Type 2 Diabetes Mellitus Research Articles

Characterisation of islet antibody‐negative type 1 diabetes mellitus in Indian children

AbstractAimsIslet antibody‐negative type 1 diabetes mellitus (T1DM) has not been well characterised. We determined the frequency of antibody‐negative T1DM and compared it with antibody‐positive T1DM in a cohort of north Indian children.MethodsIn a multi‐centre, prospective, observational study, 176 Indian children (age 1–18 years) were assessed within 2 weeks of diagnosis of T1DM. Antibodies against GAD65 (GADA), islet antigen‐2 (IA‐2A) and zinc transporter 8 (ZnT8A), were estimated using validated ELISA. HLA‐DRB1, DQA1 and DQB1 alleles were studied by Luminex‐based typing. Monogenic diabetes was determined by targeted next‐generation sequencing using the Illumina platform.ResultsAfter excluding 12 children with monogenic diabetes, GADA, IA‐2A and ZnT8A were present in 124 (76%), 60 (37%) and 62 (38%) o children, respectively, while 24 (15%) were negative for all antibodies. A single antibody (most frequently GADA) was present in 68 (41%) of children, while all three antibodies were found in 34 (21%). Islet antibody‐negative T1DM (n = 24, 15%) did not differ from antibody‐positive children in their clinical features, HbA1c or plasma C‐peptide, both at onset or after 1 year follow‐up (available in 62 children). The frequency of other organ‐specific antibodies or high‐risk HLA‐DR and DQ alleles were also similar. Children with a single islet antibody did not differ from those with multiple antibodies.ConclusionsThe frequency of various islet‐antibodies, in isolation and combination, differed considerably from studies among children of European descent with T1DM. Children with T1DM who were islet antibody‐negative were indistinguishable from those who were antibody‐positive.

Is glucose‐induced hypersecretion of glicentin after the revision surgery using Roux‐en‐Y gastric bypass related to improved glycemic control due to insulin hypersecretion in a type 2 diabetes patient without diabetes remission after laparoscopic sleeve gastrectomy?

ABSTRACTWe report case details of a morbidly obese patient with type 2 diabetes mellitus (T2DM) who became a failure of diabetes remission after laparoscopic sleeve gastrectomy (LSG). He had a marked improvement of hyperglycemia after the revision surgery using Roux‐en‐Y gastric bypass (RYGB), where passage failure of a solid food intake at the gastric angle portion disappeared after the revision surgery. Interestingly, he showed improvements of insulin and a marked glicentin secretions with minor changes in glucagon related peptide 1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) secretions in the oral glucose tolerance test OGTT after the RYGB surgery compared with post‐LSG. Although a marked increase in glucose‐induced glicentin secretion after RYGB surgery with increased insulin secretion, further studies are needed to confirm if the increased glicentin secretion after RYGB surgery is linked to stimulation of insulin secretion.

Dependent censoring bias assessment using inverse probability of censoring weights: Type 2 diabetes mellitus risk in patients initiating bisoprolol versus other antihypertensives in a Clinical Practice Research Datalink cohort study.

Dependent censoring involves a preferential attrition of a subgroup of interest; occurring in survival analysis, it may impact interpretation by introducing a selection bias. To assess the potential bias in a comparison of bisoprolol to other antihypertensives in terms of Type 2 diabetes mellitus (T2DM) incidence, inverse probability of censoring weights (IPCW) was used. It was further used to contextualize results obtained through competing risks analysis. Two estimands were considered to assess T2DM incidence while accounting for deviations from the initial antihypertensive monotherapy (DFM). A hypothetical estimand using IPCW, treating DFM as censoring, was interpreted together with a 'while-on-treatment' estimand, treating DFM as a competing risk. We illustrated our application with a cohort study based on Clinical Practice Research Datalink (CPRD) including 267,352 patients with newly diagnosed arterial hypertension between 2000 and 2017, initiating antihypertensive monotherapy among bisoprolol, other beta-blockers, renin-angiotensin system drugs (ACEi/ARB), diuretics and calcium-channel blockers. A mild dependent censoring process was hypothesized, leading to slight overestimation of T2DM incidence. Although subject to some limitations, a nonsignificant trend toward an excess of risk associated with ACEi/ARB was yielded consistently by IPCW and competing risks analyses. Conversely, in comparisons of bisoprolol versus either diuretics, other beta-blockers or calcium channel blockers, no significant differences or critical dependent censoring impact were found. Concurrent use of complementary estimands allowed formulating a refined interpretation of our findings: though not significant, the trend toward an excess of T2DM risk associated with a ACEi/ARB monotherapy compared with bisoprolol is likely not originating only from the minor dependent censoring. Reassessing identical estimands in other cohorts would provide insights to corroborate or refute this result.

Association Between Nontraditional Lipid Profiles and the Risk of Type 2 Diabetes Mellitus in Chinese Adults With Hypertension: Findings From the China Hypertension Registry Study.

The relationship between nontraditional lipid profiles and type 2 diabetes mellitus (T2DM) remains ambiguous within the hypertension population. The objective of this study is to examine the association between nontraditional lipid profiles and T2DM in Chinese adults with hypertension. The current investigation encompassed 13728 participants with hypertension from the China Hypertension Registry Study. Logistic regression analysis and smooth curve fitting were employed to evaluate the association between nontraditional lipid profiles and T2DM. The prevalence of T2DM was found to be 17.8%. In the fully adjusted model, atherogenic index of plasma (AIP) exhibited the highest odds ratios (ORs) for T2DM (OR: 2.71, 95% confidence interval [CI]: 2.26-3.26). Conversely, the fully adjusted ORs (95% CI) for total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)/HDL-C, and non-high-density lipoprotein cholesterol (Non-HDL-C) were 1.33 (1.25-1.41), 1.40 (1.29-1.51), and 1.41 (1.34-1.49), respectively. Additionally, the study demonstrated that AIP had a superior ability to identify T2DM. Subgroup analyses indicated that the relationship between AIP and Non-HDL-C with T2DM was more significant in the lighter weight population. In addition, the association of TC/HDL-C with LDL-C/HDL-C with T2DM was stronger in the lower homocysteine level population. Among the southern Chinese population with hypertension, all nontraditional lipid indices positively correlated with the risk of T2DM. Among these lipid indices, AIP exhibited superior discriminatory power in identifying T2DM compared to TC/HDL-C, LDL-C/HDL-C. Trial Registration: ChiCTR1800017274.

Urinary titin as a biomarker of sarcopenia in diabetes: a propensity score matching analysis.

Measuring urinary titin levels is expected to be useful in screening for muscle damage or injury in various diseases. We evaluated whether urinary titin levels were elevated in individuals with type 2 diabetes mellitus (T2DM) and how urinary titin levels were associated with the diagnosis of sarcopenia in T2DM. We performed a cross-sectional analysis of 114 controls and 515 patients with T2DM. Multivariate-adjusted models were used to determine the odds ratios (OR) of urinary titin cutoff values for diagnosing sarcopenia. Urinary titin levels were higher in the T2DM group than in the non-diabetes group after propensity score matching (median [IQR] 3.2 [2.3, 4.6] vs. 4.4 [2.7, 6.9] pmol/mg·creatinine). T2DM was associated with high titin levels after correction for comorbidities (odds ratio 2.46, 95% confidence interval (CI) 1.29-4.70, P = 0.006) but not after correction for sarcopenia-associated factors. Urinary titin levels above the cutoff value showed an odd ratio of 6.61 (age- and body mass index-adjusted, 1.26-34.6, P = 0.021) for the diagnosis of sarcopenia in men with T2DM aged ≥ 75 years. Results indicated that T2DM was associated with a high-titin state and that the urinary titin cutoff value could be useful for identifying candidates at high risk for sarcopenia, such as elderly men.

Quality priorities related to the management of type 2 diabetes in primary care: results from the COMPAS + quality improvement collaborative.

This study aims to describe the main type 2 diabetes mellitus (T2DM) quality improvement (QI) challenges identified by primary care teams in the province of Quebec who participated in the COMPAS + QI collaborative. A qualitative descriptive design was used to analyse the results of 8 COMPAS + workshops conducted in 4 regions of the province between 2016 and 2020. Deductive content analysis was performed to classify the reported QI priorities under the Consolidated Framework for Implementation Research domains; and proposed change strategies under the Behavior Change Wheel (BCW) intervention functions. A total of 177 participants attended the T2DM COMPAS + workshops. Three QI priorities were identified: (1) lack of coordination and integration of T2DM care and services; (2) lack of preventive services for pre-diabetes and T2DM; and (3) lack of integration of the patients-as-partners approach to support T2DM self-management. The proposed QI strategies to address those priorities were classified under the education, training, persuasion, habilitation and restructuring BCW intervention functions. This study provides insights on how QI collaboratives can support the identification of QI priorities and strategies to improve T2DM management in primary care.

Blood metabolomic profile in patients with type 2 diabetes mellitus with diabetic peripheral neuropathic pain.

This study aimed to identify metabolic markers for diabetic peripheral neuropathic pain (DPNP) in patients with type 2 diabetes mellitus (T2DM). Blood metabolite levels in the amino acid, biogenic amine, sphingomyelin, phosphatidylcholine (PC), carnitines, and hexose classes were analyzed in nondiabetic control (n = 27), T2DM without DPNP (n = 58), and T2DM with DPNP (n = 29) using liquid chromatography tandem mass spectrometry. Variable importance projection (VIP) evaluation by partial least squares discriminant analysis was performed on clinical parameters and metabolites. Sixteen variables with VIP > 1.0 (P < 0.05) were identified across all patient groups, and 5 variables were identified to discriminate between the two T2DM groups. DPNP patients showed elevated fasting blood glucose, glutamate, PC aa C36:1, lysoPC a C18:1, and lysoPC a C18:2, while low-density lipoprotein cholesterol, phenylalanine, and tryptophan were reduced. Glutamate, lysoPC a C18:1, and lysoPC a C18:2 discriminated T2DM with DPNP from those without DPNP with an AUC of 0.671. The AUC was improved to 0.765 when ratios of metabolite pairs were considered. Blood metabolites include glutamate, and phospholipid-related metabolites implicated in neuropathic pain may have the potential as biomarkers for DPNP. Further investigation is required to understand the mechanism of action of these altered metabolites in DPNP.

Identification of Metabolic Patterns in Korean Patients with Type 2 Diabetes Mellitus and their Association with Diabetes-Related Complications.

Resolving metabolic heterogeneity in patients with type 2 diabetes mellitus (T2DM) gives them access to precision medicine. Despite ethnic diversity in pathophysiological processes in individuals with T2DM, studies on subtypes of diabetes related to clinical characteristics in Asians are insufficient. This study aims to identify metabolic patterns in middle-aged patients with T2DM in Republic of Korea (Korea) and determine the incidence of diabetes-related complications according to patterns. We analyzed 6,603 patients with T2DM aged 30 to 64 who visited three centers of general hospital in Korea. Three metabolic patterns were derived: Obesity and Hypertension pattern (OH-P), Liver Function-related HyperGlycemia pattern (LFHG-P), and Decreased Kidney Function pattern (DKF-P). The highest tertile of the OH-P score was associated with an increased risk of peripheral vascular disease compared to the lowest tertile (HR = 1.26, 95% CI = 1.02-1.57). The highest tertile of the LFHG-P score was associated with an increased risk of myocardial infarction (HR = 1.79, 95% CI = 1.13-2.82) and atrial fibrillation (HR = 1.54, 95% CI = 1.07-2.23). No association with complications was found in the DKF-P. This study suggests the need for proper management and treatment according to metabolic patterns in patients with T2DM.

Relationship of serum calcium concentration with chronic kidney disease and mortality in type 2 diabetes mellitus patients: evidence from the NHANES 1999-2018.

This study aims to explore the relationship of serum calcium (Ca) concentration with diabetic kidney disease (DKD) and all-cause mortality among type 2 diabetes mellitus (T2DM) patients using National Health and Nutrition Examination Surveys (NHANES). Data of T2DM patients aged ≥ 40 years were screened from the NHANES database from 1999 to 2018. The outcomes were the risk of DKD diagnosed by urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 and the risk of all-cause mortality ascertained by linkage to National Death Index (NDI) records through 31 December 2019. The weighted univariate and multivariate logistic regression model and cox proportional hazard model were utilized to explore the relationships of serum Ca concentration with DKD and all-cause mortality, respectively, with odds ratios (ORs), hazard ratios (HRs) and 95% confidence interval. The relationships were further explored stratified by age, gender, body mass index (BMI), the duration of T2DM, and the history of cardiovascular disease (CVD), cancer and DKD. Totally, 6595 T2DM patients were included. Of these patients, 2441 (37.01%) had DKD and 1868 (28.32%) deaths occurred over a mean follow-up of 104.50 (± 1.61) months. In fully adjusted model, we observed high serum Ca concentration was associated with high risk of DKD (OR = 1.45, 95% CI 1.18-1.77) and high all-cause mortality risk (HR = 1.33, 95% CI 1.16-1.52). These relationships remained significant after performing subgroup analyses. The Restricted cubic spline curves shown that linear correlations were observed between serum Ca concentration and DKD as well as all-cause mortality (P < 0.05). Elevated serum Ca concentration may predict the high risk of DKD and poor prognosis in T2DM patients, and future large-scale and well-designed prospective cohort study is needed to explore the association of serum Ca concentration and DKD and prognosis in T2DM patients.

Developmental Origins of Non-Communicable Chronic Diseases: Role of Fetal Undernutrition and Gut Dysbiosis in Infancy

There is an increasing prevalence of non-communicable chronic diseases (NCCDs) like obesity, metabolic syndrome, type 2 diabetes mellitus (T2DM), hypertension, allergic asthma, and neuro-developmental/psychiatric problems in many parts of the world. A suboptimal lifestyle as an adult is often blamed for the occurrence of NCCDs. This review discusses the developmental origin of health and disease theory and how suboptimal nutrition in intrauterine life and the establishment of a suboptimal gut microbiome during infancy can influence the predisposition to NCCDs.

Association Between Type 1 Diabetes Mellitus and Dental Caries in Children: A Systematic Review

Background: Diabetes mellitus is one of the diseases with chronic prevalence. Keep going increased, not only in adults but also in children. Diabetes mellitus type 1, the most common, occurs in children. Dental caries is an infection caused by metabolizing bacteria Streptococcus mutans, and Lactobacilli that convert carbohydrates into acid that damages tooth enamel. Diabetes can cause changes in saliva composition and flow. Saliva is vital in guarding a healthy tooth by neutralizing acid and providing minerals for remineralizing tooth enamel. Method: A systematic review was done by reviewing research through English data sources Pub Med, Proquest, Cochran, and Wiley. Four studies were included according to the inclusion criteria. Result: The results of a review of these four journals showed that children aged 6-18 who have type 1 or type 2 diabetes mellitus have a higher risk of developing dental caries or dental diseases. Children with diabetes are predisposed to have more glucose in their saliva. High glucose can become a source of nutrition for bacteria cariogenic, which contributes to the formation of plaque and acids that damage teeth. Conclusion: Diabetes mellitus is a risk factor for oral health. Diabetes Mellitus had a significant correlation with dental caries in children. Keywords: Diabetes Mellitus, Children.

Preliminary guidelines for the detection and management of drug-related problems in cancer patients with type 2 diabetes mellitus: a practical resource for oncology pharmacists.

The prevalence of type 2 diabetes mellitus (T2DM) in cancer patients is high. During the medication review process, clinical pharmacists could detect and manage drug-related problems (DRP) to optimize pharmacotherapy but there is a need to standardize pharmacists' interventions (PI) especially for T2DM-related DRP. The present study aims to describe DRP in cancer patients with T2DM undergoing anticancer treatment (AT) and to propose related preliminary guidelines to manage T2DM-related DRP. The study was conducted in one oncology outpatient hospital where a clinical pharmacy team performs medication reviews to detect and manage DRP by performing PI in cancer patients undergoing AT. All the data from November 23rd, 2015 to November 23rd, 2019 were extracted and demographic, clinical, oncological, and biological data were collected and analyzed. Based on these results and a literature review, a working group (2 pharmacists and one diabetologist) was constituted to propose a first set of preliminary guidelines clinical pharmacists that were then reviewed using the Delphi method by an expert panel of oncologists and pharmacists. A total of 161 T2DM cancer patients were included in the study (19.7% of all cancer patients screened). Overall, 152 DRP (mean 1.67/patient) were detected (49.3% drug interaction) and 152 PI were performed by clinical pharmacists, mainly drug monitoring (48.0) and drug discontinuation (25.7%). Specifically, there was 24 T2DM-related DRP (including 29.2% drug interactions). Twenty-four DRPs were directly related to T2DM status. The five proposed guidelines reached a consensus after revisions and a sixth has been added. DRPs were frequent among cancer patients with T2DM and we hypothesize that the preliminary guidelines should improve the detection of DRPs directly related to T2DM. The implementation of the preliminary guidelines should now be assessed in clinical practice.

Discovery of α-amylase and α-glucosidase dual inhibitors from NPASS database for management of Type 2 Diabetes Mellitus: A chemoinformatic approach.

Postprandial hyperglycemia, typical manifestation of Type 2 Diabetes Mellitus (T2DM), is associated with notable global morbidity and mortality. Preventing the advancement of this condition by delaying the rate of glucose absorption through inhibition of α-amylase and α-glucosidase enzymatic activities is of utmost importance. Finding a safe antidiabetic drug is essential since those that are currently on the market have drawbacks like unpleasant side effects. The current study utilized computer-aided drug design (CADD), as a quick and affordable method to find a substitute drug template that can be used to control postprandial hyperglycemia by modulating the activity of α-amylase and α-glucosidase enzymes. The Natural Products Activity and Species database (NPASS) (30,926 compounds) was screened in silico, with a focus on evaluating drug-likeness, toxicity profiles and ability to bind on a target protein. Two molecules NPC204580 (Chrotacumine C) and NPC137813 (1-O-(2-Methoxy-4-Acetylphenyl)-6-O-(E-Cinnamoyl)-Beta-D-Glucopyranoside) were identified as potential dual inhibitors for α-amylase and α-glucosidase with free binding energies of -14.46 kcal/mol and -12.58 kcal/mol for α-amylase, and -8.42 kcal/mol and -8.76 kcal/mol for α-glucosidase, respectively. The molecules showed ionic, H-bonding and hydrophobic interactions with critical amino acid residues of both enzymes. Moreover, 100 ns molecular dynamic simulations showed that both molecules are stable on the receptors' active sites based on root mean square deviation (RMSD), root mean square fluctuation (RMSF), and the Generalized Born surface area (GBSA) energy calculated. The two compounds are thus promising therapeutic agents for T2DM that merit further investigation due to their excellent binding energies, encouraging pharmacokinetics, toxicity profiles, and stability as demonstrated in simulated studies.

Chromium supplementation and type 2 diabetes mellitus: an extensive systematic review.

Diabetes is a global public health concern with increasing prevalence worldwide. Chromium (Cr), a trace element found in soil, water, and food, has been proposed to have a possible positive effect in glucose metabolism and diabetes mellitus prevention. However, the relationship between trivalent chromium [Cr(III)] exposure, mainly through the consumption of diet supplements, and type 2 diabetes mellitus (T2DM) remains controversial. An extensive systematic review of the current literature on randomized controlled studies (RCTs) was conducted from 1 January 2000, to January 2024 using the databases PubMed, Scopus, ScienceDirect, and Cochrane, with specific keywords and inclusion as well as exclusion criteria. After close screening of the research studies retrieved from the mentioned websites was conducted, the most related studies were included in the final systematic review. The studies were evaluated for the degree of relevance, quality, and risk bias, using appropriate quality assessment tools. Several of the included RCT studies reported possible benefits of Cr(III) supplementation, mainly in the form of chromium picolinate (CrPic), chromium yeast (CY), chromium chloride (CrCl3), and chromium nicotinate (CrN). The dosage of chromium was between 50 and 1000μg/day and it was consumed from 2 to 6months. Glycemic control markers, including FPG, insulin, HbA1C, and HOMA-IR levels, significantly decrease following chromium supplementation, mainly in studies with a longer intervention period. Supplementing with chromium (Cr) indicated that could significantly improve lipid profile by raising high-density lipoprotein and lowering triglyceride and total cholesterol while having little effect on low-density lipoprotein. However, most research findings include significant limitations, such as inconsistent dosage and type of chromium, formulation of supplements, and study duration. Further well-designed and high-quality research is needed to fully understand the role of chromium dietary supplementation and the potential risks related to its mechanisms of action, type, and dose, in the prevention and treatment of type 2 diabetes mellitus.

Exploring the Relationship Between Refractive Errors and Common Chronic Diseases Via Blood Biochemistry Tests: A Large Prospective Cohort Study.

The purpose of this study was to examine the association between refractive errors and common chronic diseases using blood biochemistry tests, and to investigate the associated modifiable risk factors, with the goal of informing and developing effective preventive strategies. A total of 116,245 participants with refractometry at baseline enrolled in the UK Biobank were included in this prospective cohort study. Restricted cubic spline and Cox proportional hazards models were used to detect associations between refractive error, blood biochemistry tests, and common chronic diseases. Interaction effects on the additive scale and effect modification analysis were used to explore excess modifiable risk factors for disease prevention. Spherical equivalent significantly associated with vitamin D, sex hormone binding globulin, apolipoprotein A, blood glucose, and aspartate aminotransferase levels. Subjects with myopia demonstrated a 13% higher risk of type 2 diabetes mellitus (T2DM) incidence compared to those without myopia (hazard ratio [HR] = 1.13, 95% confidence interval [CI] = 1.08-1.19) throughout a median follow-up of 9.12years. Interaction analysis revealed 15% (95% CI = 9%-21%) of this risk was due to myopia-obesity interaction. However, active engagement in physical activity could potentially mitigate this risk (HR = 1.06, 95% CI = 0.93-1.20). Refractive errors were associated with specific blood indicators, particularly noting the association between myopia and higher T2DM incidence in middle-aged and elderly populations. This effect interacts with obesity, and promoting physical activity among myopia individuals provides greater benefits in the prevention of T2DM compared to non-myopic individuals.

Simvastatin reduces chronic kidney disease and renal failure risk in type 2 diabetes patients: post hoc ACCORD trial analysis.

Type 2 diabetes mellitus (T2DM) poses a substantial global health concern. Statins are widely used among T2DM patients for managing dyslipidemia, preventing cardiovascular disease (CVD), and offering renal protection. However, the extent to which their renal protective effects contribute to reducing the incidence of severe renal complications, including chronic kidney disease (CKD) and renal failure, is not well-defined. This investigation scrutinizes the impact of simvastatin versus placebo on renal outcomes among T2DM patients utilizing data from the ACCORD trial. It encompasses incidence rate comparisons, Kaplan-Meier estimates, Cox proportional hazards models, and mediation analyses. The study consisted of 3,619 individuals diagnosed with T2DM, among which 2,753 were treated routinely with simvastatin, while 866 did not receive any statin therapy. After adjusting for baseline characteristics and time-dependent covariates, simvastatin treatment was associated with a 71% reduction in the risk of CKD (HR 0.29, 95% CI 0.27-0.31, p < 0.01) and a 47% reduction in the risk of renal failure (HR 0.53, 95% CI 0.44-0.65, p < 0.01) compared to the statin-free group. Further subgroup analysis, accounting for the initial lipid and kidney profiles, indicated variable impacts of simvastatin on CKD and renal failure outcomes. Nevertheless, a consistent reduction in CKD risk was observed across all subgroups within the statin-treated population. Additional mediation analysis revealed that the reduction in low-density lipoprotein cholesterol (LDL-C) may be a potential mediator in the association between simvastatin and CKD, with a mediation effect of 14.9%, (95% CI 0.11-0.19, p < 0.01). Administering statins, specifically simvastatin, to T2DM patients at elevated risk for CVD, is likely to offer augmented renal advantages, notably in lowering the occurrence of CKD and renal failure. This protective effect against CKD manifests regardless of initial lipid profiles, albuminuria, and estimated glomerular filtration rate (eGFR) levels. The association between simvastatin and CKD may be partially mediated by LDL-C reduction.

Association of Low Protein-to-Carbohydrate Energy Ratio with Cognitive Impairment in Elderly Type 2 Diabetes Patients

Background/Objectives: The relationship between macronutrient intake and cognitive decline in older adults with type 2 diabetes mellitus (T2DM) remains underexplored. Methods: This cross-sectional study aimed to evaluate the association between the protein-to-carbohydrate energy ratio (%E:P) and cognitive impairment among 192 elderly T2DM patients. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the Self-Administered Gerocognitive Exam (SAGE), while dietary intake data, including (%E:P), was gathered using a validated semi-quantitative food frequency questionnaire. Results: Participants had a mean age of 71 ± 6 years, 46.4% were female, and the median BMI was 30 ± 4 kg/m2. After adjusting for confounding variables, patients in the highest (%E:P) tertile showed significantly higher MoCA and SAGE scores compared to those in the lowest tertile (p &lt; 0.005). We identified an optimal (%E:P) threshold of 0.375 for predicting cognitive impairment, with a sensitivity of 53% and specificity of 64%. Conclusions: These findings suggest that a lower (%E:P) ratio may be a risk factor for cognitive impairment in elderly T2DM patients. Monitoring this ratio may serve as an early detection tool for cognitive deterioration. Moreover, current protein intake recommendations for older adults with T2DM may be insufficient to prevent cognitive impairment. Further research is needed to establish optimal dietary guidelines for this population.

Combined Coronary Artery Bypass Grafting and Orthopedic Fixation in a Patient with Multiple Comorbidities: A Case Report

Background: Coronary artery disease (CAD) is a prevalent cardiovascular condition and leading cause of morbidity and mortality worldwide. The management of orthopedic injuries requiring surgical fixation is particularly complex in patients with comorbidities such as diabetes mellitus (DM) and hypertension (HTN). Coordinating the sequence, timing, and execution of coronary artery bypass grafting (CABG) and orthopedic fixation requires careful consideration of the patient’s overall health, surgical risks, and recovery potential. Case presentation: A 55-year-old male presented with a right distal tibial fracture following a fall. His medical history included HTN, type 2 diabetes mellitus (T2DM), and Kyrle’s skin disease. During his hospital stay, he was diagnosed with non-ST-segment elevation myocardial infarction (NSTEMI). Severe multivessel CAD was confirmed by catheterization. After interdisciplinary consultation, simultaneous CABG and open reduction and internal fixation (ORIF) of the tibial fracture were performed. He was discharged in good condition and showed positive recovery during a one-month follow-up. Discussion: This case highlights the complexities of managing patients with multiple comorbidities who require both cardiac and orthopedic surgeries. This simultaneous approach allows for efficient treatment, leading to a shorter hospital stay and recovery period. This report supports the feasibility and benefits of simultaneous surgery in complex clinical scenarios, although further studies are required to establish broader guidelines. Conclusion: Our case emphasizes the importance of a multidisciplinary approach for managing patients with multiple comorbidities who require concurrent surgical intervention. Preoperative planning and specialty coordination ensured optimal outcomes. Further research is needed to develop standardized guidelines for intraoperative care of patients undergoing simultaneous procedures.

Chronobiological disruptions: unravelling the interplay of shift work, circadian rhythms, and vascular health in the context of stroke risk.

Shift work, particularly night shifts, disrupts circadian rhythms and increases stroke risk. This manuscript explores the mechanisms connecting shift work with stroke, focusing on circadian rhythms, hypertension, and diabetes. The circadian system, controlled by different mechanisms including central and peripheral clock genes, suprachiasmatic nuclei (SCN), and pineal gland (through melatonin production), regulates body functions and responds to environmental signals. Disruptions in this system affect endothelial cells, leading to blood pressure issues. Type 2 diabetes mellitus (T2DM) is significantly associated with night shifts, with circadian disturbances affecting glucose metabolism, insulin sensitivity, and hormone regulation. The manuscript examines the relationship between melatonin, insulin, and glucose balance, highlighting pathways that link T2DM to stroke risk. Additionally, dyslipidemia, particularly reduced HDL-c levels, results from shift work and contributes to stroke development. High lipid levels cause oxidative stress, inflammation, and endothelial dysfunction, increasing cerebrovascular risks. The manuscript details the effects of dyslipidemia on brain functions, including disruptions in blood flow, blood-brain barrier integrity, and neural cell death. This comprehensive analysis emphasizes the complex interplay of circadian disruption, hypertension, diabetes, and dyslipidemia in increasing stroke risk among shift workers. Understanding these mechanisms is essential for developing targeted interventions to reduce stroke susceptibility and improve cerebrovascular health in this vulnerable population.

Neuregulin 4 attenuates pancreatic β-cell apoptosis induced by lipotoxicity via activating mTOR-mediated autophagy

ABSTRACT Neuregulin 4 (Nrg4) is a brown fat-enriched endocrine factor that ameliorates lipid metabolism disorders. Autophagy is critical for pancreatic β-cell to counteract lipotoxicity-induced apoptosis. This study aimed at exploring whether Nrg4 attenuates lipotoxicity-induced β-cell apoptosis by regulating autophagy. The mouse pancreatic β-cell line MIN6 was cultured in palmitic acid (PA) with or without Nrg4 administration. Apoptosis rate, together with anti-apoptotic and pro-apoptotic protein levels, was investigated. Autophagic flux and autophagy-related protein levels along with related signaling pathways that regulate autophagy were also evaluated. Results showed that Nrg4 decreased PA-induced MIN6 apoptosis, enhanced anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) expression and reduced pro-apoptotic proteins Bcl-2-associated X protein (Bax) and cleaved-caspase 3 expressions. Autophagy levels in MIN6 also decreased with PA treatment and Nrg4 administration reactivated autophagy. Further, Nrg4 administration activated autophagy via the mammalian target of rapamycin (mTOR) signaling pathway. In addition, when the mTOR pathway was stimulated or autophagy was suppressed, the beneficial effects of Nrg4 administration on MIN6 apoptosis were diminished. These results imply that Nrg4 administration attenuates MIN6 apoptosis by promoting mTOR-dependent autophagy and thus may lead to a new therapeutic method for type 2 diabetes mellitus (T2DM).