Incretin-based agents, including dipeptidyl peptidase-4 inhibitors (DPP-4Is) and glucagon-like peptide-1 agonists (GLP-1As), work via GLP-1 receptor for hyperglycemic control directly or indirectly, but have different effect on cardiovascular (CV) outcomes. The present study is to evaluate and compare effects of incretin-based agents on CV and pancreatic outcomes in patients with type 2 diabetes mellitus (T2DM) and high CV risk. Six prospective randomized controlled trials (EXMAINE, SAVOR-TIMI53, TECOS, ELIXA, LEADER and SUSTAIN-6), which included three trials for DPP-4Is and three trials for GLP-1As, with 55,248 participants were selected to assess the effect of different categories of incretin-based agents on death, CV outcomes (CV mortality, major adverse CV events, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization), pancreatic events (acute pancreatitis and pancreatic cancer) as well as on hypoglycemia. When we evaluated the combined effect of six trials, the results suggested that incretin-based treatment had no significant effect on overall risks of CV and pancreatic outcomes compared with placebo. However, GLP-1As reduced all-cause death (RR = 0.90, 95% CI 0.82–0.98) and CV mortality (RR = 0.84, 95% CI 0.73–0.97), whereas DPP-4Is had no significant effect on CV outcomes but elevated the risk for acute pancreatitis (OR = 1.76, 95% CI 1.14–2.72) and hypoglycemia (both any and severe hypoglycemia), while GLP-1As lowered the risk of severe hypoglycemia. GLP-1As decreased risks of all-cause and CV mortality and severe hypoglycemia, whereas DPP-4Is had no effect on CV outcomes but increased risks in acute pancreatitis and hypoglycemia.

Aims/Introduction: To investigate the relationship between the metabolic score for insulin resistance (METS‐IR) index and major adverse cardiac events (MACEs) and to compare its ability to predict MACEs with other IR indices including homeostatic model assessment for IR (HOMA‐IR) and triglyceride glucose (TyG) index‐related parameters.Materials and Methods: We conducted a cohort study enrolling 7,291 participants aged ≥40 years. Binary logistic regression and restricted cubic splines were performed to determine the association between METS‐IR and MACEs, and the receiver operating curve (ROC) was utilized to compare the predictive abilities of IR indices and to determine the optimal cut‐off points.Results: There were 348 (4.8%) cases of MACEs during a median follow‐up of 3.8 years. Compared with participants with a METS‐IR in the lowest quartile, the multivariate‐adjusted RRs and 95% CIs for participants with a METS‐IR in the highest quartile were 1.47 (1.05–2.77) in all participants, 1.42 (1.18–2.54) for individuals without diabetes, and 1.75 (1.11–6.46) for individuals with diabetes. Significant interactions were found between the METS‐IR and the risk of MACEs by sex in all participants and by age and sex in individuals without diabetes (all P values for interaction < 0.05). In the ROC analysis, the METS‐IR had a higher AUC value than other indices for predicting MACEs in individuals with diabetes and had a comparable or higher AUC than other indices for individuals without diabetes.Conclusions: The METS‐IR can be an effective clinical indicator for identifying MACEs, as it had superior predictive power when compared with other IR indices in individuals with diabetes.

Diabetes is a chronic disease that affects many people, with both its incidence and prevalence rising globally. Diabetes can lead to various complications, among which cognitive impairment in diabetic patients significantly impacts their daily life and blood glucose management, complicating treatment and worsening prognosis. Therefore, the early diagnosis and treatment of cognitive impairment are essential to ensure the health of diabetic patients. However, there is currently no widely accepted and effective method for the early diagnosis of diabetes-related cognitive impairment. This review aims to summarize potential screening and diagnostic methods, as well as biomarkers, for cognitive impairment in diabetes, including retinal structure and function examination, brain imaging, and peripheral blood biomarkers, providing valuable information and support for clinical decision making and future research.

Cognitive impairment is a significant complication of type 2 diabetes mellitus (T2DM). However, the mechanisms underlying the development of cognitive dysfunction in individuals with T2DM remain elusive. Herein, we discussed the role of Bmal1, a core circadian rhythm-regulating gene, in the process of T2DM-associated cognitive dysfunction. We identified a marked decrease in BMAL1 levels in the hippocampus of db/db mice, followed by gain- and loss-of-function studies to explore the impact of BMAL1 on cognitive function. Our findings indicated that BMAL1 downregulation led to cognitive deficits, characterized by tau hyperphosphorylation and accumulated amyloid plaque. Conversely, BMAL1 overexpression mitigated these Alzheimer-like pathologies. Further investigation revealed that BMAL1 directly activated the transcription of Areg, thereby activating the PI3K/Akt/GSK-3β pathway and ameliorating cognitive dysfunction. Moreover, these effects of BMAL1 were attenuated by LY294002, a PI3K inhibitor. Collectively, these results underscore the significant role of BMAL1 in T2DM-associated cognitive impairment, proposing a novel intervention strategy for individuals exposed to risk factors of T2DM.

Background: An antidiabetic medication regimen is crucial for maintaining glycemic control. Type 2 diabetes mellitus (T2DM) and cognitive dysfunction have a bidirectional relationship. This study aims to explore the impact that adjusting antidiabetic medication regimens has on medication adherence, glycemic control, and cognitive function in patients with T2DM and mild cognitive impairment (MCI). Methods: This is an observational cross-sectional analysis that includes 364 consecutive inpatients with T2DM. Clinical data were collected, medication adherence was assessed using the Medication Adherence Report Scale (MARS-5), and cognitive status was evaluated using the Chinese version of the Montreal Cognitive Assessment (MoCA) and Mini-mental State Examination (MMSE). These data were obtained both during hospitalization and at a three-month follow-up. Multivariable logistic regression analysis was applied to determine the association between changes in medication regimens and medication adherence, glycemic control, and cognitive function. Results: Baseline medication adherence was high across all three different cognitive status groups, with no significant difference in MARS-5 scores. At the 3-month follow-up, the group with a high adjustment ratio of antidiabetic medication regimens showed an increase in their hemoglobin A1c (HbA1c) level compared to the baseline, while the group with a low adjustment ratio showed a decrease in this level. In addition, the MoCA, MMSE, and MARS-5 scores of the high-adjustment group were significantly lower than those of the low-adjustment group. Conclusions: A high ratio of medication adjustment was significantly associated with worse medication adherence and glycemic control in T2DM patients with MCI. Patients with a low ratio of medication adjustment had good adherence and better glycemic control. Clinicians should take cognitive status into account when adjusting antidiabetic regimens for T2DM patients and may need to provide additional guidance to patients with cognitive impairment to improve adherence and glycemic outcomes.