BACKGROUND: Patients with diabetes (DM) and heart failure (HF) have worse outcomes than normoglycaemic HF patients. Cardiovascular magnetic resonance (CMR) can identify ischaemic heart disease (IHD) and quantify coronary microvascular dysfunction (CMD) using myocardial perfusion reserve (MPR). We aimed to quantify extent of silent IHD and CMD in patients with DM presenting with HF.
METHODS: Prospectively recruited outpatients undergoing assessment into the aetiology of HF underwent inline quantitative perfusion CMR for calculation of stress and rest myocardial blood flow (MBF) and MPR. Exclusions included angina or history of IHD. Patients were followed up (median 3.0 years) for major adverse cardiovascular events (MACE).
RESULTS: Final analysis included 343 patients (176 normoglycaemic, 84 with pre-diabetes and 83 with DM). Prevalence of silent IHD was highest in DM (31%), then pre-diabetes (20%) then normoglycaemia (17%). Stress MBF was lowest in DM (1.53±0.52), then pre-diabetes (1.59±0.54) then normoglycaemia (1.83±0.62). MPR was lowest in DM (2.37±0.85) then pre-diabetes (2.41±0.88) then normoglycaemia (2.61±0.90). During follow up 45 patients experienced at least one MACE. On univariate Cox regression analysis MPR and presence of silent IHD were both associated with MACE. However, after correction for HbA1c, age and left ventricular ejection fraction the associations were no longer significant.
CONCLUSIONS: Patients with DM and HF had higher prevalence of silent IHD, more evidence of CMD and worse cardiovascular outcomes than their non-diabetic counterparts. These findings highlight the potential value of CMR for assessment of silent IHD and CMD in patients with DM presenting with HF.

UNASSIGNED: Diabetes mellitus (DM) is associated with the increased risk of development and the advancement of cholangiocarcinoma (CCA). High glucose levels were previously shown for upregulating interleukin-1β (IL-1β) in CCA cells with unclear functions. The present study, thus, aimed to investigate molecular mechanisms linking DM to CCA progression, with IL-1β hypothesized as a communicating cytokine.
UNASSIGNED: CCA cells were cultured in media with normal (5.6 mM) or high (25 mM) glucose, resembling euglycemia and hyperglycemia, respectively. Expressions of IL-1β and IL-1 receptor (IL-1R) in CCA tissues from patients with and without DM were examined using immunohistochemistry. Functional analyses of IL-1β were performed using siRNA and recombinant human IL-1R antagonist (rhIL-1RA), in which Western blots investigated the knockdown efficacy. BALB/c Rag-2-/- Jak3-/- (BRJ) mice were implanted with CCA xenografts to investigate hyperglycemia\'s effects on CCA growth and the anti-tumor effects of IL-1RA.
UNASSIGNED: CCA tumors from patients with hyperglycemia showed significantly higher IL-1β expression than those from non-DM patients, while IL-1β was positively correlated with fasting blood glucose (FBG) levels. CCA cells cultured in high glucose showed increased IL-1β expression, resulting in increased proliferation rates. Suppressing IL-1β signaling by si-IL-1β or rhIL-1RA significantly reduced CCA cell proliferation in vitro. Anakinra, a synthetic IL-1RA, also exerted significant anti-tumor effects in vivo and significantly reversed the effects of hyperglycemia-induced growth in CCA xenografts.
UNASSIGNED: IL-1β plays a crucial role in CCA progression in a high-glucose environment. Targeting IL-1β might, then, help improve therapeutic outcomes of CCA in patients with DM and hyperglycemia.

Diabetes mellitus type 2 (T2DM) can be managed by targeting dipeptidyl peptidase-4 (DPP-4), an enzyme that breaks down and deactivates peptides such as GIP and GLP-1. In this context, a new series of 2-(2-substituted hydrazineyl)thiazole derivatives 4, 5, 6, 8, 10, and 11 conjugated with the 2-hydroxy-5-(pyrrolidin-1-ylsulfonyl)benzylidene fragment were designed and synthesized. The virtual screening of the designed derivatives inside DPP-4 demonstrated good to moderate activity, with binding affinity ranging from -6.86 to -5.36 kcal/mol compared to Sitagliptin (S=-5.58 kcal/mol). These results encourage us to evaluate DPP-4 using in-vitro fluorescence-based assay. The in-vitro results exhibited inhibitory percentage (IP) values ranging from 40.66 to 75.62 % in comparison to Sitagliptin (IP=63.14 %) at 100 µM. Subsequently, the IC50 values were determined, and the 5-aryl thiazole derivatives 10 and 11 revealed strong potent IC50 values 2.75 ± 0.27 and 2.51 ± 0.27 µM, respectively, compared to Sitagliptin (3.32 ± 0.22 µM). The SAR study exhibited the importance of the substituents on the thiazole scaffold, especially with the hydrophobic fragment at C5 of the thiazole, which has a role in the activity. Compounds 10 and 11 were further assessed toward α-glucosidase and α-amylase enzymes and give promising results. Compound 10 showed good activity against α-glucosidase with IC50 value of 3.02 ± 0.23 µM compared to Acarbose 3.05 ± 0.22 µM and (11 = 3.34 ± 0.10 µM). On the other hand, for α-amylase, compound 11 was found to be most effective with IC50 value of 2.91 ± 0.23 µM compared to compound 10 = 3.30 ± 0.16 µM and Acarbose (2.99 ± 0.21 µM) indicating that these derivatives could reduce glucose by more than one target. The most active derivatives 10 and 11 attracted great interest as candidates for oral bioavailability and safe toxicity profiles compared to positive controls. The in-silico docking simulation was performed to understand the binding interactions inside the DPP-4, α-glucosidase, and α-amylase pockets, and it was found to be promising antidiabetic agents through a number of interactions.

BACKGROUND: Sarcopenia and diabetes mellitus (DM) have been shown to be related. It has been demonstrated that pesticides/insecticides are linked to various health issues, including DM. This study investigated the relationships between exposure to pesticides/insecticides and muscle strength among community-dwelling DM patients in a national sample of the United States (US).
METHODS: Data from the 2011-2012 and 2013-2014 U.S. National Health and Nutrition Examination Survey (NHANES) on people aged 20 years with diabetes were retrieved. A digital dynamometer was used to quantify handgrip strength, and urine pesticide concentrations were determined through laboratory testing. Regression models were used to investigate the relationship between pesticide/insecticide exposure and handgrip strength.
RESULTS: After weighting, the data from 412 NHANES participants represented 6,696,865 U.S. inhabitants. The mean age of the participants was 58.8 years. High para-nitrophenol levels (tertile 3 vs. tertile 1) were shown to be associated with lower handgrip strength in both males (aBeta = -7.25, 95% CI: -11.25, -3.25) and females (aBeta = -3.73, 95% CI: -6.89, -0.56). Further, females with elevated 2-isopropyl-4-methyl-pyrimidinol had decreased handgrip strength. Desethyl hydroxy N, N-diethyl-m-toluamide (DEET) was inversely related to handgrip strength in men aged ≥60 years. DEET acid and para-nitrophenol were inversely correlated to handgrip strength in women over 60 years.
CONCLUSIONS: This study has linked certain pesticides/insecticides to decreased muscle strength in people with diabetes. Para-nitrophenol, in particular, is negatively related to muscular strength in both males and females, and 2-isopropyl-4-methyl-pyrimidinol is inversely related to muscle strength in females.

Diabetes mellitus (DM) is a metabolic disease that heightens the risks of many vascular complications, including peripheral arterial disease (PAD). Various types of cells, including but not limited to endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages (MΦs), play crucial roles in the pathogenesis of DM-PAD. Long non-coding RNAs (lncRNAs) are epigenetic regulators that play important roles in cellular function, and their dysregulation in DM can contribute to PAD. This review focuses on the developing field of lncRNAs and their emerging roles in linking DM and PAD. We review the studies investigating the role of lncRNAs in crucial cellular processes contributing to DM-PAD, including those in ECs, VSMCs, and MΦ. By examining the intricate molecular landscape governed by lncRNAs in these relevant cell types, we hope to shed light on the roles of lncRNAs in EC dysfunction, inflammatory responses, and vascular remodeling contributing to DM-PAD. Additionally, we provide an overview of the research approach and methodologies, from identifying disease-relevant lncRNAs to characterizing their molecular and cellular functions in the context of DM-PAD. We also discuss the potential of leveraging lncRNAs in the diagnosis and therapeutics for DM-PAD. Collectively, this review provides a summary of lncRNA-regulated cell functions contributing to DM-PAD and highlights the translational potential of leveraging lncRNA biology to tackle this increasingly prevalent and complex disease.

Diabetes is a chronic medical condition that causes high glycaemic levels, leading to damage to vital organs over time. It is a common disease worldwide, affecting around 422 million individuals living in middle- and low-income countries, which make up most of the population. Unfortunately, diabetes results in 1.5 million deaths annually. Diabetic patients are at a higher risk for developing cardiovascular conditions. Diabetic heart disease constitutes multiple genres, including diabetic cardiomyopathy, coronary artery disease, and heart failure. Hypoglycaemic agents aim to prevent these metabolic issues however some of these are cardiotoxic in nature. In contrast, other hypoglycaemic agents work beyond controlling glycaemic levels with their cardioprotective properties. Given that there is an alarming increase in diabetic heart disease cases universally, we have attempted to review the existing data on the topic and the effects of hypoglycaemic drugs on heart diseases.

Diabetes mellitus is a metabolic disorder characterized by high blood sugar levels. In recent years, T2DM has become a worldwide health issue due to an increase in incidence and prevalence. Diabetic kidney disease (DKD) is one of the devastating consequences of diabetes, especially owing to T2DM and the key clinical manifestation of DKD is weakened renal function and progressive proteinuria. DKD affects approximately 1/3rd of patients with diabetes mellitus, and T2DM is the predominant cause of end-stage kidney disease (ESKD). Several lines of studies have observed the association between vitamin D deficiency and the progression and etiology of type II diabetes mellitus. Emerging experimental evidence has shown that T2DM is associated with various kinds of kidney diseases. Recent evidence has also shown that an alteration in VDR (vitamin D receptor) signaling in podocytes leads to DKD. The present review aims to examine vitamin D metabolism and its correlation with T2DM. Furthermore, we discuss the potential role of vitamin D and VDR in diabetic kidney disease.

OBJECTIVE: This study aimed to characterize the most updated utilization of eye care services and obtain a holistic understanding of barriers among patients with diabetes in China.
METHODS: This was a convergent mixed methods study.
METHODS: A convergent triangulation mixed methods approach was used, with a quantitative cross-sectional survey of patients with diabetes and semistructured interviews involving patients and health workers. Following the conceptual framework of the World Health Organization Determinants of Health Behaviours, multivariate logistic regression for quantitative analysis and thematic analysis for qualitative data were used to examine barriers to seeking eye care among patients with diabetes. Triangulation was used to integrate quantitative and qualitative results.
RESULTS: Among 1167 surveyed patients who participated in the quantitative component, 29.1% had undergone eye examinations within the last 12 months, and 9.3% had received eye surgery. Awareness that diabetes causes eye diseases (P < 0.001) and knowing laser treatment can treat diabetic retinopathy (DR; P < 0.001) were associated with higher examination rates. In the qualitative component, involving 20 patients and 11 health workers, barriers were identified from individual, social, and cultural environmental factors. Integration of data highlighted the complex interplay of these factors in shaping care-seeking behaviors and the importance of non-economic factors, including patients\' information about costs of DR services and cultural environmental factors.
CONCLUSIONS: Diabetic eye care utilization remains suboptimal in China, emphasizing the impact of cultural and contextual factors. Comprehensive education strategies, along with training for primary health workers and task-shifting, are likely to enhance eye care service utilization in underserved settings.

UNASSIGNED: The use of alirocumab and evolocumab is generally safe and well-tolerated. However, concerns remain about their long-term safety, especially with regard to new-onset or worsening diabetes mellitus (DM). We aim to assess the safety profile of alirocumab and evolocumab compared to comparator.
UNASSIGNED: Studies were retrieved comparing the safety of PCSK9i vs. comparator (placebo or statin with or without ezetimibe). The primary outcome was adverse events leading to death. Secondary outcomes included serious adverse events, new onset diabetes mellitus (DM), worsening of DM, neurocognitive dysfunction, creatine kinase (CK) elevation, elevation of liver enzymes and local injection site reaction. Factors associated with the treatment effect were determined by meta-regression analysis. Subgroup analyses were done to explore potential treatment effect differences based on PCSK9i type and treatment duration.
UNASSIGNED: We identified 56 studies with 85,123 adults (29.14% females). PCSK9i was not associated with adverse events that lead to death (OR 0.94, 95% CI 0.84 to 1.04, p = 0.22). Between the two PCSK9i, alirocumab decreased adverse events leading to death (OR 0.79, 95% CI, 0.67 to 0.94, p = 0.008). PCSK9i was associated with less serious events compared to the comparator (OR 0.93, 95% CI 0.89 to 0.98, p < 0.001). This reduction was driven mainly by alirocumab (OR 0.89, 95% CI, 0.85 to 0.93, p < 0.001). Evolocumab worsened DM (OR 2.3, 95% CI 1.26 to 4.2, p = 0.041). Subgroup analysis showed worsening of DM in the first 24 weeks of treatment with odds being highest in the first 12 weeks of treatment (<12 weeks: OR 3.82, 95% CI 1.13 to 12.99, p = 0.03; 12-24 weeks OR 2.12, 95% CI 1.20 to 3.73, p = 0.01. On the other hand, therapy >24 weeks reduced the odds of worsening DM (OR 0.89, 95% CI 0.79 to 0.99, p = 0.04). PCSK9i did not increase cognitive dysfunction, (OR 1.02, 95% CI 0.88 to 1.18, p = 0.76), or cause elevations in liver enzyme (OR 0.91, 95% CI 0.81 to 1.03, p = 0.14), or CK (OR 0.82, 95% CI 0.65 to 1.04, p = 0.10). However, PCSK9i was associated with local injection site reaction (OR 1.54, 95% CI 1.37 to 1.73, p < 0.01).
UNASSIGNED: Alirocumab decreased adverse events leading to death. Alirocumab and Evolocumab both decreased serious adverse events. PCSK9i did not increase new onset DM however evolocumab worsened DM in the first 24 weeks of treatment. PCSK9i did not increase neurologic dysfunction, and did not elevate liver enzymes and CK, however it was associated with local injection site reaction.

Background The associations and risk factors for venous thromboembolism (VTE) among hospitalized COVID-19 patients remain ambiguous in the literature, with some conflicting findings, especially in Saudi Arabia. In this study, we aim to elaborate on these data by examining regional patient populations and exploring the incidence, lab findings, and outcomes of VTE among hospitalized COVID-19 patients known to have diabetes mellitus (DM). Methodology This cross-sectional study was conducted at King Abdulaziz Medical City in Riyadh. The BestCare system was used to collect patients\' data between September 2020 and February 2022. JMP15 was used for data analysis. Frequencies and percentages were used for categorical data, and median and interquartile ranges were used for quantitative data. The chi-square and Kruskal-Wallis rank-sum tests were used to assess the difference between categorical and quantitative variables, respectively. Nominal logistical regression was used to assess diabetes as a risk factor for developing VTE among COVID-19 patients. Results Data from 153 admitted patients were collected after they satisfied the inclusion criteria. Of these patients, 39 (25.49%) developed VTE. The demographic data included age group, gender, and DM status presented as frequencies and percentages. Through bivariate analysis, patients with longer hospital stays had at least one episode of VTE (p = 0.0072). Using nominal logistic regression analysis, diabetes as a risk factor (odds ratio = 4.11, confidence interval = 0.955-5.05, p = 0.0287) was significantly associated with the development of VTE in COVID-19 patients. Conclusions Based on our study, diabetes proved significant when evaluating the possible factors regarding VTE development in COVID-19 patients. In addition, the length of stay also played a critical role in the severity of VTE in COVID-19 patients. Similar studies should be conducted on a national scale in Saudi Arabia to accomplish two goals: first, to gain further understanding of the impact of the variables investigated in our population, and second, to publish data that are more generalizable to the larger population of Saudi Arabia.