BACKGROUND:The etiology of diabetic kidney disease is complex, and the role of lipoproteins and their lipid components in the development of the disease cannot be ignored. However, phospholipids are an essential component, and no Mendelian randomization studies have yet been conducted to examine potential causal associations between phospholipids and diabetic kidney disease.METHODS:Relevant exposure and outcome datasets were obtained through the GWAS public database. The exposure datasets included various phospholipids, including those in LDL, IDL, VLDL, and HDL. IVW methods were the primary analytical approach. The accuracy of the results was validated by conducting heterogeneity, MR pleiotropy, and F-statistic tests. MR-PRESSO analysis was utilized to identify and exclude outliers.RESULTS:Phospholipids in intermediate-density lipoprotein (OR: 0.8439; 95% CI: 0.7268-0.9798), phospholipids in large low- density lipoprotein (OR: 0.7913; 95% CI: 0.6703-0.9341), phospholipids in low- density lipoprotein (after removing outliers, OR: 0.788; 95% CI: 0.6698-0.9271), phospholipids in medium low- density lipoprotein (OR: 0.7682; 95% CI: 0.634-0.931), and phospholipids in small low-density lipoprotein (after removing outliers, OR: 0.8044; 95% CI: 0.6952-0.9309) were found to be protective factors.CONCLUSIONS:This study found that a higher proportion of phospholipids in intermediate-density lipoprotein and the various subfractions of low-density lipoprotein, including large LDL, medium LDL, and small LDL, is associated with a lower risk of developing diabetic kidney disease.

Objective: To explore the effects and the possible mechanism of electroacupuncture (EA) on diabetic bladder dysfunction (DBD) in streptozotocin-high fat diet (STZ-HFD) induced type 2 diabetes mellitus (T2DM) rats. Methods: The experiment was divided into Control, diabetic bladder dysfunction, electroacupuncture, and Sham electroacupuncture group. After 8 weeks of electroacupuncture intervention, the body mass, 24 h urine volume, intraperitoneal glucose tolerance test (IPGTT), and urodynamics were detected. After the wet weight of the bladder was detected, the hematoxylin-eosin (HE), Masson’s trichrome, and TUNEL were used to analyze histological changes. The PACAP38 expressions in the bladder were detected by Real-time PCR and Western blot. Results: Compared to the Control group, the bladder wet weight, 24 h urine volume, blood glucose, maximum bladder capacity, bladder compliance, bladder wall thickness, the smooth muscle/collagen ratio, and apoptosis rate of the diabetic bladder dysfunction group were significantly increased. Moreover, the body mass and leak point pressure were significantly reduced. Compared with the Sham electroacupuncture group, the bladder wet weight, maximum bladder capacity, bladder compliance, bladder wall thickness, and apoptosis rate of the electroacupuncture group were significantly reduced. In contrast, the leak point pressure was increased. The PACAP38 mRNA and PACAP38 protein expression of the diabetic bladder dysfunction group were significantly lower than the Control group, while electroacupuncture treatment could upregulate PACAP38 mRNA levels and PACAP38 protein expression of diabetic bladder dysfunction model rats. Conclusion: electroacupuncture could ameliorate bladder dysfunction in the diabetic bladder dysfunction model rats by reversing bladder remodeling, which might be mainly mediated by regulating the PACAP38 level.

BackgroundGlucose-dependent insulinotropic polypeptide (GIP) and GLP-1 are the main incretin hormones, and be responsible for the insulinotropic incretin effect. The addition of a GIP agonist to a GLP-1agonist has been hypothesized to significantly potentiate the weight-losing and glycemia control effect, which might offer a new therapeutic option in the treatment of type 2 diabetes. The current meta-analysis aims to synthesize evidence of primary efficacy and safety outcomes through clinically randomized controlled trials to evaluate integrated potency and signaling properties.MethodWe conducted comprehensive literature searches in Cochrane Library, Web of Science, Embase and PubMed for relevant literatures investigating the efficacy and/or safety of Tirzepatide published in the English as of May 30, 2023 was retrieved. We synthesized results using standardized mean differences (SMDs) and 95% confidence intervals (95 CIs) for continuous outcomes, and odds ratios (ORs) along with 95 Cis for dichotomous outcomes. All analyses were done using Revman version 5.3, STATA version 15.1 and the statistical package 'meta'.ResultsParticipants treated with weekly Tirzepatide achieved HbA1c and body weight target values significantly lower than any other comparator without clinically significant increase in the incidence of hypoglycemic events, serious and all-cause fatal adverse events. However, gastrointestinal adverse events and decreased appetite events were reported more frequently with Tirzepatide treatment than with placebo/controls.ConclusionThe Tirzepatide, a dual GIP/GLP-1 receptor co-agonist, for diabetes therapy has opened a new era on personalized glycemia control and weight loss in a safe manner with broad and promising clinical implications.

Background/AimsCurrently, glycemic variability has more deleterious effects than sustained hyperglycemia and is closely associated with acute and chronic complications of diabetes. Reducing glycemic excursion is becoming another vital goal of glycemic control in clinical practice. This study aimed to determine whether insulin degludec (IDeg) or insulin glargine (IGla) was more beneficial for reducing glycemic fluctuations.Materials and MethodsThis research was constructed according to the PRISMA guidelines. We searched eight databases and ClinicalTrials.gov from their inception to 30 November 2021. All randomized controlled trials comparing the efficacy of glucose variability between IDeg and IGla in diabetic patients were included.ResultsFourteen trials with 8,683 participants were included. In patients with T1DM, IDeg was associated with a lower mean (MD: −16.25, 95% CI −29.02 to −3.07, P = 0.01) and standard deviation (P = 0.03) compared to IGla in fasting blood glucose (FBG); in people with T2DM, IDeg was related to a lower mean of FBG versus insulin glargine 100 U/ml (IGla100) (P <0.001) and had a more extended time in the range (TIR) than IGla100 (SMD: 0.15, 95% CI 0.02 to 0.27, P = 0.02) but not longer than insulin glargine 300 U/ml (IGla300). Moreover, IDeg had a lower coefficient of variation of FBG than IGla (P = 0.0254). For other indicators of glycemic variability, namely, standard deviation of blood glucose for 24 h, the mean of 24-h blood glucose, mean amplitude of glycemic excursion, the coefficient of variation for 24 h, the mean of daily differences, area under the glucose curve, and M-value, no significant differences were identified between IDeg and IGla, regardless of T1DM or T2DM.ConclusionsBased on the current studies, there was comparable efficacy between IDeg and IGla from multiple aspects of glycemic variability, regardless of T1DM or T2DM. However, IDeg may be superior to IGla in reducing FBG variability in T1DM and T2DM. Nonetheless, due to the limitations of the original studies, it is still unclear whether IDeg is superior to both IGla100 and IGla300. In T2DM, IDeg had more extended TIR than IGla100 but not longer than IGla300. Additionally, more well-designed randomized controlled trials comparing IDeg with IGla300 for different indicators of glycemic variability are still warranted.Systematic Review RegistrationPROSPERO, CRD42021283203.

Background: Cinnamon is a spice used in cooking and in large quantities as a medical complement with hypoglycemic and lipid-lowering properties. The potential pharmacological mechanisms underlying cinnamon's anti-diabetic properties and its active ingredients have not been adequately determined. The current meta-analysis aims to systematically review the potential pharmacological mechanisms underlying the hypoglycemic and hypolipidemic efficacy of cinnamon administration and summarize clinical recommendations of cinnamon and its active ingredients. Method: Relevant randomized clinical trials (RCTs) were identified through a literature search that spanned the years January 2005 to April 2022. Retrieve electronic databases including Web of Science, PubMed, Embase, Medline, and the Cochrane Library. To obtain standardized mean differences (SMDs), continuous outcomes were pooled and 95 percent confidence intervals (CIs) were provided. Categorical outcomes were aggregated to calculate relative risks (RRs) and were accompanied by 95% CIs. Heterogeneity was measured using the Cochrane Q-test and I2 statistics, with a p < 0.05 considered as substantial heterogeneity. If I2 was less than 50%, a fixed effect model was employed; otherwise, a random effect model was used. Subgroup analyses and sensitivity analyses were performed to identify the origins of heterogeneity. Publication bias was retrieved by means of a funnel-plot analysis and Egger's test. The data were analyzed using revman (V.5.3) and stata (V.15) software packages. Results: These 16 RCTs included a total of 1,020 patients who were followed for a duration ranging from 40 days to 4 months. According to the current meta-analysis results, glycolipid levels in diabetic individuals who received cinnamon were significantly improved as compared to those who got placebo (All p < 0.05). An adverse effect was only detected in one patient. Conclusion: These findings imply that cinnamon has a significant influence on lipid and glucose metabolism regulation. An even more pronounced effect was observed in patients with HbA1c of 8%. The results of this study suggested that cinnamon may be utilized as hypoglycemic and lipid-lowering supplement in clinical settings with a guaranteed safety profile.Systematic Review Registration: [PROSPERO], identifier [CRD42022322735].

Background/AimOmega-3 fatty acids (OM3-FA), a promising treatment for high triglycerides, have gradually attracted public attention. However, some studies showed that their application presented tricky problems, like increasing low-density lipoprotein cholesterol (LDL-C) levels. This study aimed to systematically evaluate the effect of OM3-FA or their combination with statins on the lipid profile in patients with hypertriglyceridemia.Materials and methodsThis study followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA 2020) guidelines. PubMed, Embase, Web of science, and Cochrane library were searched up to May 15, 2022. The random-effects model was applied to calculate the mean difference (MD) and associated 95% confidence intervals (CI).ResultsThis meta-analysis included 32 studies with 15,903 subjects. When OM3-FA was used as monotherapy compared with placebo, it significantly decreased TG (MD: −39.81, 95% CI: −54.94 to −24.69; p < 0.001), TC (MD: −2.98, 95% CI: −5.72 to −0.25, p = 0.03), very low-density lipoprotein cholesterol (VLDL-C) (MD: −25.12, 95% CI: −37.09 to −13.14; p < 0.001), and non-high-density lipoprotein cholesterol (non-HDL-C) levels (MD: −5.42, 95% CI: −8.06 to−2.78; p < 0.001), and greatly increased LDL-C (MD: 9.10, 95% CI: 4.27 to 13.94; p < 0.001) and HDL levels (MD: 1.60, 95% CI: 0.06 to 3.15; p = 0.04). Regarding apolipoprotein B (Apo-B) and apolipoprotein AI (Apo-AI), no significant effect was identified. When OM3-FA was combined with statins, significant reductions were observed in the concentrations of TG (MD: −29.63, 95% CI: −36.24 to −23.02; p < 0.001), TC (MD: −6.87, 95% CI: −9.30 to −4.45, p < 0.001), VLDL-C (−20.13, 95% CI: −24.76 to −15.50; p < 0.001), non-HDL-C (MD: −8.71, 95% CI: −11.45 to −5.98; p < 0.001), Apo-B (MD: −3.50, 95% CI: −5.37 to −1.64; p < 0.001), and Apo-AI (MD: −2.01, 95% CI: −3.07 to −0.95; p < 0.001). However, the combined therapy did not exert significant changes on the levels of high-density lipoprotein cholesterol (HDL-C) and LDL-C compared to control group.ConclusionThe use of OM3-FA either as monotherapy or in combination with statins may potentially reduce the levels of TG, TC, VLDL-C, non-HDL-C, Apo-B, and Apo-AI while increasing the levels of LDL-C and HDL-C. Nevertheless, the effects of OM3-FA observed in this review should be interpreted with caution due to the high heterogeneity between the included studies.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022329552].

垂体腺苷酸环化酶激活肽(Pituitary adenylate cyclase activating polypeptide,PACAP)参与血管扩张、肾上腺素、糖皮质激素、胰岛素和胃酸的分泌,具有多种生物学功能,其在糖尿病及并发症神经源性膀胱(Diabetic neurogenic bladder,DNB)的发生发展具有重要意义.但目前PACAP与糖尿病的病因学关系及在调控DNB功能方面的特殊作用尚未完全阐明.而针刺对糖尿病并发症的作用机制研究是补充与替代医学长久以来的热点方向.因此,本文进行综述后提出针灸治疗DNB的始动环节可能是对PACAP表达的调控,推测PACAP、PKA和肌球蛋白系统(MLCK、MYPT1、MLC等)之间可以形成信号传导通路:PACAP→AC→cAMP→PKA→MLCK/MYPT1→MLC,从而调控逼尿肌收缩过程,最终改善膀胱功能.目前针刺治疗DNB尚无PACAP信号途径与肌球蛋白系统的实验研究,以期为今后的科学探索提供新的思路.

Background:Insulin regulates many aspects of brain function related to mild cognitive impairment (MCI) or dementia, which can be delivered to the brain center via intranasal (IN) devices. Some small, single-site studies indicated that intranasal insulin can enhance memory in patients with MCI or dementia. The pathophysiology of Alzheimer's disease (AD) and diabetes mellitus (DM) overlap, making insulin an attractive therapy for people suffering from MCI or dementia.Objective:The goal of the study is to evaluate the effectiveness of IN insulin on cognition in patients with MCI or dementia.Methods:We searched the electronic database for randomized controlled trials (RCTs) that verified the effects of insulin on patients with MCI or dementia.16 studies (899 patients) were identified.Results:The pooled standard mean difference (SMD) showed no significant difference between IN insulin and placebo groups; however, statistical results suggested a difference between study groups in the effects of ADCS-ADL; AD patients with APOE4 (-) also showed improved performance in verbal memory; other cognitions did not improve significantly.Conclusion:In view of IN insulin's promising potential, more researches should be conducted at a larger dose after proper selection of insulin types and patients.Systematic review registration:http://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022353546.

Diabetic nephropathy is one of the major causes of end-stage renal disease, and the pathogenesis of the disease has not been elucidated. While the immunoinflammatory response plays an essential role in the progression of diabetic nephropathy. Glomerular expression dataset in diabetic nephropathy was obtained from the GEO database. Differentially expressed genes were identified and functional enrichment analysis was performed to find genes associated with immunity and inflammation from them. The hub genes of immunoinflammatory were identified using MCODE after establishing the PPI network and gene expression was verified with diabetic nephropathy model rats. Xcell was used to assign immune cells to diabetic nephropathy glomerular samples to detect significant changes in immune cells and to analyze correlations with the hub gene. We found 120 DEGs associated with immunity and inflammation, Ribonuclease 6 was the Hub gene with the highest MCODE score. Xcell analysis revealed significant changes of immune cells in DN glomeruli, including upregulated Activated DCs, Conventional DCs, CD4+ Tem, Epithelial cells, Macrophages, Macrophages M1, and Memory B-cells. RNase6 expression showed the highest positive correlation with Macrophages M1, Activated DCs, and Conventional DCs. We verified through the Nephroseq v5 database that RNase6 expression was elevated in DN glomeruli and negatively correlated with glomerular filtration rate. Animal studies revealed that the kidney of DN model rats showed increased RNase6 expression together with inflammatory factor TNF-alpha and chemokine MCP-1. Our study identified RNase6 as a diagnostic and prognostic biomarker for diabetic nephropathy and found that it may play an essential role in the immunoinflammatory damage to the glomerulus.

Background and rationale: Obesity is a metabolic condition brought on by the interplay of hereditary and environmental factors, making it one of the most common diseases in the world. Insulin resistance (IR) and obesity have a close connection and can both be advantageous. One of the main methods of epigenetic regulation is DNA methylation modification. Studies have demonstrated over the past few years that DNA methylation is crucial to the emergence of obesity and DNA methylation can lead to IR. Adipose tissue participates in the physiopathological processes of obesity and IR and functions as an endocrine organ controlling the body’s balanced metabolism, thus, adipose tissue-associated gene DNA methylation affects the development of obesity and IR by influencing the function of adipose tissue. Hence, an explanation of current research on DNA methylation, IR, and obesity, following the most recent developments, exploring changes in DNA methylation in different types of adipose tissue in insulin-resistant patients and obese patients may enable the identification of novel targets in clinical obesity prevention and treatment. Method and analysis: The following electronic bibliographic databases will be searched from inception for peer-reviewed original research published: MEDLINE (through PubMed), Scopus, and EMBASE. Cochrane Library, Cochrane Clinical Trials Registry, the National Institutes for Health Clinical Trials Registry, and the WHO International Clinical Trials Registry Platform from inception to December 31, 2021 will be conducted. Systematic reviews will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. The development of search strategies will make use of medical issue phrases and keywords associated with DNA methylation, Adipose tissue DNA methylation, obesity, and IR. Identified citations will be independently reviewed by two authors to determine eligibility at the title and abstract level, and then at the full text and data extraction phases. Disagreements and conflicts will be resolved through discussion with a third author. Two authors will extract the necessary data from the included studies independently, and The Cochrane Risk of Bias Assessment Tool will be used to assess the bias of randomized controlled studies, and the Newcastle–Ottawa scale for nonrandomized controlled studies. If the interventions and outcomes evaluated are sufficiently homogeneous, results from subgroups of studies will be pooled together in a meta-analysis.

BackgroundThe previous studies of our research group indicate that the weakening of mitochondrial autophagy function is the key mechanism of obesityinduced insulin resistance, and Mitochondrial autophagy mediated by PINK1/Parkin pathway can reverse mitochondrial dysfunction.Recently, we found that FOXO3a, as an upstream regulator of PINK1, has been found to play a key role in regulating mitochondrial autophagy.However,FOXO3a is regulated by deacetylation. ObjectiveTo explore whether Modified Dachaihu Decoction can regulate liver mitochondrial autophagy mediated by the PINK1/Parkin signal pathway by regulating the expression of FOXO3a acetylation. MethodsEstablish cell models.They were divided into three groups (blank control group, model control group, and Modified Dachaihu Decoction group).The supernatant was extracted and determined by a biochemical method; The insulin sensitivity of each group was evaluated by a 3H-D-glucose incorporation test; MDA and TNFα、IL-6 in the supernatant were detected by ELISA level; The level of SOD was detected by spectrophotometry.The expression of mitochondrial autophagy-related proteins and the expression of FOXO3a and ace-FOXO3a were measured by Western blot. ResultsCompared with the model control group, the Modified Dachaihu Decoction group increased insulin sensitivity, and The levels of TNF-α、IL-6, and MDA decreased, while the activity of SOD increased (P < 0.05).Western blot showed that compared with the model control group, the expression of mitochondrial autophagy-related proteins and FOXO3a in the Modified Dachaihu Decoction group increased, and the expression of ace-FOXO3a decreased (P < 0.05). ConclusionsWe speculate that in this experiment, Modified Dachaihu Decoction may regulate mitochondrial autophagy mediated by PINK1/ Parkin signal pathway by downregulating the expression of FOXO3a acetylation, to reduce Hepatic Insulin Resistance in Obesity.