Death In Diabetic Patients Research Articles

Progress in the Study of Diabetic Nephropathy Markers

Diabetic nephropathy (DN) is the principal consideration of end-stage diabetic nephropathy in China, second only to chronic glomerulonephritis. It is the most common complication of diabetes and the cause of death in diabetic patients. The clinical manifestations of DN are proteinuria, edema, hypertension, and progressive renal damage, and its continuous development can turn into nephrotic syndrome and uremia. It has been reported that urinary microalbumin, cystatin C and homocysteine are related to the diagnosis of renal diseases. In addition, pathological examination of renal biopsy, as the golden standard, plays a vital role in clinical diagnosis of DN. In the meantime, with the rise of biomarkers research, such as Genetic Markers, miRNAs and AGEs, we can evaluate the renal function of diabetic patients by detecting these markers as early as possible. Taking into account the above information, we focus on research advances in the association of microalbuminuria, urinary inhibitory C, serum homocysteine, renal biopsy and biomarkers with DN.

Evaluating the budget impact of Empagliflozin in managing heart failure with reduced ejection fraction: Proposing strategic policies for Malaysian public healthcare.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors such as Empagliflozin, are increasingly recommended as part of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) in many developed nations. This recommendation is based on robust clinical evidence showing that adding Empagliflozin to GDMT improves heart failure symptoms, clinical outcomes, functional status, and overall quality of life. In Malaysia, where healthcare is predominantly public and heavily subsidized, the introduction of new treatments can significantly impact costs, requiring detailed economic assessments. This study evaluates the budget impact of incorporating Empagliflozin into GDMT for HFrEF from the perspective of the public healthcare system. A five-year budget impact model was developed, integrating local data such as population, drug use, costs, clinical outcomes, and healthcare expenses. In the current scenario (GDMT alone), the projected five-year expenditure is MYR 6.12 billion (USD 3.92 billion). With Empagliflozin, the total cost rises by 0.71% to MYR 6.16 billion (USD 3.95 billion), driven by drug acquisition costs of MYR 160.12 million (USD 102.64 million) and adverse event costs of MYR 211,543 (USD 135,604). However, these costs are offset by savings from reduced HF hospitalizations, fewer cardiovascular deaths, and improved renal outcomes. Sensitivity analysis identified hospitalization costs, the price of Empagliflozin, and cardiovascular deaths in diabetic patients as key factors influencing the budget impact. Policymakers can improve the affordability of Empagliflozin through strategies like price negotiations, cost-sharing, and focusing on high-risk groups to optimize healthcare expenditure while ensuring effective treatment access.

Sleep restriction exacerbates cardiac dysfunction in diabetic mice by causing cardiomyocyte death and fibrosis through mitochondrial damage.

Diabetic cardiomyopathy (DCM) is a cardiovascular complication of diabetes mellitus with a poor prognosis and is the leading cause of death in diabetic patients. Sleep deficiency is not only recognized as an important risk factor for the development of type 2 DM, but is also associated with increased morbidity and mortality of cardiovascular disease. The underlying role and mechanisms of sleep restriction (SR) in DCM are far from clear. The KK/Upj-Ay mouse model of T2 DM was used as a study subject, and the small animal ultrasound imaging system was used to detect the function of the heart; immunopathological staining was used to clarify the histo-structural pathological alterations of the heart; and TUNEL staining, qPCR, transmission electron microscopy (TEM), and ELISA kits were used to detect apoptosis, oxidative stress, inflammation, and mitochondrial damage, and related molecular alterations. SR led to a significant increase in mortality, cardiac hypertrophy, necrosis, glycogen deposition and fibrosis further deteriorated in DM KK mice. SR increased cardiomyocyte death in KK mice through the Bax/Bcl2 pathway. In addition to this, SR not only exacerbated the inflammatory response, but also aggravated mitochondrial damage and promoted oxidative stress in KK mice through the PRDM16-PGC-1α pathway. Overall, SR exacerbates structural alterations and dysfunction through inflammation, oxidative stress, and apoptosis in DM KK mice, increasing the risk of death. Clinicians and diabetic patients are prompted to pay attention to sleep habits to avoid accelerating the transition of DCM to heart failure and inducing death due to poor sleep habits.

The relationship of short-term exposure to meteorological factors on diabetes mellitus mortality risk in Hefei, China: a time series analysis.

The study aims to explore whether short-term exposure to meteorological factors has a potential association with the risk of diabetes mellitus (DM) mortality. During the period 2015-2018, we collected daily data on meteorological factors and deaths of diabetic patients in Hefei. A total of 1101 diabetic deaths were recorded. We used structural equation modeling to initially explore the relationships among air pollutants, meteorological variables, and mortality, and generalized additive modeling (GAM) and distributional lag nonlinear modeling (DLNM) to explore the relationship between meteorological factors and the mortality risk of DM patients. We also stratified by age and gender. The mortality risk in diabetic patients was expressed by relative risks (RR) and 95% confidence intervals (CI) for both single and cumulative days. Single-day lagged results showed a high relative humidity (RH) (75th percentile, 83.71%), a fairly high average temperature (T mean) (95th percentile, 30.32°C), and an extremely low diurnal temperature range (DTR) (5th percentile, 3.13°C) were positively related to the mortality risk of DM. Stratified results showed that high and very high levels of T mean were significantly positively linked to the mortality risk of DM among females and the elderly, while very high levels of DTR were linked to the mortality risk in men and younger populations. In conclusion, this study found that short-duration exposure to quite high T mean, high RH, and very low DTR were significantly positively related to the mortality risk of DM patients. For women and older individuals, exposure to high and very high T mean environments should be minimized. Men and young adults should be aware of daily temperature changes.

WTAP and METTL14 regulate the m6A modification of DKK3 in renal tubular epithelial cells of diabetic nephropathy

Diabetic nephropathy (DN) is an important cause of death in diabetes patients, which is mainly due to its complex pathogenesis. Here, we explored the role of N6-methyladenosine (m6A) RNA methylation in DN development. Renal tubular epithelial cells from DN patients and experimental DN mice treated with streptozotocin (STZ) exhibited a considerable increase in METTL14 and WTAP expression as well as overall m6A methylation. Knocking down the expression of METTL14 and WTAP inhibited the migration and proliferation of tubular epithelial cells. MeRIP-seq analysis of the renal tissues of DN patients revealed that the genes with elevated m6A methylation were concentrated in the Wnt/β-Catenin signaling pathway. Dickkopf homolog 3 (DKK3) was screened out as the gene with the most significant increase in m6A methylation. In addition, the expression change pattern of DKK3 under DN circumstances is in line with those of METTL14 and WTAP. DKK3's m6A methylation sites were confirmed to be located in the 3′UTR region, which is how METTL14 and WTAP improved DKK3's mRNA stability. Finally, YTHDF1, a m6A reader, was demonstrated to recognize m6A-methylated DKK3 and promote DKK3 expression.

Macrophages regulate plaque progression in diabetic Apoe−/− mice dependent on Pi4p/Nlrp3 signaling pathway

Background and aimsAtherosclerotic cardiovascular disease complicated by diabetes mellitus (DM) is the leading cause of death in diabetic patients, and it is strongly associated with macrophages and inflammasomes. It has been found that activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is closely associated with phosphatidylinositol 4-phosphate (PI4P) on the trans-Golgi. However, how PI4P and NLRP3 regulate macrophage function and its role in diabetic atherosclerotic plaques is unclear. MethodsThe expression of Pi4p and Nlrp3-inflammasome-related proteins in atherosclerosis in apolipoprotein E-deficient (Apoe−/−) and Apoe−/− DM mice was investigated. Then, Pi4p levels were affected by shRNA-Pi4kb or cDNA-Sac1 plasmid to investigate the effects of changes in Pi4p-related metabolic enzymes on macrophage function. Finally, genetically modified macrophages were injected into diabetic Apoe−/− mice to explore the effects on atherosclerosis. ResultsDM promoted plaque progression in atherosclerotic mice and increased expression of Pi4p and Nlrp3 in plaques. In addition, impaired macrophage function induced by high glucose was reversed by transfected shRNA-Pi4kb or cDNA-Sac1 plasmid. Furthermore, decreased levels of Pi4p reduced plaque area in diabetic Apoe−/− mice. ConclusionsOur data suggests that Pi4p/Nlrp3 in macrophages play an important role in the exacerbation of atherosclerosis in diabetic mice. Pi4p-related metabolizing enzymes (PI4KB and SAC1) may be a potential therapeutic strategy for diabetic atherosclerosis, and macrophage therapy is also a potential treatment.

Abstract Tu117: Unraveling the Role of Mitochondrial Ribosomal Protein L7/L12 (MRPL12) in Diabetic Cardiomyopathy

Diabetic cardiomyopathy (DMCM) is a major cause of death in diabetic patients. Emerging evidence shows that mitochondrial dysfunction contributes to heart failure in diabetes. However, the molecular mechanisms of mitochondrial dysfunction mediating heart failure in diabetes are still poorly understood. The current study aimed to investigate the role of mitochondrial ribosomal protein L7/L12 (MRPL12) in human and mouse models of type II diabetes (db/db mice, and high-fat diet fed (HFD) mice) with or without induction of myocardial infarction (MI). Mitochondrial respiration was measured by using sea horse and mitochondrial membrane potential was measured by using confocal microscopy. Data was analyzed by using the mean of the groups was compared using a student t-test (for 2 groups) and ANOVA. We found increased MRPL12 levels in diabetic patients with ischemic heart disease compared to non-diabetic patients. Further we found elevated MRPL12 levels in the LV tissue of HFD fed mice with MI compared to low-fat diet-fed mice with MI. With the overexpression of MRPL12 under hyperglycemic conditions, the level of oxidative phosphorylation (OXPHOS) was found downregulated, but cellular ATP and human cardiomyocyte cell death remained unchanged, However, there was notable impairment in mitochondrial membrane potential (MMP) in hyperglycemia condition, along with changes in basal respiration oxygen consumption rate (OCR) and maximal respiratory capacity OCR. Overall, our results suggest MRPL12 may have a compensatory role in the diabetic hearts with ischemic heart disease. Therefore, our finding proposes new insights into the role of MRPL12 in the pathophysiology of MI in diabetes.

Role of mitochondrial ribosomal protein L7/L12 (MRPL12) in diabetic ischemic heart disease

BackgroundMyocardial infarction (MI) is a significant cause of death in diabetic patients. Growing evidence suggests that mitochondrial dysfunction contributes to heart failure in diabetes. However, the molecular mechanisms of mitochondrial dysfunction mediating heart failure in diabetes are still poorly understood. MethodsWe examined MRPL12 levels in right atrial appendage tissues from diabetic patients undergoing coronary artery bypass graft (CABG) surgery. Using AC-16 cells overexpressing MRPL12 under normal and hyperglycemic conditions we performed mitochondrial functional assays OXPHOS, bioenergetics, mitochondrial membrane potential, ATP production and cell death. ResultsWe observed elevated MRPL12 levels in heart tissue samples from diabetic patients with ischemic heart disease compared to non-diabetic patients. Overexpression of MRPL12 under hyperglycemic conditions did not affect oxidative phosphorylation (OXPHOS) levels, cellular ATP levels, or cardiomyocyte cell death. However, notable impairment in mitochondrial membrane potential (MMP) was observed under hyperglycemic conditions, along with alterations in both basal respiration oxygen consumption rate (OCR) and maximal respiratory capacity OCR. ConclusionsOverall, our results suggest that MRPL12 may have a compensatory role in the diabetic myocardium with ischemic heart disease, suggesting that MRPL12 may implicate in the pathophysiology of MI in diabetes.

A NOVEL CIRC_SUPT3/MIR-185-5P/G3BP2 CERNA NETWORK REGULATES HIGH GLUCOSE-INDUCED INJURY IN MOUSE PODOCYTE MPC5 CELLS.

Background: Diabetic nephropathy (DN) is a complication of diabetes that is the leading cause of death in diabetic patients. Circular RNA (circRNA) is a hot topic in the research of human diseases. However, the role of circ_Supt3 in DN remains unclear. Methods: High glucose (HG) treatment of mouse podocyte (MPC5) cells to mimic DN cell injury. Quantitative real-time polymerase chain reaction was performed to detect the expression of circ_Supt3, microRNA-185-5p (miR-185-5p), and GTPase-activating protein-binding protein 2 (G3bp2). 5-Ethynyl-2'-deoxyuridine (EdU) and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium Bromide (MTT) assays were used to examine cell proliferation, and flow cytometry was used to detect cell apoptosis. Western blot was used to assess the levels of relative proteins. Enzyme-linked immunosorbent assay detected the inflammation cytokines. Dual-luciferase reporter and RNA pull-down assays were used to confirm the interaction of miR-185-5p and circ_Supt3 or G3bp2. Results: Circ_Supt3 and G3bp2 were highly expressed and miR-185-5p expression was diminished in DN mice. HG treatment inhibited cell proliferation and accelerated cell apoptosis and inflammation response, and the knockdown of circ_Supt3 reversed these effects. Bioinformatics predicted that circ_Supt3 contained a binding site for miR-185-5p, and G3bp2 was a direct target of miR-185-5p. Circ_Supt3 regulated G3bp2 expression by miR-185-5p. Moreover, the circ_Supt3/miR-185-5p/G3bp2 axis regulated the cell behavior of HG-induced MPC5 cells. Conclusion: Our findings suggest that the knockdown of circ_Supt3 protects mouse MPC5 cells against HG-induced cell injury via the miR-185-5p/G3bp2 axis.

The U-shaped association between remnant cholesterol and risk of all-cause and cardiovascular deaths in diabetic adults: Findings from NHANES 1999–2018

Background and aimsWe aimed to explore the association between remnant cholesterol (RC) level and risks of all-cause and cardiovascular deaths among American diabetic adults. Methods and resultsThe data of 4,095 diabetic participants from the National Health and Nutrition Examination Survey (1999–2018) were included for analysis. Deaths were ascertained till December 31, 2019. RC level associated with death was assessed on a continuous scale with restricted cubic splines and by pre-defined quartile groups with Cox regression analysis. After a median follow-up of 6.9 years, 1,060 all-cause and 289 cardiovascular deaths occurred. Association between RC and death was U-shaped, and RC level correlated with the lowest risks of both all-cause and cardiovascular deaths was 0.85 mmol/L. After adjusting for confounders, compared with Quartile 3 (0.66–0.93 mmol/L), hazard ratios for all-cause deaths were 1.43 (95%CI 1.18–1.72, P = 0.0002) in Quartile 1 (≤0.47 mmol/L), 1.20 (95%CI 1.00–1.44, P = 0.05) in Quartile 2 (0.47–0.66 mmol/L), and 1.25 (95%CI 1.05–1.49, P = 0.02) in Quartile 4 (>0.93 mmol/L). Higher risk was also observed for cardiovascular deaths in Quartile 1 (HR 1.66, 95%CI 1.15–2.41, P = 0.007), Quartile 2 (HR 1.39, 95%CI 0.97–2.00, P = 0.08), and Quartile 4 (HR 1.54, 95% CI 1.08–2.19, P = 0.02), as compared with Quartile 3. ConclusionIn US adults with diabetes, low and high levels of RC were associated with increased risks of all-cause and cardiovascular deaths, and the lowest risk was observed at RC level of 0.85 mmol/L. These findings suggested that maintaining appropriate RC level may help reduce risk of death in diabetic patients.

HMOX1 as a therapeutic target associated with diabetic foot ulcers based on single-cell analysis and machine learning.

Diabetic foot ulcers (DFUs) are a serious chronic complication of diabetes mellitus and a leading cause of disability and death in diabetic patients. However, current treatments remain unsatisfactory. Although macrophages are associated with DFU, their exact role in this disease remains uncertain. This study sought to detect macrophage-related genes in DFU and identify possible therapeutic targets. Single-cell datasets (GSE223964) and RNA-seq datasets (GSM68183, GSE80178, GSE134431 and GSE147890) associated with DFU were retrieved from the gene expression omnibus (GEO) database for this study. Analysis of the provided single-cell data revealed the distribution of macrophage subpopulations in the DFU. Four independent RNA-seq datasets were merged into a single DFU cohort and further analysed using bioinformatics. This included differential expression (DEG) analysis, multiple machine learning algorithms to identify biomarkers and enrichment analysis. Finally, key results were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western bolt. Finally, the findings were validated using RT-qPCR and western blot. We obtained 802 macrophage-related genes in single-cell analysis. Differential expression analysis yielded 743 DEGs. Thirty-seven macrophage-associated DEGs were identified by cross-analysis of marker genes with macrophage-associated DEGs. Thirty-seven intersections were screened and cross-analysed using four machine learning algorithms. Finally, HMOX1 was identified as a potentially valuable biomarker. HMOX1 was significantly associated with biological pathways such as the insulin signalling pathway. The results showed that HMOX1 was significantly overexpressed in DFU samples. In conclusion, the analytical results of this study identified HMOX1 as a potentially valuable biomarker associated with macrophages in DFU. The results of our analysis improve our understanding of the mechanism of macrophage action in this disease and may be useful in developing targeted therapies for DFU.

Metformin use is associated with reduced mortality risk in diabetic patients with Parkinson's disease

IntroductionParkinson’s disease (PD) and type-2 diabetes (T2D) arguably share pathophysiologic mechanisms, resulting in a more severe phenotype and progression and diabetes is currently considered a risk factor of PD. Besides, research suggests antidiabetic therapies as potential disease-modifying strategies. The main aim was to assess the impact of a metformin-inclusive antidiabetic treatment on patient all-cause mortality. MethodsA nested case-control prospective study including newly diagnosed PD patients reporting the onset of T2D within ±2 years from the onset of PD (n=159) and matched (1:5; gender, year of PD onset and age at PD onset) non-diabetic cases (n=795) followed until death or censoring. Patients on a metformin-inclusive treatment regimen were compared to those receiving other oral anti-diabetics (OADs). ResultsAmong patients with T2D, 123 were treated with a drug regimen containing metformin (alone [65.0%] or in combination with other drugs [35.0%]) and 36 were prescribed other OADs. During a median PD duration of 96 months [IQR, 60-144], 171 patients died. Diabetes was not associated with reduced survival: fully-adjusted HR=1.19 [95%CI, 0.81-1.76] (P=0.37). After stratifying for T2D treatment, a metformin-inclusive regimen was not associated with increased risk of death (HR=1.06 [95%CI, 0.61-1.84]; P=0.83), while patients receiving other OADs had reduced survival (HR=1.83 [95%CI, 1.01-3.32]; P=0.034). ConclusionsMetformin use was not associated with increased risk of death in diabetic patients with PD reporting concomitant onset of the two diseases. Metformin appears to be a promising disease-modifying therapy given also the preclinical background, low cost and satisfactory safety and tolerability. Further studies are warranted to investigate its impact on disease progression.

Herbal-based therapeutics for diabetic patients with SARS-Cov-2 infection.

Human SARS Coronavirus-2 (SARS-CoV-2) has infected more than 170 million people worldwide, being responsible for about 3.5 million deaths so far. Despite ongoing investigations, there is still more tounderstand the mechanism of COVID-19 infection completely. However, it has been evidenced that SARS-CoV-2 can cause Coronavirus disease (COVID-19) notably in diabetic people. Approximately 35% of the patients who died of this disease had diabetes. A growing number of studies have evidenced that hyperglycemia is a significant risk factor for severe SARS-CoV-2 infection and plays a key role in COVID-19 mortality and diabetes comorbidity. The uncontrolled hyperglycemia can produce low-grade inflammation and impaired immunity-mediated cytokine storm that fail multiple organs and sudden death in diabetic patients with SARS-CoV-2 infection. More importantly, SARS-CoV-2 infection and interaction with ACE2 receptors also contribute to pancreatic and metabolic impairment. Thus, using of diabetes medications has been suggested to be beneficial in the better management of diabetic COVID-19 patients. Herbal treatments, as safe and affordable therapeutic agents, have recently attracted a lot of attention in this field. Accordingly, in this review, we intend to have a deep look into the molecular mechanisms of diabetic complications in SARS-CoV-2 infection and explore the therapeutic potentials of herbal medications and natural products in the management of diabetic COVID-19 patients based on recent studies and the existing clinical evidence.

D-pinitol alleviates diabetic cardiomyopathy by inhibiting the optineurin-mediated endoplasmic reticulum stress and glycophagy signaling pathway.

Diabetic cardiomyopathy (DCM) is an important complication resulting in heart failure and death of diabetic patients. However, there is no effective drug for treatments. This study investigated the effect of D-pinitol (DP) on cardiac injury using diabetic mice and glycosylation injury of cardiomyocytes and its molecular mechanisms. We established the streptozotocin-induced SAMR1 and SAMP8 mice and DP (150 mg/kg/day) intragastrically and advanced glycation end-products (AGEs)-induced H9C2 cells. H9C2 cells were transfected with optineurin (OPTN) siRNA and overexpression plasmids. The metabolic disorder indices, cardiac dysfunction, histopathology, immunofluorescence, western blot, and immunoprecipitation were investigated. Our results showed that DP reduced the blood glucose and AGEs, and increased the expression of heart OPTN in diabetic mice and H9C2 cells, thereby inhibiting the endoplasmic reticulum stress (GRP78, CHOP) and glycophagy (STBD1, GABARAPL1), and alleviating the myocardial apoptosis and fibrosis of DCM. The expression of filamin A as an interaction protein of OPTN downregulated by AGEs decreased OPTN abundance. Moreover, OPTN siRNA increased the expression of GRP78, CHOP, STBD1, and GABARAPL1 and inhibited the expression of GAA via GSK3β phosphorylation and FoxO1. DP may be helpful to treat the onset of DCM. Targeting OPTN with DP could be translated into clinical application in the fighting against DCM.

Profiling of T cell repertoire in peripheral blood of patients from type 2 diabetes with complication

PurposeMore than 90% of patients with diabetes worldwide are type 2 diabetes (T2D), which is caused by insulin resistance or impaired producing insulin by pancreatic β cells. T2D and its complications, mainly large cardiovascular (LCV) and kidney (Ne) complications, are the major cause of death in diabetes patients. Recently, the dysregulation of peripheral T cell immune homeostasis was found in most T2D patients. However, the characteristics of T-cell receptors (TCR) remain largely unexplored in T2D patients.Patients and methodsHere we investigated the TCR repertoire using high-throughput sequencing in peripheral blood collected from T2D patient with (8 LCV and 7 Ne) or without complications.ResultsOur analysis of TCR repertoires in peripheral blood samples showed that TCR profiles in T2D patients with complications tended to be single and specific compared to controls, according to the characteristics of TCR repertoire in V-J combination number, diversity, principal component analysis (PCA) and differential genes. And we identified some differentially expressed V-J gene segments and amino acid clonotypes, which had the potential to contribute to distinguishing T2D patient with or without complications. As the progression of the disease, we found that the profiling of TCR repertoire was also differential between T2D patients with LVD and Ne complications base on this pilot analysis.ConclusionThis study demonstrated the protentional unique property of TCR repertoire in peripheral blood of T2D patient with and without complications, or T2D patients with LVD and Ne complications, which provided the possibility for future improvements in immune-related diagnosis and therapy for T2D complications.

Effects of SGLT2 Inhibitors and DPP-4 Inhibitors on Advanced Glycation End Products.

Clinical trials have revealed that sodium glucose cotransporter 2 (SGLT2) inhibitors suppress the onset of heart failure and cardiovascular death in diabetic patients. On the other hand, few reports have been published concerning such effects of dipeptidyl peptidase-4 (DPP-4) inhibitors. We undertook the present study to evaluate the effects of SGLT2 inhibitors and DPP-4 inhibitors on the advanced glycation end products (AGEs), well known as a risk factor for the development of cardiovascular disorders.Type 2 diabetes mellitus were divided into two groups and treated with either SGLT2 inhibitors or DPP-4 inhibitors for 3 months. Before and after the 3-month treatment period with each drug, the AGEs and diabetes-related parameters were measured. Methylglyoxal-derived hydroimidazolone-1 (MG-H1) was measured as one of the AGEs.In the SGLT2 inhibitor group, both the blood HbA1c and MG-H1 levels decreased significantly after the 3-month treatment period. In the DPP-4 inhibitor group, only the blood HbA1c level decreased significantly, with no significant change of the blood MG-H1 level.SGLT2 inhibitor reduced both the blood levels of HbA1c and AGEs (MG-H1). Considering that the blood levels of AGEs are associated with the risk of heart failure and cardiovascular disorders, the results of the present study suggest that the effect of SGLT2 inhibitors in suppressing cardiovascular death might be mediated by the reduction in the blood levels of AGEs induced by this class of drugs. DPP-4 inhibitors showed no significant effects on the blood levels of AGEs.

Evaluation of salivary glycopatterns based diagnostic models for prediction of diabetic vascular complications

Diabetic vascular complications (DVC) are the main cause of death in diabetic patients. However, there is a lack of effective biomarkers or convenient methods for early diagnosis of DVC. In this study, the salivary glycopatterns from 130 of healthy volunteers (HV), 139 patients with type 2 diabetes mellitus (T2DM) and 167 patients with DVC were case-by-case analyzed by using lectin microarrays. Subsequently, diagnostic models were developed using logistic regression and machine learning algorithms based on the data of lectin microarrays in training set. The performance of diagnostic models was evaluated in an independent blind cohort. The results of lectin microarrays indicated that the glycopatterns identified by 16 lectins (e.g. BS-I, PWM and EEL) were significantly altered in DVC patients compared with patients with T2DM, which suggested the alterations in salivary glycopatterns could reflect onset of DVC. Notably, K-Nearest Neighbor (KNN) model exhibited better performance for distinguishing DVC (accuracy: 0.939) than other models in blind cohort. The integrated classifier, which combined three machine learning models, exhibited a higher overall accuracy (≥ 0.933) than other models in blind cohort. Our study provided a cost-effective and non-invasive method for auxiliary diagnosis DVC based on the combination of salivary glycopatterns and machine learning algorithms.

Predictors of COVID-19 outcome in type 2 diabetes mellitus: a hospital-based study

Abstract Background Diabetes has become a significant risk factor for COVID-19-related severe illness and death. Methods This was a retrospective cohort study of 104 patients, with or without type 2 (diabetes mellitus) DM, diagnosed with COVID-19 between June and September 2021 in Benha University Hospital, Egypt. Outcome measures including discharge after recovery, transfer to ICU and intubation, or death were recorded. Univariate and multivariate logistic regression analysis was done for the prediction of death in diabetic patients. Results Length of hospital stay was significantly higher in diabetic (median 15 days) compared to non-diabetic patients (median 10 days). ICU admission and intubation among diabetic patients were substantially higher than non-diabetics. Univariate regression analysis established that old age (p = 0.02: OR = 1.03: CI 1.00–1.07), multiple comorbidities (p = 0.005: OR = 8.66: CI 1.9–38.5), diabetic complications (p = 0.000: OR = 6.401:CI 2.5–16.3), HbA1c (p = 0.01: OR = 1.22: CI 1.04–1.43), length of hospital stay (p = 0.005: OR = 1.07: CI 1.02–1.12), and ICU admission (p = 0.00: OR = 44.1: CI 9.4–205.3) were predictors of death for diabetic patients as well as neutrophilic count, D-dimer, and CRP levels. Multivariate regression analysis concluded that ICU admission was the most significant predictor of death in diabetic patients. Conclusion Type 2 DM patients, infected with the COVID-19 virus exhibited more admission to ICU and intubation with longer hospital stays compared to those without diabetes with a similar death rate. Old age, HbA1C, comorbidities, diabetic complications, length of hospital stay and ICU admission, and inflammatory parameters were significant predictors of death in diabetic patients.

The nurse’s role in recognizing dermatological changes in individuals with diabetes mellitus

Diabetes is a chronic, progressive metabolic disease that has now reached pandemic proportions. It’s estimated that 10.5% of the world’s population has diabetes, making it a global challenge that requires attention and innovative strategies from healthcare systems worldwide. While macrovascular complications remain the leading cause of death in diabetes patients, this study provides a detailed description of dermatological changes in these individuals, with a particular emphasis on the severity of diabetic foot conditions. Within the realm of dermatological manifestations, specific changes such as acanthosis nigricans, diabetic dermopathy, and xerosis are thoroughly described, and they are all specific for individuals with type 2 diabetes. Other manifestations, such as diabetic blisters and vitiligo, which are more common in individuals with type 1 diabetes, are also analysed. The study places a special focus on the crucial role of nurses in recognizing skin changes in diabetes patients. It highlights the importance of continuous education about precise insulin application and emphasises the need for regular systematic skin examinations, particularly in areas that are not easily visible to the patient, such as the feet or back. Nurse educators, like physicians, also share the responsibility for demonstrating self-examination skills or conducting joint examinations of these areas during consultations. Ultimately, this study advocates for an active partnership between healthcare professionals and individuals with diabetes to collectively address the challenges presented by diabetes, particularly in terms of dermatological changes.

Diabetic cardiomyopathy in rats was attenuated by endurance exercise through the inhibition of inflammation and apoptosis

Diabetic cardiomyopathy (DCM), as a ventricular dysfunction, is one of the main causes of death in diabetic patients. Former evidence revealed the beneficial effects of exercise on cardiovascular complications of diabetes. We aimed to investigate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on DCM. Male Wistar rats were divided into control, diabetic, metformin (300 mg/kg), HIIT, MICT, metformin + HIIT, and metformin + MICT diabetic groups. Serum biochemical, inflammatory, and oxidative stress indicators, gene expression of BCL2 and BAX, and histopathologic changes of cardiac tissue were assessed. Our analysis revealed an increase in fasting blood sugar (FBS), creatine kinase MB (CK-MB), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) in diabetes. Also, the superoxide dismutase (SOD) and catalase (CAT) activity, and the total thiol were decreased, in contrast, malondialdehyde (MDA) levels increased in the cardiac tissue of the diabetic group. All of these changes were significantly ameliorated in diabetic animals treated with exercise and metformin + exercise. The level of tumor necrosis factor-α (TNF-α) and Interleukin-1β (IL-1β), as well as the infiltration of inflammatory cells, were decreased in the heart of all exercise training groups. Up-regulation of BCL2 and down-regulation of BAX gene expressions were observed in the cardiac tissue of all exercise-treated groups. In conclusion, HIIT and MICT exercises are effective in preventing DCM development. Exercise training, besides improving oxidative stress and inflammation in cardiac tissue, alleviates cardiac damage by modulating the apoptotic gene expression in diabetic rats.