This study is designed to investigate the effect of artemether on type 2 diabetic db/db mice. The experiments consisted of three groups: normal control (NC, db/+, 1% methylcellulose, intragastric administration), diabetic control (DM, db/db, 1% methylcellulose, intragastric administration), and artemether treated (artemether, db/db, 200 mg/kg of artemether, intragastric administration). The treatment lasted for two weeks. The food intake, body weight, and fasting blood glucose of mice were measured every three days. At the start and end of the experiment, the intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (IPITT) were performed. We determined the serum insulin and glucagon levels by ELISA kits and calculated insulin resistance index (HOME-IR). HE staining was used to observe the morphologies of pancreas and liver in mice. The damage of pancreatic beta cells was evaluated by TUNEL staining and immunofluorescence. We found the following: (1) compared with the DM group, the food intake and weight increase rate of artemether group significantly reduced (P < 0.05); (2) compared with pretreatment, artemether significantly reduced the fasting blood glucose levels, and the areas under the curves (AUCs) of IPGTT were decreased significantly, increasing the tolerance to glucose of db/db mice. (P < 0.05); (3) artemether improved hyperinsulinemia and decreased the AUCs of IPITT and HOME-IR, increasing the insulin sensitivity of db/db mice. (4) Artemether significantly ameliorated islet vacuolar degeneration and hepatic steatosis in db/db mice. (5) Artemether reduced the apoptosis of pancreatic beta cells and increased insulin secretion in db/db mice compared with DM group (P < 0.05). Our results indicated that artemether significantly improved glucose homeostasis and insulin resistance and had the potential activity to prevent obesity, reduced the severity of fatty liver, and protected pancreatic beta cells, promising to treat type 2 diabetes.

Background: Artemether, a commonly used artemisinin derivative, has been shown to possess potential antidiabetic activities. However, only limited information is available on the mechanisms of artemether in type 2 diabetes. Therefore, in this study, we examined some of the possible mechanisms of artemether (ATM) upon glycolipid metabolism in the db/db mouse model of diabetes. Materials and Methods: Male C57BL/KsJ-db/db and C57BL/KsJ-db/+ mice at 4 weeks of age were divided into four groups (N=6/group): ( 1) NC (normal controldb/+ mice, 1% methylcellulose, intragastric administration), ( 2) DM (diabetic modeldb/db mice, 1% methylcellulose, intragastric administration), (3) ATM 100 (DM + 100 mg/kg of artemether) and ( 4) ATM 200 (DM + 200 mg/kg of artemether). A number of assays related to diabetes were then performed following a 4-week period of these treatments.Results: Artemether at both doses significantly reduced rates of weight gain and fasting blood glucose levels, improved islet function and insulin resistance and reduced serum lipid levels to varying degrees in db/db mice. Artemether exerted a positive effect on islet vacuolar degeneration and hepatic steatosis, and increased expressions of AMP-activated protein kinase, glucose transporter 4 and Insulin receptor β protein in the liver of these db/db mice. With the use of liver protein chip detection, we found that artemether significantly improved the immune microenvironment, downregulated the expression of inflammatory factors and activated the cytokine-mediated signaling pathway through cytokine-cytokine receptor interactions. Conclusion:Artemether may regulate glycolipid metabolism in db/db mice by improving the immune microenvironment. The results of this study provide important new information that can serve as the foundation for future research into the use of artemether as a means to improve glycolipid metabolism.

Objective. Cardiovascular autonomic neuropathy (CAN) is a common but severe problem of diabetes, which a timely diagnosis may have important clinical implications. This study was carried out to investigate the diagnostic performance of Composite Autonomic Symptom Score 31 (COMPASS 31) combined with heart rate variability (HRV) for cardiovascular autonomic neuropathy in type 2 diabetes. Methods. A total of 103 hospitalized subjects with type 2 diabetes were recruited in the study. All cases received clinical data collection, laboratory examination, and related complication examinations. Cardiovascular autonomic function was assessed using CARTs, COMPASS 31, and HRV analyses. A score of at least 2 based on CARTs was defined as CAN. Results. Of the 103 subjects with type 2 diabetes, 41.8% were diagnosed with confirmed CAN. Participants with CAN had considerably higher COMPASS 31 scores. The CAN group showed a significant decrease in all HRV indices. COMPASS 31 scores and HRV indices were closely correlated with CARTs ( P < 0.05 ). Receiver operating characteristics (ROC) curve results showed that COMPASS 31 score identified CAN with an AUC value of 0.816, while the AUC values of HRV indices were 0.648 to 0.919, among which SDNN and LF had the best diagnostic value, with the AUC values of 0.919 and 0.865, respectively. When combining COMPASS 31 score with SDNN and LF, the AUC value increased to 0.958, with a sensitivity of 90.7% and a specificity of 86.7%. Conclusions. The combination of COMPASS 31 and HRV could improve the diagnostic performance of CAN in type 2 diabetes, which might be conducive to the diagnosis of CAN.

Aim: To evaluate henagliflozin, a novel sodium-glucose co-transporter-2 inhibitor, as monotherapy in patients with type 2 diabetes and inadequate glycaemic control with diet and exercise.Materials and Methods: This multicentre trial included a 24-week, randomized, double-blind, placebo-controlled period, followed by a 28-week extension period.Four hundred and sixty-eight patients with an HbA1c of 7.0%-10.5% were randomly assigned (1:1:1) to receive once-daily placebo, or 5 or 10 mg henagliflozin. After 24 weeks, patients on placebo were switched to 5 or 10 mg henagliflozin, and patients on henagliflozin maintained the initial therapy. The primary endpoint was the change in HbA1c from baseline after 24 weeks.Results: At Week 24, the placebo-adjusted least squares (LS) mean changes from baseline in HbA1c were −0.91% (95% CI: −1.11% to −0.72%; P < .001) and −0.94% (−1.13% to −0.75%; P < .001) with henagliflozin 5 and 10 mg, respectively; the placebo-adjusted LS mean changes were −1.3 (−1.8 to −0.9) and −1.5 (−2.0 to −1.1) kg in body weight, and −5.1 (−7.2 to −3.0) and −4.4 (−6.5 to −2.3) mmHg in systolic blood pressure (all P < .05). The trends of these improvements were sustained for an additional 28 weeks. Adverse events occurred in 81.0%, 78.9% and 78.9% of patients in the placebo, henagliflozin 5 and 10 mg groups, respectively. No diabetic ketoacidosis or major episodes of hypoglycaemia occurred.Conclusions: Henagliflozin 5 mg and 10 mg as monotherapy provided effective glycaemic control, reduced body weight and blood pressure, and was generally well tolerated.

Aim: To evaluate the efficacy and safety of henagliflozin in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin.Material and Methods: This multicentre phase 3 trial included a 24-week randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. Patients with a glycated haemoglobin (HbA1c) level of 7.0% (53 mmol/mol) to 10.5% (91 mmol/mol) were randomized and treated with once-daily placebo (n = 161), henagliflozin 5 mg (n = 162), or henagliflozin 10 mg (n = 160). After 24 weeks, patients on placebo were switched to 5 mg or 10 mg henagliflozin for the additional 28-week treatment, and patients on henagliflozin during 24-week treatment period maintained this initial therapy. The primary endpoint was change in HbA1c from baseline to Week 24.Results: At Week 24, the least squares mean HbA1c changes versus placebo from baseline were − 0.76% (−8.3 mmol/mol) and − 0.80% (−8.7 mmol/mol) for henagliflozin 5 and 10 mg, respectively (all P < 0.0001). Compared with the placebo group, both doses of henagliflozin lowered fasting plasma glucose, 2-hour postprandial plasma glucose, body weight and blood pressure, and increased the proportions of patients achieving HbA1c <7.0% (53 mmol/mol) at Week 24. The trends in these improvements were sustained over an additional 28 weeks. Slightly higher proportions of ketosis and presence of urine ketone bodies were observed in patients treated with henagliflozin compared to placebo at Week 24. No diabetic ketoacidosis or episodes of severe hypoglycaemia were reported.Conclusions: Henagliflozin 5 mg or 10 mg as add-on therapy to metformin provided a new therapeutic option for the treatment of T2DM patients who have inadequate glycaemic control with metformin alone, and was generally well tolerated.