Aims/Introduction: There is potential for mobile applications to deliver new self‐management interventions for chronic disease, especially in diabetes. The aim of the present study was to evaluate the effects of a mobile phone application (MPA) combined with or without self‐monitoring of blood glucose (SMBG) on glycemic control in patients with diabetes.Materials and Methods: The study was a 24‐week period, four‐arm parallel group, non‐blinded, randomized trial. A total of 185 patients with mean age of 52 years were randomized to group A (no MPA and no SMBG), group B (SMBG only), group C (MPA only) and group D (both MPA and SMBG were used). Changes in glycated hemoglobin (HbA1c), fasting plasma glucose and 1,5‐anhydroglucitol from baseline to week 24 were analyzed.Results: At 24 weeks, the HbA1c levels in patients of all groups decreased significantly from baseline. There were significant differences in the proportions of patients that achieved HbA1c <7% between groups, especially in group C and group D, compared with group A at week 24 (60.4%, 62.2% vs 25.5%, all P < 0.05). 1,5‐Anhydroglucitol changes were obvious in group A and group C at week 24 from baseline (all P < 0.05 within groups). Factorial analysis of anova showed that MPA intervention was the main effective factor for HbA1c change (F = 4.59, P = 0.034), and there was no effect on HbA1c change for SMBG intervention (P = 0.975).Conclusions: Implementation of the MPA, Diabetes‐Carer, is effective in improving the proportion of HbA1c <7% in patients with type 2 diabetes.

The aim of this study was to evaluate the association between circulating oxLDL/LDL-C ratio and the severity of coronary atherosclerosis, along with other emerging biomarkers of cardiovascular disease (CVD) in patients with type 2 diabetes. We recruited 152 patients with type 2 diabetes for our study. ELISA measured the plasma levels of oxLDL and other biomarkers. The severity of coronary lesions was evaluated using Gensini scores, which were calculated based on results of coronary computed tomographic angiography (CCTA). All patients were allocated into four groups according to CCTA findings and Gensini score: normal group (score = 0), mild coronary atherosclerosis group (0 < scores ≤ 3), moderate coronary atherosclerosis group (3.01 ≤ scores ≤ 32.67) and severe coronary atherosclerosis group (32.68 ≤ scores ≤ 180). Association between the oxLDL/LDL-C ratio and the severity of coronary atherosclerosis were evaluated using logistic regression models. Multivariate logistic regression analysis showed that the oxLDL/LDL-C ratio was positively associated with severity of coronary atherosclerosis (OR 2.03, 95% CI 1.31-3.14, p < 0.01). Interleukin 33 (IL33) correlated positively with oxLDL/LDL-C ratio (r = 0.274, p < 0.01). However, vascular cell adhesion molecular-1 (VCAM-1) had similar trends with oxLDL/LDL-C ratio in these 4 groups. OxLDL/LDL-C ratio is considered as a potential biomarker in patients with diabetes for early recognition and intervention of severe coronary atherosclerosis, and will be more effective if tested IL33 and VCAM-1 at the same time.

Statins are cholesterol-lowering agents that increase the incidence of diabetes and impair glucose tolerance via their detrimental effects on nonhepatic tissues, such as pancreatic islets, but the underlying mechanism has not been determined. In atorvastatin (ator)-treated high-fat diet–fed mice, we found reduced pancreatic β-cell size and β-cell mass, fewer mature insulin granules, and reduced insulin secretion and glucose tolerance. Transcriptome profiling of primary pancreatic islets showed that ator inhibited the expression of pancreatic transcription factor, mechanistic target of rapamycin (mTOR) signaling, and small G protein (sGP) genes. Supplementation of the mevalonate pathway intermediate geranylgeranyl pyrophosphate (GGPP), which is produced by 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, significantly restored the attenuated mTOR activity, v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) expression, and β-cell function after ator, lovastatin, rosuvastatin, and fluvastatin treatment; this effect was potentially mediated by sGP prenylation. Rab5a, the sGP in pancreatic islets most affected by ator treatment, was found to positively regulate mTOR signaling and β-cell function. Rab5a knockdown mimicked the effect of ator treatment on β-cells. Thus, ator impairs β-cell function by regulating sGPs, for example, Rab5a, which subsequently attenuates islet mTOR signaling and reduces functional β-cell mass. GGPP supplementation could constitute a new approach for preventing statin-induced hyperglycemia.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2i) are antihyperglycemic agents that provide additional renal-protective effects in patients with DKD, independent of their glucose-lowering effects. However, the underlying mechanism remains unclear. This study hypothesized that SGLT2i could alleviate diabetic kidney injury by inhibiting ferroptosis and explored its potential mechanisms. C57BL/6J mice were randomly divided into the control, DKD, DKD+dapagliflozin, and DKD+insulin treatment groups. Blood glucose levels and body weight were monitored. Renal function, tissue pathology, mitochondrial morphology and function, and lipid peroxidation biomarkers (lipid peroxidation [LPO], malondialdehyde [MDA], glutathione peroxidase 4 [GPX4], glutathione [GSH], and cystine transporter solute carrier family 7 member 11 [SLC7A11]) were evaluated. Human proximal tubule cells (HK2 cells) were exposed to high glucose alone or in combination with dapagliflozin. The mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) level, NAD+/NADH ratio (oxidized/reduced ratio of nicotinamide adenine dinucleotide), and lipid peroxidation were measured. In addition, the role of the β-hydroxybutyrate- Calcium/Calmodulin Dependent Protein Kinase Kinase 2 (BHB-CaMKK2) axis in mediating dapagliflozin regulating ferroptosis was examined. Dapagliflozin significantly ameliorated kidney injury in mice with DKD. Typical changes in ferroptosis, including lipid peroxidation and impaired antioxidant capacity, increased in mice with DKD and HG-treated HK-2 cells. Dapagliflozin significantly improves ferroptosis-related lipid peroxidation and mitochondrial dysfunction. Furthermore, dapagliflozin suppressed the expression of CaMKK2, a key ferroptosis regulator. Specific CaMKK2 inhibitors alleviated mitochondrial damage and ferroptosis, whereas a CaMKK2 agonist counteracted the protective effects of dapagliflozin against mitochondrial, antioxidant, and anti-ferroptosis effects. In addition, dapagliflozin increased BHB production, which mediates its nephroprotective effects. Dapagliflozin improves DKD by inhibiting ferroptosis, promoting BHB production, and regulating CaMKK2.

Background: It has been reported that glucagon-like peptide-1 (GLP-1) can alleviate diabetic osteoporosis (DOP). This study was to investigate the effects of GLP-1RA liraglutide and dipeptidyl peptdase-4 (DPP-4) inhibitor vildagliptin on the advanced glycation end products (AGEs)-induced bone injury in ApoE^−/− mice with euglycemia. Methods: The bone markers OC, PINP, PTH, TRACP and CTX, the mRNA and protein expressions of RAGE in the femur, and the femoral morphology index were determined to evaluate whether the osteoporosis was improved by liraglutide or vildagliptin. Results: AGEs adversely affected the bone metabolism, characterized by reduced OC and increased CTX. However, vildagliptin reduced AGEs and increased OC, and liraglutide significantly decreased AGEs and PTH. Both vildagliptin and liraglutide had no effects on the bone metrology and RAGE expression in the femurs of ApoE^−/− mice. Conclusions: The elevated AGEs may exacerbate osteogenesis and increase bone resorption, and vildagliptin/liraglutide may improve bone metabolism.

Studies have shown that the cholesterol-lowering medicine statins alter the gut microbiome, induce chronic metabolic inflammation, and disrupt glycemic homeostasis. In this study, we aimed to investigate whether effects of atorvastatin (Ator) on gut microbiome and metabolic inflammation could be causally correlated. Mice at 8-week age were fed with high-fat diet (HFD) or HFD with Ator (HFD+Ator) for 16 weeks. 16S rRNA sequencing of stool and RNA sequencing of colon tissue were employed to analyze the intestinal alterations that could be induced by Ator. A human colon carcinoma cell line (Caco₂) was used for in vitro experiments on barrier function. Compared to HFD, HFD+Ator induced more weight gain, impaired glucose tolerance, and led to gut microbiota dysbiosis, such as suppressing Akkermansia muciniphila in mice. The expressions of tight junction (TJ) proteins were attenuated in the colon, and the serum LPS-binding-protein (LBP) level was elevated in HFD+Ator mice, so as to transcriptionally activate the intestinal nuclear factor-k-gene binding (NF-κB) signaling pathway. Consistently, Ator impaired the barrier function of Caco₂, and treatment of supernatant of A. Muciniphila culture could decrease the intestinal permeability and recover the attenuated expression of TJ proteins induced by Ator. In conclusion, long-term use of Ator with HFD may alter gut microbiota, induce intestinal barrier dysfunction, and hence promote chronic inflammation that contributes to disrupted glycemic homeostasis.