Glucose Levels Research Articles

CTNI-64. TRIAL IN PROGRESS: DIET2TREAT -- A RANDOMIZED MULTICENTER PHASE 2 TRIAL OF A KETOGENIC DIET VS STANDARD DIETARY GUIDANCE IN COMBINATION WITH STANDARD-OF-CARE TREATMENT FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract BACKGROUND Many glioblastoma (GBM) patients inquire about the potential therapeutic benefits of a high fat / low carbohydrate ketogenic diet (KD). Preclinical models and early-phase trials have shown encouraging results, but definitive evidence of clinical efficacy is lacking. METHODS We are conducting a multicenter randomized controlled phase 2 clinical trial (NCT05708352) of KD vs standard dietary guidance (SD) for patients with newly diagnosed GBM. All patients receive standard-of-care chemoradiation. Inclusion criteria: newly diagnosed GBM, age ≥ 18 years, Karnofsky Performance Status ≥ 70. Exclusion criteria: inability to wean steroids below 8 mg dexamethasone/day, Body Mass Index < 21 kg/m2, food preferences incompatible with KD. Patients are randomized 1:1 to implement either KD or SD for a study period of 18 weeks, starting alongside chemoradiation. The primary outcome is overall survival for patients randomized to the KD arm compared to those randomized to the SD arm. Secondary outcomes include progression-free survival, health-related quality-of-life (FACT-BR, FACIT-F), cognitive performance (HVLT-R, Trail-Making Test A/B), and physical activity (modified Godin leisure questionnaire, continuous activity monitoring (Fitbit)). Patients randomized to the KD arm will be provided a fingerstick monitor to check blood ketone and glucose levels twice daily. Glucose and ketone levels are also periodically monitored for patients on the SD arm. Blood, tumor, and stool samples are being collected for high throughput profiling to assess the effects of KD on metabolic markers and immune response. Target accrual is 170 patients over 5 years. Enrollment began in July 2023 and is ongoing. As of May 2024, the trial is open for enrollment at Cedars-Sinai and UCSF, and will be opening soon at Duke, St. John’s Cancer Institute, and the Medical College of Wisconsin. 13 patients have been randomized to date. Funding provided by NIH R01CA276919 and the Foundation for Metabolic Cancer Therapies.

Time in tight range: A key metric for optimal glucose control in the era of advanced diabetes technologies and therapeutics.

Compared to glycated haemoglobin A1c (HbA1c), the rapidly developing continuous glucose monitoring (CGM) technology provides more detailed information about glycemic control. Amongst the new glucose metrics derived from CGM, time in target range of 3.9-10.0 mmol/L (time in range, TIR) has been widely used for the assessment of glucose control. In recent years, the rise of new technologies and therapies including advanced hybrid closed-loop automated insulin delivery systems and new hypoglycemic drugs has made it possible to achieve better glycemic control. In this context, the concept of time in tight range (TITR), defined as the percentage of time spent in target glucose range of 3.9-7.8 mmol/L, has gained increasing attention. Whilst TITR is highly correlated with TIR, there are still differences between the two metrics. These differences make TITR a more appropriate indicator in certain situations, such as when glucose levels are close to normal or when tighter glycemic control is required. This review summarizes recent studies related to TITR.

Biochar enhances soil interactions and the initial development of sugarcane.

The present study evaluated the effects of biochar derived from sugarcane straw on the physicochemical and biological properties of soil and the initial development of sugarcane. Microcosm and pot experiments were conducted over 60 days to monitor variables such as pH, water retention capacity, microbial activity, initial growth, and the metabolomic profile of the plant leaves. The results indicated that biochar increased the soil water retention capacity without significantly affecting the pH. The biochar significantly promoted root length and mass and favored the growth of the soil microbiota, as reflected by an increase in the amount of microbial biomass carbon. Metabolomic analysis of sugarcane leaves revealed that soil conditioning with biochar at application rates of 3 and 5% w/w led to increased concentrations of the amino acids isoleucine and valine, accompanied by a reduction in galactose, maltose, and glucose levels. Furthermore, biochar treatment resulted in a decrease in aconitic acid and an increase in acetic and succinic acid concentrations. These findings suggest that biochar may be a promising strategy for enhancing the productivity and sustainability of sugarcane cultivation.

Retrospective cohort study on treatment outcomes of early vs late onset gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) affects roughly 14% of pregnancies, its prevalence is increasing, and it is associated with a significant risk of complications for both mother and offspring. A high proportion of women with GDM can be detected early in pregnancy. In Italy, early GDM screening occurs in a selective way, as it is performed only in the presence of important risk factors. It remains to be elucidated not only how and when to diagnose early GDM but especially whether to treat it. This study aimed to compare the characteristics and complications of early vs late GDM as assessed and treated in a real-world setting, according to the Italian guidelines of the Istituto Superiore di Sanità. We conducted a retrospective cohort study in women with GDM delivering singletons between 2017 and 2021. Women with early GDM had higher BMI and a higher proportion of Middle Eastern or African women. Early GDM was independently associated with the use of insulin (p < 0.001). It required also higher doses of insulin, possibly due to the higher BMI. Early GDM was also independently associated with higher post-prandial (after dinner) glucose levels during the 3° trimester (p = 0.04). Nevertheless, early GDM women achieved glucose targets and put on less weight during gestation. Early GDM was independently associated with preeclampsia (p = 0.05). Otherwise, there were no other differences between early and late GDM in terms of pregnancy complications. After delivery, early GDM was independently associated with abnormal glucose tolerance. Early GDM women exhibited more severe GDM features. However, after achieving recommended glucose and body weight targets, there were no substantial differences between early and late GDM in terms of pregnancy complications apart from preeclampsia. These data support diagnosis and treatment of women with early GDM.

MECHANISMS OF ACTION OF PROTEIN SHAKES IN NORMALIZING METABOLIC PROCESSES, THEIR ROLE IN IMPROVING GLYCEMIC CONTROL IN PATIENTS WITH TYPE 2 DIABETES, AND IN PREVENTING CARDIOVASCULAR DISEASES

This review article delves into the significance of protein shakes, particularly whey protein, in various health and fitness contexts. The primary focus is on their biochemical properties, metabolic benefits, and their role in supporting muscle mass, weight loss, and metabolic health. The article synthesizes findings from multiple studies to highlight the potential of protein shakes in improving glycemic control, reducing inflammation, and enhancing overall health, particularly for individuals with type 2 diabetes, obesity, and sarcopenia. The review also explores the effectiveness of protein shakes in athletic performance and recovery, as well as their impact on glucose metabolism and homeostasis. It underscores the necessity for further research to optimize the use and dosage of protein shakes for diverse populations to fully harness their benefits. Whey proteins are rich in essential amino acids, particularly leucine, which stimulates muscle protein synthesis via the mTOR pathway. This makes them highly effective in muscle building and recovery. Whey protein consumption enhances glycemic control by increasing insulin secretion and improving insulin sensitivity. Studies have shown significant reductions in fasting glucose levels and HbA1c in patients with type 2 diabetes. Protein shakes aid in weight loss by promoting satiety and increasing thermogenesis. They help maintain muscle mass during weight loss, which is crucial for sustaining metabolic rate. Clinical trials have demonstrated their efficacy in reducing body fat and improving metabolic markers. Whey protein, combined with resistance training, significantly improves muscle mass and strength in older adults, helping to prevent sarcopenia. This is essential for maintaining physical functionality and reducing the risk of falls and fractures. In the rehabilitation of patients with severe obesity, protein shakes are effective in reducing body weight, improving metabolic health, and maintaining muscle mass. They play a crucial role in comprehensive rehabilitation programs that include diet and physical exercise. Protein shakes support metabolic adaptations by preserving muscle mass and enhancing thermogenesis, which helps maintain a high metabolic rate and prevent weight regain. Whey proteins enhance muscle mass and strength, speed up recovery after training, and boost endurance. They also support the immune system and reduce oxidative stress, contributing to better overall athletic performance . Proteins shakes aid in regulating blood glucose levels and improving insulin sensitivity, which is crucial for preventing and managing diabetes. Their antioxidant and anti-inflammatory properties further enhance metabolic health.

Association between selenium biomarkers and insulin resistance in women with obesity: A case-control study.

Although literature demonstrates controversial results regarding the association between selenium and glucose metabolism, no studies have specifically targeted a population with obesity even though this group is vulnerable to insulin resistance. To evaluate the association between selenium biomarkers and insulin resistance in women with obesity. This case-control study recruited 84 women with obesity and 129 with healthy weight (control). Selenium intake was assessed by 3-day food record. Selenium concentration in plasma, erythrocyte, and urine was assessed by inductively coupled plasma optical emission spectrometry. Serum glucose, insulin, and glycated hemoglobin (HbA1c) were assessed in a fasting blood sample. Homeostasis Model Assessment of Beta Cell Function (HOMA-β) and Homeostasis Model Assessment of Insulin Resistance were calculated according to standard methods. Women with obesity had higher dietary selenium intake in comparison to the control group (p < 0.001). Further, the plasma and erythrocyte concentrations were lower in individuals with obesity (p < 0.001), while selenium in urine was higher (p < 0.001) than in controls. No significant differences in insulin resistance markers were observed between groups. Selenium intake was positively associated with HOMA-β in both groups. In women with obesity, selenium intake was also positively associated with insulin and HbA1c, while in the controls the clearance of selenium was negatively associated with insulin and HbA1c. There was a positive correlation between dietary selenium intake, fasting insulin, HbA1c, and HOMA-β (p < 0.05). Women with obesity present impaired selenium metabolism. Further, we observed an association between dietary selenium and markers of insulin resistance, which may reflect the possible negative action of selenium on insulin signaling.

COVID-19 inflammatory signature in a Mozambican cohort: unchanged red blood series and reduced levels of IL-6 and other proinflammatory cytokines.

Alterations in haematological, biochemical parameters and cytokine levels, were reported in patients with COVID-19, however, there is an underrepresentation of the African population, which could provide evidence for understanding SARS-CoV-2 pathogenesis and useful tools for clinical management of cases. In this study, we aimed to determine the haematological, biochemical and cytokine profile in Mozambican individuals with SARS-CoV-2. A cohort of 85 Mozambican individuals with RT-PCR SARS-CoV-2 results, was stratified into negative, asymptomatic, mild, moderate, and severe categories. Haematological, biochemical and cytokines measurement were performed on samples from the study participants. Principal component analysis (PCA) was performed to identify similar patterns among the study cases. Comparisons between groups were performed using the Kruskal-Wallis test. Receiver operating characteristic (ROC) and area under the curve (AUC) analysis were conducted to evaluate the ability of these parameters to distinguish severe from non-severe cases of SARS-CoV-2 infection. SARS-CoV-2 infection was associated with a significant (p < 0.05) decrease in peripheral blood absolute counts of total lymphocytes and eosinophils, below the reference values along with no abnormal change (p > 0.05) in red blood cell count, haemoglobin, platelets and other red series parameters. At the serum level, SARS-CoV-2 infection was associated with an increase in serum levels of C-reactive protein (C-RP) and glucose above the reference values and to a significant reduction a significant (p < 0.05) reduction in levels of interferon-gamma (INF-γ), Tumour Necrosis Factor alfa (TNF-α) and the interleukin 1 beta (IL-1β) and IL-6 in severe cases, when compared to negative cases. Haematological, biochemical and cytokine profiles segregate severe from non-severe cases of COVID-19 with an excellent performance of C-RP (AUC = 0.95; p < 0.001) and good performance of lymphocytes (AUC = 0.88; p < 0.001) and IL-15 (AUC = 0.86; p < 0.001). The lack of variation in red and platelet series, coupled with a decrease in the levels of classical pro-inflammatory in severe cases, deviates from what has been reported in other contexts suggesting, that there may be peculiarities in COVID-19 manifestation within the context of this study population. Furthermore, these results identify parameters with potential for clinical management of COVID-19 and therefore good resource allocation, particularly for severe cases.

Risk factors associated with the false positive of cardiopulmonary exercise test in the diagnosis of coronary heart disease.

Cardiopulmonary exercise test (CPET) is a common method for preliminary evaluating coronary heart disease (CHD), but it may experience false positive. The present study aimed to reveal the potential factors relating to the false positive of CPET, including blood glucose and lipids. This observational cohort study included 103 subjects with false positive of CPET and 65 subjects with true positive of CPET. The baseline characteristics, blood glucose, and blood lipids between the true and false positive groups were compared. After adjusting for the age and sex, logistic regression analysis was performed to reveal the potential risk factors of false positive. Receiver operating characteristic curve analysis was performed to evaluate the potential of related factors in distinguishing between true and false positive results. Males, smokers, and patients with diabetes were less likely to suffer from false positive of CPET. Compared with the true positive group, the false positive group exhibited significantly higher levels of high-density lipoprotein (HDL) and apolipoprotein A1 (Apo-A1), and lower levels of fasting blood glucose (FBG) and glycosylated hemoglobin (GHb). After adjustment, FBG and GHb were protective factors of the true positive of CPET, and they both had moderate ability to distinguish false positive from true positive in females. However, their combination did not improve the discriminative effect more obviously than FBG alone. Sex, smoking, diabetes, and blood glucose were associated with the false positive of CPET. FBG was valuable in predicting the risk of false positive of CPET in females with suspected CHD. The present study is registered in Chinese Clinical Trial Register (ChiCTR2400089239).

CSIG-13. TARGETING GENETIC DEPENDENCIES EXPOSES DIFFUSE MIDLINE GLIOMA CELL OF ORIGIN VULNERABILITIES

Abstract Diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG), are uniformly fatal brain cancers affecting children, adolescents, and young adults. These tumors are characterized by ‘oncohistone’ mutations in histone H3 genes (H3F3A, HIST1H3B, HIST1H3C), resulting in the substitution of lysine 27 to methionine (H3K27M), resulting in dominant negative hypomethylation at lysine 27 (H3K27) and a global loss of gene silencing. CRISPR-Cas9 loss-of-function gene deletion screens identified mutation-independent dependencies on PIK3CA and MTOR genes for tumor growth and proliferation, highlighting a targetable molecular dependency across DMG patient-derived models (n=38). However, systemic PI3K/mTOR inhibition increased blood glucose and insulin levels, promoting hyperinsulinemia/hyperglycemia and reduced efficacy in vivo. To exploit genetic dependencies while maintaining compliance and therapeutic benefit, we optimized combinations of clinically relevant PI3K inhibitors (paxalisib, GCT007, everolimus) with the antiglycemic drug metformin to restore glucose homeostasis and decrease DMG insulin receptor activity in vivo, extending the survival of DIPG xenograft models. Phosphoproteomic profiling of DIPG models treated with PI3K/mTOR inhibitors promoted calcium-activated PKC signaling. The brain-penetrant PKC inhibitor enzastaurin in combination with paxalisib, synergistically extended the survival of DIPG xenograft models, including those mimicking disease progression, with further benefits potentiated using metformin in a multimodality approach. Combined PI3K-PKC inhibition in vivo promoted differentiation of OPC-like DMG to more OC-like cells, enhancing PDGFRA-JAK/STAT proinflammatory signaling, showing features of demyelination and MHC-II+ antigen expression, including PD1/PDL1. In parallel, combined PI3K/mTOR and PDGFRA inhibition using paxalisib and avapritinib synergistically extended the survival of patient-derived xenograft models, showing the preclinical relevance of simultaneously targeting these vulnerabilities. Together, we reveal that therapeutic inhibition of PI3K/mTOR and compensatory PKC signaling, while mitigating side effects with metformin, altered the chromatin architecture, leading to cellular differentiation and opening the door for clinically relevant checkpoint inhibitors. This combination strategy addresses DMG genetic dependencies, cellular and systemic responses to precision therapies, while harnessing the immune system for potential clinical translation.

Determination of the Biochemical Compositions of Stored Expressed Human Breast Milk of Healthy Lactating Mothers

Aims: This study is aimed at determining the biochemical compositions and immunological components of expressed human breast milk (HBM) gotten from healthy lactating mothers stored under varying low temperatures. Place and Duration of Study: Department of Microbiology, University of Benin, Benin, Edo State; and Quick Diagnostic Centre, Umuahia, Abia State. It was a three (3) months study. Methodology: Sixty (60) samples of expressed HBM were collected from healthy lactating mothers (at varying ages) in Abia State, Nigeria. Employing basic biochemical analyses, the quantification of total protein, glucose, and triacylglycerol levels, in addition to the confirmation tests of vitamin, minerals, and immune cells etc, were carried out. Results: The findings of this study demonstrated that triacylglycerol levels were constantly higher than glucose and protein level and this clearly was manifested across the ages of the lactating mothers (15 - 25 years, 26 - 35 years, and 36 - 45 years). Under room temperature and varying refrigeration, the changes in the biochemical compositions in the expressed HBM were also evaluated. Conclusion: From our findings, expressed HBM shows good nutritive profile with various bioactive factors that are essential for supporting infant growth, and immunity. Although references demonstrated that storage conditions can impact the nutritional value of expressed HBM, the result of this study was suggestive of expressed HBM having the ability to retain good amount of its bioactive compounds when refrigerated to 24 hours, ensuring that microbial infestations were properly controlled.

Global, regional, and national burden of tuberculosis and attributable risk factors for 204 countries and territories, 1990-2021: a systematic analysis for the Global Burden of Diseases 2021 study.

Tuberculosis (TB) remains a major global health threat. Despite ongoing efforts to control and eradicate TB, various factors including socioeconomic issues, policy modifications, and unexpected public health crises like COVID-19 pandemic have posed new obstacles to achieving TB elimination. This study aims to analyze the changes in global tuberculosis burden over the past 32 years, and provide scientific support for global initiatives targeting the eradication of TB in the post-pandemic period. The data for this study were obtained from the Global Burden of Disease (GBD) 2021 database, with age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASDR), and disability-adjusted life years (DALYs) as the primary assessment indicators. Dynamic changes in the TB burden were analyzed by estimating the annual percentage changes (EAPCs). The attributable ratios of six main risk factors to TB burden were calculated, and the correlation between the Socio-Demographic Index (SDI) and the TB burden was analyzed using Pearson correlation tests. The global TB incidence decreased from 8.6million cases in 1990 to 8.4million cases in 2021, with a corresponding decline in deaths. However, the TB burden remains higher among men than women. The highest incidence and mortality rates were observed in the age group of 15-69 years, with a notable gender disparity, especially in Eastern Europe. These rates were generally elevated in low-income and lower-middle-income regions, with significantly higher Age-Standardized Incidence Rates and Age-Standardized Death Rates in males compared to females. A significant negative correlation was found between SDI values and TB burden. Analyzing risk factors from the Global Burden of Disease study, it was determined that globally, dietary risks, high body-mass index, high fasting plasma glucose, low physical activity, tobacco, and alcohol use were the main contributors to TB age-standardized Disability-Adjusted Life Years, with tobacco and alcohol use having the most significant impact. Analysis of risk factors suggests that tailored public health interventions for specific genders and regions can effectively lessen the TB burden.

Isotretinoin increases non-insulin-based surrogate markers of insulin resistance in acne vulgaris patients

Background Lipid indices, particularly the triglyceride-glucose index (TyG index) and the triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio, are simple, reliable, non-insulin-based surrogate markers of insulin resistance that have recently gained prominence. The aim of this study was to evaluate the effect of isotretinoin treatment on surrogate markers of insulin resistance, in particular the TyG index, in patients with acne vulgaris (AV). Materials and methods This retrospective study reviewed the records of 200 patients who received isotretinoin treatment for acne vulgaris at the Department of Dermatology and Venereology between September 2023 and March 2024. Serum fasting glucose, fasting lipid profile [triglyceride (TG), total cholesterol (TC), very low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)] and other biochemical parameters were recorded. Triglyceride-glucose (TyG) index value was calculated with the formula Ln [fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2]. Pre-treatment values were compared with values after 5 months of treatment. Results TyG index and TG/HDL, TC/HDL, and LDL/HDL ratios all increased statistically significantly (p < 0.001). In addition, a positive correlation was found between pre- and post-treatment TyG index values and pre- and post-treatment TC/HDL, LDL/HDL and TG/HDL ratio values (p < 0.001). Among lipid measurements, triglycerides, total cholesterol, VLDL-C, LDL-C increased statistically significantly (p < 0.001), while HDL-C decreased statistically significantly (p < 0.05). Conclusion The results of this study suggest that isotretinoin treatment may increase insulin resistance in AV patients by increasing surrogate biomarkers of insulin resistance. We also suggest that the TyG index and other lipid indices can be used in treatment follow-up.

Hypoglycemic and intestinal microbiota-regulating effects of melanoidins in diabetic mice.

The aqueous extraction of sesame oil is a traditional process that generates a large amount of melanoidins. However, little is known about the characteristics and bioactive functions of these melanoidins. Electronic tongue, fluorescence emission spectroscopy, and Fourier transform infrared spectroscopy analyses indicated that melanoidins from sesame residues (MELs) are brown macromolecular compounds with protein skeletons and heteroaromatic ring structures, a bitter taste, and instability in strong oxidative and reductive environments. The MELs demonstrated inhibitory effects on α-glucosidase, α-amylase and pancreatic lipase in vitro. These MELs mitigated weight loss in mice with type 2 diabetes (T2DM), reduced their fasting blood glucose to 54.73% (500 mg kg-1 day-1) of the initial value, increased the glycogen levels in the liver and skeletal muscles, lowered blood lipid levels, and protected the liver. Western blot analysis revealed that MELs inhibited the activities of enzymes such as PEPCK, FBPase, and G6Pase through the IRS-1/PI3K/Akt and AMPK pathways, increased the activity of the enzymes hexokinase (HK) and pyruvate kinase (PK), enhanced liver glycolytic ability, and promoted liver glycogen synthesis, thereby reducing blood glucose levels in T2DM mice. Moreover, MELs reduced the ratio of Firmicutes to Bacteroides (F/B) in the intestines of T2DM mice, increased the relative abundance of beneficial bacteria such as Lactobacillus, Coprococcus, and Ruminococcus, and reduced the propionic acid content. Melanoidins can regulate T2DM by activating the IRS-1/PI3K/Akt and AMPK-signaling pathways and ameliorating gut microbiota imbalances in T2DM mice. © 2024 Society of Chemical Industry.

Elevated glucose levels increase vascular calcification risk by disrupting extracellular pyrophosphate metabolism.

Vascular calcification is a major contributor to cardiovascular disease, especially diabetes, where it exacerbates morbidity and mortality. Although pyrophosphate is a recognized natural inhibitor of vascular calcification, there have been no prior studies examining its specific deficiency in diabetic conditions. This study is the first to analyze the direct link between elevated glucose levels and disruptions in extracellular pyrophosphate metabolism. Rat aortic smooth muscle cells, streptozotocin (STZ)-induced diabetic rats, and diabetic human aortic smooth muscle cells were used to assess the effects of elevated glucose levels on pyrophosphate metabolism and vascular calcification. The techniques used include extracellular pyrophosphate metabolism assays, thin-layer chromatography, phosphate-induced calcification assays, BrdU incorporation for DNA synthesis, aortic smooth muscle cell viability and proliferation assays, and quantitative PCR for enzyme expression analysis. Additionally, extracellular pyrophosphate metabolism was examined through the use of radiolabeled isotopes to track ATP and pyrophosphate transformations. Elevated glucose led to a significant reduction in extracellular pyrophosphate across all diabetic models. This metabolic disruption was marked by notable downregulation of both the expression and activity of ectonucleotide pyrophosphatase/phosphodiesterase 1, a key enzyme that converts ATP to pyrophosphate. We also observed an upregulation of ectonucleoside triphosphate diphosphohydrolase 1, which preferentially hydrolyzes ATP to inorganic phosphate rather than pyrophosphate. Moreover, tissue-nonspecific alkaline phosphatase activity was markedly elevated across all diabetic models. This shift in enzyme activity significantly reduced the pyrophosphate/phosphate ratio. In addition, we noted a marked downregulation of matrix Gla protein, another inhibitor of vascular calcification. The impaired pyrophosphate metabolism was further corroborated by calcification experiments across all three diabetic models, which demonstrated an increased propensity for vascular calcification. This study demonstrated that diabetes-induced high glucose disrupts extracellular pyrophosphate metabolism, compromising its protective role against vascular calcification. These findings identify pyrophosphate deficiency as a potential mechanism in diabetic vascular calcification, highlighting a new therapeutic target. Strategies aimed at restoring or enhancing pyrophosphate levels may offer significant potential in mitigating cardiovascular complications in diabetic patients, meriting further investigation.

Consuming spicy food and type 2 diabetes incidence in Southwestern Chinese aged 30–79: a prospective cohort study

BackgroundCapsaicin is the main component of chili peppers and is believed to have antidiabetic effects. However, the association between spicy food consumption and the incidence of diabetes remains unclear.MethodsA cohort of 20,490 Han residents aged 30–79 without diabetes at baseline were followed from enrollment to June 2, 2023. The consumption of spicy food was obtained through face-to-face surveys conducted during the baseline survey from October 2018 to February 2019. The definition of type 2 diabetes onset was based on the ICD-10 code of E11 in the diabetes case reporting system and death system; Additionally, self-reported diagnosis of diabetes by a physician in active follow-ups, or a fasting blood glucose level of ≥ 7 mmol/L or a glycated hemoglobin percentage of ≥ 6.5% found on-site during the resurvey. Both Cox proportional hazard regression and competing risk regression were used to calculate hazard ratios (HRs) and confidence intervals (CIs).ResultsDuring the follow-up period (53.5 ± 3.0 months), 182 individuals (1.1%) were newly diagnosed with T2D with an incidence rate of 246.2 per 100,000 person-years. Cox regression analyses revealed that spicy food consumers had a 34% reduced risk of developing type 2 diabetes (HR: 0.66, 95% CI: 0.48, 0.91) compared to non-consumers. The HRs (95% CIs) for participants consuming spicy food 3–5 days/week, 6–7 days/week, and with weak pungency were 0.45 (95% CI: 0.25, 0.81), 0.69 (0.49, 0.98), and 0.64 (0.46, 0.90), respectively. However, little significant protective effect was observed among those who consumed spicy food for 1–2 days/week, with moderate pungency, or with strong pungency (all P > 0.05).ConclusionsConsuming spicy food may lower the risk of developing type 2 diabetes, particularly at a frequency of 3–5 days/week, and with weak pungency. Further multicenter prospective studies or interventional studies are needed to confirm these findings.

Design, synthesis, and evaluation of novel substituted imidazo[1,2-c]quinazoline derivatives as potential α-glucosidase inhibitors with bioactivity and molecular docking insights.

α-Glucosidase inhibitors are important in the treatment of type 2 diabetes by regulating blood glucose levels and reducing carbohydrate absorption. The present study focuses on identifying new inhibitors bearing imidazo[1,2-c]quinazoline backbone through multi-step synthesis. The inhibitory potencies of the novel derivatives were tested against Saccharomyces cerevisiae α-glucosidase, revealing IC50 values ranging from 50.0 ± 0.12 µM to 268.25 ± 0.09 µM. Among them, 2-(4-(((2,3-diphenylimidazo[1,2-c]quinazolin-5-yl)thio)methyl)-1H-1,2,3-triazol-1-yl)-N-(2-methoxyphenyl)acetamide (19e) and 2-(4-((benzo[4,5]imidazo[1,2-c]quinazolin-6-ylthio)methyl)-1H-1,2,3-triazol-1-yl)-N-(2-methoxyphenyl)acetamide (27e) emerged as the most potent inhibitors and were further investigated in various assessments. Finally, molecular docking studies were performed to reveal the crucial binding interactions and to confirm the results obtained from structure-activity relationship (SAR) analysis.

Potential effects of peripheral neuropathy on brain function in patients with type 2 diabetes mellitus

BackgroundThe mechanisms associated between diabetic peripheral neuropathy (DPN) and various brain function abnormalities in patients remains unclear. This study attempted to indirectly evaluate the effect of DPN on brain function in patients with type 2 diabetes mellitus (T2DM) by characterizing the resting-state functional connectivity (FC) of the lower limb sensorimotor cortex (LSM).MethodsForty-four T2DM patients with diabetic peripheral neuropathy (DPN), 39 T2DM patients without diabetic peripheral neuropathy (ND), and 43 healthy controls (HCs) underwent a neuropsychological assessment and resting-state functional magnetic resonance imaging examinations to examine the differences in FC between the LSM and the whole brain. The relationships of FC with clinical/cognitive variables were examined.ResultsIn comparison with the HCs group, the ND group showed reduced FC of the LSM with the right lateral occipitotemporal cortex (LOTC) and increased FC with the medial superior frontal gyrus (SFGmed), while the DPN group showed reduced FC of the LSM with the right cerebellar lobule VI, the right LOTC, the rostral prefrontal cortex (rPFC), and the anterior cingulate gyrus (ACC). Moreover, in comparison with the ND group, the DPN group showed reduced FC of the LSM with the ACC, SFGmed, and rPFC. In the DPN group, the FC between the LSM and right cerebellar lobule VI was significantly correlated with fasting blood glucose levels (r = -0.490, p = 0.001), and that between the LSM and ACC was significantly correlated with the Montreal Cognitive Assessment score (r = 0.479, p = 0.001).ConclusionsPatients with T2DM may show abnormal motion-related visual perceptual function before the appearance of DPN. Importantly, DPN can influence the brain regions that maintain motion and motor control, and this effect is not limited to motor function, which may be the central neuropathological basis for diabetic peripheral neuropathy.

Insulin potential in preventing brain damage after traumatic brain injury: What we know.

Traumatic brain injury (TBI) is a major global cause of disability and mortality. TBI results in a spectrum of primary and secondary injuries that impact neural function and overall survival. Insulin, beyond its well-known role in regulating blood glucose levels, plays critical roles in the central nervous system (CNS). These roles include the modulation of synaptic plasticity, neurotransmitter levels, neurogenesis, and neuroprotection. Central insulin resistance, a reduced sensitivity to insulin in the brain, has been observed in TBI patients. This insulin resistance impairs insulin function in the brain and increases the risk of neurodegenerative processes. This review will delve into the central role of insulin resistance in the pathological changes observed after TBI and explore the potential benefits of insulin therapy as a treatment approach for TBI.

Antidiabetic activity of Inonotus obliquus water extract in alloxan-induced diabetic mice.

The Inonotus obliquus is a medicinal mushroom that grows on mature birch trees and is commonly used in traditional medicine for various ailments. The current study aimed to explore the hypoglycemic, hypolipidemic, and pancreatic protective effects of the water extract of Mongolian natural Inonotus obliquus on alloxan-induced diabetic mice. Alloxan monohydrate (200 mg/kg) was intraperitoneally single injected into C57BL/6 mice to induce diabetes. Alloxan-induced diabetic mice were orally given the water extract of inonotus obliquus (WEIO) at doses of 500 mg/kg and subcutaneously administered with insulatard 0.6 IU for 4weeks. Subsequently, the levels of factors related to blood glucose, insulin and lipids were assessed. WEIO significantly restored body weight, reduced fasting blood glucose levels, improved glucose tolerance ability, and increased insulin levels compared to the control diabetic mice. WEIO also enhanced cholesterol transportation in the liver, correlated with increased HDL-C levels and decreased TC, TG and LDL-C levels. Histologic examinations revealed that WEIO alleviated alloxan-induced pancreatic tissue damage. Natural Mongolian I. Obliquus water extracts have an antihyperglycemic effect and enhance islet cell function in alloxan-induced diabetic mice. It is a good candidate for a hypoglycemic functional food or medicine.

The Relationship between Dietary Habits and Type 2 Diabetes for Contribution to Health Promotion: Literature Review

Introduction: Type 2 Diabetes Mellitus (T2DM) is a chronic condition largely influenced by dietary habits and eating behaviors. Poor dietary choices, such as high consumption of refined sugars, unhealthy fats, and low intake of fiber, are well-established risk factors for the development of T2DM. The promotion of healthy eating behaviours and active lifestyles is essential to address the increasing prevalence of T2DM and improve public health. Objective: This study aimed to examine the impact of various dietary patterns and specific food intakes on the risk of T2DM, as well as the role of meal timing and dietary quality in influencing blood glucose levels and insulin sensitivity. Method: This research employs a literature review method by analyzing several relevant studies. The articles were sourced from Scopus and Google Scholar, using keywords such as "feeding behavior," "eating behavior," "feeding patterns," "food habits," "dietary habits," and "type 2 Diabetes," "diabetes Type 2," "type 2 diabetes mellitus," "diabetes mellitus type 2," and "T2DM." Result: The results of the article search revealed 13 articles from 2019-2024 that matched the criteria set. The results showed that Eating habits have a significant effect on the risk of developing Type 2 Diabetes Mellitus (T2DM). Poor food choices and irregular eating patterns increase the risk. Conclusion: The paper highlights the significant impact of dietary habits and eating behaviors on the development and progression of Type 2 Diabetes Mellitus. It emphasises the importance of healthy food choices and regular eating patterns in managing blood glucose levels and insulin sensitivity. These insights could contribute to designing an effective health promotion program.