This review aims to provide a comprehensive overview to understand the role of pollution in the development of noncommunicable diseases (NCDs), with a focus on metabolic diseases.

In the context of NCDs, the incidence of metabolic diseases such as obesity and diabetes are increasing at an alarming rate. In addition to the well-known role of the so-called "obesogenic" environment, characterized by unhealthy diet and physical inactivity, great attention has been paid in recent years to the effects of pollution. Indeed, progressive urbanization has been associated with increased exposure to pollutants. The harmful effects of some pollutants on the endocrine system have been known for decades, but data on the metabolic impact of pollution are rather recent. Pollution in its various forms promotes a systemic inflammatory state, insulin resistance, and oxidative stress, which appear to be closely associated with increased risk of NCD, particularly obesity and diabetes.

In conclusion, urbanization has so far had a predominantly negative impact on collective health, but a better understanding of the mechanisms linking pollution to metabolic health is crucial to implement preventive strategies, including careful urban planning to improve community health, understood not only as the absence of disease but also as psychological and social well-being, overcoming the risks associated with urbanization.

Bitter gourd (Momordica charantia L.) is known for its ability to reduce parameters of diabetes, but its effects on prediabetic subjects have been scarcely studied.

To assess the efficacy of Momordica charantia supplementation in a prediabetic population on markers of glucose homeostasis.

Two randomized controlled studies were conducted to assess the effect of bitter gourd supplementation in a prediabetic population. Study 1 was a 4-week cross-over intervention trial (n = 30), with freeze-dried bitter gourd (BG) fruit juice (2.4 g/day) or a cucumber-based control product (CC). Study 2 was a parallel trial (n = 38) lasting 12 weeks, with freeze-dried whole fruits (3.6 g/day) or a cucumber-based matched control supplement. Effects on fasting plasma glucose (FPG), insulin, HbA1c, fructosamine, postprandial glucose after an oral glucose tolerance test, and several safety biomarkers were also analyzed in both trials before and after the interventions.

In Study 1, no significant differences were found between the bitter gourd and placebo interventions. However, a reduction in FPG in subjects with higher baseline values were found following bitter gourd supplementation, which was not observed in the control group. However, in Study 2, we observed significant reductions of FPG (p = 0.014), fasting insulin (p = 0.007), and HOMA-IR (p = 0.003) after a 12-week intervention with the bitter gourd supplement. In addition, between treatment analysis resulted in significant effects on FPG levels (p = 0.026) and HOMA-IR (p = 0.045) with no significant effects on other biomarkers related to glucose metabolism. On average, bitter gourd intervention reduced FPG by ∼0.05 mmol/L per week, whereas FPG remained unchanged following placebo. In both studies, there were no indications of health risks or side effects from consumption of the supplements.

Results suggest that supplementation with bitter gourd fruit can have positive effects on fasting plasma glucose and insulin among prediabetic subjects when provided over an extended period of at least 12 weeks.

This study investigated the correlation between the type of health insurance membership as a proxy for the economic status of patients and the severity of their type two diabetes mellitus (T2DM) in Indonesia.

The study conducted a secondary analysis of National Health Insurance (Jaminan Kesehatan Nasional) claim data provided by the Indonesian Social Security Agency, Badan Penyelenggara Jaminan Sosial (BPJS). We used ordered logistic regression with four severity levels for T2DM (0=outpatient, I=mild, II=moderate, III=severe) as dependent variables. The main independent variables (insurance membership categories) included subsidised insurance members (PBI), a combination of formally employed and nonsalaried informal workers (PBPU & PPU) and nonworkers (BP).

Secondary healthcare facilities in Indonesia.

The dataset included 2 989 618 claims for hospital visits of people with T2DM from 2018 to 2022.

Severity level of T2DM patients.

A higher percentage of T2DM patients who visited healthcare facilities with subsidised insurance (PBI), which represents a low-income group, have severe disease (6.9%) than patients in the PBPU & PPU (4.9%) and BP categories (5.5%). Moreover, regression analysis revealed that having PBI membership status was associated with a greater OR of having severe T2DM than nonsubsidised members. Among T2DM patients in the nonsubsidised insurance category, workers (PBPU & PPU) had an OR of 0.74 (95% CI: 0.735 to 0.745; p<0.0001) for having severe disease during hospital visits. Moreover, non-workers (BP) had a lower OR of 0.718 (95% CI: 0.711 to 0.725; p<0.0001) for severe disease than the PBI category.

These findings illustrate the lack of optimal access to health services for diabetes patients in low-income insurance membership categories and the challenges of better treatment in health facilities for low-income patients.

In SURMOUNT-2, a phase 3, randomized clinical trial, tirzepatide treatment resulted in clinically meaningful reduction in bodyweight among people with obesity or overweight and T2D. The current analysis evaluated the effects of tirzepatide treatment on self-reported health-related quality of life (HRQoL) outcomes among SURMOUNT-2 participants.

SURMOUNT-2 participants were randomly assigned (1:1:1) to receive either tirzepatide 10 mg (n = 312), tirzepatide 15 mg (n = 311), or placebo (n = 315) for 72 weeks as an adjunct to diet and exercise. Self-reported HRQoL was assessed in terms of changes from baseline to week 72 in Short Form-36 Version 2 Health Survey acute form (SF-36v2), Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT), EQ-5D 5-level Version (EQ-5D-5L) Health State Index (UK) and associated EQ visual analog scale (VAS), and Patient Global Impression of Status (PGIS) for Physical Activity. Post hoc analyses evaluated changes in HRQoL outcomes by categorical percent weight reduction targets (> 0 to < 5%, ≥ 5%, ≥ 10%, ≥ 15%, ≥ 20%, ≥ 25%, and ≥ 30%) and by self-reported baseline physical function limitations (based on PGIS) among tirzepatide-treated participants.

At week 72, tirzepatide treatment was associated with significantly larger improvements than placebo in the SF-36v2 Physical Component Summary score, SF-36v2 physical functioning, bodily pain, general health, vitality, and social functioning domain scores, all IWQOL-Lite-CT scores, and EQ VAS score. Tirzepatide-treated participants who achieved greater weight reduction targets showed numerically larger improvements in HRQoL scores relative to those with lower percent weight reduction. For all HRQoL measures, participants with physical function limitations at baseline showed greater improvements than those without limitations.

Tirzepatide treatment was associated with improved self-reported HRQoL outcomes compared with placebo among people with obesity or overweight with T2D. Participants achieving greater bodyweight reductions and those with physical function limitations at baseline showed greater improvements in HRQoL. CLINICAL TRIAL REGISTRATION NUMBER FOR SURMOUNT-2: NCT04657003.

Ultrasound stimulation of internal organs and peripheral nerves has demonstrated promising potential in regulating blood glucose metabolism. This study aims to assess the effectiveness of low-intensity pulsed ultrasound stimulation (LIPUS) on intestine in improving insulin resistance with type 2 diabetes mellitus (T2DM).

C57BL/6J mice, both normal and T2DM, were randomly divided into three groups: Control, T2D-sham, and T2D-LIPUS. The T2D-LIPUS group received LIPUS stimulation in the intestine. The parameters were as follows: 1 MHz frequency, 1.0 kHz pulse repetition frequency (PRF), 20% duty cycle, 100 mW/cm² intensity spatial average temporal average (ISATA), for 20 minutes per session, five days per week, over four weeks.

Blood glucose analysis indicated that mice in the T2D-LIPUS group displayed significantly lower area under the curve (AUC) of glucose tolerance tests (GTT) and insulin tolerance tests (ITT) (p < 0.001), HOMA-IR (p < 0.001), and fasting serum insulin levels (p < 0.01) compared to the T2D-sham group. LIPUS treatment effectively lowered serum levels of IL-1β (p < 0.001) and TNF-α (p < 0.01) along with mRNA expression levels of IL-1β (p < 0.01) and IL-18 (p < 0.001) in the intestines of T2DM mice. Additionally, Western blot analysis revealed a reduction in the protein levels of NLRP3, caspase-1, and GSDMD-N in the intestinal tissues of mice treated with LIPUS.

These findings suggest that LIPUS can reduce inflammation and cellular apoptosis, while improving insulin resistance by inhibiting the NLRP3/Caspase-1/GSDMD signaling pathway. This research introduces a novel, non-pharmacological approach for managing T2DM.

AS2034178, an agonist of free fatty acid receptor-1 or G protein-coupled receptor 40, enhances pancreatic β-cell function. Its impact on ionic currents in excitable cells, particularly pituitary tumor (GH3) cells, was investigated. AS2034178 suppressed transient (INa(T)) and late (INa(L)) components of voltage-gated Na+ current (INa) with IC50 values of 29.8 and 5.3 µM, respectively. It did not alter current-voltage relationship but shifted steady-state inactivation curve of INa(T) leftward. AS2034178 also blocked persistent Na+ current (INa(P)) activated by long-lasting ramp voltages, and subsequent application of deltamethrin or tefluthrin attenuated its suppression. The compound prolonged recovery of INa(P) inactivation, shifted its inactivation curve, and shortened time constant for IN(P) decay. Additionally, AS2034178 suppressed delayed-rectifier K+ current (IK(DR)) with a dissociation constant of 6.23 µM. Docking studies suggested AS2034178's ability to interact with amino acid residues in hNaV1.7 channels.(supplementary data). AS2034178's effects on ionic currents (INa and IK(DR)) contribute to its mechanisms of action in culture or in vivo.

Stroke is a sudden neurological decline caused by cerebrovascular diseases or impaired blood circulation. Research investigating the connection between glycated hemoglobin A1c (HbA1c) levels and stroke severity is limited. This study examined the connection between HbA1c levels and stroke severity in patients with acute ischemic stroke. A retrospective cross-sectional analysis of the medical records of 1103 patients with acute ischemic stroke from January 2020 to January 2024 was conducted. Patients were divided into seven groups on the basis of their HbA1c levels. Stroke severity within these groups was assessed via the National Institutes of Health Stroke Scale (NIHSS), with the aim of identifying correlations between stroke severity and glycemic status. This study examined the impact of various HbA1c levels on a range of demographic and clinical characteristics in stroke patients. The patients were grouped into seven categories on the basis of their HbA1c levels, and characteristics such as age; body mass index (BMI); LDL, HDL, and creatinine levels; and NIHSS scores at hospital admission were compared across these groups. Significant differences were observed in age, LDL levels (F = 3.999, P < 0.001), and creatinine levels (F = 1.303, P = 0.253) among the HbA1c categories. However, there were no significant differences in BMI, HDL levels, or length of hospital stay. A positive correlation was found between HbA1c levels and NIHSS scores, indicating that higher HbA1c levels are associated with greater stroke severity. This study revealed that the risk of severe stroke increases significantly when HbA1c levels exceed 6.5%. In contrast, maintaining HbA1c levels below 6.5% is linked to a reduced risk of severe stroke and lower mortality. Additionally, older adults are at greater risk and tend to experience more severe strokes.

The phase angle is a mathematical concept representing the time relationship between two periodic waveforms, and has gained some importance for its potential clinical applications. The purpose of this review was to investigate the role of phase angle in diabetes mellitus.Studies have investigated the relationship between the phase angle and glycemic control, insulin resistance, and diabetes-related complications. Phase angle has demonstrated its potential as a prognostic marker for diabetic complications, enabling early identification and intervention. It might be beneficial for evaluating disease severity, monitoring treatment response, and predicting long-term results in diabetics.

Although the phase angle offers significant advantages, its clinical use in managing diabetes is still in its early stages, and there are certain issues that need to be resolved. Standardization of measurement techniques and interpretation criteria is essential to ensure consistency and comparability across studies and clinical settings. Investigating the role of phase angle in the treatment of diabetes provides significant knowledge about its potential as a non-invasive and informative parameter. Identifying the importance of phase angle in diabetes might help to improve risk stratification, treatment strategies, and patient outcomes. Additional research is required to determine its therapeutic value and discover the mechanisms underlying its association with diabetes and its complications.

Diabetes mellitus (DM) is a major public health problem worldwide. Numerous traditional plants are used for preventing DM. However, limited evidence supports the association between garlic consumption and DM.

Data used in this study was from the 2008-2018 Chinese Longitudinal Healthy Longevity Survey. Data on garlic consumption was obtained by questionnaire, and DM by self-reported diagnosis. A multivariate adjusted Cox regression model was used to estimate haz-ard ratios (HR) and 95% confidence intervals (CI) to determine the incidence of DM.

A total of 1927 participants were included in this study, of which 24.08% consumed garlic daily and 20.08% developed DM. The HR for daily garlic consumption decreased by 42%, when compared to rare or no garlic con-sumption. Our subgroup analyses revealed that daily garlic consumption significantly reduced the risk of DM in older adults aged 65-79, rural, non-drinkers informal education, financial dependence, and working in agriculture (aged 65-79: HR = 0.54, 95% CI: 0.36-0.80; rural area: HR = 0.48, 95% CI: 0.29-0.77; non-drinkers: HR = 0.60, 95% CI: 0.41-0.86; informal education: HR = 0.46, 95% CI: 0.29-0.74; financial dependence: HR = 0.39, 95% CI: 0.23-0.65; agricultural work: HR = 0.49, 95% CI: 0.32-0.76).

Garlic consumption can reduce the risk of DM in older Chinese adults. This benefit varies by age, current residence, drinking status, education level, occupation, and economic source. Future efforts should focus on developing dietary intervention strategies that consider demographic, educational, financial, and occupational disparities to effectively prevent diabetes in older populations.

Fagonia indica from Zygophyllaceae family is a medicinal specie with significant antidiabetic potential. The present study aimed to investigate the in vitro antidiabetic activity of Fagonia indica crude extract followed by an in silico screening of its phytoconstituents. For this purpose, crude extract of Fagonia indica was prepared and divided in three different parts, i.e., n-hexane, ethyl acetate, and methanolic fraction. Based on in vitro outcomes, the phytochemical substances of Fagonia indica were virtually screened through a literature survey and a screening library of compounds (1-13) was prepared. The clinical potential of these novel drug candidates was assessed by applying an ADME screening profile. Findings of SwissADME indicators (Absorption, Distribution, Metabolism, and Excretion) for the compounds (1-13) presented relatively optimal physicochemical characteristics, drug-likeness, and medicinal chemistry. The antidiabetic action of these leading drug candidates was optimized through molecular docking analysis against 3 different human pancreatic α-amylase macromolecular targets with (PDB ID 1B2Y), (PDB ID 3BAJ), and (PDB ID: 3OLI) by applying Virtual Docker (Molegro MVD). Metformin was taken as a reference standard for the sake of comparison. In vitro antidiabetic evaluation gave good results with promising α-amylase inhibitory action in the form of IC50 values, as for n-hexane extract = 206.3 µM, ethyl acetate = 41.64 µM, and methanolic extract = 9.61 µM. According to in silico outcomes, all 13 phytoconstituents possess the best binding affinity with successful MolDock scores ranging from - 97.2003 to - 65.6877 kcal/mol and show a great number of binding interactions than native drug metformin. Therefore, the current work concluded that the diabetic inhibition prospective of extract and the compounds of Fagonia indica may contribute to being investigated as a new class of antidiabetic drug or drug-like candidate for further studies.

Ultraviolet B (UVB) irradiation can damage skin tissue. Diabetes aggravates skin lesions. Fibroblast growth factor 21 (FGF21) is significantly involved in exerting protective effects and facilitating tissue repair. Therefore, this study aimed to investigate the impact of recombinant human FGF21 (rhFGF21) on diabetic skin affected by UVB damage.

UVB irradiation (270 mJ/cm2) was administered to diabetic mice for 5 consecutive days to establish UVB-irradiated skin injury, and rhFGF21 was administered daily after irradiation. Human immortalized keratinocytes (HaCaT) and mouse peritoneal macrophages (MPMs) were cultured under high glucose (HG) conditions for 3 days, followed by treatment with rhFGF21 for 1 h before UVB irradiation or lipopolysaccharide (LPS) stimulation. We analyzed the effects of UVB irradiation on diabetic skin via laser Doppler flowmetry, histopathological staining, TUNEL assays, RT-PCR, Western blotting, MTT assays and Hoechst 33258 staining.

Our findings indicated that the skin of diabetic mice was more severely damaged by UVB irradiation, and rhFGF21 alleviated this damage. RhFGF21 inhibited apoptosis and inflammatory responses in the skin tissues of diabetic mice. These changes were primarily reflected in increase of the sirtuin 1 (SIRT1) level in epidermal cells and peritoneal macrophages of mice. Moreover, rhFGF21 not only increased the survival rate of HaCaT cells but also decreased the generation of pro-inflammatory cytokines in MPMs. Notably, SIRT1 inhibitor (EX527) was capable of reversing these effects.

RhFGF21 attenuates UVB-induced damage to the skin of diabetic mice, predominantly by suppressing epidermal cell apoptosis and macrophage-mediated inflammatory responses via the SIRT signaling pathway.

The extensive use of smokeless tobacco and the worldwide occurrence of diabetes mellitus (DM) poses significant public health obstacles. A comprehensive review of the literature was undertaken to assess epidemiological research, clinical trials, and meta-analyses that examine the link between smokeless tobacco use and DM. The key results indicate that the biological constituents of smokeless tobacco may interfere with the process of glucose metabolism and lead to an increase in insulin resistance. An association between consumption levels and diabetes risk is evident, with higher levels of usage being positively correlated with an increased chance of developing diabetes. Smokeless tobacco usage is identified as a significant risk factor for DM. This highlights the need to implement focused public health initiatives and policies aimed at decreasing the usage of smokeless tobacco and its influence on the incidence of diabetes. Future research should prioritize elucidating the processes behind this correlation and developing efficacious preventative methods to mitigate the worldwide burden of diabetes.

Understanding the relationship between serum ferritin levels and cardiovascular outcomes in type 2 diabetes is crucial for improving risk stratification and guiding therapeutic interventions aimed at preventing major adverse cardiovascular events (MACE). This study aimed to identify distinct clusters of individuals with type 2 diabetes who have varying risks of MACE using a data-driven clustering approach.

This retrospective cohort study analyzed data from 49,506 individuals within a multicenter, population-based primary care registry in Catalonia, Spain. Individuals diagnosed with type 2 diabetes at age 35 or older were recruited between January 2010 and December 2021 and followed for at least 10 years. Biomarkers associated with cardiovascular risk-including serum glucose, HbA1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, blood pressure, serum ferritin, leukocyte, and monocyte counts-were examined. Clustering analysis was applied to identify patient subgroups, and Cox proportional hazards models were used to assess associations with cerebrovascular events, coronary events, and composite MACE.

Five distinct clusters were identified, characterized by differences in serum glucose, HbA1c, lipid profiles, blood pressure, and serum ferritin levels. Individuals with discordantly high serum ferritin levels relative to their body mass index (BMI) exhibited a lower risk of adverse cardiovascular outcomes. In men, hazard ratios (HR) were 0.68 (95% confidence interval [CI]: 0.53-0.87) for cerebrovascular events, 0.65 (95% CI 0.49-0.88) for coronary events, and 0.68 (95% CI 0.56-0.83) for MACE. In women, HRs were 0.81 (95% CI 0.67-0.92) for cerebrovascular events, 0.73 (95% CI 0.57-0.95) for coronary events, and 0.79 (95% CI 0.67-0.92) for MACE.

Individuals with type 2 diabetes who exhibit higher-than-expected serum ferritin levels relative to their BMI may have a lower risk of cardiovascular events. These findings suggest that ferritin may play a more complex role in cardiovascular risk than previously assumed and highlight the potential for refined risk stratification strategies in type 2 diabetes management.

Background/Objectives: Individuals with metabolic syndrome (MetS) present reduced 25(OH)D levels. We performed a two-sample Mendelian randomization (MR) study to investigate whether causal relationships exist between 25(OH)D levels and MetS/MetS risk traits, including waist circumference, body mass index (BMI), hypertension (systolic/diastolic blood pressure), triglyceride, high-density lipoprotein cholesterol, and glucose levels. Methods: We employed genetic variants related to 25(OH)D levels from the SUNLIGHT Consortium and a European genome-wide association study meta-analysis, including UK Biobank (UKB) data, as well as variants for MetS and MetS risk traits from UKB and multiple European consortia. Several MR methods were used, i.e., inverse-variance weighted, weighted median, and MR-Egger regression. Heterogeneity and horizontal pleiotropy analyses were performed to ensure the stability of candidate single-nucleotide polymorphisms (SNPs) as the instrumental variable. We first conducted univariable MR to investigate the relationship between 25(OH)D levels and MetS, including its related risk traits, and subsequently performed multivariable MR to adjust for potential confounders. Results: This study did not provide evidence of a causal relationship between 25(OH)D levels and MetS/MetS risk traits. However, we found that several risk traits of MetS, such as waist circumference, BMI, and TG, had an inverse-causal relationship with 25(OH)D levels, suggesting that 25(OH)D levels could be secondary consequences of metabolic illnesses. Conclusions: We identified no causal relationship between 25(OH)D levels and MetS/MetS risk factors. However, 25(OH)D levels may result from MetS traits.

The Haribhanga is one of the most renowned varieties of mango native to the Rangpur region of Bangladesh. The study aimed to explore the in vitro and in vivo pharmacological potentialities of the methanolic extract of Mangifera indica (Haribhanga) (MEMI) peel. The antioxidant, antimicrobial, and antiarthritic activities of MEMI peel were conducted by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, disc diffusion, and protein denaturation assays, respectively. The extract was administered to STZ-induced diabetic mice for 7 days for the observation of blood glucose, body weight, lipid profile, and liver enzyme levels. The gas chromatography-mass spectrometry (GC-MS) analysis was performed to identify phytochemicals in the extract. Subsequently, molecular docking was conducted to predict the binding affinity of the identified compounds. The MEMI peel exhibited notable antioxidant potentiality with an IC50 value of 4.43 ± 0.68 μg/mL and antimicrobial activity against Bacillus cereus with a zone of inhibition of 20.67 ± 1.52 mm. Furthermore, MEMI peel demonstrated substantial antiarthritic activity, with the highest inhibition of denaturation of protein (88%) observed at the highest dose (500 μg/mL). In the in vivo experiments, MEMI peel led to a significant increase in high-density lipoprotein (p < 0.001, p < 0.05), with a significant decrease in blood glucose (p < 0.001), triglycerides, total cholesterol, and low-density lipoprotein (p < 0.0001) in STZ-induced diabetic mice. Comparing the diabetic control mice, the MEMI peel substantially decreased (p < 0.001) the high serum levels of aspartate aminotransferase and alanine aminotransferase. Moreover, the extract significantly improved the body weight (p < 0.001) of diabetic mice after 7 days of treatment. GC-MS analysis identified 28 bioactive compounds, primarily fatty acid esters in the MEMI peel. Di-n-octyl phthalate, terpinen-4-ol, 8,11,14-docosatrienoic acid methyl ester, and phenol, 2-methoxy-4-(2-propenyl)-acetate exhibited the most favorable binding potential in molecular docking studies. The results suggest that MEMI peel possesses antimicrobial, antiarthritic, antidiabetic, antihyperlipidemic, and liver enzyme protective activities as a promising antioxidant.

Diabetic retinopathy (DR), as the main ophthalmic complication of diabetes mellitus, is a major eye disorder contributing to blindness. Oxidative stress and inflammation in retinal Müller cells participate in the pathogenesis of DR. This work aims to study the biological role of moscatilin in the progression of DR and the underlying mechanism. High glucose (HG)-stimulated mouse primary retinal Müller cells and high-fat diet + streptozotocin (STZ)-induced DR mouse models were constructed as in vitro and in vivo models, respectively. The effects of moscatilin treatment on oxidative stress and inflammation in HG-stimulated Müller cells and DR mice were evaluated by detecting intracellular reactive oxygen species production, malondialdehyde levels, superoxide dismutase and catalase activities, glutathione/oxidized glutathione ratio, as well as proinflammatory cytokine levels through CM-H2DCFDA staining, commercial kits, and enzyme-linked immunosorbent assay. Dual immunofluorescence staining of glial fibrillary acidic protein and vimentin was used to evaluate the development of Müller cells in mouse retinas. The activity of p38 mitogen-activated protein kinase (MAPK)/c-Jun N-terminal kinase (JNK) and nuclear factor kappa-B (NF-κB) signaling pathway was assessed through western blotting and immunofluorescence staining. Moscatilin pretreatment prevented HG-induced decrease in Müller cell viability. Moscatilin mitigated oxidative stress, inflammation, and extracellular matrix remodeling in HG-stimulated Müller cells and DR mice. Mechanically, moscatilin reduced the levels of receptor for advanced glycation end products, phosphorylated I-kappa-B-alpha, p-p65 NF-κB, p-p38 MAPK, and p-JNK in both HG-stimulated Müller cells and DR mice. Moscatilin plays an antioxidant and anti-inflammatory role in DR by inhibiting the p38 MAPK/JNK and NF-κB signaling pathways.

Approximately 537 million adults worldwide have diabetes, more than 90 % of which is type 2 diabetes mellitus (T2DM). China has the largest number of people living with diabetes. Understanding the epidemiological mechanism can guide diabetes surveillance and control.

Utilizing the most recent Global Burden of Disease 2021 (GBD2021) data on T2DM and risk factor exposure values, we developed a modelling framework that employs systems of difference equations to project the future burden of diabetes among the Chinese population. The model characterized the diabetes progression process from no diabetes, undiagnosed diabetes, and diagnosed diabetes with and without complications, in which genetic and lifestyle factors modulate the rate of development at these stages. We focused on the long-term dynamics of diabetes progression with the impacts of influence factors. We then fit the model to the longitudinal numbers of T2DM patients by Markov chain Monte Carlo (MCMC) algorithm.

The model with the influencing factors fitted an R2 of 98 % for the T2DM cases in China during the period 1990-2021. The incidence rate would keep increasing from 299.93/100,000 in 2022 to 421.58/100,000 in 2050 and 500.16/100,000 in 2080. The prevalence rates in 2040, 2060, and 2080 could be 14.62 %, 23.57 % and 34.83 %, respectively. The number of new cases was the most sensitive to high body mass index (BMI), followed by smoking and low physical activity. A 50 % reduction in single risk factor exposure would reduce new cases in 2022-2080 by 4.24 %, 2.52 %, and 1.12 %, respectively.

This study provided a modelling framework to explore the mechanism of T2DM development, which allows to quantify the impacts of risk factors on T2DM progression. The results highlight the high burden of T2DM in China and emphasized the importance of lifestyle interventions.

Recent research has shown that type 2 diabetes mellitus (T2DM) has increased the burden of Alzheimer's disease (AD) in the US aging population. However, trends in mortality from this comorbidity among adults aged ≥ 65 years have not been investigated.

This study examined trends and disparities in AD-related mortality among older US adults with T2DM from 1999 to 2019.

Data from the CDC WONDER database were analysed to assess AD-related mortality in patients with T2DM aged ≥ 65 between 1999 and 2019. Age-adjusted mortality rates (AAMRs) per 100,000 people and annual percent change (APC) were calculated and stratified by year, sex, race/ethnicity, age, urbanisation and geographical region.

From 1999 to 2019, there were 71,550 deaths with T2DM and AD among adults aged ≥ 65. AAMRs rose from 4.12 in 1999 to 11.65 in 2019, with the sharpest increase between 2014 and 2017 (APC: 10.81; 95% CI: -3.20 to 13.43). Women had slightly higher AAMRs than men, with rates increasing from 4.71 in 1999 to 11.61 in 2019 for women, and from 4.08 to 11.70 for men. Hispanic individuals saw the highest increase in AAMR (11.15), followed by non-Hispanic Black (9.30) and White populations (7.92). AAMRs were highest in the West (10.91) and the Midwest (9.62), while the Northeast (4.70) had the lowest. Nonmetropolitan areas had consistently higher AAMRs (10.74) than large metropolitan areas (6.68) and small/medium metropolitan areas (9.25). States in the top 90th percentile for T2DM-AD mortality included California, South Dakota and Kentucky, where rates were approximately eight times higher than in states in the lowest 10th percentile.

This study reveals a significant rise in T2DM-AD comorbidity-related mortality among older adults, especially among Hispanics, women and rural residents. These findings underscore the need for targeted interventions to reduce the burden in vulnerable populations.

This study analyzes U.S. diabetes mortality trends from 1968 to 2019 using CDC WONDER data. It reveals fluctuating age-adjusted mortality rates (AAMRs), with a decline halted between 2010-2019. Males saw rising AAMRs, while females experienced a decline. Racial disparities were evident, with higher AAMRs in the Black population.

Evidence is limited regarding the relationship between sleep factors (self-reported sleep disorder diagnosis, subjective sleep difficulties, and sleep duration), sleep patterns, and risk of type 2 diabetes mellitus (T2D). Thus, this study aims to investigate the relationship between sleep factors, sleep patterns, and the risk of T2D using data from the National Health and Nutrition Examination Survey (NHANES).

A total of 14,652 individuals aged ≥18 years from the NHANES (2005-2014) were enrolled with complete data on sleep factors, T2D, and covariates. Information on self-reported sleep disorder diagnosis, subjective sleep difficulties, and sleep duration was collected during in-home visits by trained interviewers using the Computer-Assisted Personal Interviewing system. The sleep pattern was derived from scoring three mentioned factors: no self-reported sleep disorder diagnosis, no subjective sleep difficulties, and sleep duration of 7-9 h were classified as low-risk (score 0), while the presence of self-reported sleep disorder diagnosis, subjective sleep difficulties, or sleep duration <7 or >9 h were classified as high-risk (score 1). Cumulative scores range from 0 to 3, with 0 indicating a healthy sleep pattern, 1 an intermediate sleep pattern, and 2-3 a poor sleep pattern, respectively. Weighted logistic regression was conducted to assess the association of sleep factors and sleep patterns with the risk of T2D.

Self-reported sleep disorder diagnosis (odds ratio (OR) = 1.32, P = 0.01), subjective sleep difficulties (OR = 1.29, P = 0.001), and sleep deprivation (<7 h; OR = 1.20, P = 0.01) were significantly positive with T2D. Poor sleep pattern also significantly increased T2D risk (OR = 1.52, P < 0.0001). Moreover, subgroup analyses stratified by age and BMI (body mass index) further confirmed that the positive association between sleep patterns and T2D was consistent and robust across groups.

Our findings indicate that poorer sleep patterns are associated with an increased risk of T2D. These results emphasize the importance of sleep management in T2D prevention. Further prospective studies are needed to investigate the causal or bidirectional relationship between sleep and T2D risk, as well as the underlying molecular mechanisms.

Diabetic neuropathy (DN) is characterized by nerve damage as a consequence of diabetes mellitus. Diabetes causes high blood glucose and triglyceride levels, which destroy the nerve blood vessels over time and trigger DN. Peripheral neuropathy is the most common type of DN, which encompasses a broad range of symptoms. One fourth of patients with diabetes suffer from neuropathic pain, which decreases their quality of life and puts them at high risk for emotional disturbances and depression. Finding an adequate therapy is an essential element in the cure of painful DN (PDN). Since the pathophysiology of this disease still needs to be elucidated, this has led to the development of various in vivo diabetic models. Animal models of DN not only provide insights into this disease but also are significant drivers for treatment assessment and improvement. In this review, we present the major features of the most commonly used chemically and diet-induced models of PDN in rodents and their progress to date, which are utilized for a better understanding of the disease mechanism for finding novel therapeutics. Considering the role of Ca2+ homeostasis in pain, we also review our recent research data on the Na+/Ca2+ exchanger blocker KB-R7943, which is a potential neuropathic pain reliever in a rodent model of DN.

The leading cause of death in type 2 diabetes mellitus (T2DM) patients is cardiovascular-related events, including myocardial infraction-induced ventricular arrhythmia. Previous studies have shown that T2DM-induced functional remodeling of cardiac vagal postganglionic (CVP) neurons contributes to ventricular arrhythmogenesis. As leptin resistance is common in T2DM patients, and CVP neurons are located in epicardial adipose pads, a tissue that secretes leptin, in this study we aimed to elucidate a correlation between leptin resistance and CVP neuronal dysfunction in T2DM.

A high fat-diet/low dose streptozotocin-induced T2DM rat model was used in this study to characterize T2DM-induced alterations in cardiac parasympathetic tone, determined by changes in baroreflex sensitivity and CVP neuronal excitability. The impact of leptin resistance on CVP neurons was also studied by examining the expression of leptin in epicardial adipose pads, and leptin receptors and uncoupling protein 2 (UCP2) in CVP neurons.

T2DM rats exhibited diminished baroreflex sensitivity, and decreased CVP neuronal excitability, demonstrated by a reduced frequency of action potentials, diminished nAChR currents, and an attenuated response to nicotine stimulation. Additionally, compared to sham animals, the expression of leptin receptors and UCP2 in CVP neurons was reduced as early as 4 weeks post-T2DM although the leptin levels in epicardial adipose pads was increased during the progression of T2DM, which demonstrated the occurrence of leptin resistance in T2DM CVP neurons.

Cardiac parasympathetic dysfunction in T2DM rats is due, in part, to functional remodeling of CVP neurons. As leptin resistance develops as early as 4 weeks post-T2DM induction, diminished leptin receptors-UCP2 signaling may contribute to CVP neuronal dysregulation.

Type 2 diabetes (T2D) is a disease with high morbidity and mortality and a disproportionate impact on minority groups. Machine learning (ML) is increasingly used to characterize T2D risk factors; however, it has not been used to study T2D health disparities. Our objective was to use explainable ML methods to discover and characterize T2D health disparity risk factors. We applied SHapley Additive exPlanations (SHAP), a new class of explainable ML methods that provide interpretability to ML classifiers, to this end. ML classifiers were used to model T2D risk within and between self-identified race and ethnicity (SIRE) groups, and SHAP values were calculated to quantify the effect of T2D risk factors. We then stratified SHAP values by SIRE to quantify the effect of T2D risk factors on prevalence differences between groups. We found that ML classifiers (random forest, lightGBM, and XGBoost) accurately modeled T2D risk and recaptured the observed prevalence differences between SIRE groups. SHAP analysis showed the top seven most important T2D risk factors for all SIRE groups were the same, with the order of importance for features differing between groups. SHAP values stratified by SIRE showed that income, waist circumference, and education best explain the higher prevalence of T2D in the Black or African American group, compared to the White group, whereas income, education and triglycerides best explain the higher prevalence of T2D in the Hispanic or Latino group. This study demonstrates that explainable ML can be used to elucidate health disparity risk factors and quantify their group-specific effects.

In this study, we aimed to clarify the relationship between physical activity (PA) and diabetes mellitus (DM), as well as the mediating role of Systemic Immune-Inflammatory Index (SII) in the relationship.

A cross-sectional study.

National Health and Nutrition Examination Survey (NHANES) data collection took place in the USA at participants' homes and mobile examination centres with specialised equipment.

The study population consisted of 9493 American adults aged 20 and above from the NHANES 2005 to 2018.

Information on the specific PA was reported through self-administered questionnaire by participants and we used this information to calculate a metabolic equivalent score for the particular PA. The calculation of SII follows a standard formula: SII=P (platelets)×N (neutrophils)/L (lymphocytes).

A total of 9493 participants were included, with 1672 diagnosed with DM. The participants with DM were more inclined to have lower levels of PA while having higher levels of SII. In all three models, high levels of PA were significantly negatively associated with the risk of DM compared with moderate levels of PA, and a non-linear association between natural logarithm-physical activity (Ln-PA) and DM was observed. Furthermore, there was a significant reduction in DM risk for Ln-PA >6.71 in all models. Mediation analysis showed that SII mediated the relationship between PA and DM, as well as between Ln-PA and DM, with respective mediation proportions of 4.32% and 12.141%, as well as 3.12% and 10.46% after adjusting for covariates.

This study investigated the relationship among PA, SII and DM. We provide robust evidence supporting the inverse association between PA and DM risk while highlighting the mediating role of inflammation, as reflected by SII. These findings contribute valuable insights to inform public health strategies and clinical interventions aimed at reducing the global burden of DM.

Gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) are public health concerns worldwide. These two diseases share the same pathophysiological and genetic similarities. This study aimed to investigate the T2DM known single nucleotide polymorphisms (SNPs) of the adiponectin C1Q and collagen domain containing (ADIPOQ), cyclin-dependent kinase inhibitor 2A and 2B (CDKN2A/2B), and signal sequence receptor subunit 1 (SSR1) genes in a cohort of Romanian GDM pregnant women and perinatal outcomes. DNA was isolated from the peripheral blood of 213 pregnant women with (n = 71) or without (n = 142) GDM. Afterward, ADIPOQ (rs266729), CDKN2A/2B (rs10811661), and SSR1 (rs9505118) gene polymorphisms were genotyped using TaqMan Real-Time PCR analysis. Women with GDM had a higher pre-pregnancy body mass index (BMI) (p < 0.0001), higher BMI (p < 0.0001), higher insulin resistance homeostatic model assessment (IR-HOMA) (p = 0.0002), higher insulin levels (p = 0.003), and lower adiponectin levels (p = 0.004) at birth compared to pregnant women with normoglycemia. GDM pregnant women had gestational hypertension (GH) more frequently during pregnancy (p < 0.0001), perineal lacerations more frequently during vaginal birth (p = 0.03), and more macrosomic newborns (p < 0.0001) than pregnant women from the control group. We did not find an association under any model (allelic, genotypic, dominant, or recessive) of ADIPOQ rs266729, CDKN2A/2B rs10811661, and SSR1 rs9505118 polymorphisms and GDM. In correlation analysis, we found a weak positive correlation (r = 0.24) between the dominant model GG + CG vs. CC of rs266729 and labor induction failure. In the dominant model TT vs. CC + CT of rs10811661, we found a weak negative correlation between this model and perineal lacerations. Our results suggest that the ADIPOQ rs266729, the CDKN2A/2B rs10811661, and the SSR1 rs9505118 gene polymorphisms are not associated with GDM in a cohort of Romanian pregnant women.

Cdk5 regulatory associated protein 1-like 1 (CDKAL1) is one of the most reliable risk genes for type 2 diabetes mellitus (T2DM). Because CDKAL1 controls glucose-induced insulin secretion by KATP channel responsiveness and faithful decoding of Lys codons to prevent mistranslation in pancreatic β-cells, a rescuer of CDKAL1 defects is expected as a new antidiabetes drug. We found that eperisone analogs effectively rescued mistranslation in a MiaB-deficient Escherichia coli dual-luciferase reporter gene system (MiaB is a prokaryotic homologue of eukaryotic CDKAL1). Among them, compounds 1f and 1t demonstrated significant antihyperglycemic efficacy in an oral glucose tolerance test by subcutaneous administration in Wister rats, along with a significant enhancement of insulin secretion in the MIN6 insulinoma cell line without cytotoxicity. These results indicate that CDKAL1 could be a viable molecular target for a new anti-T2DM medication.

 The parasite Toxoplasma gondii is the source of toxoplasmosis. This infection can spread from mother to fetus during pregnancy, through contaminated food or water, or contact with infected cat feces. This study aims to investigate whether chronic toxoplasmosis is associated with an increased risk of type 2 diabetes mellitus (T2DM) in women.

A total of 274 samples were collected from women of reproductive age (18-55 years) as they were relevant for both chronic toxoplasmosis and T2DM. Serological testing was performed to detect the presence of T. gondii antibodies (IgM and IgG) to assess chronic infection, and fasting plasma glucose and HbA1c levels were measured for T2DM diagnosis.

Among the participants, 46 (16.8%) were seropositive for chronic toxoplasmosis, and 68 (24.8%) were diagnosed with T2DM. Statistical analysis revealed that women with chronic toxoplasmosis were 2.3 times more likely to have T2DM compared to women without toxoplasmosis (OR = 2.289, CI: 1.171-4.473, p-value < 0.05). The study also found a significant association between education level and T2DM, with educated women being at lower risk of having T2DM (p-value < 0.05).

This study highlights a statistically significant association between chronic toxoplasmosis and T2DM. Women who were seropositive for chronic toxoplasmosis were more likely to have T2DM compared to seronegative individuals. These findings contribute to the growing body of evidence suggesting a potential link between chronic infections and metabolic disorders. Further research is needed to establish causation, elucidate underlying mechanisms, and explore potential interventions to mitigate the risk of T2DM in individuals with chronic toxoplasmosis.

Diabetes mellitus is considered as one of the principal global health urgencies of the twenty first century. In the present investigation, novel N-substituted 2,4-thiazolidinedione derivatives were designed, synthesized, and characterized by spectral techniques. All the newly synthesized N-substituted 2,4-thiazolidinedione derivatives were tested for in vitro α-glucosidase inhibitory activities and compounds A-12 and A-14 were found to be the most potent which were further subjected to in-vivo disaccharide loading test. The most potent compound was also found to be non-toxic in cytotoxicity studies. Further, docking studies were carried out to investigate the binding mode and key interactions with amino acid residues of α-glucosidase. Molecular dynamic simulations studies for the compounds acarbose, A2, A12, and A14 were done with α-glucosidase protein. Further, ΔG was calculated for acarbose, A2, A12, and A14. In silico studies and absorption, distribution, metabolism, excretion (ADME) prediction studies were also executed to establish the 'druggable' pharmacokinetic profiles. Here, we have developed novel N-substituted TZD analogues with different alkyl groups as α-glucosidase inhibitors.Communicated by Ramaswamy H. Sarma.

Although several investigations have been conducted on the association between serum vitamin D levels and prediabetes and type 2 diabetes mellitus (T2DM) in children and adolescents, their findings are inconsistent.

We conducted a systematic review and dose-response meta-analysis to summarize this subject.

The electronic databases of ISI Web of Science, Scopus, PubMed, and motor engineering of Google Scholar were comprehensively searched up to May 2023.

Epidemiologic studies that investigated the risk of hyperglycemia and insulin resistance in relation to serum 25-hydroxy vitamin D levels in children and adolescents were included.

Twenty-two investigations, with a total of 38 622 participants, were systematically reviewed. Meta-analysis of 15 studies (n = 32 720 participants) showed that participants with the highest serum vitamin D levels had 42% lower risk of hyperglycemia, compared with those in the lowest category of serum vitamin D levels (relative risk [RR] = 0.58; 95%CI, 0.48, 0.71). Moreover, pooling 8 studies (n = 10 465 participants) illustrated that highest serum vitamin D level was associated with a 44% lower risk of insulin resistance compared with the lowest serum vitamin D level (RR = 0.56; 95%CI, 0.37, 0.83). Based on linear dose-response analysis, each 10 nmol/L increment in serum 25-hydroxy vitamin D was associated with a 6% decreased risk of hyperglycemia and insulin resistance in children. Furthermore, nonlinear dose-response analysis revealed that increasing serum vitamin D concentration from 40 nmol/L to sufficient values (>50 nmol/L) was associated with a decreasing trend in risk of hyperglycemia and insulin resistance.

This meta-analysis revealed inverse associations between serum vitamin D levels and hyperglycemia and insulin resistance in children and adolescents, in a dose-response manner. Increasing serum vitamin D concentration from 40 nmol/L to sufficient values (>50 nmol/L) was associated with a decreasing trend in hyperglycemia and insulin resistance risk. Systematic Review Registration: PROSPERO registration no. CRD42023458155.

The rising global prevalence of diabetes poses a serious threat to public health, national economies, and the healthcare system. Despite a high degree of disease heterogeneity and advancing techniques, there is still an unclear diagnosis of patients with diabetes compounded by the array of long-term microvascular and macrovascular complications associated with the disease. In addition to environmental variables, diabetes susceptibility is significantly influenced by genetic components. The risk stratification of genetically predisposed individuals may play an important role in disease diagnosis and management. Precision medicine methods are crucial to reducing this global burden by delivering a more personalised and patient-centric approach. Compared to the European population, genetic susceptibility variants of type 2 diabetes mellitus (T2DM) are still not fully understood in other major populations, including South Asians, Latinos, and people of African descent. Polygenic risk scores (PRS) can be used to identify individuals who are more susceptible to complex diseases such as diabetes. PRS is selective and effective in developing novel diagnostic interventions. This comprehensive predictive approach facilitates the understanding of distinct response profiles, resulting in the development of more effective management strategies. The targeted implementation of PRS is especially advantageous for people who fall into a higher-risk category for diabetes. Through early risk assessment and the creation of individualised diabetes treatment plans, the integration of PRS in clinical practice shows potential for reducing the prevalence of diabetes and its complications. Diabetes self-management depends significantly on patient empowerment, with behavioural monitoring emerging as a vital facilitator. The main aim of this review article is to formulate a more structured intervention strategy by advocating for increased awareness of the clinical utility of PRS and counseling among healthcare practitioners, patients, and individuals at risk of diabetes.

Type 2 diabetes mellitus (T2DM) poses a significant global health challenge due to various lifestyle factors contributing to its prevalence and associated complications. Chronic low-grade inflammation, characterized by elevated levels of inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), plays a pivotal role in the pathogenesis of T2DM. Modulation of the gut microbiota through microbiome-targeted therapy (MTT), including probiotics, prebiotics, and synbiotics, has emerged as a potential strategy to mitigate inflammation and improve metabolic outcomes in T2DM.

A systematic review and meta-analysis were conducted following PRISMA guidelines to evaluate the impact of MTT on inflammatory markers in patients with T2DM. Searches were performed in PubMed, Scopus, and Web of Science databases up to June 2024, with inclusion criteria limited to English-language meta-analyses of randomized controlled trials (RCTs) assessing the effects of probiotics, prebiotics, or synbiotics on inflammatory markers in T2DM patients.

Ten meta-analyses met the inclusion criteria, comprising studies investigating the effects of various MTT interventions on CRP, IL-6, and TNF-α levels in T2DM patients. Meta-analysis results indicated significant reductions in CRP (SMD: -0.070; 95 % CI: -0.119 to -0.020) and TNF-α (SMD: -0.370; 95 % CI: -0.554 to -0.186) levels following MTT, while IL-6 reductions (SMD: -0.070; 95 % CI: -0.269 to 0.129) did not reach statistical significance. However, heterogeneity in study quality, intervention protocols, and participant demographics posed challenges in interpretation.

While improvements in inflammatory markers with MTT have been observed, significant limitations-such as heterogeneity in study quality and variation in intervention protocols-highlight the need for further research to confirm its efficacy and clarify underlying mechanisms. Future studies should aim to address these limitations by exploring variations in dosage, supplement formulations, and bacterial strains, which are crucial for improving the reliability and broader applicability of MTT in the management of T2DM.

Inhibition of dipeptidyl peptidase-4 (DPP4) activity has emerged as a promising therapeutic approach for the treatment of type 2 diabetes mellitus (T2DM). Bioinformatics-driven approaches have emerged as crucial tools in drug discovery. Molecular docking and molecular dynamics (MD) simulations are effective tools in drug discovery, as they reduce the time and cost associated with experimental screening. In this study, we employed structure-assisted in-silico methods, including molecular docking and MD simulations, to identify SRT2183, a small molecule that may potentially inhibit the activity of DPP4 enzyme. The interaction between the small molecule "SRT2183" and DPP4 exhibited a binding affinity of -9.9 Kcal/Mol, leading to the formation of hydrogen bonds with the amino acid residues MET348, SER376, and THR351 of DPP4. The MD simulations over a period of 100 ns indicated stable protein-ligand interactions, with no significant conformational rearrangements observed within the simulated timeframe. In conclusion, our results suggest that the small molecule SRT2183 may have the potential to inhibit the DPP4 enzyme and pave the way for the therapeutics of T2DM.Communicated by Ramaswamy H. Sarma.

Cinnamic acid (CA) is a bioactive compound isolated from cinnamon. It has been demonstrated to ameliorate inflammation and metabolic diseases, which are associated with endothelial dysfunction. This study was aimed to study the potential protective effects of CA against diabetes-associated endothelial dysfunction and its underlying mechanisms.

High-fat diet (HFD) with 60 kcal% fat was used to induce obesity/diabetes in C57BL/6 mice for 12 weeks. These diet-induced obese (DIO) mice were orally administered with CA at 20 or 40 mg/kg/day, pioglitazone (PIO) at 20 mg/kg/day or same volume of vehicle during the last 4 weeks. Isolated mouse aortic segments and primary culture rat aortic endothelial cells (RAECs) were induced with high glucose (HG) to mimic hyperglycemia and co-treated with different concentrations of CA.

In DIO mice, four-week administration of CA, particularly at 40 mg/kg/day, diminished the body weights, blood pressure, fasting blood glucose and plasma lipid levels, and ameliorated endothelium-dependent relaxations (EDRs) and oxidative stress in aortas. The beneficial effects of CA were comparable to the positive control group, PIO. Western blotting results indicated that CA treatment upregulated the expression of peroxisome proliferator-activated receptor delta (PPARδ), and activated nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) and AMP-activated protein kinase (AMPK)/ protein kinase B (Akt)/ endothelial nitric oxide synthase (eNOS) signaling pathways in mouse aortas in vivo and ex vivo. HG stimulation impaired EDRs in mouse aortas and inhibited nitric oxide (NO) production but elevated reactive oxygen species (ROS) levels in RAECs. CA reversed these impairments. Importantly, PPARδ antagonist GSK0660 abolished the vasoprotective effects of CA. Molecular docking analysis suggested a high likelihood of mutual binding between CA and PPARδ.

CA protects against endothelial dysfunction and oxidative stress in diabetes and obesity by targeting PPARδ through Nrf2/HO-1 and Akt/eNOS signaling pathways.

Among people with abdominal obesity, women are more likely to develop diabetes than men. Mobile health (mHealth)-based technologies provide the flexibility and resource-saving opportunities to improve lifestyles in an individualized way. However, mHealth-based diabetes prevention programs tailored for busy mothers with abdominal obesity have not been reported yet.

The aim of this study is to evaluate the feasibility and acceptability of an mHealth-based diabetes prevention program and its preliminary efficacy in reducing weight-related variables, behavioral variables, psychological variables, and diabetes risk among Chinese mothers with abdominal obesity over 6 months.

A randomized controlled trial was conducted at health management centers in 2 tertiary hospitals in Changsha, China. The mHealth group (n=40) received 12 weekly web-based lifestyle modification modules for diabetes prevention, 6 biweekly individualized health education messages based on their goal settings, and a Fitbit tracker. The control group (n=40) received 12 weekly web-based general health education modules, 6 biweekly general health education messages, and a Fitbit tracker. Data were collected at baseline, 3 months, and 6 months on the feasibility and acceptability outcomes, weight-related variables (waist circumference and BMI), diabetes risk scores, glycemic levels, behavioral variables (daily step count, active minutes, fruit and vegetable intake, calorie consumption, and sleep duration), and psychological variables (self-efficacy and social support for physical activity and diet, perceived stress, and quality of life). Generalized estimating equations were used for data analysis.

Approximately 85% (68/80) of the participants completed 6 months of follow-up assessments. Regarding the feasibility and acceptance of the program in the mHealth group, the average number of modules reviewed was 7.9 out of 12, and the satisfaction score was 4.37 out of 5. Significant improvements at 6 months between the intervention and control groups were found in waist circumference (β=-2.24, 95% CI -4.12 to -0.36; P=.02), modifiable diabetes risk scores (β=-2.5, 95% CI -4.57 to -0.44; P=.02), daily steps (β=1.67, 95% CI 0.06-3.29; P=.04), self-efficacy for physical activity (β=1.93, 95% CI 0.44-3.43; P=.01), social support for physical activity (β=2.27, 95% CI 0.80-3.74; P=.002), and physical health satisfaction (β=0.82, 95% CI 0.08-1.55; P=.03). No differences were found in BMI, total diabetes risk score, daily active minutes, daily intake of fruits and vegetables, sleep duration, daily calorie consumption, self-efficacy, and social support for diet (P>.05).

This study addresses the potential role of tailored lifestyle interventions based on mHealth technology by offering tailored web-based health modules and health information in managing diabetes risk among mothers with abdominal obesity. The mHealth diabetes prevention program provides a flexible, customized, and resource-saving model for busy mothers. Future research could further explore the efficacy improvement on dietary behaviors to better serve the health care needs of this population.

Chinese Clinical Trial Registry ChiCTR2400090554; https://www.chictr.org.cn/showproj.html?proj=226411.

Previous studies have indicated an association between UHR and diabetes risk, but evidence from large-scale and diverse populations remains limited. This study aims to verify UHR's independent role in diabetes risk prediction in a large sample population and assess its applicability across different populations. We drew upon data from 30,813 participants collected during the 2005-2018 NHANES cycle. The association between UHR and the risk of diabetes was explored using multivariate logistic regression models, with key predictive factors identified through LASSO regression. Model effectiveness was evaluated through receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and calibration metrics. Additionally, restricted cubic spline (RCS) and threshold effect assessments were applied to examine the nonlinear association between UHR and diabetes risk. The results showed that UHR levels were notably elevated in individuals with diabetes when compared to those without diabetes (p < 0.001). The occurrence of diabetes showed a marked increase across ascending UHR quartiles (6.63%, 10.88%, 14.15%, 18.02%; p < 0.001). Results from multivariate logistic regression indicated that elevated UHR was strongly linked to a heightened risk of diabetes; participants in the highest UHR quartile were found to have nearly four times the risk compared to those in the lowest quartile (OR = 4.063, 95% CI: 3.536-4.669, p < 0.001). Subgroup analyses demonstrated that the predictive effect of UHR was more pronounced in females. Key variables selected via LASSO regression improved the model's performance. Restricted cubic spline (RCS) analysis indicated an inflection point at UHR = 10; beyond this point, diabetes risk accelerated, and when UHR exceeded 18, the risk increased significantly (OR > 1). ROC curve analysis showed the baseline model (M1) had an area under the curve (AUC) of 0.797, while the multivariable model (M4) after LASSO selection had an AUC of 0.789. Decision curve analysis and calibration curves validated the model's predictive ability and consistency. This study indicates that UHR may be an independent predictor of diabetes risk, showing a positive correlation with diabetes and a more pronounced predictive effect in females.

Metabolic syndrome (MetS) refers to a group of risk factors that cause health problems, such as obesity, diabetes, dyslipidemia, and hyperglycemia. MetS is characterized by insulin resistance, which leads to abnormal insulin sensitivity. Cirsium japonicum var. maackii (CJ) is perennial herbaceous species found in Asia that exhibits antioxidant, antidiabetic, antitumor, antifungal, and anti-inflammatory activities. In this study, we aimed to measure the effects of CJ on MetS by improving insulin resistance in a db/db type 2 diabetes mouse model. After administrating CJ extract (CJE) for db/db mouse for 6 weeks, we measured with the evaluation of Insulin resistance, lipid profiles, histological analysis of liver, damage of liver and kideny.

The results showed that CJE was effective in reducing body weight and fat mas and showed a positive effect on lowering blood glucose and improving insulin sensitivity. CJE improved dyslipidemia by increasing serum-HDL levels and decreasing serum-LDL levels. In addition, CJE reduced liver and kidney damage in histological analysis.

These results demonstrate the anti-diabetic effects of CJE and suggest its potential for improving MetS. Therefore, CJE may have potential values as a functional food material for managing MetS.

Type 2 diabetes mellitus (T2DM) is a prevalent, chronic health condition of global significance, with low- and middle-income countries (LMICs) disproportionately affected. Diabetes self-management practices (DSMP) are the gold-standard treatment approach, yet uptake remains challenge in LMICs.

This study aimed to explore the barriers to and facilitators of DSMP and preferences for intervention design and delivery in Bangladesh, an LMIC, with prevalent T2DM.

Sixteen qualitative focus group discussions (FGDs) with adults with T2DM and their caregivers were conducted in rural Bangladesh to explore preferences, barriers, and facilitators for community DSMP-related intervention programs. Data were thematically analyzed using a deductive theoretical domains framework (TDF) underpinned by the socio-ecological model.

Overall, 117 participants (n = 58 with T2DM and n = 59 caregivers) were included in the analysis. Five overarching themes were identified, including (i) implementation of DSMP, (ii) community spirit and interconnectedness, (iii) environmental influences, (iv) healthcare professionals' role in DSMP, and (v) government support. Key barriers to DSMP identified for T2DM patients include knowledge implementation gaps, cultural practices, limited resources, and financial constraints. Facilitators include motivation, support from family and peers, and religious practices. Rural Bangladeshis prefer programs delivered at community clinics, viewing them as reliable, culturally appropriate central 'hubs' to assemble.

Barriers to and facilitators of DSMP were identified, and preferences for intervention design and delivery for implementing DSMP were explored. The findings provide a foundation for the critical need to implement programs that improve DSMP in Bangladesh, with the potential to translate to other LMIC settings.

Type 2 diabetes (T2D) is a heterogeneous disease influenced by both genetic and environmental factors. Recent studies suggest that T2D subtypes may exhibit distinct gene expression profiles. In this study, we aimed to identify T2D cluster-specific miRNA expression signatures for the previously reported five clinical subtypes that characterize the underlying pathophysiology of long-standing T2D: severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), and mild early-onset diabetes (MEOD). We analyzed the circulating microRNAs (miRNAs) in 45 subjects representing the five T2D clusters and 7 non-T2D healthy controls by single-end small RNA sequencing. Bioinformatic analyses identified a total of 430 known circulating miRNAs and 13 previously unreported novel miRNAs. Of these, 71 were upregulated and 37 were downregulated in either controls or individual clusters. Each T2D subtype was associated with a specific dysregulated miRNA profile, distinct from that of healthy controls. Specifically, 3 upregulated miRNAs were unique to SIRD, 1 to MARD, 9 to MOD, and 18 to MEOD. Among the downregulated miRNAs, 11 were specific to SIRD, 9 to SIDD, 2 to MARD, and 1 to MEOD. Our study confirms the heterogeneity of T2D, represented by distinguishable subtypes both clinically and epigenetically and highlights the potential of miRNAs as markers for distinguishing the pathophysiology of T2D subtypes.