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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.)

Background: The pathogenesis of the progressive loss of beta cell function latent autoimmune diabetes in adults (LADA) remains still elusive. We aim to study the fatty acid (FA) profile in LADA., Subjects and Methods: Data from 116 patients with diabetes and GADA and 249 diabetes controls without GADA selected by Propensity Score Matching were collected. FA was analyzed with liquid chromatography-tandem mass spectrometry analysis., Results: Principal factor analysis found component 1 explains 82.6% of total variance contained fatty acids from a mixed of lard oil, seafood, and vegetable diet, followed by diet predominantly from vegetable oil, a diet of high fat diet, and a diet of seafood diet. The FA heatmap looked clearly different among the three groups with more similar type 1 (t1dm) and LADA fatty acid profile. n-3 α-linolenic acid (ALA), n-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA), such as Eicosapentaenoic Acid and Docosapentaenoic Acid, n-3/n-6 ratio and triene/tetraene ratio were higher in patients with type 2 diabetes (t2dm) compared with LADA and t1dm. Saturated FAs were lower in t2dm than t1dm and LADA. Arachidic acid and n-6 LC-PUFAs were lower in t2dm than in t1dm and LADA. The characteristics of FAs in LADA were in between of classical t1dm and t2dm. Patients were classified into 6 clusters by FA clusters. Only cluster 2, 3, 5 contained enough patients to be analyzed. Cluster 5 showed an insulin deficient phenotype containing more than 60% of patients with t1dm and LADA and only 12.8% of t2dm. Cluster 2 and 3 were similar. β cell function and glycemic control was better in cluster 3 homing 25% of t2dm. Cluster 2 held 28% of t1dm and LADA, in this cluster more than 60% of patients was t2dm. n-3 linolenic acid, n-3 LC-PUFAs, some n-6 LC-PUFAs, n-3/n-6 ratio and triene/tetraene ratio were negatively associated with GADA positivity while n-6 Arachidonic Acid was associated positively with GADA. Similar findings were found for insulin sensitivity and beta cell function., Conclusion: PUFA are associated with insulin sensitivity and beta cell function, and like other clinical features, FA profile distributed differently, but could not be used as makers to differentiate LADA from t1dm and t2dm., Ethics and Dissemination: This study has been approved by the Ethical Review Committee of Second Hospital of Dalian Medical University (approval number: 2021-005)., Clinical Trial Registration: none., 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 Tian, Wang, Deng, Xing, Zhao, Zhang, Zhang, Liu and Su.)

Objective: To investigate whether the existence of obstructive sleep apnea syndrome (OSAS) in patients with type 2 diabetes (T2DM) is associated with low grade chronic inflammation., Methods: Fifty-four patients hospitalized for poor glycemic control from 12/2008 to 12/2009 were divided into 2 groups, OSAS group (T2DM with OSAS, 27 cases) and NOSAS group (T2DM without OSAS, 27 cases). The control group consisted of 26 people from a health check-up program without diabetes and OSAS. Biochemical indexes were analyzed in central laboratory of the hospital. Serum tumor necrosis factor-α(TNF-α), lipopolysaccharides (LPS), monocyte chemoattractant protein-1 (MCP), and plasminogen activator inhibitor-1 (PAI) levels were determined with commercial ELISA kits. Apnea hypopnea index (AHI), the lowest pulse oxygen saturation (LSpO₂) at night were measured with a portable home sleep monitor., Results: Homeostasis model assessment insulin resistance index (HOMA-IR), AHI in OSAS group were higher than those in NOSAS group and control group [for HOMA-IR, 2.7 ± 1.5 vs 1.7 ± 0.9 vs 1.2 ± 0.7, and for AHI, (17.0 ± 13.0) vs (3.4 ± 1.3) vs (3.2 ± 1.2) per hour], and LSpO₂ was lower than that in NOSAS group and control group [(78 ± 11)% vs (87 ± 4)% vs (89 ± 6)%]. Compared with normal control, levels of TNF-α [(0.73 ± 0.19) vs (1.97 ± 0.13) vs (1.09 ± 0.29) ng/ml], LPS [(50 ± 11) vs (303 ± 70) vs (171 ± 49) pg/ml], MCP [(302 ± 41) vs (514 ± 122) vs (473 ± 134) pg/ml] and PAI [(0.89 ± 0.25) vs (2.27 ± 0.85) vs (1.59 ± 0.13) ng/ml] in patients with OSAS and with NOSAS group increased significantly. Pearson univariate correlation analysis revealed that TNF-α and PAI were both positively associated with HOMA-IR, FBG and AHI, and negatively with LSpO₂, LPS, MCP were both associated positively with FBG and AHI, and negatively with LSpO₂. Multiple linear regression stepwise analysis found that TNF-α and LPS were independently associated with AHI and FBG, MCP with LSpO₂, PAI with both AHI and HOMA-IR., Conclusions: Patients with diabetes and OSAS show raised level of chronic inflammatory activity.

Adipose tissue glyceroneogenesis generates glycerol 3-phosphate, which could be used for fatty acid esterification during starvation. To determine whether increased glyceroneogenesis leads to increased fat mass and to explore the role of obesity in the development of insulin resistance, we overexpressed PEPCK, a regulatory enzyme of glyceroneogenesis in adipose tissue. Transgenic mice showed a chronic increase in PEPCK activity, which led to increased glyceroneogenesis, re-esterification of free fatty acids (FFAs), increased adipocyte size and fat mass, and higher body weight. In spite of increased fat mass, transgenic mice showed decreased circulating FFAs and normal leptin levels. Moreover, glucose tolerance and whole-body insulin sensitivity were preserved. Skeletal muscle basal and insulin-stimulated glucose uptake and glycogen content were not affected, suggesting that skeletal muscle insulin sensitivity is normal in transgenic obese mice. Our results indicate the key role of PEPCK in the control of FFA re-esterification in adipose tissue and, thus, the contribution of glyceroneogenesis to fat accumulation. Moreover, they suggest that higher fat mass without increased circulating FFAs does not lead to insulin resistance or type 2 diabetes in these mice.