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Amomum dealbatum Roxb. parts have been traditionally used as remedies for joint pain, diabetes, muscular rheumatism, antiseptic, and abscesses in Arunachal Pradesh, Assam, and Tripura. Ethyl acetate sub-fraction E3 had significantly inhibited the α-glucosidase (IC50 5.385 μg/mL). The molecular docking revealed quercetin-3-O-galactoside to be the most potent α-glucosidase inhibitor (binding energy −43.214 kcal/mol). Using the QSAR model, the pIC50 values of myricetin, gallic acid, quercetin-3-O-galactoside, and acarbose were predicted to be 5.65235, 4.39858, 5.65235, and 6.03058, respectively. For the first time, quercetin-3-O-galactoside, myricetin, and gallic acid have been isolated from the flowers of A. dealbatum (ADF). E3 decreased blood glucose level to a near-normal concentration (100.60 ± 2.94 mg/dL) in comparison to diabetic control rats (575.20 ± 24.80 mg/dL). The results have strongly suggested the potential of ADF in treating diabetes. This lesser-known plant has the potential to uncover its full medicinal properties through further in-depth research. [ABSTRACT FROM AUTHOR]

Background: Despite major primary health care (PHC) reforms in China with the 2009 launch of the National Essential Public Health Service Package, the country experiences many challenges in improving the management of non-communicable diseases in PHC facilities. "EMERALD" is a multifaceted implementation strategy to strengthen the management of hypertension and type-2 diabetes mellitus (T2DM) in PHC facilities. The study aims to: (1) examine the effectiveness of EMERALD in improving hypertension and T2DM management; (2) evaluate the implementation of the interventions; and (3) use the study findings to model the long-term health economic impact of the interventions. Methods: The EMERALD intervention components include: (1) empowerment for PHC providers through training and capacity building; (2) empowerment for patient communities through multi-media health education; and (3) empowerment for local health administrators through health data monitoring and strengthening governance of local PHC programs. An interrupted time series design will be used to determine the effectiveness of the interventions based on routinely collected health data extracted from local health information systems. The primary effectiveness outcome is the guideline-recommended treatment rates for people with hypertension and T2DM. Secondary effectiveness outcomes include hypertension and T2DM diagnosis and control rates, and enrolment and adherence rates to the recommended care processes in the National Essential Public Health Service Package. A mixed-methods process evaluation will be conducted to evaluate the implementation of the interventions, including the reach of the target population, adequacy of adoption, level of implementation fidelity, and maintenance. Qualitative interviews with policy makers, health administrators, PHC providers, and patients with hypertension and/or T2DM will be conducted to further identify factors influencing the implementation. In addition, health economic modelling will be performed to explore the long-term incremental costs and benefits of the interventions. Discussion: This study is expected to generate important evidence on the effectiveness, implementation, and health economic impact of complex PHC interventions to strengthen the primary care sector's contribution to addressing the growing burden of non-communicable diseases in China. Trial registration: The study has been registered on Chinese Clinical Trial Registry at https://www.chictr.org.cn/ (Registration number ChiCTR2400082036, on March 19th 2024). [ABSTRACT FROM AUTHOR]

Linoleic acid (LA), as a part of the wider debate about saturated, omega-6 and omega-3 fatty acids (FAs) and health, continues to be at the center of controversy in the world of fatty acid research. A robust evidence base, however, demonstrates that higher intakes and blood levels of LA are associated with improved cardiometabolic health outcomes. LA lowers total and low-density lipoprotein cholesterol when compared with saturated fatty acids and carbohydrates. Using large prospective datasets, higher blood levels of LA were associated with lower risk of coronary heart disease, stroke and incident type-2 diabetes mellitus compared with lower levels, suggesting that, across the range of typical dietary intakes, higher LA is beneficial. Recent trials of LA-rich oils report favorable outcomes in people with common lipid disorders. However, an LA intake that is too high can impair endogenous synthesis of eicosapentaenoic acid (EPA) from alpha-linolenic acid (ALA), but the threshold at which this becomes clinically relevant is not known. In the absence of a significant intake of EPA and docosahexaenoic acid, an ideal dietary ratio of LA and ALA may be theoretically useful as it provides insight into the likely extent of endogenous EPA synthesis from ALA. Updating dietary reference intakes (DRIs) for LA and ALA is needed; however, there are insufficient data to establish RDAs for these fatty acids. The omega-6 (n-6) to omega-3 (n-3) PUFA ratio is not informative and does not shed meaningful insight about the amount of individual fatty acids in each class needed to confer health benefits. [ABSTRACT FROM AUTHOR]

This study investigated the beneficial effects and mechanisms of Lactobacillus plantarum (LP) on neuropathy in type-2 diabetic mice. Twenty db/db mice were randomly assigned to either a control group (group C) or a treated group (group LP). Weekly blood glucose levels were measured using a glucose meter. Neuropathy was assessed through thermal sensation, Von Frey responses and sensory nerve conduction velocity. Tight junction protein expression in colorectal tissues was analysed via immunofluorescence. ELISA measured serum inflammatory factors, while faecal samples at the intervention's end assessed gut microbiota changes. Western blot analysed the JAK-STAT signalling pathway in mouse brain tissue. Group LP showed significantly lower blood glucose levels and improved thermal nociceptive sensitivity in db/db mice compared to group C. Additionally, LP intervention increased the expression of the intestinal tight junction protein occludin and enhanced intestinal flora diversity, including higher levels of probiotics like Akkermansia muciniphila. In group LP, serum levels of the anti-inflammatory factor IL-10 increased significantly, while pro-inflammatory factors TNF-α, IL-6, IL-17A and LPS decreased. Additionally, the JAKSTAT signalling pathway was notably inhibited in the brain tissue of these mice. LP may potentially alleviate neuropathy in type-2 diabetic mice by modulating the immune system, repairing the intestinal mucosal barrier, and balancing the gut microbiome. [ABSTRACT FROM AUTHOR]

Background & Objective: Hypovitaminosis D has shown to be linked with T2DM development and control in numerous studies. The association of SNPs in genes related to VitD metabolism with T2DM has not been sufficiently studied. Consequently, our aim in the present study was to explore the association between genetic variants in genes connected with VitD, mainly a SNP in GC (rs1155563), a SNP in DHCR7 (rs12785878) and a SNP in CYP2R1 (rs10500804) with glycaemic parameters in females with T2DM in Saudi Arabia. Methods: The cross-sectional study included 149 females (age 38-52 years) with T2DM from Jeddah, Saudi Arabia (September 2022-March 2023). Blood was extracted from the participants for biochemical tests including measuring VitD [25(OH)D] concentration, parameters of glycaemia (HbA1c, insulin, fasting glucose and insulin sensitivity indices including HOMA2-IR and HOMA2-%β), and for genomic DNA isolation. Sanger DNA sequencing was used to screen for VitD genetic polymorphisms (rs1155563, rs12785878 and rs10500804). Results: Minor allele frequency for rs1155563C, rs12785878T and rs10500804G was 0.21, 0.23 and 0.37, respectively. Levels of 25(OH)D and glycaemic parameters as well did not show any significant difference between the genotypes of each SNP. Conclusion: This study showed lack of association of rs1155563 in GC, rs12785878 in DHCR7 and rs10500804 in CYP2R1 with VitD level primarily and with glycaemic parameters secondarily. Additional research is required to explore further other VitD genetic polymorphisms influencing T2DM which might lead consequently to genetically-based personalized management for T2DM. [ABSTRACT FROM AUTHOR]

Background: Previous studies examined the association of Helicobacter pylori infection (H. pylori) with complications of diabetes, but the results have been inconsistent. The aim of this study of patients with type-2 diabetes (T2D) was to determine the association of H. pylori infection with the major complications of diabetes. Methods: This single-center retrospective study examined patients with T2D who received H. pylori testing between January 2016 and December 2021. Logistic regression analyses were used to evaluate the association of H. pylori infection with four major complications of diabetes. Results: We examined 960 patients with T2D, and 481 of them (50.1%) were positive for H. pylori. H. pylori infection was significantly associated with diabetic nephropathy (odds ratio [OR] = 1.462; 95% confidence interval [CI]: 1.006,2.126; P = 0.046). In addition, the co-occurrence of H. pylori positivity with hypertension (OR = 4.451; 95% CI: 2.351,8.427; P < 0.001), with glycated hemoglobin A1c (HbA1c) of at least 8% (OR = 2.925; 95% CI: 1.544,5.541; P = 0.001), and with diabetes duration of at least 9 years (OR = 3.305; 95% CI:1.823,5.993; P < 0.001) further increased the risk of diabetic nephropathy. There was no evidence of an association of H. pylori infection with retinopathy, neuropathy, or peripheral vascular disease. Conclusions: Our study of T2D patients indicated that those with H. pylori infections had an increased risk of nephropathy, and this risk was greater in patients who also had hypertension, an HbA1c level of 8% or more, and diabetes duration of 9 years or more. [ABSTRACT FROM AUTHOR]

Abstract Background Despite major primary health care (PHC) reforms in China with the 2009 launch of the National Essential Public Health Service Package, the country experiences many challenges in improving the management of non-communicable diseases in PHC facilities. “EMERALD” is a multifaceted implementation strategy to strengthen the management of hypertension and type-2 diabetes mellitus (T2DM) in PHC facilities. The study aims to: (1) examine the effectiveness of EMERALD in improving hypertension and T2DM management; (2) evaluate the implementation of the interventions; and (3) use the study findings to model the long-term health economic impact of the interventions. Methods The EMERALD intervention components include: (1) empowerment for PHC providers through training and capacity building; (2) empowerment for patient communities through multi-media health education; and (3) empowerment for local health administrators through health data monitoring and strengthening governance of local PHC programs. An interrupted time series design will be used to determine the effectiveness of the interventions based on routinely collected health data extracted from local health information systems. The primary effectiveness outcome is the guideline-recommended treatment rates for people with hypertension and T2DM. Secondary effectiveness outcomes include hypertension and T2DM diagnosis and control rates, and enrolment and adherence rates to the recommended care processes in the National Essential Public Health Service Package. A mixed-methods process evaluation will be conducted to evaluate the implementation of the interventions, including the reach of the target population, adequacy of adoption, level of implementation fidelity, and maintenance. Qualitative interviews with policy makers, health administrators, PHC providers, and patients with hypertension and/or T2DM will be conducted to further identify factors influencing the implementation. In addition, health economic modelling will be performed to explore the long-term incremental costs and benefits of the interventions. Discussion This study is expected to generate important evidence on the effectiveness, implementation, and health economic impact of complex PHC interventions to strengthen the primary care sector’s contribution to addressing the growing burden of non-communicable diseases in China. Trial registration The study has been registered on Chinese Clinical Trial Registry at https://www.chictr.org.cn/ (Registration number ChiCTR2400082036, on March 19th 2024).

Abstract Linoleic acid (LA), as a part of the wider debate about saturated, omega-6 and omega-3 fatty acids (FAs) and health, continues to be at the center of controversy in the world of fatty acid research. A robust evidence base, however, demonstrates that higher intakes and blood levels of LA are associated with improved cardiometabolic health outcomes. LA lowers total and low-density lipoprotein cholesterol when compared with saturated fatty acids and carbohydrates. Using large prospective datasets, higher blood levels of LA were associated with lower risk of coronary heart disease, stroke and incident type-2 diabetes mellitus compared with lower levels, suggesting that, across the range of typical dietary intakes, higher LA is beneficial. Recent trials of LA-rich oils report favorable outcomes in people with common lipid disorders. However, an LA intake that is too high can impair endogenous synthesis of eicosapentaenoic acid (EPA) from alpha-linolenic acid (ALA), but the threshold at which this becomes clinically relevant is not known. In the absence of a significant intake of EPA and docosahexaenoic acid, an ideal dietary ratio of LA and ALA may be theoretically useful as it provides insight into the likely extent of endogenous EPA synthesis from ALA. Updating dietary reference intakes (DRIs) for LA and ALA is needed; however, there are insufficient data to establish RDAs for these fatty acids. The omega-6 (n-6) to omega-3 (n-3) PUFA ratio is not informative and does not shed meaningful insight about the amount of individual fatty acids in each class needed to confer health benefits.

Abstract Type 2 diabetes (T2D) and Clear-cell renal cell carcinoma (ccRCC) are both complicated diseases which incidence rates gradually increasing. Population based studies show that severity of ccRCC might be associated with T2D. However, so far, no researcher yet investigated about the molecular mechanisms of their association. This study explored T2D and ccRCC causing shared key genes (sKGs) from multiple transcriptomics profiles to investigate their common pathogenetic processes and associated drug molecules. We identified 259 shared differentially expressed genes (sDEGs) that can separate both T2D and ccRCC patients from control samples. Local correlation analysis based on the expressions of sDEGs indicated significant association between T2D and ccRCC. Then ten sDEGs (CDC42, SCARB1, GOT2, CXCL8, FN1, IL1B, JUN, TLR2, TLR4, and VIM) were selected as the sKGs through the protein–protein interaction (PPI) network analysis. These sKGs were found significantly associated with different CpG sites of DNA methylation that might be the cause of ccRCC. The sKGs-set enrichment analysis with Gene Ontology (GO) terms and KEGG pathways revealed some crucial shared molecular functions, biological process, cellular components and KEGG pathways that might be associated with development of both T2D and ccRCC. The regulatory network analysis of sKGs identified six post-transcriptional regulators (hsa-mir-93-5p, hsa-mir-203a-3p, hsa-mir-204-5p, hsa-mir-335-5p, hsa-mir-26b-5p, and hsa-mir-1-3p) and five transcriptional regulators (YY1, FOXL1, FOXC1, NR2F1 and GATA2) of sKGs. Finally, sKGs-guided top-ranked three repurposable drug molecules (Digoxin, Imatinib, and Dovitinib) were recommended as the common treatment for both T2D and ccRCC by molecular docking and ADME/T analysis. Therefore, the results of this study may be useful for diagnosis and therapies of ccRCC patients who are also suffering from T2D.

Abstract Background Previous studies examined the association of Helicobacter pylori infection (H. pylori) with complications of diabetes, but the results have been inconsistent. The aim of this study of patients with type-2 diabetes (T2D) was to determine the association of H. pylori infection with the major complications of diabetes. Methods This single-center retrospective study examined patients with T2D who received H. pylori testing between January 2016 and December 2021. Logistic regression analyses were used to evaluate the association of H. pylori infection with four major complications of diabetes. Results We examined 960 patients with T2D, and 481 of them (50.1%) were positive for H. pylori. H. pylori infection was significantly associated with diabetic nephropathy (odds ratio [OR] = 1.462; 95% confidence interval [CI]: 1.006,2.126; P = 0.046). In addition, the co-occurrence of H. pylori positivity with hypertension (OR = 4.451; 95% CI: 2.351,8.427; P

Type 2 diabetes (T2D) represents a growing disease burden in South Africa. While glycated haemoglobin (HbA1c) testing is the gold standard for long-term blood glucose management, recommendations for HbA1c monitoring frequency are based on expert opinion. This study investigates the effectiveness and cost-effectiveness of alternative HbA1c monitoring intervals in the management of T2D. A Markov model with three health states (HbA1c <7%, HbA1c ≥ 7%, Dead) was used to estimate lifetime costs and quality-adjusted life years (QALYs) of alternative HbA1c monitoring intervals among patients with T2D, using a provider's perspective and a 3% discount rate. HbA1c monitoring strategies (three-monthly, four-monthly, six-monthly and annual tests) were evaluated with respect to the incremental cost-effectiveness ratio (ICER) assessing each comparator against a less costly, undominated alternative. The scope of costs included the direct medical costs of managing diabetes. Transition probabilities were obtained from routinely collected public sector HbA1c data, while health service utilization and health-related-quality-of-life (HRQoL) data were obtained from a local cluster randomized controlled trial. Other parameters were obtained from published studies. Robustness of findings was evaluated using one-way and probabilistic sensitivity analyses. A South African indicative cost-effectiveness threshold of USD2665 was adopted. Annual and lifetime costs of managing diabetes increased with HbA1c monitoring, while increased monitoring provides higher QALYs and life years. For the overall cohort, the ICER for six-monthly vs annual monitoring was cost-effective (USD23 22.37 per QALY gained), whereas the ICER of moving from six-monthly to three-monthly monitoring was not cost effective (USD6437.79 per QALY gained). The ICER for four-monthly vs six-monthly monitoring was extended dominated. The sensitivity analysis showed that the ICERs were most sensitive to health service utilization rates. While the factors influencing glycaemic control are multifactorial, six-monthly monitoring is potentially cost-effective while more frequent monitoring could further improve patient HrQoL. [ABSTRACT FROM AUTHOR]

Abstract Olive (Olea europaea) phytochemicals are associated with a reduced risk of type 2 diabetes. Table olives typically have higher phytochemical concentrations than olive oil, but their impact on human intestinal α-glucosidase is largely unknown. Shinzuke, the most common trade preparation in Japan, are alkali-treated non-fermented green olives. In contrast, natural olives are debittered by brining, which may enhance phytochemical retention. We evaluated the α-glucosidase inhibitory effect of Shinzuke and natural green olives produced in-house and compared them with commercial table olives. Eight types of table olives were tested against human intestinal α-glucosidase. Shinzuke Mission was the least effective (IC50 0.710 ± 0.058 mg/mL), while Natural green olives showed double to triple activity, with a non-competitive mechanism. Natural table olives retained more phytochemicals than shinzuke and other treated olives, and are good inhibitors of human α-glucosidase in vitro, exhibiting potential as a functional food for the management of postprandial glycaemia. Graphical Abstract

Olive (Olea europaea) phytochemicals are associated with a reduced risk of type 2 diabetes. Table olives typically have higher phytochemical concentrations than olive oil, but their impact on human intestinal α-glucosidase is largely unknown. Shinzuke, the most common trade preparation in Japan, are alkali-treated non-fermented green olives. In contrast, natural olives are debittered by brining, which may enhance phytochemical retention. We evaluated the α-glucosidase inhibitory effect of Shinzuke and natural green olives produced in-house and compared them with commercial table olives. Eight types of table olives were tested against human intestinal α-glucosidase. Shinzuke Mission was the least effective (IC50 0.710 ± 0.058 mg/mL), while Natural green olives showed double to triple activity, with a non-competitive mechanism. Natural table olives retained more phytochemicals than shinzuke and other treated olives, and are good inhibitors of human α-glucosidase in vitro, exhibiting potential as a functional food for the management of postprandial glycaemia. [ABSTRACT FROM AUTHOR]

This paper reports on the hardware implementation of a digital insulin-glucose regulator for type 2 diabetic patients by using a Field Programmable Gate Array board. For a real time-control of the patient insulin concentration, the insulin-regulator needs to measure only his blood glucose concentration. With respect to other reported solutions using general-purpose programmable hardware's, the proposed insulin-glucose regulator allows to design a software-free, fully-hardware architecture of the system here described in detail. A prototype has been developed so to validate its functionality in the following two operating modes: (i) in the open loop condition for which only the insulin-glucose regulator is operating; (ii) in the closed loop condition for which the insulin-glucose regulator acting as an artificial pancreas is connected to a population of one hundred virtual patients individuated by employing a comprehensive theoretical model recognized by the U.S. Food and Drug Administration for the pre-clinical validation of glucose control strategies. These virtual patients present the same trend of the variation of the glucose concentration achieving different maximum and minimum values of glucose concentrations when eating a meal. The paper presents and discusses the experimental results by comparing them with those ones obtained by implementing the theoretical model through numerical simulations performed in SIMULINK. Relative errors lower than ±1% have been achieved by performing this comparison so demonstrating a very high accuracy of the proposed insulin-glucose regulator digital system. The implemented hardware solution of the digital controller can process the input data related to the glucose concentration of each virtual patient in about 1.1 μs with an estimated power consumption of about 36 mW. These achievements open the way for further investigations on digital architectures for glucose regulators to be integrated in VLSI as System-on-Chips and/or Lab-on-Chips for portable, wearable, and implantable solutions in real biomedical applications. [ABSTRACT FROM AUTHOR]

The escalating global prevalence of type-2 diabetes (T2D) and obesity necessitates the development of novel oral medications. Agonism at G-protein coupled receptor-119 (GPR119) has been recognized for modulation of metabolic homeostasis in T2D, obesity, and fatty liver disease. However, off-target effects have impeded the advancement of synthetic GPR119 agonist drug candidates. Non-systemic, gut-restricted GPR119 agonism is suggested as an alternative strategy that may locally stimulate intestinal enteroendocrine cells (EEC) for incretin secretion, without the need for systemic drug availability, consequently alleviating conventional class-related side effects. Herein, we report the preclinical acute safety, efficacy, and pharmacokinetics (PK) of novel GPR119 agonist compounds ps297 and ps318 that potentially target gut EEC for incretin secretion. In a proof-of-efficacy study, both compounds demonstrated glucagon-like peptide-1 (GLP-1) secretion capability during glucose and mixed-meal tolerance tests in healthy mice. Furthermore, co-administration of sitagliptin with investigational compounds in diabetic db/db mice resulted in synergism, with GLP-1 concentrations rising by three-fold. Both ps297 and ps318 exhibited low gut permeability assessed in the in-vitro Caco-2 cell model. A single oral dose PK study conducted on healthy mice demonstrated poor systemic bioavailability of both agents. PK measures (mean ± SD) for compound ps297 (Cmax 23 ± 19 ng/mL, Tmax range 0.5 – 1 h, AUC0–24 h 19.6 ± 21 h*ng/mL) and ps318 (Cmax 75 ± 22 ng/mL, Tmax range 0.25 – 0.5 h, AUC0–24 h 35 ± 23 h*ng/mL) suggest poor oral absorption. Additionally, examinations of drug excretion patterns in mice revealed that around 25 % (ps297) and 4 % (ps318) of the drugs were excreted through faeces as an unchanged form, while negligible drug concentrations (

Betel quid (BQ), a prevalent social habit in Asia, is often used without awareness of its harmful effects. This study explored the impact of BQ chewing on hyperglycemia among diabetic patients in northeastern Bangladesh. Specifically, this study focused on the role of areca nut, a key addictive component in BQ, in influencing hyperglycemia. Random blood glucose (RBG) tests were conducted on 961 diabetic patients, alongside lifestyle data, from August 2018 to February 2019 at Sylhet Diabetic Hospital, Bangladesh. Statistical analyses, including t-tests, Analysis of the variance (ANOVA), Fisher's exact test, and Multivariate regression, were employed to assess RBG status in BQ chewer vs. non-chewer. BQ chewers had higher RBG levels than non-chewers (263.3 ± 4.768 vs. 251.0 ± 5.915). Notably, raw areca nut users in the BQ group had significantly higher RBG levels than dry nut users (278.0 ± 8.790 vs. 252.1 ± 6.835 mg/dl), with up to 50 times more hyperglycemic effect. BQ chewing was associated with elevated RBG levels across different demographic and lifestyle groups. Lack of awareness was also prevalent among BQ chewers while individuals with desk jobs showed higher RBG levels. In conclusion, diabetic BQ chewers experience elevated hyperglycemia levels, highlighting the. urgent need to discourage BQ use for effective diabetes management. [ J Adv Biotechnol Exp Ther 2024; 7(3.000): 460-471]

Abstract Background The current research targeted to study the impact of nutritional intervention by two sourdough breads in improvement of cognitive dysfunction in diabetic rats. Methods Type-2 diabetes was induced in rats by Streptozotocin-Nicotinamide (STZ-NC). Diabetic rats were fed on balanced diet or balanced diet containing 20% of sourdough bread I or II for a month. Lipid profile, oxidative stress, inflammatory markers and cognitive functions were assessed in all rats. Gene expression of brain-derived neurotrophic factor (BDNF) and nuclear respiratory factor 2 (NRF-2) were assessed in hippocampal tissue, while expression of phosphoenol pyruvate carboxy kinase (PEPCK), and glucose transporter 2 (GLUT2) genes were evaluated in hepatic tissue. Chemical composition and fatty acids profile were evaluated in the prepared sourdough bread. Results Sourdough bread II showed higher content of phenolic compounds, fat, fiber and carbohydrates. Fatty acids profile revealed that sourdough bread I was higher in saturated fatty acids (16.08%), while sourdough bread sample II was higher in unsaturated fatty acids (79.33%). Sourdough bread I or II feeding rats’ showed significant improvement in hyperglycemia, oxidative stress markers, inflammatory markers, lipid profile, liver and kidney functions in association with improvement in cognitive function. Gene expression of BDNF and NRF2 in hippocampal tissue were increased significantly, while hepatic GLUT2 and PEPCK gene expression were down-regulated in diabetic given sourdough bread I or II. Conclusion Sourdough bread II was superior in all the studied parameters. The anti-diabetic effect and protection from cognitive dysfunction of sourdough bread samples may be ascribed to the occurrence of dietary fibers, phenolic compounds, and polyunsaturated fatty acids.

This paper presents a novel capacitive sensor-based device for detecting type-2 diabetes through blood analysis. The proposed methodology measures changes in the complex permittivity of red blood cells (RBCs) caused by elevated glucose levels, affecting their rheological and electrical properties, such as viscosity, volume, relative permittivity, dielectric loss, and AC conductivity. These changes, well-documented in the literature, alter the bio-impedance signature of RBCs, serving as an indicator for type-2 diabetes. The study examines various concentrations of normal and diabetic RBCs within a frequency range of 50 kHz to 200 kHz, chosen for its relevance to bio-impedance responses. Experimental results show that healthy RBCs in a 200 μL PBS solution have a complex permittivity (ɛmix) of 65.12 and conductivity (σmix) of 0.63 S/m, while diabetic RBCs measure 73.44 and 0.68 S/m, respectively. Additionally, the complex permittivity decreases as the cell concentration increases for both normal and diabetic RBCs. At 100% cell concentration, the average bio-impedance for diabetic blood cells is 50.3 kΩ, compared to 56.7 kΩ for healthy blood cells over the entire frequency range. The standard deviation of bio-impedance (Zmix) between 50 kHz and 200 kHz highlights the difference between healthy and diabetic RBCs, with 200 kHz measurements proving more reliable. To detect these bio-impedance changes, an interdigitated electrode (IDE) capacitive sensor with 40 capacitive elements was simulated. The complex bio-impedance (Zmix) was measured within the 50 kHz–200 kHz frequency range, providing clear differentiation between healthy and diabetic blood cells. Simulation using Finite Element Method (FEM) through COMSOL® software supports these findings, showcasing the sensor’s efficacy in type-2 diabetes detection.

The beneficial cardiovascular effects of exercise are well documented, however the mechanisms by which exercise improves vascular function in diabetes are not fully understood. This study investigates whether there are (1) improvements in blood pressure and endothelium-dependent vasorelaxation (EDV) and (2) alterations in the relative contribution of endothelium-derived relaxing factors (EDRF) in modulating mesenteric arterial reactivity in male UC Davis type-2 diabetes mellitus (UCD-T2DM) rats, following an 8-week moderate-intensity exercise (MIE) intervention. EDV to acetylcholine (ACh) was measured before and after exposure to pharmacological inhibitors. Contractile responses to phenylephrine and myogenic tone were determined. The arterial expressions of endothelial nitric oxide (NO) synthase (eNOS), cyclooxygenase (COX), and calcium-activated potassium channel (KCa) channels were also measured. T2DM significantly impaired EDV, increased contractile responses and myogenic tone. The impairment of EDV was accompanied by elevated NO and COX importance, whereas the contribution of prostanoid- and NO-independent (endothelium-derived hyperpolarization, EDH) relaxation was not apparent compared to controls. MIE 1) enhanced EDV, while it reduced contractile responses, myogenic tone and systolic blood pressure (SBP), and 2) caused a shift away from a reliance on COX toward a greater reliance on EDH in diabetic arteries. We provide the first evidence of the beneficial effects of MIE via the altered importance of EDRF in mesenteric arterial relaxation in male UCD-T2DM rats.

BackgroundBrain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in regulating synaptic activity and plasticity.ObjectiveGiven that type-2 diabetes (T2DM) increases the risk of cognitive decline, and studies have suggested lower BDNF levels may be a risk factor of diabetic neurovascular complications, we sought to investigate total white matter hyperintensities (WMH) as a moderator of the effect of BDNF on hippocampal volume and cognition.MethodsOlder adults without dementia from the Alzheimer's Disease Neuroimaging Initiative (N = 454 including 49 with T2DM and 405 without diabetes) underwent neuropsychological evaluation, magnetic resonance imaging to quantify hippocampal and WMH volumes, and blood draw to assess BDNF.ResultsAdjusting for age, sex, and APOE ɛ4 carrier status, there was a significant interaction between total WMH and BDNF on bilateral hippocampal volume in the non-T2DM group (t = 2.63, p = 0.009). Examination of main effect models with a dichotomous high/low BNDF group revealed a significant main effect for low BDNF (t = -4.98, p

The classification of diabetes into type-1 (T1D) and type-2 (T2D) is a critical step in tailoring effective treatment strategies. This distinction relies on a nuanced evaluation of clinical and biochemical features. While age at diagnosis, autoimmune markers, and beta-cell function are among the crucial clinical parameters, biochemical indicators like C-peptide levels and antibody analyses play a pivotal role. This review comprehensively examines the utility of these features in accurately categorizing individuals into T1D and T2D subtypes, providing valuable insights for clinical practice. This scoping review systematically analyses 32 studies aimed at classifying T1D and T2D using various predictor variables. Clinical parameters including family history of diabetes, age at diagnosis, sex, history of insulin use, percent desirable weight or body mass index, waist, and blood pressure emerge as pivotal diagnostic tools. C-peptide measures, encompassing urinary C-peptide to creatinine ratio (UCPCR), and serum fasting and stimulated C-peptide levels further augment classification. Biochemical markers beyond C-peptide, such as serum level of adiponectin, triglycerides (TG), high-density lipoprotein–cholesterol (HDL-C), low-density lipoprotein (LDL-C), Total cholesterol, fasting and postprandial plasma glucose, and glycated hemoglobin (HbA1c), provide supplementary information for classification. Ketonuria and postglucagon or meal-stimulated C-peptide measurements contribute to nuanced classification, particularly in insulin-treated populations. Antibody analyses, particularly presence of GAD65, Zinc Transporter, and IA2 antibodies, highlight the autoimmune nature of T1D. In conclusion, this scoping review underscores the importance of a comprehensive approach that integrates clinical, biochemical, and immunological markers in accurately differentiating between T1D and T2D in clinical practice. [ABSTRACT FROM AUTHOR]

The authors sought to correlate the complex sequel of obesity with various parameters known to develop metabolic syndrome viz. insulin resistance, dyslipidemia, hypertension etc., as these anomalies are linked to vascular atherosclerosis and outbreak of cardiovascular and cerebrovascular diseases. A comprehensive online survey using MEDLINE, Scopus, PubMed and Google Scholar was conducted for relevant journals from 1970 till present time (2023) with key search terms like: 'obesity', 'leptin', type-2 diabetes', 'atherosclerosis', 'cardiovascular and cerebrovascular diseases'. The findings of the reports were compared and correlated. The information was then collated for developing this review. Reports showed that in human obesity, hyper-leptinemia could induce hyperglycemia, which in turn templates hypercholesterolemia. Persisting hypercholesterolemia over a period of time may en-route atherosclerosis in blood vessels. Thus obesity has been considered as a template for originating hyperglycemia, hypercholesterolemia and outbreak of vascular atherogenesis or in other words, obesity in long run can trigger atherosclerosis and its related disorders e.g. heart attack and stroke. Literature survey shows that primarily, co-morbidities of human obesity start with leptin and insulin resistance and then multiplies with metabolic irregularities to an extreme that results in pathogenesis of heart attack and stroke. Atherosclerosis associated cardiovascular and cerebrovascular events are independent risks of obese subjects and particularly in the cases of persisting obesity. [ABSTRACT FROM AUTHOR]

Objective: Multiple scores validate long-term type-2 diabetes mellitus (T2DM) remission after metabolic and bariatric surgery (MBS). However, studies comparing Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) have not adequately controlled for certain parameters, which may influence procedure selection. Methods: We conducted a multicenter retrospective review of patients with T2DM who underwent RYGB or SG between 2008 and 2017. Data on demographics, clinical, laboratory, and metabolic values were collected annually for up to 14 years. Each eligible RYGB patient was individually matched to an eligible SG patient based on diabetes severity, weight loss, and follow-up duration. Results: Among 1149 T2DM patients, 467 were eligible for matching. We found 97 matched pairs who underwent RYGB or SG. RYGB showed significantly higher T2DM remission rates (46.4%) compared to SG (33.0%) after matching. SG patients had higher insulin usage (35.1%) than RYGB patients (20.6%). RYGB patients also experienced greater decreases in HbA1c levels and diabetes medication usage than SG patients. Conclusions: RYGB demonstrates higher efficacy for T2DM remission compared to SG, regardless of baseline characteristics, T2DM severity, weight loss, and follow-up duration. Further studies are needed to understand the long-term metabolic effects of MBS and the underlying pathophysiology of T2DM remission after MBS. [ABSTRACT FROM AUTHOR]

To explore to which extent neurodegeneration and cerebral small vessel disease (SVD) could mediate the association between type-2 diabetes and higher dementia risk. The analytical sample consisted in 2228 participants, out of the Three-City study, aged 65 and older, free of dementia at baseline who underwent brain MRI. Diabetes was defined by medication intake or fasting or non-fasting elevated glucose levels. Dementia status was assessed every 2 to 3 years, during up to 12 years of follow-up. Brain parenchymal fraction (BPF) and white matter hyperintensities volume (WMHV) were selected as markers of neurodegeneration and cerebral SVD respectively. We performed a mediation analysis of the effect of baseline BPF and WMHV (mediators) on the association between diabetes and dementia risk using linear and Cox models adjusted for age, sex, education level, hypertension, hypercholesterolemia, BMI, smoking and alcohol drinking status, APOE-ε4 status, and study site. At baseline, 8.8% of the participants had diabetes. Diabetes (yes vs. no) was associated with higher WMHV (βdiab = 0.193, 95% CI 0.040; 0.346) and lower BPF (βdiab = −0.342, 95% CI −0.474; −0.210), as well as with an increased risk of dementia over 12 years of follow-up (HRdiab = 1.65, 95% CI 1.04; 2.60). The association between diabetes status and dementia risk was statistically mediated by higher WMHV (HRdiab=1.05, 95% CI 1.01; 1.11, mediated part = 10.8%) and lower BPF (HRdiab = 1.12, 95% CI 1.05; 1.20, mediated part = 22.9%). This study showed that both neurodegeneration and cerebral SVD statistically explained almost 30% of the association between diabetes and dementia. [ABSTRACT FROM AUTHOR]

In this paper, we present an efficient deep-learning hybrid model comprising an extreme gradient boosting (XGBoost) supervised learning algorithm and convolutional neural networks (CNN) for the automated detection of diseases. The proposed model is implemented and tested to detect type-2 diabetes by measuring the acetone concentration in the exhaled breath. Acetone will be present in much higher concentrations in type-2 diabetic patients compared to non-diabetic people. A novel sensing module is designed and implemented in our study to measure the acetone concentration in exhaled breath. The proposed approach delivered good results, with a classification accuracy of 97.14%. The findings of this study show how effectively the proposed detection module functions in disease diagnosis applications. As the detection process is simple and non-invasive, people can undergo routine checks for diabetes with the proposed detection module. [ABSTRACT FROM AUTHOR]

Background: The current research targeted to study the impact of nutritional intervention by two sourdough breads in improvement of cognitive dysfunction in diabetic rats. Methods: Type-2 diabetes was induced in rats by Streptozotocin-Nicotinamide (STZ-NC). Diabetic rats were fed on balanced diet or balanced diet containing 20% of sourdough bread I or II for a month. Lipid profile, oxidative stress, inflammatory markers and cognitive functions were assessed in all rats. Gene expression of brain-derived neurotrophic factor (BDNF) and nuclear respiratory factor 2 (NRF-2) were assessed in hippocampal tissue, while expression of phosphoenol pyruvate carboxy kinase (PEPCK), and glucose transporter 2 (GLUT2) genes were evaluated in hepatic tissue. Chemical composition and fatty acids profile were evaluated in the prepared sourdough bread. Results: Sourdough bread II showed higher content of phenolic compounds, fat, fiber and carbohydrates. Fatty acids profile revealed that sourdough bread I was higher in saturated fatty acids (16.08%), while sourdough bread sample II was higher in unsaturated fatty acids (79.33%). Sourdough bread I or II feeding rats' showed significant improvement in hyperglycemia, oxidative stress markers, inflammatory markers, lipid profile, liver and kidney functions in association with improvement in cognitive function. Gene expression of BDNF and NRF2 in hippocampal tissue were increased significantly, while hepatic GLUT2 and PEPCK gene expression were down-regulated in diabetic given sourdough bread I or II. Conclusion: Sourdough bread II was superior in all the studied parameters. The anti-diabetic effect and protection from cognitive dysfunction of sourdough bread samples may be ascribed to the occurrence of dietary fibers, phenolic compounds, and polyunsaturated fatty acids. [ABSTRACT FROM AUTHOR]

To measure the effects of diabetes clubs on peer support, disclosure of diabetes status, and the source of information regarding the management of diabetes among persons living with type-2 diabetes (T2D) in rural Vietnam. A pre- and post-pilot intervention study was carried out in Thai Binh Province, Vietnam (n = 222). Post-intervention, 57.7 % reported using experiences shared by other persons with T2D during the diabetes club sessions. Compared to pre-intervention, there was an increase in the proportion of persons with T2D who disclosed their diabetes status to friends and/or community members (an increase of 15.3 and 13.8 percentage points, respectively). The proportion of persons who reported gathering their own information regarding diabetes management without any support from others decreased from 15.7 % to 6.3 %. Those who reported a relative inside their home or a relative outside their household as their primary source of T2D-relevant information increased from 10.8 % to 18.6 % and from 2.7 % to 9.5 %, respectively. Persons who mentioned that they did not have a need for further support for their diabetes care increased from 18.5 % to 32.0 %. Specific support regarding diabetes-related knowledge received from family members, friends, and/or community members increased from 27.5 % to 62.2 % These findings suggest a promising potential for the implementation of diabetes clubs to enhance diabetes-relevant knowledge and the quality of self-management among persons living with T2D diabetes in rural areas of Vietnam. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the blood pressure (BP) lowering ability of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), in individuals with type-2 diabetes (T2D). Methods: Randomized controlled trials (RCTs) comparing subcutaneous or oral semaglutide with placebo or other antihyperglycemic agents (AHAs) in T2D patients were identified by searching PubMed, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library. These screened studies included the outcomes of interest: systolic and/or diastolic BP. Weighted mean differences (WMDs) and 95 % confidence intervals (CIs) were used to present the meta-analysis results. Pooled and sensitivity analyses were performed, and the risk of bias was evaluated. Results: Twenty-nine RCTs with a total of 26985 participants were recruited in the final analysis. The WMD in change from baseline in systolic BP (SBP) of semaglutide versus placebo or other AHAs was −2.31 mmHg (95% CI: −3.11 to −1.51), while that for diastolic BP (DBP) was 0.09 mmHg (95% CI: −0.16 to 0.33). It also reduced glycated hemoglobin A1c (HbA1c) by 0.75% (95% CI: −0.92 to −0.58) and body weight loss by 2.80 kg (95% CI: −3.51 to −2.08). The reduction in SBP was similar for subcutaneous and oral administration of semaglutide, with −2.36 (95% CI: −3.38 to −1.35) and −2.50 (95% CI: −3.48 to −1.53), respectively. Conclusions: In T2D, SBP decreased significantly in the semaglutide group compared with placebo or other active controls. According to the efficacy results from this meta-analysis, subcutaneous and oral semaglutide have similar SBP-reducing effects. Therefore, the treatment of T2D patients with subcutaneous semaglutide or oral preparations is beneficial for reducing SBP. [ABSTRACT FROM AUTHOR]

CD10, a zinc-dependent metalloprotease found on the cell surface, plays a pivotal role in an array of physiological and pathological processes including cardiovascular regulation, immune function, fetal development, pain response, oncogenesis, and aging. Recognized as a biomarker for hematopoietic and tissue stem cells, CD10 has garnered attention for its prognostic potential in the progression of leukemia and various solid tumors. Recent studies underscore its regulatory significance and therapeutic promise in combating Alzheimer's disease (AD), and it is noted for its protective role in preventing heart failure (HF), obesity, and type-2 diabetes. Furthermore, CD10/substance P interaction has also been shown to contribute to the pain signaling regulation and immunomodulation in diseases such as complex regional pain syndrome (CRPS) and osteoarthritis (OA). The emergence of COVID-19 has sparked interest in CD10's involvement in the disease's pathogenesis. Given its association with multiple disease states, CD10 is a prime therapeutic target; inhibitors targeting CD10 are now being advanced as therapeutic agents. This review compiles recent and earlier literature on CD10, elucidating its physicochemical attributes, tissue-specific expression, and molecular functions. Furthermore, it details the association of CD10 with various diseases and the clinical advancements of its inhibitors, providing a comprehensive overview of its growing significance in medical research. [ABSTRACT FROM AUTHOR]

Type-2 diabetes mellitus (DM-2) is a complicated endocrine and metabolism condition recognized as the most major non-communicable disease in the world. The complications associated with DM-2 involve cardiovascular disease, diabetic retinopathy and neuropathy. This article proposes the Fourier decomposition method for non-invasive automated type-2 diabetes detection using photoplethysmography (PPG) signals. The proposed research work comprises three major phases. In the first phase, the 5-min duration of the toe PPG signal is split into 10-s segments and decomposed into frequency subbands known as Fourier intrinsic band functions (FIBFs). Two features from each FIBF are extracted in the second phase, including kurtosis and log energy entropy. The last stage involves passing the features on to various machine learning techniques. The least-square support vector machine (radial basis function) algorithm yielded better classification results with an accuracy of 98.61%, a sensitivity of 98.96%, and a selectivity of 98.26%. [ABSTRACT FROM AUTHOR]

SUMMARY: The plant‐specialized metabolite montbretin A (MbA) is being developed as a new treatment option for type‐2 diabetes, which is among the ten leading causes of premature death and disability worldwide. MbA is a complex acylated flavonoid glycoside produced in small amounts in below‐ground organs of the perennial plant Montbretia (Crocosmia × crocosmiiflora). The lack of a scalable production system limits the development and potential application of MbA as a pharmaceutical or nutraceutical. Previous efforts to reconstruct montbretin biosynthesis in Nicotiana benthamiana (Nb) resulted in low yields of MbA and higher levels of montbretin B (MbB) and montbretin C (MbC). MbA, MbB, and MbC are nearly identical metabolites differing only in their acyl moieties, derived from caffeoyl‐CoA, coumaroyl‐CoA, and feruloyl‐CoA, respectively. In contrast to MbA, MbB and MbC are not pharmaceutically active. To utilize the montbretia caffeoyl‐CoA biosynthesis for improved MbA engineering in Nb, we cloned and characterized enzymes of the shikimate shunt of the general phenylpropanoid pathway, specifically hydroxycinnamoyl‐CoA: shikimate hydroxycinnamoyl transferase (CcHCT), p‐coumaroylshikimate 3′‐hydroxylase (CcC3′H), and caffeoylshikimate esterase (CcCSE). Gene expression patterns suggest that CcCSE enables the predominant formation of MbA, relative to MbB and MbC, in montbretia. This observation is supported by results from in vitro characterization of CcCSE and reconstruction of the shikimate shunt in yeast. Using CcHCT together with montbretin biosynthetic genes in multigene constructs resulted in a 30‐fold increase of MbA in Nb. This work advances our understanding of the phenylpropanoid pathway and features a critical step towards improved MbA production in bioengineered Nb. Significance Statement: The rare specialized metabolite montbretin A (MbA), produced by montbretia (Crocosmia) plants, is a new treatment option for type‐2 diabetes and obesity. However, lack of a scalable production system limits its development and application for human health. We identified and characterized genes and enzymes of the montbretia phenylpropanoid pathway and utilized them in a bioengineering approach to improve heterologous MbA production in transiently transformed Nicotiana benthamiana. [ABSTRACT FROM AUTHOR]

The epidemic of type-2 diabetes in First Nations communities is tragic. Culturally-appropriate approaches addressing multiple components, focusing beyond glycemic control, are urgently needed. Using an intention-to-treat framework, 13 processes of care indicators were assessed to compare proportions of patients who received care at baseline relative to 2-year follow-up. Clinical improvements were demonstrated across major process of care indicators (e.g. screening, education, and vaccination activities). We found RADAR improved reporting for most diabetes processes of care across seven FN communities and was effective in supporting diabetes care for FN communities, in Alberta Canada. ● Reporting impacts of diabetes processes of care for First Nations communities in Alberta, Canada. ● Clinical improvements were demonstrated across major processes of care indicators. ● Indicators included blood pressure, kidney screening, eye/foot exams, vaccinations. [ABSTRACT FROM AUTHOR]

The progression from prediabetes to type-2 diabetes depends on multiple pathophysiological, clinical, and epidemiological factors that generally overlap. Both insulin resistance and decreased insulin secretion are considered to be the main causes. The diagnosis and approach to the prediabetic patient are heterogeneous. There is no agreement on the diagnostic criteria to identify prediabetic subjects or the approach to those with insufficient responses to treatment, with respect to regression to normal glycemic values or the prevention of complications. The stratification of prediabetic patients, considering the indicators of impaired fasting glucose, impaired glucose tolerance, or HbA1c, can help to identify the sub-phenotypes of subjects at risk for T2DM. However, considering other associated risk factors, such as impaired lipid profiles, or risk scores, such as the Finnish Diabetes Risk Score, may improve classification. Nevertheless, we still do not have enough information regarding cardiovascular risk reduction. The sub-phenotyping of subjects with prediabetes may provide an opportunity to improve the screening and management of cardiometabolic risk in subjects with prediabetes. [ABSTRACT FROM AUTHOR]

Pollutants in ambient air have been linked with type-2 diabetes mellitus (T2DM) in low as well as high pollution scenarios. Mechanisms of action include disruption of endothelial function, imbalance in the autonomic nervous system and direct translocation. Although reductions in exposure to ambient air pollution (AP) could translate to meaningful clinical and public health benefits, policy changes targeting AP are usually at the population level, multisectoral, and time consuming. The human gut microbiome (GM) is an ecosystem within individuals which has been linked with health in both beneficial and detrimental ways. During the last decade, mechanistic and epidemiological research on GM suggests altered microbial diversity and differential composition influencing T2DM through inflammation, metabolites, and microbial functions. This offers a scope to design individual level interventions to target AP related T2DM through GM. In this paper, we presented a combination approach of evidence synthesis by literature review and application of causal inference framework to investigate the role of GM in the association of AP and T2DM, to help design epidemiological studies and direct data analysis. We formulated Directed Acyclic Graphs with methodological considerations for mediatory, interacting, or effect modification role of GM in the association of AP and T2DM. Additionally, we considered the emerging links between gut and oral microbiome, the different T2DM disease patterns in South Asia, and unique co-exposures in these settings (for example, indoor air pollution).

Recent literature extensively investigates the crucial role of energy metabolism in determining the inflammatory response and polarization status of macrophages. This rapidly expanding area of research highlights the importance of understanding the link between energy metabolism and macrophage function. The metabolic pathways in macrophages are intricate and interdependent, and they can affect the polarization of macrophages. Previous studies suggested that glucose flux through cytosolic glycolysis is necessary to trigger pro-inflammatory phenotypes of macrophages, and fatty acid oxidation is crucial to support anti-inflammatory responses. However, recent studies demonstrated that this understanding is oversimplified and that the metabolic control of macrophage polarization is highly complex and not fully understood yet. How the metabolic flux through different metabolic pathways (glycolysis, glucose oxidation, fatty acid oxidation, ketone oxidation, and amino acid oxidation) is altered by obesity- and type 2 diabetes (T2D)-associated insulin resistance is also not fully defined. This mini-review focuses on the impact of insulin resistance in obesity and T2D on the metabolic flux through the main metabolic pathways in macrophages, which might be linked to changes in their inflammatory responses. We closely evaluated the experimental studies and methodologies used in the published research and highlighted priority research areas for future investigations.

The Differential Gene Expression (DGE) approach to find out the expressed genes relies on measures such as log-fold change and adjusted p-values. Although fold change is commonly employed in gene expression studies, especially in microarray and RNA sequencing experiments to quantify alterations in a gene’s expression level, a limitation and potential hazard of relying on fold change in this context is its inherent bias. As a consequence, it might incorrectly categorize genes that have significant differences but minor ratios, resulting in poor detection of mutations in genes with high expression levels. In contrast, machine learning offers a more comprehensive view, adept at capturing the non-linear complexities of gene expression data and providing robustness against noise that inspired us to utilize machine learning models to explore differential gene expression based on feature importance in Type 2 Diabetes (T2D), a significant global health concern, in this study. Moreover, we validated biomarkers based on our findings expressed genes with previous studies to ensure the effectiveness of our ML models in this work which led us to go through to analysis pathways, gene ontologies, protein-protein interactions, transcription factors, miRNAs, and drug predictions to deal with T2D. This study aims to consider the machine learning technique as a good way to know about expressed genes profoundly not relying on the DGE approach, and to control or reduce the risk of T2D patients by helping drug developer researchers.

Considering the adverse effects of procrastination on the care and treatment of patients with type-2 diabetes, examining the how, why, and contributing factors of procrastination in this group of patients through in-depth studies seems essential. This is a grounded theory research in which 28 participants were selected by theoretical purposive sampling from patients with type-2 diabetes, their families, and healthcare personnel. Data were collected through interviews, observations, field notes and memos. The data were analyzed using Corbin and Strauss approach (2015) and MAXQDA 2010 software. The data obtained were classified into seven main categories. Health-related procrastination in patients with type-2 diabetes began to form in the patients when they perceived the hardships of self-care as their main concern. The ominous shadow of the disease, the prison of family care, patient-related factors, health system shortfalls, sociocultural background, and the onslaught of the COVID-19 pandemic laid the groundwork for abandoning diabetes self-care. Patients tried to abandon their diabetes selfcare by adopting strategies such as escaping the reality of the disease, selfmedication and procrastination. Wavering health-related procrastination was identified as the central category of this research. The formation of health-related procrastination in patients with type-2 diabetes is a multidimensional process depending on the patients' background that consists of their interactivity with their family, the health system, and the society. The findings of this research can be used for the design, implementation and monitoring of treatment and care programs for these patients. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical effect of calcium plus Vitamin-D combined with calcitriol in the treatment of patients with type-2 diabetes mellitus (T2DM) patients and osteoporosis. Methods: In this retrospective observational study clinical records of 90 patients with T2DM combined with osteoporosis, treated in The Quzhou Affiliated Hospital of Wenzhou Medical University from October 2019 to April 2022 were incuded. All patients received basic hypoglycemic treatment. Of 90 patients, 43 received calcium plus Vitamin-D adjuvant therapy (Control-group), and 47 patients received calcium plus Vitamin-D combined with calcitriol adjuvant therapy (Observation-group). Clinical efficacy, adverse reactions, bone metabolism levels, and changes in bone density levels were compared between the two groups. Results: The clinical efficacy of the treatment was significantly higher in the Observation-group (93.6%) compared to the Control-group (83.7%; p<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (p>0.05). After treatment, bone metabolism and bone density indicators in both groups improved, and were significantly better in the Observation-group compared to the Control-group (p<0.05). Conclusions: Combination of calcium plus Vitamin-D and calcitriol adjuvant therapy in patients with T2DM and osteoporosis is safe and associated with better treatment efficacy, improved bone metabolism and bone density parameters than calcium plus Vitamin-D treatment alone. [ABSTRACT FROM AUTHOR]

Background: Morphometric image analysis enables the quantification of differences in the shape and size of organs between individuals. Methods: Here we have applied morphometric methods to the study of the liver by constructing surface meshes from liver segmentations from abdominal MRI images in 33,434 participants in the UK Biobank. Based on these three dimensional mesh vertices, we evaluated local shape variations and modelled their association with anthropometric, phenotypic and clinical conditions, including liver disease and type-2 diabetes. Results: We found that age, body mass index, hepatic fat and iron content, as well as, health traits were significantly associated with regional liver shape and size. Interaction models in groups with specific clinical conditions showed that the presence of type-2 diabetes accelerates age-related changes in the liver, while presence of liver fat further increased shape variations in both type-2 diabetes and liver disease. Conclusions: The results suggest that this novel approach may greatly benefit studies aiming at better categorisation of pathologies associated with acute and chronic clinical conditions. [ABSTRACT FROM AUTHOR]

Objective: This study evaluates the impact of metformin combined with liraglutide on the glucose and lipid metabolism, oxidative stress, and vascular endothelium of patients with type-2 diabetes mellitus (T2DM) and metabolic syndrome. Methods: Medical records of 78 patients with T2DM and metabolic syndrome, admitted to Caoxian People’s Hospital from July 2021 to July 2022, were retrospectively analysed. Thirty five patients were treated with metformin (control group), and 43 patients were treated with metformin combined with liraglutide (observation group). Indexes of glucose and lipid metabolism, function of vascular endothelium and the oxidative stress of both groups were compared before and after the treatment. Results: There was a significant decrease in the levels of fasting plasma glucose (FPG), Glycosylated Hemoglobin A1c (HbA1c), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP) and waist circumference in both groups three months after the treatment, These indexes were significantly lower in the observation group compared to the control group (P<0.05). Highdensity lipoprotein cholesterol (HDL-C) levels were higher in the observation group (P<0.05). There was a significant improvement in the levels of nitric oxide (NO), endothelin-1 (ET-1), superoxide dismutase (SOD), and malondialdehyde (MDA) after the treatment, and these indexes were markedly better in the observation group compared to the control group (P<0.05). Conclusions: Metformin combined with liraglutide treatment is associated with better outcomes than metformin alone in patients with T2DM and metabolic syndrome. Combined treatment results in improved glucose and lipid metabolism, vascular endothelial function, and oxidative stress index values. [ABSTRACT FROM AUTHOR]

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The effect of Eucalyptus globulus in diabetic cardiac dysfunction and the possible mechanisms involved have not been explored. To evaluate the effect of ethanol leaf extract of E. globulus (NEE) on the cardiac function of fructose/streptozotocin-induced diabetic rats. Type-2 diabetes was induced in rats with 10% fructose feeding for 14 days and an intraperitoneal administration of 40 mg/kg streptozotocin. Diabetic animals were treated with NEE (100–400 mg/kg) or 5 mg/kg glibenclamide orally for 21 days. Biochemical assays, histopathological examination and analyses of PCSK9, Rho kinase and Cardiac troponin expression were performed. The untreated diabetic group showed decreased expression of the genes, oxidative stress, dyslipidemia, increased activities of creatine kinase MB and lactate dehydrogenase, reduced nitric oxide level, and depletion of cardiomyocytes, which were reversed in NEE treated groups. Eucalyptus globulus ameliorated diabetic cardiac dysfunction through increased PCSK9, Rho kinase and Cardiac troponin expression. [ABSTRACT FROM AUTHOR]

This study aimed to determine the effect of Bacillus Coagulans symbiotic supplementation on metabolic factors and inflammation in patients with type-2 diabetes. In this clinical trial, 50 patients with type-2 diabetes were randomly assigned to the symbiotic (containing Bacillus Coagulans + Lactobacillus rhamnosus + Lactobacillus acidophilus and fructooligosaccharide) or placebo groups to receive one sachet daily for 12 weeks. Glycaemic Index, lipid profile, and hs-CRP were measured at the beginning and end of the study. Analysis of covariance demonstrated that fasting blood glucose (FBG), insulin, homeostatic Model Assessment for Insulin Resistance (HOMA-IR), β-cell function (HOMA-β) (p <.05) and hs-CRP (p <.05) significantly declined in the treatment group compared with the placebo group. So, the current study indicated that Bacillus Coagulans symbiotic supplementation could improve metabolic factors and inflammation in patients with type-2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Organ measurements derived from magnetic resonance imaging (MRI) have the potential to enhance our understanding of the precise phenotypic variations underlying many clinical conditions. Methods: We applied morphometric methods to study the kidneys by constructing surface meshes from kidney segmentations from abdominal MRI data in 38,868 participants in the UK Biobank. Using mesh-based analysis techniques based on statistical parametric maps (SPMs), we were able to detect variations in specific regions of the kidney and associate those with anthropometric traits as well as disease states including chronic kidney disease (CKD), type-2 diabetes (T2D), and hypertension. Statistical shape analysis (SSA) based on principal component analysis was also used within the disease population and the principal component scores were used to assess the risk of disease events. Results: We show that CKD, T2D and hypertension were associated with kidney shape. Age was associated with kidney shape consistently across disease groups. Body mass index (BMI) and waist-to-hip ratio (WHR) were also associated with kidney shape for the participants with T2D. Using SSA, we were able to capture kidney shape variations, relative to size, angle, straightness, width, length, and thickness of the kidneys, within disease populations. We identified significant associations between both left and right kidney length and width and incidence of CKD (hazard ratio (HR): 0.74, 95% CI: 0.61–0.90, p < 0.05, in the left kidney; HR: 0.76, 95% CI: 0.63–0.92, p < 0.05, in the right kidney) and hypertension (HR: 1.16, 95% CI: 1.03–1.29, p < 0.05, in the left kidney; HR: 0.87, 95% CI: 0.79–0.96, p < 0.05, in the right kidney). Conclusions: The results suggest that shape-based analysis of the kidneys can augment studies aiming at the better categorisation of pathologies associated with chronic kidney conditions. [ABSTRACT FROM AUTHOR]

Background: Medial arterial calcification (MAC) is a vascular disease distinct from atherosclerosis. Recently, several studies have demonstrated that MAC is an important marker of cardiovascular events. We aim to assess the presence of MAC during ultrasound screening of lower-limb vasculature and its association with both cardiovascular (CV) and lower-limb events in patients with type-2 diabetes. Methods: A retrospective cohort study was conducted on 1119 patients with type-2 diabetes free from CV disease. A CV work-up, including vascular ultrasound, was performed for each patient. The presence of MAC was assessed on posterior tibial arteries and ankle–brachial index (ABI) was measured. Major acute CV events (MACEs) and lower-limb events (MALEs) were recorded as a composite endpoint for a 5-year period. Results: We identified MAC among 212 (18.9%) patients. The independent determinants of MAC were age and diabetic retinopathy. Over a period of 5 years, 125 MACEs and 22 MALEs occurred. MAC was significantly associated with the composite outcome MACE + MALE (HR = 1.94; 95% CI: 1.23, 3.08, p = 0.005) or with MACE (HR = 1.85; 95% CI: 1.16, 2.95, p = 0.010). Adjusted for ABI and diabetic foot wound, MAC remained a determinant of MALE (HR = 5.49; 95% CI: 2.19, 13.76, p < 0.001). Considering each ABI group, MAC was associated with both MACE and MALE in the normal ABI group. Conclusions: Ultrasound-detected MAC on tibial arteries seems to be a determinant of both CV and lower-limb events, independent from ABI. MAC helps to refine the CV risk in patients with normal ABI. [ABSTRACT FROM AUTHOR]

The complex progression of type-2 diabetes (T2DM) may result in increased susceptibility to myocardial ischemia-reperfusion (IR) injury. IR injuries in multiple organs involves ferroptosis. Recently, the clock gene Rev-erbα has aroused considerable interest as a novel therapeutic target for metabolic and ischemic heart diseases. Herein, we investigated the roles of Rev-erbα and ferroptosis in myocardial IR injury during T2DM and its potential mechanisms. A T2DM model, myocardial IR and a tissue-specific Rev-erbα−/− mouse in vivo were established, and a high-fat high glucose environment with hypoxia-reoxygenation (HFHG/HR) in H9c2 were also performed. After myocardial IR, glycolipid profiles, creatine kinase-MB, AI, and the expression of Rev-erbα and ferroptosis-related proteins were increased in diabetic rats with impaired cardiac function compared to non-diabetic rats, regardless of the time at which IR was induced. The ferroptosis inhibitor ferrostatin-1 decreased AI in diabetic rats given IR and LPO levels in cells treated with HFHG/HR, as well as the expression of Rev-erbα and ACSL4. The ferroptosis inducer erastin increased AI and LPO levels and ACSL4 expression. Treatment with the circadian regulator nobiletin and genetically targeting Rev-erbα via siRNA or CRISPR/Cas9 technology both protected against severe myocardial injury and decreased Rev-erbα and ACSL4 expression, compared to the respective controls. Taken together, these data suggest that ferroptosis is involved in the susceptibility to myocardial IR injury during T2DM, and that targeting Rev-erbα could alleviate myocardial IR injury by inhibiting ferroptosis. [Display omitted] • The T2DM in rats have a higher susceptibility to myocardial IR, relating to the clock gene Rev-erbα and ferroptosis. • ACSL4 participates in diabetic myocardial IR injury, also characterized by rhythmic expression across the circadian cycle. • Pharmacological or genetic targeting of Rev-erbα attenuated myocardial IR injury during T2DM by inhibiting ferroptosis. [ABSTRACT FROM AUTHOR]

Purpose: The association between non-alcoholic fatty liver disease (NAFLD) and metabolic disorders, especially type-2 diabetes (T2DM), has been proven to be bidirectional. Hypoglycemic agents may be promising treatments for those disorders. However, there is currently no approved hypoglycemic therapy for NAFLD. In this review, we aimed to compare the efficacy and safety of twelve different hypoglycemic treatments in patients with NAFLD and T2DM. Methods: We systematically screened randomized controlled trials (RCTs) published from March 2013 to March 2023 by searching PubMed, Embase, Medline, and Web of Science without any language restriction. We registered this project on the PROSPERO website: https://www.crd.york.ac.uk/PROSPERO/(ID: CRD42023429701). All subsequent analyses were performed under the registered protocol. The mean difference (MD) and 95% confidence interval (95% CI) were adapted to evaluate the effect size of the treatment. The surface under the cumulative sorting curve (SUCRA) was used to rank the efficacy of the included treatments. Results: We included 19 trials involving 1212 patients in total. Insulin plus glucagon-like peptide-1 receptor agonist (GLP1RA) combination therapy was probably the most effective treatment for reducing weight and body mass index (BMI) (SUCRA: 0.93 and 1.00). Thiazolidinediones (TZD) were probably the most effective treatment for reducing glycosylated hemoglobin (HbA1c) and γ-glutamyltranspeptidase (γ-GGT) levels (SUCRA: 0.78 and 0.97). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) had the highest probability of presenting good therapeutic efficacy in reducing triglyceride (TG) levels (SUCRA: 0.72). The most common adverse reactions were gastrointestinal disorders, mainly after the administration of GLP1RA, and mild hypoglycemia, which was closely related to the use of insulin. Conclusion: GLP1RA plus insulin combination therapy, GLP1RA, SGLT2i, and TZD may be the most effective therapeutic methods for patients with NAFLD and T2DM. [ABSTRACT FROM AUTHOR]