive oil, delayed and exaggerated postprandial hypertriglyceridemia and diabetic gastroparesis were markedly presented in alloxan-induced diabetic mice. Domperidone shortened the time of triglycerides (TG) peak levels in diabetic mice. After intraperitoneal and intraduodenal administration of olive oil, no delay of TG peak levels occurred in diabetic mice. Simultaneously, serum post-heparin lipoprotein lipase activities significantly decreased just at the time of prolonged and elevated TG peak levels resulting from diabetic gastroparesis, and further deteriorated postprandial hypertriglyceridemia in diabetic mice. The results indicate that diabetic gastroparesis can be one of the important reasons for delayed and exaggerated postprandial hypertriglyceridemia in diabetes mellitus.