BackgroundInsulin 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.ObjectiveThe goal of the study is to evaluate the effectiveness of IN insulin on cognition in patients with MCI or dementia.MethodsWe 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.ResultsThe 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.ConclusionIn 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 registrationhttp://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022353546.

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/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].

Background: Diabetic kidney disease (DKD) is a chronic progressive disorder which is a leading cause of chronic kidney disease (CKD). As an important pathogenesis of DKD, the overproduction of reactive oxygen species (ROS) and the inflammatory response have been considered central mediators in the progression of DKD. Herbal products are increasingly being applied as antioxidants and anti-inflammatory agents. Of those, the effect of hydroxyl safflower yellow A (HSYA) on oxidative stress and inflammatory reactions has gradually been investigated for DKD treatment, which may provide therapies for DKD with new insights and promote its application in clinical practice.Methods: We searched CNKI, the Chinese Biomedical Literature Database, the Wanfang Database, PubMed, and Embase from the establishment date of the database to 22 April 2022. The included literature in our study was randomized controlled trials (RCTs) using HSYA to treat DKD. We performed a meta-analysis by calculating the standard mean difference (SMD) with a 95% confidence interval (CI). The inverse-variance method with a random effect was used in our meta-analysis using Stata software and RevMan software.Results: A total of 31 articles with 31 groups containing a total of 2487 participants were included in this meta-analysis. The pooled results showed a statistical improvement in the following measurements: fasting blood glucose (FBG), postprandial blood glucose (PBG), blood urea nitrogen (BUN), urinary albumin excretion rates (UAER), serum creatinine (SCR), hypersensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), fasting insulin (FINS), total cholesterol (TC), triglycerides (TGs), hemoglobin A1c (HbA1C), homeostasis model assessment insulin resistance (HOMA-IR), and malondialdehyde (MDA).Conclusion: HSYA can effectively treat DKD by inhibiting inflammatory reactions and oxidative stress, decreasing blood glucose and blood lipids, and improving renal function indices. However, more RCTs are still needed in the future to further demonstrate the effect of HSYA on biomarkers of oxidative stress and inflammatory reactions in patients with DKD due to the low quality and small sample size of the literature included in this study.Systematic Review Registration: PROSPERO: CRD 42021235689