Type 2 Diabetes Mellitus Research Articles

Triglyceride-glucose index is associated with microcirculatory resistance in patients with type 2 diabetes and STEMI undergoing primary PCI

The triglyceride-glucose (TyG) index is emerging as a promising marker for insulin resistance and serves as an independent risk predictor for cardiovascular outcomes. The coronary angiography-derived index of microcirculatory resistance (AMR) is computed to evaluate coronary microcirculation. However, the association between the TyG index and the AMR in patients with type 2 diabetes mellitus (T2DM) and ST-segment elevation myocardial infarction (STEMI) remains unclear. We consecutively recruited 168 patients with T2DM and STEMI who underwent primary percutaneous coronary intervention (pPCI) at Taizhou People’s Hospital from January 2022 to December 2023. Patients were classified into low AMR group (AMR < 2.5) and high AMR group (AMR ≥ 2.5). The TyG index was calculated using the formula: ln [plasma triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. The study enrolled 81 patients in the low AMR group and 87 in the high AMR group, with the TyG index being significantly higher in the high AMR group. Multivariable logistic regression analysis revealed a significant association between the TyG index and high AMR after adjusting for confounding variables (odds ratio: 2.449, 95% confidence interval: 1.421–4.220, and p = 0.001). The area under the curve for the TyG index predicting high AMR was 0.650 (95% confidence interval: 0.57–0.73, p < 0.001), with a cut-off value of 9.57. Our findings indicate that the TyG index is significantly associated with AMR in T2DM patients with STEMI undergoing pPCI, suggesting it may serve as a valuable predictor of high AMR in this population.

Identification and study of mood-related biomarkers and potential molecular mechanisms in type 2 diabetes mellitus.

A significant correlation between type 2 diabetes mellitus (T2DM) and mood has been reported. However, the specific mechanism of mood's role in T2DM is unclear. This study aims to discover mood-related biomarkers in T2DM and further elucidate their underlying molecular mechanisms. The GSE81965 and GSE55650 datasets were sourced from public databases, and mood-related genes (MRGs) were retrieved from previous literature. Initially, differentially expressed MRGs (DE-MRGs) were obtained by combining differential expression analysis and weighted gene co-expression network analysis (WGCNA). Subsequently, the DE-MRGs were incorporated into the LASSO and SVM to identify diagnostic biomarkers for T2DM. Four machine learning methods were utilized to construct the diagnostic models in T2DM, and the model with the optimal algorithm was screened. Further, based on biomarkers, functional enrichment, immune infiltration, and regulatory network analyses were conducted to excavate deeper into the pathogenesis of T2DM. In vivo experiments were used to validate the expression of the biomarkers. A total of 23 DE-MRGs were identified by overlapping 723 DEGs and 64 key modules, and there were strong positive correlations between these DE-MRGs. Afterward, KCTD16, SLC8A1, RAB11FIP1, and RASGEF1B were identified as biomarkers associated with mood in T2DM, and they had favorable diagnostic performance. Meanwhile, the RF diagnostic model constructed based on biomarkers was performed optimally and had high diagnostic accuracy for T2DM patients. Animal experiments indicated that expression levels of SLC8A1, RAB11FIP1, and RASGEF1B in T2DM were consistent with the microarray results.In conclusion, KCTD16, SLC8A1, RAB11FIP1, and RASGEF1B were identified as biomarkers related to mood in T2DM.

A sex-disaggregated analysis of the prognostic value of lean type 2 diabetes mellitus in the adult population with acute myocardial infarction

BackgroundEmerging evidence has demonstrated the unfavourable cardiovascular risk of individuals with lean type 2 diabetes mellitus (T2DM). Our study aims to investigate the prognostic value of lean T2DM in patients with acute myocardial infarction (AMI), stratified by sex.MethodsThe study cohort examines the clinical characteristics and long-term outcomes of individuals with AMI, stratified by four phenotypes based on T2DM and lean body category—lean T2DM, non-lean T2DM, lean non-T2DM and non-lean non-T2DM. The primary outcome was long-term all-cause mortality. Cox regression model was constructed to investigate the associations of lean and non-lean T2DM phenotypes with mortality, adjusted for age, ethnicity, previous AMI, AMI type, chronic kidney disease, angiotensin converting enzyme inhibitor or angiotensin receptor blockers, beta-blockers, and smoking status.ResultsA cohort of 9545 AMI patients was examined, with a mean follow-up duration of 3.4 ± 2.4 years. Majority had the non-lean T2DM phenotype (40.4%), followed by non-lean non-T2DM (29.8%), lean non-T2DM (15.9%), and lean T2DM (13.9%). In the T2DM group, one-quarter was lean (N = 1324), while the vast majority (74.5%) was non-lean. Individuals with lean T2DM tended to be female and older. Patients with lean T2DM had the highest rates of heart failure (23.3%, p < 0.001), cardiogenic shock (9.1%, p = 0.036), and long-term all-cause mortality (32.6%, p < 0.001). Cox regression demonstrated that lean T2DM was an independent predictor of mortality (adjusted hazard ratio [aHR] 1.171, 95% CI 1.040–1.319, p = 0.009) after adjustment. The presence of higher mortality risk following AMI was present in males (aHR 1.201, 95% CI 1.037–1.391, p = 0.015), but not in females (aHR 1.066, 95% CI 0.869–1.308, p = 0.538).ConclusionsThe lean T2DM phenotype was present in one-quarter of the AMI cohort with T2DM. The lean T2DM phenotype was an independent predictor of long-term mortality following AMI, although this association was stronger in males than in females.

Baseline atherogenic index of plasma and its trajectory predict onset of type 2 diabetes in a health screened adult population: a large longitudinal study

BackgroundThe Atherogenic Index of Plasma (AIP) is a novel biomarker for assessing the severity of atherosclerosis and has been shown to be closely associated with the risk of Type 2 Diabetes Mellitus (T2DM). However, no prospective cohort study has comprehensively evaluated both the immediate risk stratification through baseline AIP and the long-term risk assessment through multi-time point AIP trajectories in health screened adults in relation to T2DM risk.MethodsThis longitudinal study included data from 42,850 participants who underwent health check-ups at Henan Provincial People’s Hospital between January 2018 and August 2024. AIP was calculated as the logarithm of the ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C). The Kaplan-Meier method was employed to analyze the incidence of T2DM across different AIP groups. A Cox model with restricted cubic splines assessed the dose-response relationship between AIP and T2DM risk, while latent class trajectory models (LCTM) evaluated the trends of AIP over multiple time points. Cox proportional hazards models were used to examine the relationship between baseline AIP quartiles, AIP trajectories, and T2DM risk.ResultsDuring an average follow-up of 47.95 months, 3,228 participants developed T2DM. Stratifying by baseline AIP quartiles revealed that higher AIP levels were associated with an increased risk of T2DM. Compared to the lowest quartile, the highest quartile had a hazard ratio (HR) of 2.10 (95% CI: 1.74, 2.53). The LCTM identified three trajectory patterns for AIP: with the low-stable group as the reference, the medium-stable and high-stable groups had HRs of 1.72 (95% CI: 1.50, 1.96) and 2.50 (95% CI: 2.06, 3.03), respectively, indicating a significantly elevated risk of T2DM (P < 0.05).ConclusionElevated baseline AIP levels, medium stable trajectories and high stable trajectories are associated with an increased risk of T2DM in health screened adults.

Telemedicine-supported lifestyle intervention for glycemic control in patients with CHD and T2DM: multicenter, randomized controlled trial.

Patients with coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM) have a substantially increased risk for major cardiovascular events and mortality. Increasing physical activity and improving a healthy diet may effectively reduce cardiovascular risk factors; however, the effects are often transient. In a multicenter, 1:1 randomized controlled trial including 502 patients with combined CHD and T2DM (68 ± 8 years; 84% men), we assessed the effects of a home-based telemedicine-supported lifestyle intervention (exercise training, nutritional recommendations and health literacy training) with regular individualized feedback versus usual care. The study met its primary endpoint of reduced glycated hemoglobin after 6 months in favor of the lifestyle intervention group (mean between-group difference in the complete-case analysis (n = 197 and n = 193), -0.13% (95% confidence interval, -0.25 to -0.01), P = 0.04). When individualized feedback and health literacy training were discontinued after 6 months (while other telemedicine tools were maintained), no statistically significant between-group differences were observed at 12 months. At 12 months, 31 patients (6.2%) had a major adverse cardiovascular event (lifestyle intervention, n = 20 (8.0%); usual care, n = 11 (4.4%); P = 0.15), with the main reason being hospitalization for angina or revascularization (lifestyle intervention, n = 15; usual care, n = 8). There were five deaths (lifestyle intervention, n = 2; usual care, n = 3), none of which were categorized as related to the intervention. However, three events that resulted in hospitalization were categorized as potentially related to the intervention (decompensation of heart failure, vertebral disc prolapse and inguinal hernia). In conclusion, a home-based lifestyle intervention with telemedicine support showed modest effects in patients with CHD and T2DM. ClinicalTrials.gov registration: NCT03835923 .

The protective role of SGLT2 inhibitors on aortic aneurysm mediated by oxidative stress and inflammation in type 2 diabetes mellitus

BackgroundSodium-glucose transport protein 2 inhibitors (SGLT2i) have been widely used to treat patients with type 2 diabetes mellitus (T2DM) and have demonstrated protective effects against certain cardiovascular diseases. However, no clinical research has been conducted to explore the relationship between SGLT2i and the risk of aortic aneurysm (AA).MethodsWe extracted and analyzed the data of 4964 patients with T2DM from the First Affiliated Hospital of Zhengzhou University during July 2017 to January 2023. Multivariate Cox models, interaction analysis and Kaplan–Meier curves were performed to approximate the associations of SGLT2i therapy on the risk of AA. A sensitivity analysis was performed to test the robustness of results. Mediation analyses explored the roles of inflammatory (neutrophils, lymphocytes, C-reactive protein and alkaline phosphatase) and oxidative stress (gamma glutamyl transferase, total bilirubin, and uric acid) markers in the associations between SGLT2i and AA.ResultsA total of 1942 SGLT2 inhibitor (SGLT2i) users (39.12%) and 3022 non-SGLT2 inhibitor (NonSGLT2i) users were included in final analysis. After full adjustment for potential risk factors, SGLT2i patients were associated with a lower risk of aortic aneurysm (HR, 95% CI 0.91, 0.89–0.98, p = 0.001). Dapagliflozin showed the greatest difference for reduction of aortic aneurysm incidence (HR, 95% CI 0.84, 0.80–0.95, p = 0.011). Subgroup analysis indicated that use of SGLT2i lower the risk of aortic aneurysm in some subgroups of T2DM patients. The sensitivity analysis demonstrated the robustness of the results. CRP, lymphocytes, neutrophils, and uric acid were significantly associated with both SGLT2i and AA, with mediation proportions of 13.35%, 8.83%, 9.67% and 31.17%, respectively.ConclusionsOur study suggested that patients using SGLT2i may have a lower risk of aortic aneurysm, and this effect could potentially be mediated by inflammation and oxidative stress. Further mechanistic and prospective studies are required to verify this association.Graphical abstract

Muscle quality index is correlated with insulin resistance and type 2 diabetes mellitus: a cross-sectional population-based study

BackgroundMuscle quality index (MQI), an emerging health index, is calculated by dividing handgrip strength by skeletal muscle mass. Current evidence on the correlation between MQI and type 2 diabetes mellitus (T2DM), insulin resistance (IR) is limited. This work aims to study that correlation.MethodsThis study involves a cross-sectional analysis on data from the National Health and Nutrition Examination Survey (NHANES) during the period from 2011 to 2014. To explore the correlation between MQI, IR and T2DM, multivariate logistic regression, receiver operating characteristic (ROC) curve, subgroup analysis, and restricted cubic spline regression were employed.ResultsA total of 2816 American adults were enrolled in this study, among whom 1264 (44.9%) had IR, and 300 (10.7%) had T2DM. Logistic regression and RCS regression analyses showed a significant negative linearly correlation between MQI and the prevalence of IR (OR = 0.708, 95%=0.514, 0.976) and T2DM (OR = 0.676, 95%CI = 0.472, 0.969). Subgroup analysis further revealed a stronger correlation between MQI and IR among individuals with obesity. ROC analysis showed that compared with skeletal muscle and grip strength, MQI (AUC = 0.679 for IR and 0.688 for T2DM) can serve as a more reliable identification factor for IR and T2DM.ConclusionThis study provides evidence that decreased levels of MQI are correlated with an increased risk of IR and T2DM, indicating the potential utility as a marker for identifying IR and T2DM.

Iron overload is closely associated with metabolic dysfunction-associated fatty liver disease in type 2 diabetes.

The relationship between iron metabolism disturbances and metabolic dysfunction-associated fatty liver disease (MAFLD) remains controversial. This study aimed to investigate the association of iron overload with MAFLD in patients with type 2 diabetes mellitus (T2DM). This study included 155 Chinese inpatients with T2DM. MAFLD was diagnosed and grouped using magnetic resonance imaging (MRI). MRI biomarkers such as proton density fat fraction and iron accumulation ( ) were measured. Their clinical characteristics were compared, and the association of iron metabolism markers with MAFLD in patients with T2DM was analyzed. Iron metabolism markers, including MRI- , ferritin, serum iron, hepcidin, and total iron-binding capacity, were overloaded in groups with MAFLD (p < 0.001 for trend). They were positively correlated with MAFLD and reflected the severity of MAFLD. The five markers of logistic regression analysis revealed an increased MAFLD risk (p < 0.001 for trend). The areas under the curve of five markers all exceeded 0.5, indicating certain predictive values for MAFLD. MAFLD is associated with significant iron overload in Chinese patients with T2DM. Serum iron, ferritin, total iron-binding capacity, hepcidin, and value are essential iron metabolism markers to evaluate and predict the progression of MAFLD in patients with T2DM.

Adipose tissue-derived microRNA-450a-5p induces type 2 diabetes mellitus by downregulating DUSP10

Type 2 diabetes mellitus (T2DM) has rapidly increased worldwide, emerging as the fifth leading cause of death. The treatment of T2DM is challenging due to the side effects of oral hypoglycemic drugs and the limited efficacy of long-term insulin therapy, which can lead to insulin resistance (IR). Consequently, there is significant in discovering new drugs that have minimal side effects and a pronounced hypoglycemic effect. In obesity, microRNA levels have been implicated in glucose metabolism disorders and T2DM, although many aspects remain unresolved. Here, we confirmed that visceral adipose tissue and serum microRNA-450a-5p content increased under obesity and T2DM, and it was significantly positively associated with fasting blood glucose, triglycerides, cholesterol, low-density lipoproteins-cholesterol levels of the subjects. In high-fat diet (HFD)-induced obese mice, microRNA-450a-5p expression was increased in the serum, liver, and white adipose tissue. Moreover, the adipose Dicer-knockout mouse model was constructed to identify adipose tissue as the main source of microRNA-450a-5p. microRNA-450a-5p could inactivate the insulin signal pathway by targeting the inhibited Dual Specificity Phosphatase 10 (DUSP10) and inducing IR and glucose metabolism disorders in vitro cultured hepatocytes and adipocytes. Additionally, microRNA-450a-5p was found to regulate DUSP10 expression and insulin signaling activity, influencing glucose tolerance and insulin sensitivity across various models, including normal diet, HFD-induced obese, adipose tissue-specific microRNA-450a-5p-knockout, and db/db mice. Furthermore, gallic acid might play a potential role in inhibiting glucose levels by decreasing microRNA-450a-5p expression. Thus, microRNA-450a-5p emerges as an attractive therapeutic target for addressing obesity, IR, and T2DM.

Differential risk of cardiovascular complications in patients with type-2 diabetes mellitus in Ghana: A hospital-based cross-sectional study.

To characterize clinically relevant subgroups of patients with type-2 diabetes mellitus (T2DM) based on adiposity, insulin secretion, and resistance indices. A cross-sectional study was conducted at Eastern Regional Hospital in Ghana from July to October 2021 to investigate long-term patients with T2DM. To select participants, a systematic random sampling method was employed. Demographic data was collected using a structured questionnaire and fasting blood samples were taken to measure glycemic and lipid levels. Blood pressure and adiposity indices were measured during recruitment. The risk of cardiovascular disease (CVD) was defined using Framingham scores and standard low-density lipoprotein thresholds. To analyze the data, k-means clustering algorithms and regression analysis were used. The study identified three groups in female patients according to body mass index, relative fat mass, glycated hemoglobin, and triglyceride-glucose index. These groups included the obesity-related phenotype, the severe insulin resistance phenotype, and the normal weight phenotype with improved insulin resistance. Among male patients with T2DM, two groups were identified, including the obesity-related phenotype with severe insulin resistance and the normal weight phenotype with improved insulin sensitivity. The severe insulin resistance phenotype in female patients was associated with an increased risk of high CVD (OR = 5.34, 95%CI:2.11-13.55) and metabolic syndrome (OR = 7.07; 95%CI:3.24-15.42). Among male patients, the obesity-related phenotype with severe insulin resistance was associated with an increased intermediate (OR = 21.78, 95%CI:4.17-113.78) and a high-risk CVD (OR = 6.84, 95%CI:1.45-32.12). The findings highlight significant cardiometabolic heterogeneity among T2DM patients. The subgroups of T2DM patients characterized by obesity and/or severe insulin resistance with or without poor glycemic control, have increased risk of CVD. This underscores the importance of considering differences in adiposity, insulin secretion, and sensitivity indices when making clinical decisions for patients with T2DM.

Tear glucose is associated with the presence and severity of diabetic retinopathy

PurposeTo examine the association between tear glucose (TG) and the presence and severity of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).MethodsA cross-sectional study. TG was examined by rapid qualitative test strip in 160 patients. The severity of DR was graded as mild DR and severe DR. The presence and severity of DR were compared between patients with positive and negative TG. The association of TG with the presence and the severity of DR was estimated by multivariable regression analysis and spearman’s rank correlation test, respectively. The performance of TG to detect DR was evaluated by the receiver operating characteristic (ROC) curve.ResultsIn this study, 160 patients were included, with a median age of 64.0 years, and 88 (55.0%) patients were males. A total of 91 (56.9%) patients had positive TG, and 69 (43.1%) patients had negative TG. In TG-positive group, 41 (45.1%) patients were diagnosed with DR, among them, 8 (19.5%) patients had mild DR, and 33 (80.5%) patients were afflicted with severe DR. Multivariable logistic regression indicated that the presence of DR positively correlated with the presence of positive TG (odds ratio [OR], 3.62; 95% confidence interval [CI], 1.56–8.40; p < 0.01), longer duration of diabetes (OR, 1.11; 95% CI 1.06–1.17; p < 0.01) and higher HbA1c (OR, 1.25; 95% CI 1.01–1.54; p = 0.03). Moreover, Spearman’s correlation analysis suggested that the grading of TG increased with the severity of DR (rs = 0.28, p < 0.01). The area under the curve (AUC) of the model integrating TG, the duration of diabetes and HbA1c was 0.76 (95% CI 0.69–0.84), indicating a fair discriminative ability of DR.ConclusionTG level was associated with the presence and the severity of DR. TG might be an easy-to-use, non-invasive parameter to the screening and monitoring of DR among patients with diabetes.

Process Evaluations of Interventions for the Prevention of Type 2 Diabetes in Women With Gestational Diabetes Mellitus: Systematic Review.

Gestational diabetes mellitus (GDM) is characterized by hyperglycemia in pregnancy and typically resolves after birth. Women with GDM have an increased risk of developing type 2 diabetes mellitus (T2DM) later in life compared to those with normoglycemic pregnancy. While diabetes prevention interventions (DPIs) have been developed to delay or prevent the onset of T2DM, few studies have provided process evaluation (PE) data to assess the mechanisms of impact, quality of implementation, or contextual factors that may influence the effectiveness of the intervention. This study aims to identify and evaluate PE data and how these link to outcomes of randomized controlled trials (RCTs) of T2DM prevention interventions for women with GDM. A systematic review was conducted to identify studies published from 2005 to 2020 aiming to capture the most recent DPIs. Five electronic bibliographic databases (Cochrane Library, Cochrane Collaboration Registry of Controlled Trials, Embase, PubMed, and MEDLINE) were searched to identify relevant studies. Inclusion criteria were published (peer-reviewed) RCTs of DPIs in women with a current diagnosis or history of GDM. Exclusion criteria were studies not published in English; studies where the target population was women who had a family history of T2D or women who were menopausal or postmenopausal; and gray literature, including abstracts in conference proceedings. The Medical Research Council's PE framework of complex interventions was used to identify key PE components. The Mixed Method Appraisal Tool was used to assess the quality of included studies. A total of 24 studies were included; however, only 5 studies explicitly reported a PE theoretical framework. The studies involved 3 methods of intervention delivery, including in person (n=7), digital (n=7), and hybrid (n=9). Two of the studies conducted pilot RCTs assessing the feasibility and acceptability of their interventions, including recruitment, participation, retention, program implementation, adherence, and satisfaction, and 1 study assessed the efficacy of a questionnaire to promote food and vegetable intake. While most studies linked PE data with study outcomes, it was unclear which of the reported PE components were specifically linked to the positive outcomes. While the Medical Research Council's framework is a valuable source for conducting systematic reviews on PEs, it has been criticized for lacking practical advice on how to conduct them. The lack of information on PE frameworks in our review also made it difficult to categorize individual PE components against the framework. We need clearer guidance and robust frameworks for conducting PEs for the development and reporting of DPIs for women with GDM. PROSPERO International Prospective Register of Systematic Reviews CRD42020208212; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=208212. RR2-https://doi.org/10.1177/16094069211034010.

Assessing type-2 diabetes risk based on the Indian diabetes risk score among adults aged 45 and above in India

Millions of Indian adults are pre-diabetic with a greater risk of developing type-2 diabetes mellitus (T2DM). We conducted this study to assess the prevalence of type-2 diabetes risk among non-diabetic adults aged 45 years and above and identify the correlates for diabetes risk. We conducted a secondary analysis of Longitudinal Ageing Study in India (LASI) wave 1 data. A sample of 51,315 non-diabetic adults was extracted from LASI data and analysed. Type-2 diabetes risk was assessed based on the Indian Diabetes Risk Score (IDRS) by using four risk factor variables [i.e., (1) age of the respondent, (2) waist circumference, (3) family history of diabetes, and (4) physical activity]. A diabetes risk score of ≥ 60 was considered a high risk for diabetes. Descriptive statistics and multivariate analysis were conducted to assess the prevalence and correlates of diabetes risk respectively. About 41.2% had a high risk of diabetes. Among major Indian states, Kerala leads with 64.4% of its adults 45 years and above at high risk of diabetes. Obese level BMI (AOR 4.17; 95% CI 3.59–4.84), High cholesterol (AOR 1.51; 95% CI 1.22–1.87), History of heart disease and stroke (AOR 1.85; 95% CI 1.60–2.13), and males (AOR 1.25; 95% CI 1.16–1.34) had positive odds for high risk of diabetes. Individuals from scheduled tribes (AOR 0.85; 95% CI 0.76–0.96) had lower odds of diabetes risk. Obese individuals with a history of heart disease/stroke had a significantly higher (AOR 5.30; 95% CI 4.39–6.41) risk for diabetes. The findings suggest that it is essential to establish population-level interventions to tackle the modifiable risk factors for diabetes. Educational programs on diet and physical activity, creation of public spaces conducive to physical activity, promotion of fruit and vegetable intake, and discouragement of processed and ultra-processed diets can directly address inadequate physical activity and obesity, the two primary modifiable risk factors for type-2 diabetes. Additionally, strengthening health systems for early screening and management of diabetes and pre-diabetes is needed to prevent the diabetes epidemic.

Efficacy of high-intensity interval training in individuals with type 2 diabetes mellitus: An umbrella review of systematic reviews and meta-analyses.

High-intensity interval training (HIIT) has gained attention as a potentially effective alternative to traditional exercise modalities for individuals with type 2 diabetes mellitus (T2DM). Previous studies have evaluated this exercise strategy with various regimens, comparator groups and outcomes, limiting the generalisability of findings. We performed a novel umbrella review to generate an up-to-date synthesis of the available evidence regarding the effect of HIIT on glycaemic control and other clinically relevant cardiometabolic health outcomes in individuals with T2DM, as compared with traditional moderate-intensity continuous training (MICT) and/or non-exercise control (CON). This umbrella review followed the Preferred Reporting Items for Overviews of Reviews guideline. Seven databases were searched until August 2024. Systematic reviews with meta-analyses comparing HIIT with MICT and/or CON were included. Literature search, data extraction and methodological quality assessment (A MeaSurement Tool to Assess systematic Reviews 2 [AMSTAR-2]) were conducted independently by two reviewers. Ten systematic reviews with meta-analyses, encompassing 76 primary studies and 2954 unique participants, met the inclusion criteria. The data indicated that HIIT significantly improves glycosylated haemoglobin and cardiorespiratory fitness compared with CON (weighted mean difference [WMD]: -0.83% to -0.39% and 3.35-6.38 mL/kg/min) and MICT (WMD: -0.37% to -0.07% and 1.68-4.12 mL/kg/min) in individuals with T2DM. HIIT is also effective in improving other glycaemic parameters, including fasting blood glucose, fasting blood insulin and HOMA-IR. Improvement in body composition, lipid profiles and blood pressure has also been observed following HIIT. Most systematic reviews received moderate to low AMSTAR-2 score. This umbrella review supports HIIT as an efficacious exercise strategy for improving glycaemic control and certain relevant cardiometabolic health outcomes in individuals with T2DM. Our findings offer a comprehensive basis that may potentially contribute to informing physical activity recommendations for incorporating HIIT into T2DM management strategies.

Ionized and total magnesium levels and health outcomes in patients with type 2 diabetes mellitus

Magnesium (Mg) is a vital trace element in cellular processes, including glucose metabolism and insulin action. This study aimed to assess the prevalence of dysmagnesemia among patients with type 2 diabetes mellitus (T2DM) and its relationship with glycaemic control and diabetic complications. A cross-sectional study was conducted at Sultan Qaboos University Hospital (SQUH) from August 1, 2023, to April 30, 2024. The study included adult patients with T2DM treated with oral hypoglycemic agents (OHA), insulin, glucagon-like-peptide 1 (GLP-1) injections or their combinations. Both ionized (iMg) and total (tMg) concentrations were measured and the iMg/tMg ratio was calculated. A total of 329 patients with T2DM of which179 females (54.4%), were studied. Hypomagnesemia was observed in 10.0% based on iMg concentrations and 56.2% based on tMg concentrations, while hypermagnesemia was observed in 11.85% (iMg) and 1.82% (tMg). A positive correlation was found between iMg and tMg (r = 0.589, p < 0.01). Hypermagnesemia was associated with higher serum creatinine concentrations (p < 0.01) and lower estimated glomerular filtration rate (eGFR) (p = 0.026). An iMg/tMg ratio above 80% was associated with elevated HbA1c levels, while ratios below 60% were associated with diabetic retinopathy and hypertension. Dysmagnesemia was common among patients with T2DM. The iMg/tMg ratio was associated with diabetic control and presence of complications. The iMg/tMg ratio could be further studied as a potential marker for glycemic control.

Efficacy and safety of premixed versus basal-bolus regimens as intensification of insulin therapy in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized clinical trials.

To estimate the efficacy and safety of the basal-bolus and premixed insulin as intensification regimens in patients with type 2 diabetes mellitus (T2DM). A comprehensive search of online databases was performed until December 2022 to identify randomized controlled trials (RCTs) comparing premixed insulin versus basal-bolus regimen with treat-to-target intention. The Cochrane ROB-2 tool and GRADE approach were used for quality assessment and certainty of the evidence, respectively. Pooled weighted mean difference (WMD) and odds ratio (OR) were calculated using random-effects meta-analysis models. Eighteen RCTs were included in the meta-analysis, and 66% had a low risk of bias. We found no significant difference between the two regimens regarding HbA1c reduction (WMD: 0.03% [-0.05%, 0.10%]). The basal-bolus regimen improved fasting plasma glucose (FPG) more than the premixed regimen (WMD: 6.35 mg/dL [0.31, 12.39]). Both had similar effects on weight gain. The odds of developing overall, nocturnal, and severe hypoglycemia were comparable (pooled OR: 0.9, 1.02, and 1.00, respectively) with no heterogeneity. Findings of the model were robust. The certainty of the evidence was moderate to high for all outcomes except FPG. Two regimens are clinically comparable. Patient preference should be considered when adopting an individualized approach in a real-world setting.

Glucagon-Like Peptide 1 Receptor Agonists and Venous Thromboembolism in Type 2 Diabetes: A Target Trial Emulation.

Glucagon-like peptide 1 receptor agonists (GLP1-RA) are anti-diabetes agents recently approved for weight loss. Obesity is an established risk factor for venous thromboembolism (VTE). Moreover, preclinical studies have shown that GLP1-RA may attenuate thromboxaneinduced platelet activation. Therefore, we hypothesized that GLP1-RA use may reduce the risk of VTE. We performed a target trial emulation using a population-based database of electronic health records to evaluate whether GLP1-RA use is associated with a reduction in VTE in patients with type 2 diabetes mellitus (T2DM) compared with dipeptidyl peptidas e-4 inhibitors (DPP4i). Patients who were newly initiated on GLP1-RA were propensity scorematched to patients who were newly initiated on DPP4i. We evaluated the primary outcome, composite VTE, identified using ICD-10 codes, within 12 months of the initiation of GLP1-RA or DPP4i. The study cohort comprised 540,258 patients with 270,129 individuals receiving either GLP1-RA or DPP4i. Over 12 months of follow-up, patients who received GLP1-RA had a lower incidence of VTE compared with patients who received DPP4i (6.1 vs. 7.6 events per 1000 patient-years, hazard ratio [HR], 0.78 [95% CI: 0.73-0.83]). This was similar for PE (2.9 vs. 3.8 events per 1000 patient-years, HR, 0.74 [95% CI: 0.68-0.82]) and DVT (3.9 vs. 4.7 events per 1000 patient-years, HR, 0.81 [95% CI: 0.75-0.88]). In this propensity scorematched, target trial emulation study, patients with T2DM who received a GLP1-RA had a lower risk of VTE at one year compared with patients who received DPP4i.

The Impact of frailty on the effectiveness of intensive blood pressure control for patients with type 2 diabetes: a secondary analysis of a randomised controlled trial

BackgroundFrailty is an independent risk factor for cardiovascular events. It is uncertain whether frailty modifies the efficacy of intensive blood pressure (BP) control among participants with type 2 diabetes mellitus(T2DM).MethodsThe...

Research progress and future prospects of small-molecule glucagon-like peptide-1 receptor agonists (GLP-1RAs)

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are key agents in the treatment of type 2 diabetes mellitus (T2DM) and obesity. Small-molecule GLP-1RAs offer the advantage of oral administration while demonstrating efficacy comparable to that of peptide drugs. Despite synthetic challenges and solubility issues, compounds such as Pfizer’s PF-06882961 (Danuglipron), Eli Lilly’s LY3502970 (Orforglipron), and Hengrui Pharma’s HRS-7535 have shown potential to reduce glycosylated hemoglobin A1c (HbA1c) levels and body weight in Phase I-II trials, with mild to moderate gastrointestinal adverse effects, suggesting that they may be promising therapeutic options in the future.

Effect of exercise training on cardiac autonomic function in type 2 diabetes mellitus: a systematic review and meta-analysis.

Cardiac autonomic neuropathy (CAN) is an underdiagnosed complication of type 2 diabetes mellitus(T2DM) and is associated with cardiovascular morbidity and mortality. Cardiac autonomic reflex tests (CARTs) are the gold standard; they are non-invasive and clinically feasible for screening CAN. The objective of the present meta-analysis was to examine exercise's effect on cardiac autonomic function using CARTs in T2DM. The Preferred Reporting Items for Systematic Review and Meta-Analysis Checklist (PRISMA) was used. Electronic databases were systematically used to retrieve relevant studies after title and abstract screening. Studies utilizing exercise training with cardiac autonomic function (CARTs) outcomes in individuals with type 2 diabetes mellitus were included. The meta-analysis was conducted using RevMan 5.4.1, usingthe random effects model, and appropriate tests for heterogeneity. The Cohrane ROB-2 tool was used for randomized controlled trials (RCTs) and theROBINS-I tool for non-RCT for risk of bias assessment were used. Three studies were included (two for meta-analysis), considering the outcome of the E:I ratio, 30:15 ratio, and Valsalva ratio. The studies did not show any influence on the E:I and 30:15 ratio in the pooled analysis witha low risk of ineffectiveness for the exercise intervention. Exercise training significantly affected the Valsalva ratio. A different type of exercise intervention was utilized in all three studies. There was a low to moderate certainty for the evidence. The results indicate that further robust and high-quality randomized controlled trials utilizing cardiac autonomic reflex tests (which have clinical and physiological relevance) in type 2 diabetes mellitus are required for drawing conclusions. PROSPERO CRD42023445561.