Type 2 Diabetes Patients Research Articles

Identification of genetic loci enriched in obese or lean T2D cases in the Korean population.

Obesity causes many complex diseases including type 2 diabetes (T2D). Obesity increases the risk of T2D in Europeans, but there are many non-obese (lean) T2D patients in East Asia. To discover genetic factors enriched in obese or lean T2D patients, we conducted a genome-wide association (GWA) analysis for T2D stratified by BMI in the Korean population. In the discovery stage, 654 and 247 individuals classified as obese (BMI > 25) and lean (BMI < 23) T2D patients, respectively, were compared with 3,842 control subjects for GWA analysis. Several BMI-stratified T2D variants detected in the discovery stage were further tested in the replication stage, which included 402 obese and 220 lean T2D cases, and 3,615 controls. Meta-analysis combining the discovery and replication stages detected two variants with genome-wide significance: rs2356138 [P = 2.8 × 10-8, OR = 2.06 (1.59-2.65)] in obese T2D subjects and rs9295478 [P = 2.5 × 10-9, OR = 1.61 (1.38-1.88)] in lean ones. The SNP rs9295478 is located in CDKAL1, a well-known T2D gene previously identified in several GWA studies. Meanwhile, the SNP rs2356138 is a previously unknown variant located in PKP4. We discovered genetic loci enriched in obese or lean T2D patients in the Korean population. Our findings should facilitate more effective control of T2D in Koreans.

Metformin lowers risk of hearing loss and mortality in type 2 diabetes.

To assess the association between metformin use and the risk of sudden sensorineural hearing loss (SSNHL) in patients with Type 2 diabetes (T2D), a population at elevated risk for SSNHL. This cohort study utilized data from Taiwan's National Health Insurance Research Database, following T2D patients from 2008 to 202 database's baseline. Metformin use was defined as achieving ≥80% of the medication possession ratio (MPR) and ≥28 cumulative defined daily doses (cDDD) within three months. The control group included patients with ≥80% MPR from other antidiabetic agents, ensuring active treatment comparability. Propensity score matching was applied to balance covariates, while competing risk models accounted for mortality. Hazard ratios (HRs), incidence rates (IRs), and incidence rate ratios (IRRs) were calculated. Metformin users demonstrated a lower SSNHL incidence (IR: 11.48 per 10,000 person-years) compared to non-users (IR: 15.66 per 10,000 person-years), with an IRR of 0.73 (95% CI: 0.66-0.82; p < 0.0001). Adjusted HRs indicated a 27% reduction in SSNHL risk (HR: 0.73; 95% CI: 0.66-0.82). Higher cumulative doses (Q4: HR 0.36; 95% CI: 0.29-0.46) and daily doses ≥1 DDD (HR: 0.78; 95% CI: 0.69-0.87) were linked to further risk reductions. Metformin use was also associated with lower overall mortality. Metformin use is associated with a dose-dependent reduction in SSNHL risk and lower mortality in T2D patients. The rigorous definitions of metformin exposure and an actively treated comparator group emphasize these findings, suggesting metformin's potential role in SSNHL prevention and improved survival.

Patterns of Dyslipidemia Among Patients with Diabetes Mellitus

Background: Diabetes mellitus presents a prevalent endocrine and metabolic challenge globally. Type-2 diabetic patients exhibit a heightened incidence of dyslipidemia, characterized by elevated low-density lipoprotein (LDL), diminished high-density lipoprotein (HDL), or increased triglycerides (TG) levels. This phenomenon poses a significant public health concern both internationally and within our nation. Objective: This study aimed to assess the patterns of dyslipidemia among diabetes patients. Methods: This cross-sectional observational study was conducted at the Outpatient Department (OPD) of Shaheed Ziaur Rahman Medical College Hospital, Bogura, from July 2018 to June 2019. Both male and female patients with Type2 diabetes were considered as the study population. A total of 90 patients were selected as study subjects through purposive sampling.The study included 45 diabetic patients on therapy, divided into male (A1, n=19) and female (A2, n=26) subgroups. Additionally, 45 newly diagnosed diabetic patients were categorized into male (B1, n=15) and female (B2, n=30) subgroups.Analysis was performed by using SPSS (Statistical Package for Social Science) version 22.0. Results: The study found similar ages and BMI among groups. Elevated serum TC was noted in 31.6%, 19.2%, 26.7%, and 30% of subjects in A1, A2, B1, and B2 respectively. High serum TG levels were observed in 36.8%, 38.5%, 40%, and 66.7% of subjects in the respective groups. Dyslipidemia prevalence varied, with A1 at 57.9%, A2 at 53.8%, B1 at 46.7%, and B2 at 76.7%. High HbA1C was prevalent in B1 and B2 (100%). Conclusion: Dyslipidemia patterns among diabetes patients exhibit significant variability, with elevated serum total cholesterol, triglycerides, and low-density lipoprotein levels, alongside reduced high-density lipoprotein levels, commonly observed. These findings underscore the importance of tailored lipid management strategies in mitigating cardiovascular risk in this high-risk population. J Rang Med Col. September 2024; Vol. 9, No. 2: 78-83

Comparative estimate of glucose-lowering therapies on risk of incident pneumonia and severe sepsis: an analysis of real-world cohort data

BackgroundSodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are treatments for type 2 diabetes (T2D). Beyond glucose-lowering and cardiorenal protection, these drugs may protect against pneumonia and...

Correlation between Insulin antibodyand HbA1c in Diabetes Mellitus

Insulin antibodies (INAs) are found in both types of diabetic patients and have low binding capacity and high affinity leading to hypoglycemia or hyperglycemia in type II patients taking insulin, which differs from the insulin antibodies found in type I that contain a high capacity of insulin binding and low affinity. This work aims to detect the levels of insulin antibodies and HbA1c in diabetic patients, and find the correlation between them and its potential role in glucose control. The study involved 60 patients with diabetes, divided into two groups type I and type II, each group containing 30 patients, in addition to 30 healthy individuals as a control group. High-performance liquid chromatography in a D-10 analyzer was used to measure HbA1c while ELISA was used to measure INAs in control and patients .Results: The current finding showed significant an elevated mean levels of HbA1c and INAs in both of patients groups compare to healthy, and there was non-significant weak positive correlation between them (R= 0.107 , P= 0.4 ).Together, elevated levels of HbA1c and INA, and the positive correlation between their levels, provide evidence of the effect of insulin antibodies on glycemic control and the effects of HbA1c levels in patients with diabetes.

Efficacy and safety of the glucagon receptor antagonist volagidemab in type-1 diabetes: A systematic review and meta-analysis.

The glucagon receptor antagonist (GRA) volagidemab is the first-in-class fully human monoclonal antibody that inhibits glucagon receptor. GRA can improve glycemia by reducing endogenous glucose production and reduce risks of diabetic ketoacidosis by suppressing ketogenesis. This systematic review and meta-analysis analyzed the efficacy and safety of volagidemab in type-1 diabetes (T1D). Electronic databases were searched for randomized controlled trials (RCTs) involving T1D patients receiving volagidemab. The primary outcome was to evaluate changes in total daily dose (TDD) of insulin. The secondary outcomes were to evaluate changes in measures of glycemia, hypoglycemia, and adverse events. Data from 3 RCTs (98 patients) were analyzed. Volagidemab (70mg/week) was associated with a significant reduction in TDD of insulin requirement (mean difference [MD]: -8.45 units/day (95% confidence interval [CI]: [-12.09, -4.81]); I2=83%; p<0.01) and average blood glucose (MD: -21.42mg/dL (95% CI: [-37.10, -5.74]); I2=88%; p<0.01), compared to placebo. Volagidemab use was associated with a significant increase in time in range (blood glucose: 70-180mg/dL) (MD: 10.93% (95% CI: [6.69, 15.17]); I2=55%; p<0.01) and significant reduction in time above range (blood glucose >180mg/dL) (MD: -11.93% (95% CI: [-14.71, -9.15]); I2=6%; p<0.01) without any impact on time below range (blood glucose <70mg/dL) (MD: 0.14% (95% CI: [-0.56, 0.84]); I2=0%; p=0.70), compared to placebo. Occurrence of treatment-emergent adverse events (odds ratio [OR]: 0.96 (95% CI: [0.36, 2.56]); I2=8%; p=0.94) and hypoglycemia (OR: 0.56 (95% CI: [0.11, 2.89]); I2=0%; p=0.49) were similar among volagidemab users as compared to placebo. Short-term volagidemab use was associated with significant reduction in insulin requirement along with improvement in glycemia.

Multi-scale inferomedial femoral neck bone quality in type 2 diabetes patients with fragility fracture.

Both trabecular and cortical bone undergo changes at multiple scales. We previously demonstrated the multi-scale changes in trabecular bone quality that contribute to bone fragility in type 2 diabetes (T2D). The link between increased fragility in T2D and multi-scale changes in cortical bone and their interaction with glycation remains unclear. This study presents, first-ever, multi-scale cortical bone quality parameters in T2D patients after their first hip fracture. The study objective was to determine the association between cortical porosity (Ct.Po.), mechanical, material, and bone compositional properties in T2D. Inferomedial femoral neck (FN) bone tissue specimens were collected from patients (n = 10 with T2D, n = 25 age- and sex-matched non-diabetes controls) who underwent hip replacement surgery following the first hip fragility fracture. Bone mineral density at FN was found to be similar between groups. In T2D, Ct.Po was higher (p = 0.038), while ultimate stress (p = 0.021), ultimate strain (p = 0.040), post-yield strain (p = 0.011), toughness (p = 0.005), yield energy (p = 0.003), and post-yield energy (p = 0.004) were notably lower. Tissue compositional differences included lower gravimetric mineral/matrix (p = 0.017), higher non-enzymatic collagen cross-link ratio (NE-xLR) (p = 0.049) and higher sugar/matrix ratio (p = 0.042) in T2D. Fluorescent advanced glycation end-product (fAGEs) content was higher in T2D bone (p = 0.043). At the mesoscale, the fAGEs in the bone matrix are inversely related to the yield- and ultimate strain of T2D bone, and NE-xLR is negatively correlated with yield- and ultimate- stress in the T2D group. In conclusion, study findings demonstrate that elevated glycation weakens the mechanical integrity of cortical bone by reducing its ability to absorb energy and resist deformation, thereby contributing to bone fragility in T2D. The strong association of fAGEs with lower yield strain, along with the association of NE-xLR with lower yield- and ultimate stress, establishes a causal link between AGEs and the deterioration of cortical bone mechanical properties. These findings underscore the need for strategies targeting glycation and collagen quality to mitigate fracture risk in T2D patients.

Chinese Visceral Adipose Index is Associated with Arterial Stiffness in Type 2 Diabetes Patients: A Cross-Sectional Study.

The purpose of this study is to investigate the association between Chinese Visceral Adipose Index(CVAI) and brachial-ankle pulse wave velocity (baPWV) in type 2 diabetes (T2D) patients, in order to provide scientific evidence for the prevention and treatment of macrovascular complications in T2D. This research adopts the cross-sectional study design. Anthropometric assessment, baPWV assessment and biochemical assessment were performed in 2906 T2D patients. CVAI was calculated from the combination of triglycerides, age, high-density lipoprotein cholesterol, waist circumference, body mass index. Multivariate regression analysis and generalized additive model were used to analyze the association between bapwv and CVAI. Subgroup analysis and interaction analysis were used to analyze the influencing factors. After adjustment for covariates, baPWV tended to increase inthe quartiles of CVAI. In males, As CVAI increases by a unit, baPWV was increased by 0.28 cm/s (95% CI: -0.05, 0.61 P=0.0934). In females, As CVAI increases by a unit, baPWV was increased by 1.60 cm/s (95% CI: 1.07, 2.14). A non-linear connection in males and a linear connection in females between the CVAI and baPWV was revealed. In males, we found that CVAI interacted with baPWV in different duration of diabetes (P interaction = 0.0052), alcohol consumption status (P interaction = 0.0375). In females, CVAI interacted with baPWV in glycated hemoglobin (P interaction = 0.0003), systolic blood pressure (P interaction = 0.0001), diastolic blood pressure (P interaction<0.0001), duration of diabetes (P interaction = 0.0014), the use or non-use of glucose-lowering drugs (P interaction = 0.0006), the use or non-use antihypertensive drugs (P interaction = 0.0004), females' menopausal status (P interaction = 0.0012). The relationship between CVAI and baPWV in T2D patients is positively non-linear in males and linear in females. In all subjects, this relationship was influenced by diabetes duration. In males, drinking status affected this relationship, and in females, It is influenced by blood pressure, glycemic control, menopausal status, and the use of glucose-lowering and hypotensive drug, highlighting the complex interplay between visceral fat and arterial stiffness in the T2D population.

Impact of Sodium-Glucose Co-Transporter Type-2 Inhibitors on Alanine Aminotransferase Levels in Type-2 Diabetes Patients Having Features of Nonalcoholic Fatty Liver Disease: A Retrospective Cohort Study in Pakistan.

We aimed to elucidate the effectiveness of Sodium-glucose co-transporter-2 inhibitors (SGLT2-I) in the reduction of ALT among Type-2 diabetes patients (T2DM) with Non-alcoholic fatty liver disease (NAFLD). We retrospectively collected data from 120 files of T2DM, aged 30-60 years, with elevated ALT, and documented follow-up for one year from August 2018 - July 2019. The effects of SGLT2Is (Dapagliflozin and Empagliflozin) were evaluated using Generalized Estimating Equation (GEE) for analysis. The overall mean age was 48.9 ± 7.3 years, 57.5% were females, and the mean duration of diabetes was 8.5 ± 5.6 years. At baseline, the mean BMI was 32.5 ± 5.7 kg/m2, mean ALT was 51.6 IU/L ± 17.8 IU/L, and mean HbA1c was 8.5% ± 1.5%. There was a statistically significant reduction in mean ALT of 2.2 IU/L (p-value 0.02) with every 10 mg/dl increase in LDL among females using 10 mg Empagliflozin as compared to males not on SGLT2i. We observed an average reduction in mean ALT levels when SGLT2Is was initiated in T2DM patients having NAFLD. Apart from encouraging diet and lifestyle modification, early intervention with SGLT2Is may decrease liver-related morbidity and mortality resulting from NAFLD.

Gender Differences in the Impact of Type 2 Diabetes on Long-Term Mortality in Patients with Heart Failure and Preserved Ejection Fraction

Background: Type 2 diabetes (T2D) is frequently present as a comorbid condition in patients diagnosed with heart failure with preserved ejection fraction (HFpEF). Recent investigations have demonstrated that females with diabetes are more susceptible to the development of HF compared to males. Nevertheless, there is a lack of extensive research on the prospects of T2D patients with HF, specifically in relation to gender.Objective: We examined the varying effect of T2DM on overall mortality in males compared to females with HFpEF following hospitalization for acute HF.Methods: This prospective study included 266 patients with HFpEF who were admitted to and discharged from our hospital after being diagnosed with acute HF. This study employed a Multivariate Cox regression model to assess the association between gender, T2D, and the risk of long-term overall morbidity. Hazard ratios (HR) were used to express risk estimation.Results: The average age of the group was 68.3±7.2 years and 151 (56.8%) were female. The prevalence of T2D was comparable between males and females (47.2% vs. 53.7%; p=0.168). Following a median follow-up period of 4.2 years (with an interquartile range of 2.0-7.4 years), 158 (59.4%) patients reported mortality. In females, T2D was associated with a significantly increased risk of death from any cause (HR=2.62; 95% confidence interval, 2.36-3.16; P<0.002). However, in males, there was no significant association between T2D and mortality (HR=2.08; 95% confidence interval, 1.69-2.49; P=0.087).Conclusions: Following the diagnosis of acute HF in patients with HFpEF, females with T2D had an increased risk of mortality.

Impact of metabolic and bariatric surgery on weight loss and insulin requirements in type 1 and insulin-treated type 2 diabetes.

Metabolic and Bariatric Surgery (MBS) is effective in improving metabolic outcomes and reducing weight in patients with obesity and diabetes, with less explored benefits in type 1 diabetes (T1D). This study aimed to evaluate the impact of MBS on weight loss and insulin requirements in T1D patients compared to insulin-treated type 2 diabetes (T2D) patients over a 5-year period. This retrospective analysis included patients who underwent primary sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) with a confirmed preoperative diagnosis of either T1D or insulin-treated T2D. Primary endpoints focusing on weight loss and secondary outcomes assessing changes in insulin dosage and glycemic control. After 5 years, weight loss was similar across groups, with total weight loss at 14.2% for T1D and 17.6% for insulin-treated T2D in SG, and 22.6% for T1D vs. 26.8% for insulin-treated T2D in RYGB. Additionally, there was a significant reduction in median daily insulin doses from 140.5 units at baseline to 77.5 units at 1 year postoperatively, sustained at 90 units at 5 years. The differential impact of MBS procedure was also highlighted, where RYGB patients showed a more pronounced and enduring decrease in insulin requirements compared to SG.

Effects on HbA1c of referral of type 2 diabetes patients to secondary care

Aim To study trajectories of HbA1c in type 2 diabetes (T2D) patients referred to diabetes outpatient clinics (DOCs), and to explore characteristics of referrals and patient pathways in patients treated in DOCs. Methods We retrospectively followed T2D patients from the Norwegian population-based ROSA 4 study to identify persons with T2D who were referred to a DOC. We used latent class trajectory modelling to identify subgroups of patients with similar patterns of HbA1c one year before to one year after the first consultation at a DOC. We performed multinomial regression analyses to identify baseline characteristics associated with group membership. Results Four hundred and two of 6716 T2D patients started treatment at a DOC, constituting a yearly starting rate of 1.5%. We identified three classes of HbA1c trajectories: (1) stable moderate hyperglycaemia (75%); (2) severe hyperglycaemia with a decline in HbA1c around referral (14%) and (3) severe hyperglycaemia with a decline in HbA1c after starting treatment at the DOC (11%). HbA1c trajectories were associated with diabetes duration RRR 0.92, CI (0.87, 0.97) in class 2 vs. 1 and 0.93 (0.88, 0.98) in class 3 vs. 1. Some differences were found between clinics in rejection rate, processes of care, and duration of follow-up. Conclusions Norwegian GPs handle most T2D patients themselves. Those with T2D and severe hyperglycaemia had a considerable benefit from being referred to a DOC, though with two separate trajectories: One where HbA1c improved around the time of referral, and another that improved after starting in a DOC.

The association between chemosensitivity and the 10-year risk of type 2 diabetes in male patients with obstructive sleep apnea

PurposeObstructive sleep apnea (OSA) is associated with a variety of diseases, including type 2 diabetes (T2D). Chemosensitivity is an important component of the pathophysiological mechanisms of OSA, and it is not only elevated in patients with OSA but also in those with T2D. This study aimed to investigate the association between chemosensitivity and the risk of developing T2D in patients with OSA.MethodsA total of 135 male participants with OSA and without pre-existing T2D were enrolled in this study. Peripheral chemosensitivity was evaluated using the rebreathing test. Data on demographics, polysomnographic parameters, and clinical characteristics were collected. The QDiabetes-2018 risk calculator was employed to calculate the 10-year T2D risk. The association between peripheral chemosensitivity and 10-year T2D risk was examined using multivariate logistic regression.ResultsA total of 64 participants had moderate-to-high 10-year risk of T2D. In the fully adjusted model, participants situated within the second and fifth quantiles of peripheral chemosensitivity levels demonstrated a higher risk of developing T2D, with OR of 4.87 (95% CI, 1.22–19.43) and 5.26 (95% CI, 1.27–21.68) respectively. However, across varying levels of peripheral chemosensitivity, no significant difference in the 10-year T2D risk was observed among different severities of OSA.ConclusionHigher peripheral chemosensitivity was associated with an increased 10-year T2D risk, as calculated using a risk calculator based on clinical variables. For outcomes that reflect a moderate-to-high 10-year risk of T2D, the severity of OSA did not significantly affect the risk, irrespective of whether patients exhibited relatively low or high chemosensitivity.

Development and external validation of an algorithm for self-identification of risk for microvascular complications in patients with type 1 diabetes.

Microvascular complications, such as diabetic retinopathy (DR), diabetic nephropathy (DN) and diabetic peripheral neuropathy (DPN), are common and serious outcomes of inadequately managed type 1 diabetes (T1D). Timely detection and intervention in these complications are crucial for improving patient outcomes. This study aimed to develop and externally validate machine learning (ML) models for self-identification of microvascular complication risks in T1D population. Utilizing data from the Chinese Type 1 Diabetes Comprehensive Care Pathway program, 911 T1D patients and 15 patient self-reported variables were included. Combined with XGBoost algorithm and cross-validation, self-identification models were constructed with 5 variables selected by feature importance ranking. For external validation, an online survey was conducted within a nationwide T1D online community (N = 157). The area under the receiver-operating-characteristic curve (AUROC) was adopted as the main metric to evaluate the model performance. The SHapley Additive exPlanation was utilized for model interpretation. The prevalence rates of microvascular complications in the development set and external validation set were as follows: DR 7.0% and 12.7% (p = 0.013), DN 5.9% and 3.2% (p = 0.162) and DPN 10.5% and 20.4% (p < 0.001). The models demonstrated the AUROC values of 0.889 for DR, 0.844 for DN and 0.839 for DPN during internal validation. For external validation, the AUROC values achieved 0.762 for DR, 0.718 for DN and 0.721 for DPN. ML models, based on self-reported data, have the potential to serve as a self-identification tool, empowering T1D patients to understand their risks outside of hospital settings and encourage early engagement with healthcare services.

Effects of 3-month liraglutide treatment on oxidative stress and inflammation in type 2 diabetes patients with different urinary albumin-to-creatinine ratio categories

This study evaluates the effects of liraglutide on albuminuria, oxidative stress, and inflammation in type 2 diabetes (T2D) patients with different urinary albumin-to-creatinine ratio (UACR) categories. We enrolled 107 patients with T2D who were initiating liraglutide for glycemic control. Patients were categorized into 3 groups: group I (UACR &lt; 30 mg/g); group II (30 mg/g ≤ UACR ≤ 300 mg/g); group III (UACR &gt; 300 mg/g). We observed the changes in body mass index, fasting plasma glucose, glycated hemoglobin, lipid profile, serum liver enzymes, creatinine, uric acid, cystatin C, UACR, as well as oxidative stress and inflammation biomarkers such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase before and after 3 months of liraglutide treatment. After 3-month liraglutide treatment, fasting plasma glucose, glycated hemoglobin, and body mass index significantly decreased in all 3 groups regardless of the baseline UACR (all P &lt; .05). UACR significantly decreased in groups II (P = .005) and III (P = .001). Patients with higher UACR at baseline showed significantly greater albuminuria reduction (P &lt; .001). Compared with baseline, TNF-α, IL-6, MCP-1, and MDA were remarkably decreased, while SOD and glutathione peroxidase were significantly increased in all 3 groups (P &lt; .05). UACR at baseline showed a positive correlation with TNF-α, IL-6, and MDA, and a negative correlation with SOD at baseline. The change in UACR was negatively correlated with UACR, TNF-α, and MDA at baseline, while it was positively correlated with SOD at baseline, and also positively correlated with the change in MCP-1. Liraglutide ameliorated albuminuria in T2D patients with microalbuminuria and macroalbuminuria. The renoprotective effect of liraglutide was associated with the alleviation of oxidative stress and inflammation. These findings may provide new therapeutic strategies for patients with diabetic kidney disease.

Lipophilic index of serum phospholipids in patients with type 2 diabetes and atherosclerotic cardiovascular disease: links with metabolic control, vascular inflammation and platelet activation

BackgroundLittle is known about the mechanisms underlying the association of the serum phospholipid lipophilic index (LI) with atherosclerotic cardiovascular disease (ASCVD) in patients with type 2 diabetes (T2D). Therefore, we investigated whether the LI is associated with glucometabolic control, meta-inflammation, thrombin generation, fibrin clot properties, endothelial function and platelet activation in T2D patients with angiographically documented ASCVD.MethodsWe studied 74 T2D patients with ASCVD, aged 65.6 ± 6.8 years, with a median diabetes duration of 10 years and median HbA1c of 7.0%. Serum phospholipid fatty acids (FAs) were measured by gas chromatography. The serum phospholipid LI was calculated as the sum of the products of the proportion (% of total FAs) with the melting points (°C) of each individual FA, divided by the sum of the proportions of all FAs. Levels of HbA1c, insulin, leptin, adiponectin, lipid profiles, inflammatory markers (hsCRP, interleukin-6, TNF-α), Lp-PLA2 (a biomarker of vascular inflammation), endothelial function (sICAM-1, sVCAM-1, FMD, NMD), thrombin generation, fibrin clot properties and platelet activation, measured by light transmission aggregometry with arachidonic acid [AA] and adenosine diphosphate [ADP], were assessed.ResultsPatients with LI > 16.9 °C (median) had higher HbA1c concentrations by 5.9% compared to the remaining subjects (p = 0.035). In this group, HbA1c levels ≥ 7.0% were found more often than in individuals with LI ≤ 16.9 °C (62.2 vs. 35.1%; p = 0.020). Subjects with LI > 16.9 °C had higher levels of TCh by 17.1% (p = 0.012), LDL-Ch by 29.4% (p = 0.003), interleukin-6 by 22.2% (p = 0.031) and Lp-PLA2 by 32.4% (p = 0.040), compared to the remaining patients. Moreover, they had increased maximal platelet aggregation induced by AA (p = 0.045), but not by ADP. Serum phospholipid LI correlated with HbA1c (r = 0.24; p = 0.037), TCh (r = 0.36; p = 0.002), LDL-Ch (r = 0.38; p < 0.001), interleukin-6 (r = 0.27; p = 0.020) and Lp-PLA2 (r = 0.26; p = 0.026). There were no intergroup differences in endothelial function, thrombin generation and fibrin clot properties. Regression analysis showed that HbA1c ≥ 7.0% and serum levels of LDL-Ch, interleukin-6 and Lp-PLA2 were predictors of LI > 16.9 °C in adjusted models.ConclusionsIn well-controlled T2D patients with ASCVD, the higher serum phospholipid LI is associated with worse glucometabolic control, enhanced vascular inflammation and higher platelet reactivity during aspirin treatment at cyclooxygenase-1-selective doses.

SGLT 2 Inhibitors: Mechanisms, Clinical Applications, and Future Directions

Due to the progressive and painful nature of type 2 diabetes (T2D), treatment may require periodic evaluation of patients, intensifying glucose-lowering therapy when glycaemic targets are not achieved and testing new methods. Among the newer classes of glucose-lowering drugs, sodium-glucose cotransporter 2 inhibitors (SGLT2is), which increase urinary glucose excretion to reduce hyperglycaemia, have made an impressive entry into the T2D treatment arsenal. Given their unique insulin-independent mode of action and favourable efficacy-adverse effect profiles, and their apparent benefits on cardiovascular-renal outcomes in intermediate-high-risk T2D patients, which have led to the updating of guidelines and product monographs, the role of this drug class in multidrug regimens is promising. However, despite much speculation based on pharmacokinetic and pharmacodynamic properties, physiological rationale and potential synergism, the glycaemic and pleiotropic effects of these agents when combined with other classes of glucose-lowering drugs remain largely under-researched. Therefore, this review discusses the mechanisms, clinical applications and future therapeutic role of SGLT2 inhibitors with a review of the literature.

Short-Term Impact of Digital Mental Health Interventions on Psychological Well-Being and Blood Sugar Control in Type 2 Diabetes Patients in Riyadh.

Type 2 diabetes (T2D) management is complicated by psychological factors, yet mental health interventions are not routinely integrated into diabetes care. This study investigated the impact of a digital mental health intervention on psychological well-being and glycemic control in T2D patients. A quasi-experimental study was conducted with 120 T2D patients divided into intervention (n = 60) and control (n = 60) groups. The intervention group received a one-month digital mental health intervention alongside standard care. Psychological well-being (PHQ-9, GAD-7, and DDS) and glycemic control (HbA1c) were assessed at baseline and post-intervention. The intervention group showed significant improvements in HbA1c levels (-0.5%, p = 0.032), PHQ-9 (-3.1, p = 0.001), GAD-7 (-2.8, p = 0.006), and DDS (-7.7, p = 0.012) scores compared to the control group. Strong correlations were observed between psychological improvements and HbA1c reductions. Higher engagement with the digital platform was associated with greater improvements in both psychological and glycemic outcomes. Integrating digital mental health interventions into T2D care can significantly improve both psychological well-being and glycemic control. These findings support a more holistic approach to diabetes management that addresses both mental and physical health aspects.

Relationship between liver and cardiometabolic health in type 1 diabetes.

Type 1 diabetes (T1D) is a chronic condition marked by insulin deficiency and hyperglycemia, with an increasing global incidence, particularly among children. Despite improvements in diabetes management, individuals with T1D continue to experience higher rates of cardiovascular disease (CVD), the leading cause of mortality in this population. Traditional CVD risk factors such as dyslipidemia and poor glycemic control are insufficient to fully explain the elevated risk in T1D, prompting further investigation into additional factors. Emerging evidence suggests that metabolic dysfunction-associated steatotic liver disease (MASLD) plays a critical role in this heightened CVD risk. This narrative review aims to explore the relationship between MASLD and CVD in individuals with T1D. The review focuses on the prevalence of MASLD, its contributing risk factors, and the potential impact of liver dysfunction on cardiovascular outcomes in this population. A review of existing literature was conducted, focusing on observational studies, cohort studies, and meta-analyses that investigate the prevalence of MASLD in T1D populations and its association with CVD. The review also examines the physiological mechanisms linking MASLD and CVD, including insulin resistance, systemic inflammation, and hepatic dyslipidemia. Key studies were evaluated to identify patterns in MASLD prevalence based on diagnostic modalities and to assess the independent contribution of MASLD to cardiovascular risk in T1D patients. MASLD is increasingly recognized as a significant contributor to CVD in individuals with T1D, particularly in those with shared risk factors like obesity and insulin resistance. Evidence suggests that MASLD exacerbates hepatic and systemic metabolic dysfunction, increasing CVD risk through mechanisms such as chronic inflammation and atherogenic lipid profiles. Routine liver health assessments and tailored management strategies targeting MASLD should be incorporated into clinical care for individuals with T1D to mitigate long-term cardiovascular complications.

A post-translational cysteine-to-serine conversion in human and mouse insulin generates a diabetogenic neoepitope.

Type 1 diabetes (T1D) affects a genetically susceptible population that develops autoreactive T cells attacking insulin-producing pancreatic β cells. Increasingly, neoantigens are recognized as critical drivers of this autoimmune response. Here, we report a novel insulin neoepitope generated via post-translational cysteine-to-serine conversion (C>S) in human patients, which is also seen in the autoimmune-prone non-obese diabetic (NOD) mice. This modification is driven by oxidative stress within the microenvironment of pancreatic β cells and is further amplified by T1D-relevant inflammatory cytokines, enhancing neoantigen formation in both pancreatic β cells and dendritic cells. We discover that C>S-modified insulin is specifically recognized by CD4 + T cells in human T1D patients and NOD mice. In humans with established T1D, HLA-DQ8-restricted, C>S-specific CD4 + T cells exhibit an activated memory phenotype and lack regulatory signatures. In NOD mice, these neoepitope-specific T cells can orchestrate islet infiltration and promote diabetes progression. Collectively, these data advance a concept that microenvironment-driven and context-dependent post-translational modifications (PTMs) can generate neoantigens that contribute to organ-specific autoimmunity.