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Background: Asians bear a heavier burden of chronic kidney disease (CKD), a common comorbidity of type 2 diabetes mellitus (T2DM), than non-Asians. Nonsteroidal mineralocorticoid receptor antagonists (MRAs) have garnered attention for their potential advantages in renal outcomes. Nevertheless, the impact on diverse ethnic groups remains unknown., Methods: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, and clinical trial registries were searched through August 2023 with the following keywords: nonsteroidal MRAs (finerenone, apararenone, esaxerenone, AZD9977, KBP-5074), CKD, T2DM, and randomized controlled trial (RCT). A random effects model was used to calculate overall effect sizes., Results: Seven RCTs with 14 997 participants were enrolled. Nonsteroidal MRAs reduced urinary albumin to creatinine ratio (UACR) significantly more in Asians than non-Asians: (weighted mean difference [WMD], -0.59, 95% CI, -0.73 to -0.45, p < .01) vs (WMD, -0.29, 95% CI, -0.32 to -0.27, p < .01), respectively. The average decline of estimated glomerular filtration rate (eGFR) was similar in Asians and non-Asians (p > .05). Regarding systolic blood pressure (SBP), nonsteroidal MRAs had a better antihypertension performance in Asians (WMD, -5.12, 95% CI, -5.84 to -4.41, p < .01) compared to non-Asians (WMD, -3.64, 95% CI, -4.38 to -2.89, p < .01). A higher incidence of hyperkalemia and eGFR decrease ≥30% was found in Asians than non-Asians (p < .01)., Conclusions: Nonsteroidal MRAs exhibited significant renal benefits by decreasing UACR and lowering SBP in Asian than that of non-Asian patients with CKD and T2DM, without increase of adverse events except hyperkalemia and eGFR decrease ≥30%., (© 2024 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Type 2 diabetes mellitus (T2DM) is a common comorbidity in patients with chronic obstructive pulmonary disease (COPD) and has been associated with an increased risk of mortality in this population., Purpose: This study was designed to investigate the predictive factors of diabetes awareness (DA), including diabetes knowledge (DK), and diabetes care behaviors (DCB) among older people with both COPD and T2DM., Methods: This was a cross-sectional descriptive correlation study. One hundred thirty-three older-age patients with COPD comorbid with T2DM receiving treatment at a chest hospital were enrolled as participants. Both DK and DCB were utilized to measure DA. The Diabetes Knowledge Questionnaire was utilized to measure DK, and the Summary of Diabetes Self-Care Activities was used to evaluate DCB., Results: The average glycated hemoglobin (HbA1c) was 7.68% ( SD = 1.55%), with 74 (55.6%) participants having a level > 7%. The average DA was 46.46% ( SD = 13.34%), the average DK was 53.42% ( SD = 18.91%), and the average DCB was 39.50% ( SD = 16.66%). In terms of demographic variables, age, diabetes education, diabetes shared care, and HbA1c were all significantly associated with DA, DK, and DCB (all p s < .05). The overall variance in DA was significantly explained by diabetes education and HbA1c (all p s < .05). The overall variance in DK was significantly explained by age, diabetes education, and HbA1c. The overall variance in DCB was significantly explained by diabetes education and HbA1c (all p s < .05)., Conclusions/implications for Practice: Our study findings indicate that older adult patients with COPD comorbid with T2DM are at elevated risks of poor glycemic control and low DA. Healthcare professionals should be aware of these issues and develop appropriate DA plans to prevent poor glycemic control in this population. Providing accurate information on diabetes to older adults with COPD comorbid with T2DM is important to improving their DK and promoting better DCB., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Mazdutide is a once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist. We evaluated the efficacy and safety of 24-week treatment of mazdutide up to 6 mg in Chinese overweight adults or adults with obesity, as an interim analysis of a randomised, two-part (low doses up to 6 mg and high dose of 9 mg), double-blind, placebo-controlled phase 2 trial (ClinicalTrials.gov, NCT04904913). Overweight adults (body-mass index [BMI] ≥24 kg/m 2 ) accompanied by hyperphagia and/or at least one obesity-related comorbidity or adults with obesity (BMI ≥ 28 kg/m 2 ) were randomly assigned (3:1:3:1:3:1) to once-weekly mazdutide 3 mg, 4.5 mg, 6 mg or matching placebo at 20 hospitals in China. The primary endpoint was the percentage change from baseline to week 24 in body weight. A total of 248 participants were randomised to mazdutide 3 mg (n = 62), 4.5 mg (n = 63), 6 mg (n = 61) or placebo (n = 62). The mean percentage changes from baseline to week 24 in body weight were -6.7% (SE 0.7) with mazdutide 3 mg, -10.4% (0.7) with 4.5 mg, -11.3% (0.7) with 6 mg and 1.0% (0.7) with placebo, with treatment difference versus placebo ranging from -7.7% to -12.3% (all p < 0.0001). All mazdutide doses were well tolerated and the most common adverse events included diarrhoea, nausea and upper respiratory tract infection. In summary, in Chinese overweight adults or adults with obesity, 24-week treatment with mazdutide up to 6 mg was safe and led to robust and clinically meaningful body weight reduction., (© 2023. The Author(s).)

Aims: Diabetic kidney disease (DKD) is a severe microvascular complication frequently associated with type 1 and type 2 diabetes mellitus. The objective of this work was to evaluate the relevance of PI3K/Akt pathway polymorphisms and DKD susceptibility by a meta-analysis., Methods: Case-control studies related to the relationship between PI3K/Akt pathway polymorphisms and DKD risk were searched from Pubmed, Embase, Cochrane Library, SINOMED, CNKI, and Wanfang databases. Statistical analysis and heterogeneity test were conducted by Review Manager 5.4., Results: Totally, 52 eligible studies were enrolled, including seven single nucleotide polymorphisms (SNPs) for four genes in the PI3K/AKT pathway (GNB3: rs5443; eNOS: rs1799983, rs869109213, rs2070744; IL-6: rs1800795, rs1800796; TNFα: rs1800629). The "M" allele of eNOS rs1799983 was related to the increased risk of DKD under random effects model, especially in Asian population (Overall:M vs. W: I 2  = 75%, OR = 1.29, 95%CI 1.07-1.56; MM + WM vs. WW: I 2  = 75%, OR = 1.50, 95%CI 1.21-1.86). The "M" allele of eNOS rs869109213 was implicated with higher prevalence of DKD under random effects model, especially in Asian population (Overall:M vs. W: I 2  = 63%, OR = 1.43, 95%CI 1.22-1.68; MM + WM vs. WW: I 2  = 50%, OR = 1.36, 95%CI 1.16-1.58; MM vs. WM + WW: I 2  = 59%, OR = 2.20, 95%CI 1.41-3.43). The "M" allele of eNOS rs2070744 was implicated with higher prevalence of DKD under random effects model, especially in Indian population (Overall: M vs. W: I 2  = 47%, OR = 1.35, 95%CI 1.15-1.59; MM + WM vs. WW: I 2  = 45%, OR = 1.32, 95%CI 1.07-1.62; MM vs. WM + WW: I 2  = 65%, OR = 2.29, 95%CI 1.39-3.77). The "M" allele of IL-6 rs1800796 was predominately associated with higher DKD risks under random effects model, especially in Asian population (Overall: M versus W: I 2  = 23%, OR = 1.49, 95%CI 1.21-1.84; MM + WM vs. WW: I 2  = 1%, OR = 1.43, 95%CI 1.15-1.77; MM + WM vs. WW: I 2  = 71%, OR = 2.77, 95%CI 1.09-7.06)., Conclusions: This meta-analysis indicated that polymorphisms in the PI3K/Akt pathway in eNOS rs1799983, rs869109213, rs2070744, and IL-6 rs1800796 were related to the increased risk of DKD., (© 2023 The Authors. IUBMB Life published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

Aim: To evaluate the efficacy and safety of janagliflozin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin monotherapy., Materials 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 (N = 421) with HbA1c of 7.0% or higher and 10.5% or less were randomized (1:1:1) to receive once-daily placebo, janagliflozin 25 or 50 mg. After the 24-week treatment period, patients on placebo were re-randomized (1:1) to janagliflozin 25 or 50 mg for the additional 28-week treatment, whereas patients on janagliflozin maintained the same therapy. The primary endpoint was the change from baseline in HbA1c to week 24., Results: At week 24, the placebo-adjusted least squares mean changes of HbA1c were -0.58% and -0.58% with janagliflozin 25 and 50 mg, respectively (P < .0001 for both). The proportion of patients achieving HbA1c less than 7.0% was higher with janagliflozin 25 and 50 mg compared with placebo (41.8%, 41.7% and 28.0%, respectively). Both janagliflozin doses provided significant reductions in fasting plasma glucose, 2-hour postprandial glucose, body weight and systolic blood pressure, and improvements in high-density lipoprotein cholesterol and insulin sensitivity compared with placebo (P < .05 for all). The trends in improvement of these variables were retained during the 28-week extension period. No severe hypoglycaemia occurred throughout the whole 52-week treatment., Conclusions: Janagliflozin 25 or 50 mg once-daily added to metformin therapy significantly improved glycaemic control, reduced body weight and systolic blood pressure, improved high-density lipoprotein cholesterol and insulin sensitivity, and was generally well-tolerated by Chinese T2D patients who had poor glycaemic control with metformin monotherapy., (© 2022 John Wiley & Sons Ltd.)

Objectives: The progressive impairment of β-cell function results in prolonged deterioration in patients with type 2 diabetes mellitus (T2DM). Interestingly, the finding on pancreatitis secondary to renal injury suggests that potential communication exists between kidney and pancreas. Therefore, we aimed to investigate cell division cycle 42 (Cdc42)-mediated podocyte apoptosis and its effect on insulin secretion in islet β-cells., Methods: Type 2 diabetic nephropathy mouse models were established to identify the expression of Cdc42 in podocytes by immunohistochemistry. An in vitro co-culture of mouse podocyte MPC5 and β-TC6 cells was preliminarily established. Subsequently, podocyte apoptosis induced by high glucose and Cdc42 was detected by TUNEL staining and western blotting. In addition, the JNK pathway was examined to determine the mechanism of apoptosis in MPC5 cells. Finally, insulin secretion and expression in β-TC6 cells as well as malondialdehyde (MDA) and superoxide dismutase (SOD) levels in both cell types were examined after the regulation of Cdc42 in MPC5 cells., Results: Cdc42 was highly expressed in the podocytes of diabetic nephropathy mice. Exposure to 25 mM glucose for 48 h induced a significant upregulation of Cdc42, Bax, and cleaved caspase-3 as well as a decreased Bcl-2 expression. In addition, marked apoptosis of MPC5 cells was observed compared to normal glucose treatment. After transfection with Cdc42 plasmid, apoptosis of MPC5 cells was enhanced with an increased expression of p-JNK, whereas inhibition of Cdc42 significantly alleviated podocyte apoptosis accompanied by a downregulation of p-JNK. The glucose-stimulated insulin secretion level of β-TC6 cells decreased after the upregulation of Cdc42 in MPC5 cells. Immunofluorescence staining for insulin showed that co-culture with MPC5 cells carrying the Cdc42 plasmid significantly reduced insulin expression, whereas inhibition of Cdc42 in MPC5 cells alleviated the above-mentioned abnormality of β-TC6 cells. The expression of Cdc42 and p-p38 in β-TC6 cells increased following the upregulation of Cdc42 in MPC5 cells; this was concurrent with augmented MDA levels and decreased SOD activity. The opposite result was observed for Cdc42 knockdown in MPC5 cells., Conclusions: Cdc42 in podocytes plays a crucial role in insulin secretion by β-cells, which may provide a new therapeutic target to prevent the vicious cycle of β-cell dysfunction in T2DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiang, Xu, Yao, Zhang, Li, Zhang, Xie, Xing, Zhang, Zhou, Liao and Dong.)

Improving glucose sensitivity remains an unmet medical need in treating type 2 diabetes (T2D). Dorzagliatin is a dual-acting, orally bioavailable glucokinase activator that enhances glucokinase activity in a glucose-dependent manner, improves glucose-stimulated insulin secretion and demonstrates effects on glycemic control in patients with T2D. We report the findings of a randomized, double-blind, placebo-controlled phase 3 clinical trial to evaluate the efficacy and safety of dorzagliatin in patients with T2D. Eligible drug-naïve patients with T2D (n = 463) were randomly assigned to the dorzagliatin or placebo group at a ratio of 2:1 for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin from baseline to week 24. Safety was assessed throughout the trial. At week 24, the least-squares mean change in glycated hemoglobin from baseline (95% confidence interval) was -1.07% (-1.19%, -0.95%) in the dorzagliatin group and -0.50% (-0.68%, -0.32%) in the placebo group (estimated treatment difference, -0.57%; 95% confidence interval: -0.79%, -0.36%; P < 0.001). The incidence of adverse events was similar between the two groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin group. In summary, dorzagliatin improved glycemic control in drug-naïve patients with T2D and showed a good tolerability and safety profile., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Aims: To investigate the clinical features and mitochondrial mutations for maternally inherited diabetes and deafness., Methods: PubMed, Embase, Medline, Web of Science, the China National Knowledge Infrastructure, and Wanfang were searched with the following search terms: "Maternally inherited diabetes and deafness" OR "MIDD" OR "Mitochondrial diabetes". The mutations and clinical features were analyzed. Correlation between the heteroplasmy levels of the m.3243A>G mutation in the peripheral blood and age at the onset of diabetes was conducted by Spearman test. The significance level was set as p < 0.05. Statistical analysis was performed using the Statistical Package for the Social Sciences version 26 for Windows., Results: Totally 161 patients with 21 different mitochondrial mutations were enrolled. The most common mutation was the m.3243A>G mutation in 136 cases. Of 142 patients, 120 (84.51%) had family histories of diabetes or hearing loss. Hearing loss presented in 85.71% of the patients with mitochondrial mutations. Central nervous system diseases were found in 29.19%, myopathy in 22.98%, oculopathy in 23.60%, cardiac disease in 23.60%, and nephropathy in 13.66% of the patients. Forty-two of 101 (41.58%) patients were underweight. A significant negative correlation was found between the heteroplasmy levels of the m.3243A>G mutation in the peripheral blood and age at the onset of diabetes., Conclusions: The young onset of diabetes with low or normal BMI, maternal inheritance, and presence of impairments of multiple systems should prompt a genetic testing in order to differentiate MIDD from other types of diabetes earlier., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Xu, Xu, Cui, Jiang, Dong and Liao.)

Gliquidone was suggested to exert hypoglycemic effect through enhancing hepatic insulin sensitivity. However, inadequate in vivo evidences make this statement controversial. The aim of the present study was to clarify the insulin-sensitizer role of gliquidone in liver and muscle, so as to confirm its extra-pancreatic effects in vivo. TALEN technique was used to create Sur1 knockout (Sur1 -/- ) rats. Diabetic Sur1 -/- rat models were established by high-fat diet combined with streptozotocin, and which were randomly divided into three groups: gliquidone, metformin and saline, treated for 8 weeks. Fasting blood glucose (FBG) and body mass were tested each week. IPGTT, IPITT and hyperinsulinemic-euglycemic clamp tests were used to evaluate glucose tolerance and insulin sensitivity, respectively. Key mediators of glucose metabolism in liver and skeletal muscle and the activity of AKT and AMPK in these tissues were further analyzed. We found that gliquidone decreased FBG and increased insulin sensitivity without increasing insulin secretion in diabetic Sur1 -/- rats. Further exploration implied that gliquidone mainly increased hepatic glycogen storage and decreased gluconeogenesis, which were accompanied with activation of AKT, but not enhanced muscle GLUT4 expression. However, both these effects were still weaker than that of metformin. These results suggested that gliquidone could exerts an extra-pancreatic hypoglycemic effect by improving insulin sensitivity, which might be largely attributes to its additional insulin sensitizer role in hepatic glucose metabolism., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aims: To investigate the efficacy and safety of SGLT-2 inhibitors as an add-on treatment for metformin between Asian and non-Asian T2DM., Methods: A systematic literature search of PubMed, EMBASE, and the Cochrane Library was performed through August 2020 with the following keywords: Sodium-Glucose Transporter 2 Inhibitors, Sodium Glucose Transporter 2 Inhibitors, SGLT2 inhibitor, SGLT-2 inhibitors, type 2 diabetes, and randomized controlled trials. Double-blinded RCTs comparing SGLT-2 inhibitors as an add-on treatment for metformin and metformin monotherapy in adults with type 2 diabetes were included. A random effects model was used to calculate overall effect sizes., Results: 5 RCTs with 1193 Asian patients and 7 RCTs with 2098 non-Asian patients were investigated. The improvement in HbA1c and fasting blood glucose in the Asian patients (WMD, -0.73%; 95% CI, -1.01% to -0.46%, p < 0.01; WMD, -1.51; 95% CI, -1.81 to -1.21, p < 0.01, respectively) were both significantly better than in the non-Asians (WMD, -0.45%; 95% CI, -0.62% to -0.29%, p < 0.01; WMD, -1.03; 95% CI, -1.27 to -0.78, p < 0.01, respectively). The effect of weight loss was similar in the non-Asian patients and Asian patients. There was little difference in the improvement of systolic blood pressure between them. The risk of serious adverse events was not significantly increased between the Asian and non-Asian patients., Conclusion: SGLT-2 inhibitors as an add-on treatment for metformin are more efficacious in East Asian T2DM patients than in non-Asian T2DM patients without an additional risk of severe adverse events.

Approximately 35% of patients fail to attain ideal initial blood glucose control under metformin monotherapy. The objective of this observational study is to simulate the optimal protocol of metformin according to the different renal function.The population pharmacokinetics of metformin was performed in 125 subjects with type 2 diabetes mellitus. Plasma concentrations of metformin were quantified by high-performance liquid chromatography. A population pharmacokinetic model of metformin was developed using NONMEN (version 7.2, Icon Development Solutions, USA). Monte Carlo simulation was used to simulate the concentration-time profiles for doses of metformin for 1000 times at different stages of renal function.The mean population pharmacokinetic parameters were apparent clearance 53.0 L/h, apparent volume of distribution 438 L, absorption rate constant 1.4 hour and lag-time 0.91 hour. Covariate analyses revealed that estimated glomerular filtration rate (eGFR) and bodyweight as individual factors influencing the apparent oral clearance: CL/F = 53.0 × ( bodyweight/75) × (eGFR/102.5)EXP(0.1797). The results of the simulation showed that patients should be prescribed metformin 2550 mg/d (t.i.d.) vs 3000 mg/d (b.i.d.) as the minimum doses for patients with augmented renal clearance.eGFR had a significant impact on metformin pharmacokinetics. Patients administered metformin twice a day require higher total daily doses than those with a regimen of 3 times a day at each stage of kidney function.

The aim of the study was to evaluate the remission rate with short-term premixed insulin therapy in newly diagnosed type 2 diabetes outpatients and investigate predictors contributing to the remission rate. A 5-year prospective study was conducted with a total of 170 patients enrolled. Patients were treated with premixed insulin monotherapy or insulin in combination with one or two oral drugs. After glucose levels were well controlled, insulin and oral drugs were discontinued in a stepwise manner. The prolonged and partial remission rates were calculated and the possible factors contributing to remission were also analyzed. A total of 164 subjects completed the research study. The prolonged remission, partial remission and non-remission rates at the 5-year follow-up were 9.8, 59.8, and 30.5%, respectively. The remission rate was negatively correlated with disease duration (r=0.39). The combined rate of remission (prolonged and partial remission) significantly decreased when the duration was longer than 16 days, and reduced to approximately 50% after 1 month. Moreover, 75% of prolonged remission patients had duration of < 16 days. At the 5-year follow-up, the prolonged remission rate was 9.8% and the partial remission rate was 59.8%. Furthermore, the duration after diagnosis is an independent predictor of remission rate, and initiation of short-term premixed insulin therapy within the first 16 days of diabetes diagnosis is very important for remission. This is the first study to evaluate the remission rate associated with short-term premixed insulin therapy in recently diagnosed type 2 diabetes outpatients. At the 5-year follow-up, the prolonged remission rate was 9.8% and the partial remission rate was 59.8%. The duration of diabetes was identified as an independent predictor of drug-free remission. The initiation of short-term premixed insulin therapy within 15 days of diabetes onset is particular importance for remission., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective To investigate the association between total homocysteine (tHcy) level in plasma and methylenetetrahydrofolate reductase ( MTHFR ) C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus (T2DM) accompanied by dyslipidemia. Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively. Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C. Plasma tHcy and lipid levels were measured as well. The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test. Plasma tHcy level of T2DM patients who carried the different genotypes was compared by Student's t test. Results Finally, 82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study. There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism in T2DM patients ( t =2.27, P =0.02). Moreover, the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677 TT genotype was significantly higher than that in those with CT+CC genotype (13.62±6.97 vs . 10.95±3.62 μmol/L, t =2.20, P =0.03); while for patients without dyslipidemia, comparison of the tHcy level between those who carried the above two alleles showed no significantly difference (13.34±6.03 vs . 12.04±5.09 μmol/L, t =1.08, P =0.29). Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.

Backgrounds: As patients attending hospitals of different grades in China may receive different medical care, we investigated the clinical efficacy and safety of routine insulin therapy in patients with type 2 diabetes who were treated at grade 2 and grade 3 (highest grade) hospitals in China., Methods: 2683 patients with type 2 diabetes were enrolled in a multicenter, nonrandomized, open-label, noninterventional, 12-week clinical trial performed at 62 Chinese hospitals. Patients were divided into two groups according to the hospitals' grading. Data were analyzed for efficacy (changes and normalization of glycated hemoglobin [HbA1c] and changes in fasting plasma glucose and 2-h postprandial blood glucose [PBG] levels from baseline to the final visit) and for safety (hypoglycemia)., Results: After 12 weeks of routine human insulin (SciLin) therapy, decreases in mean HbA1c and PBG levels were significantly greater in patients treated at second-grade hospitals (all P < 0.001 vs. third-grade hospitals), and the HbA1c success rate (<7%) was significantly higher (46.94% vs. 38.85%; P = 0.0002). However, patients treated at second-grade hospitals had more weight gain (0.29 kg vs. 0.04 kg; P < 0.0001) and a higher incidence of total hypoglycemic events (21.82% vs. 16.79%; P = 0.0002)., Conclusions: Routine insulin treatment of patients with type 2 diabetes in China demonstrates acceptable safety and effectiveness, improving blood glucose control with a low incidence of severe hypoglycemia. Patients treated at second-grade hospitals had a greater HbA1c success rate than those treated at third-grade hospitals, but with more weight gain and more hypoglycemic events.

Objective: The goal of the genetic investigation was to identify the associations of serum lipid levels and DPP-4 variants in Chinese type 2 diabetes patients., Methods: We detected four variants of the DPP4 gene in 190 Chinese individuals with type 2 diabetes and tested for an association with dyslipidemia in 82 selected samples. Data including basic information, HbA1c, FPG, serum lipid parameters were collected. Statistical analysis was performed by SPSS 13.0 through ANOVA and χ 2 test., Results: The genetic polymorphism of rs4664443, rs3788979, rs7608798 and rs1558957 in Chinese type 2 diabetes were consistent with Hardy-Weinberg equilibrium. The CT genotype of rs4664443 suffered from higher serum TG (P=0.013), LDL (P=0.044) and ApoB (P=0.006) levels, whereas the TT genotype of rs7608798 exhibited a lower serum TG level (P=0.037). For rs3788979, the serum TG level (P=0.034) and BMI (P=0.04) were significantly different among genotypes. Moreover, serum TG and TC levels and BMI showed a positive correlation with the number unfavorable alleles, and individuals with more than two unfavorable alleles had higher TG (P=0.004), TC (P=0.011), and BMI (P=0.044) values., Conclusions: This is the first study to investigate DPP4 allelic distributions and their association with dyslipidemia in Chinese type 2 diabetes patients, which may have clinical significance., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The effects of statins in patients with diabetic nephropathy are controversial. With increasing interest in the potential therapeutic role of statins in diabetic nephropathy, it is essential to evaluate its real effects., Methods: PubMed, EMBASE, Web of Science databases, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure were systematically searched for randomized controlled trials (RCTs) of statins in patients with diabetic nephropathy., Results: Fourteen trials with 2866 participants were included in our meta-analysis. Compared with placebo, albuminuria and urinary albumin excretion rates in the statin group were reduced by 0.46 [95 % confidence interval (CI),-0.68 to -0.25, P < 0.0001] and 1.68 (95 % CI, -3.23 to -0.12, P = 0.03), respectively. The reduction of albuminuria was greater in patients of type 2 diabetes mellitus with diabetic nephropathy [standardized mean difference (SMD), -0.56; 95 % CI, -0.80 to -0.32, P < 0.00001] and the decrease was significant during the 1 to 3 years period of statin therapy (SMD, -0.57; 95 % CI, -0.95 to -0.19, P = 0.003). Subgroup analysis demonstrated the effects of statins were much stronger in subjects with pathologic albuminuria: change of -0.71 (95 % CI, -1.09 to -0.33, P = 0.0003) for those with urinary protein excretion 30 to 300 mg/day, -0.37 (95 % CI, -0.67 to -0.06, P = 0.02) for those with excretion more than 300 mg/day and -0.29 (95 % CI, -0.78 to 0.21, P = 0.26) for those with excretion less than 30 mg/day. In contrast, statins did not significantly reduce estimated glomerular filtration rate, serum creatinine and blood urea nitrogen levels., Conclusions: Statins decrease the albuminuria and urinary albumin excretion rates significantly. The efficacy of statins on renal function is time dependent and better in type 2 diabetic patients with nephropathy.

Background and Objective: Once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a novel class of injectable antidiabetic drugs. Previous studies indicated that GLP-1RAs (exenatide and liraglutide) might increase the incidence of pancreatitis and pancreatic cancer. Here, we evaluated the clinical safety of once-weekly GLP-1RAs with respect to tumour risk., Methods: Relevant studies were selected from ClinicalTrials.gov. Randomized controlled trials that reported the incidences of neoplasms were included in our research. Outcomes were calculated as the risk ratio using the Mantel-Haenszel method and fixed-effects model., Results: Our analysis included 26 randomized controlled trials with 16,090 patients. Once-weekly GLP-1RAs did not increase the risk for tumours compared with other antidiabetic drugs [risk ratio (RR), 1.02; 95 % confidence interval (CI), 0.74-1.41; p = 0.91]; this finding was independent of the type of GLP-1RA administered (albiglutide, exenatide extended-release and dulaglutide) and duration of the trials (limited to ≥52 weeks). Subgroup analyses revealed that once-weekly GLP-1RAs did not increase tumour risk compared with placebos, exenatide and liraglutide, insulin or oral drugs. Additionally, once-weekly GLP-1RAs did not increase tumour risk in any tissue., Conclusions: Compared with other antidiabetic drugs, once-weekly GLP-1RAs did not increase the risk for any tumour, and this finding was independent of the type of GLP-1RA administered and treatment duration. However, our study had many limitations, and further longer term trials with larger samples should be conducted in future to confirm our results.

Background: The aim of the present study was to compare the reported efficacy and safety of glucagon-like peptide-l receptor agonist (GLP-1RA) and insulin glargine (IGlar) for poorly controlled type 2 diabetes., Methods: Medline, EMBASE, Cochrane Library, and clinicaltrials.gov were carried out. References and cited papers of relevant articles were also checked., Results: Seven trials met the inclusion criteria. GLP-1RA showed equivalent or superior efficacy to IGlar for reducing hemoglobin A1c (HbA1c), with a greater proportion of patients achieving HbAlc<7%. GLP-1RA also favored decreased body weight, total cholesterol (TC), low-density lipoprotein (LDL), and systolic blood pressure (SBP). Serious adverse events were uncommon and not significantly different. More patients taking GLP-1RA experienced gastrointestinal complications: nausea, diarrhea, and vomiting. Severe hypoglycemia events were rare, and minor hypoglycemia was less common for GLP-1RA., Conclusions: GLP-1RA showed greater efficacy compared to IGlar for type 2 diabetes, and it may also prove beneficial for other diabetes-associated characteristics, including obesity, hypertension, and hyperlipidemia., (© 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Background: Few studies have given suggestions on appropriate initiation insulin dosage when combined with oral antidiabetic drugs (OADs). This research was to investigate appropriate initiation insulin doses for insulin-naive type 2 diabetes patients with different combinations and the relationship between insulin dosage and relevant factors., Methods: This was a randomized, open-label, treat to target study. The target was 20% decrease of both fasting plasma glucose (FPG) and 2 hours post-breakfast blood glucose (P2hBG). One hundred and forty-seven insulin-naive Chinese patients recruited were randomly assigned to 3 groups: group A, patients received insulin monotherapy; group B, received insulin plus metformin (0.5 g, tid) and group C, received insulin plus metformin (0.5 g, tid) and pioglitazone (15 mg, qd). Insulin doses were initiated with a dose of 0.3 U×kg(-1)×d(-1) and titrated according to FPG and P2hBG till reached the targets., Results: Both the time of getting 20% reduction of FPG and P2hBG showed significant differences among the three groups. The time was shortest in Group C. The insulin doses needed to achieve glucose reduction of 20% in three treatment groups were (0.40 ± 0.04) U×kg(-1)×d(-1) for Group A, (0.37 ± 0.04) U×kg(-1)×d(-1) for Group B, and (0.35 ± 0.03) U×kg(-1)×d(-1) for Group C, respectively. Multiple linear stepwise regression analysis showed that insulin doses correlated with body weight, FPG, diabetes duration, age and history of sulfonylurea treatment. The standardized regression coefficients were 0.871, 0.322, 0.089, 0.067 and 0.063 (with all P < 0.05)., Conclusions: To achieve blood glucose's reduction of 20% within safety context, initial insulin doses were recommended as the following: 0.40 U×kg(-1)×d(-1) for insulin mono-therapy, 0.37 U×kg(-1)×d(-1) for insulin plus metformin treatment, and 0.35 U×kg(-1)×d(-1) for insulin plus metformin and pioglitazone treatment in Chinese type 2 diabetes outpatients. Body weight is found the most closely related factor to the insulin dosage.

Objective: Recent studies on Caucasians have reported an association between diabetic microvascular complications and polymorphisms in the inducible nitric oxide synthase (iNOS) gene. In view of the differences in the pattern of diabetic complications in Asians, we studied these iNOS polymorphisms in Asians with Type 2 diabetes who do and those who do not have nephropathy., Methods: Two hundred fifty-eight Asians who have had Type 2 diabetes for at least 10 years, with overt nephropathy or with normoalbuminuria, were genotyped for the (AAAT)(n) and (CCTTT)(n) polymorphisms in the promoter region of the iNOS gene. A subanalysis was made of the findings from the three ethnic groups (Chinese, Malays, and Indians)., Results: The (AAAT)(3) polymorphism, which is the most common allele in Caucasians, was completely absent in our entire cohort of 258 Asian diabetics. The (AAAT)(4) polymorphism was the commonest, with a frequency of 0.984 as compared with 0.2 in Caucasians. We also found previously unreported alleles: (AAAT)(5) in 6 patients and (AAAT)(6) in 1 patient. There was no statistically significant association with nephropathy, in view of the highly skewed distribution of the alleles. However, the higher repeats (AAAT)(5) and (AAAT)(6) were found in the patients with a very rapid onset of severe nephropathy. The (CCTTT)(n) polymorphism also showed significant differences in allele distribution between the Asian and the Caucasian and African populations (P=.001). However, there was also no significant association with nephropathy and no significant difference in the ethnic distribution of alleles., Conclusions: We have identified significant differences in the (AAAT)(n) and (CCTTT)(n) polymorphisms in Asian diabetics. We have shown that there are significant differences in the overall allele distribution between the Asian and the Caucasian and African populations. However, our study did not demonstrate an association between iNOS gene polymorphisms and diabetic nephropathy.