Assessing the potential fasting and postprandial mechanisms involved in the acute hypoglycemic and anti-hyperglycemic effects of four selected plants from Iran used in traditional Persian medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. MATERIALS AND METHODS: The effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. RESULTS: In the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90-97% and 80-91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. CONCLUSIONS: The present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.

The association of isocarbophos and isofenphos with different types of glucose metabolism: The role of inflammatory cells.

To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.

Association between stress hyperglycemia ratio and all-cause mortality in critically ill patients with atrial fibrillation: insights from a MIMIC-IV study.

Background: The stress hyperglycemia ratio (SHR) has emerged as a potential prognostic indicator for various critical illnesses. However, its role in determining outcomes in patients with atrial fibrillation (AF) within the intensive care unit (ICU) remains unclear. This study aimed to elucidate the association between SHR and all-cause mortality in this clinical setting. Methods: We conducted a retrospective cohort study utilizing data from a large, retrospective database. Critically ill patients with documented AF were stratified based on quartiles of SHR. The primary outcome was 365-day all-cause mortality, with secondary outcomes including 90-day and 28-day mortality. COX proportional hazards models adjusted for confounders and Kaplan-Meier curve analyses were used to explore the relationship between SHR and mortality. Results: 2,679 patients with critical AF were enrolled in the final study. Among the patients studied, those in the highest SHR quartiles exhibited an increased risk of 365-day all-cause mortality (HR:1.32, 95%CI=1.06-1.65). Notably, in subgroup analyses, the prognostic value of SHR was particularly pronounced in patients with hypertension. Sensitivity analyses confirmed the persistence of these findings after excluding cohorts with malignant tumors, and heart failure. Conclusions: Our research discerns a positive association between SHR and all-cause mortality in critically ill patients with AF, highlighting the significance of acute glycemic dysregulation on patient outcomes. Longer follow-up is still needed in the future to study the association between SHR and all-cause mortality in critically ill patients with AF.

Cross-sectional comparison of the association between three different insulin resistance surrogates and frailty: NHANES 1999-2018.

Background: The correlation between various insulin resistance surrogates and frailty remains under investigation in the scientific community. Methods: Data from NHANES (1999-2018) were used. We utilized weighted binary logistic regression, trend tests, RCS analysis, and subgroup analysis to comprehensively assess the link between METS-IR, HOMA-IR, and TyG, and frailty risk. Results: The results revealed a significant positive association between high levels of METS-IR, HOMA-IR, and TyG with the risk of frailty in all models. Notably, in model 4, the highest quintile of METS-IR showed the strongest link (OR: 2.960, 95% CI: 2.219-3.949), with HOMA-IR (OR: 2.522, 95% CI: 1.927-3.301) following closely behind. Trend tests revealed a positive trend between METS-IR, HOMA-IR, and TyG with the risk of frailty (P for trend < 0.05). RCS analysis showed a linear relationship between METS-IR and the risk of frailty (P for nonlinearity > 0.05). In contrast, HOMA-IR and TyG exhibited a U-shaped nonlinear relationship (P for nonlinearity < 0.05). Conclusion: The research identified a linear association between METS-IR and frailty risk, whereas HOMA-IR and TyG displayed a U-shaped, nonlinear relationship pattern with the risk of frailty. Among the varying levels examined, the linkage between METS-IR and frailty was most pronounced in the top quintile.

Relationships between sensory processing patterns and metabolic risk factors among community dwelling people with metabolic syndrome: A cross-sectional and correlational research design.

BACKGROUND: Metabolic Syndrome (MetS) increases the risk of other serious health problems, particularly cardiovascular diseases and stroke. Sensory processing patterns (SPPs) are internal factors shaping behaviors and emotions, both healthy and unhealthy. There is a lack of studies directly examining the relationship between the SPPs and metabolic risk factors. METHOD: This study aimed to investigate SPPs and their association with metabolic risk factors in individuals with metabolic syndrome (MetS). One hundred and seventeen individuals with MetS completed questionnaires on demographic characteristics and the Thai Sensory Patterns Assessment-adult version. Data on metabolic risk factors, including fasting blood glucose, blood pressure, and waist circumference, were collected. RESULTS: The findings revealed high arousal levels in proprioceptive and auditory senses among the participants. The fasting blood glucose was significantly correlated with a preference in the tactile sense (r = -0.150, P<0.05), while waist circumference was associated with arousal level in the auditory and smell-taste senses (r = 0.140, -0.160, P<0.05). Moreover, the GLMM revealed that fasting blood glucose was associated with preferences in tactile, vestibular, and proprioceptive senses (r = -0.481, 0.726, -0.386, P<0.05). Furthermore, diastolic blood pressure was associated with preferences in vestibular sense (r = 0.099; P<0.05). CONCLUSION: The SPPs might be related to metabolic risk factors, so it is important to recognize how individual SPPs relate to metabolic risk factors. However, further studies using a larger sample may be needed to deeply explore the mechanisms underlying these associations.

Preserving insulin function in diabetes: a case report.

BACKGROUND: This case report explores the long-term dynamics of insulin secretion and glycemic control in two patients with diabetes mellitus type 2 over 20 years. The observations underscore the impact of lifestyle interventions, including weight loss and calorie restriction, on insulin secretion patterns and glucose levels during 75 g oral glucose tolerance tests. Additionally, the role of hemoglobin A1c fluctuations, influenced by various factors such as body weight, exercise, and pharmacological interventions, is investigated. CASE PRESENTATION: Case 1 involves a Japanese woman now in her late 70s who successfully maintained her hemoglobin A1c below 7% for over two decades through sustained weight loss and lifestyle changes. Despite a gradual decline in the homeostasis model assessment of ß cell function, the patient exhibited remarkable preservation of insulin secretion patterns over the 20-year follow-up. In case 2, a Japanese woman, now in her early 70s, experienced an improvement in hemoglobin A1c to 6.3% after a period of calorie limitation due to a wrist fracture in 2018. This incident seemed to trigger a temporary rescue of pancreatic ß cell function, emphasizing the dynamic nature of insulin secretion. Both cases highlight the potential for pancreatic ß cell rescue and underscore the persistence of insulin secretion over the 20-year follow-up. Additionally, we have briefly discussed three additional cases with follow-ups ranging from 10 to 17 years, demonstrating similar trends in glucose and insulin ratios. CONCLUSIONS: Long-term lifestyle interventions, such as weight loss and calorie restriction, can preserve pancreatic ß cell function and maintain glycemic control in type 2 diabetes patients over 20 years. Two patients showed stable or improved insulin secretion and favorable hemoglobin A1c levels, challenging the traditional view of irreversible ß cell decline. The findings highlight the importance of personalized, nonpharmacological approaches, suggesting that sustained lifestyle changes can significantly impact diabetes management and potentially rescue ß cell function.

Associations between different insulin resistance indices and the risk of all-cause mortality in peritoneal dialysis patients.

BACKGROUND: Insulin resistance (IR) is prevalent in individuals undergoing peritoneal dialysis (PD) and is related to increased susceptibility to coronary artery disease and initial peritonitis. In recent investigations, correlations have been found between indices of IR and the incidence of all-cause mortality in various populations. However, such correlations have not been detected among individuals undergoing PD. Hence, the present study's aim was to explore the connections between IR indices and the incidence of all-cause mortality in PD patients. METHODS: Peritoneal dialysis patients (n = 1736) were recruited from multiple PD centres between January 2010 and December 2021. Cox proportional hazards and restricted cubic spline regression models were used to evaluate the connections between the triglyceride-glucose (TyG) index, triglyceride-glucose/body mass index (TyG-BMI), and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and the occurrence of all-cause mortality. All three IR indices were integrated into the same model to assess the predictive stability. Furthermore, a forest plot was employed to display the findings of the subgroup analysis of PD patients. RESULTS: Overall, 378 mortality events were recorded during a median follow-up time of 2098 days. Among PD patients, a higher TyG index, TyG-BMI, and TG/HDL-C ratio were identified as independent risk factors for all-cause mortality according to Cox proportional hazards analyses (hazard ratio (HR) 1.588, 95% confidence interval (CI) 1.261-2.000; HR 1.428, 95% CI 1.067-1.910; HR 1.431, 95% CI 1.105-1.853, respectively). In a model integrating the three IR indices, the TyG index showed the highest predictive stability. According to the forest plot for the TyG index, no significant interactions were observed among the subgroups. CONCLUSION: Significant associations were found between the TyG index, TyG-BMI, and TG/HDL-C ratio and the incidence of all-cause mortality among PD patients. The TyG index may be the most stable of the three surrogate IR markers. Finally, a correlation was identified between IR and the risk of all-cause mortality in patients undergoing PD.

Preclinical modeling of metabolic syndrome to study the pleiotropic effects of novel antidiabetic therapy independent of obesity.

Cardiovascular-kidney-metabolic health reflects the interactions between metabolic risk factors, chronic kidney disease, and the cardiovascular system. A growing body of literature suggests that metabolic syndrome (MetS) in individuals of normal weight is associated with a high prevalence of cardiovascular diseases and an increased mortality. The aim of this study was to establish a non-invasive preclinical model of MetS in support of future research focusing on the effects of novel antidiabetic therapies beyond glucose reduction, independent of obesity. Eighteen healthy adult Beagle dogs were fed an isocaloric Western diet (WD) for ten weeks. Biospecimens were collected at baseline (BAS1) and after ten weeks of WD feeding (BAS2) for measurement of blood pressure (BP), serum chemistry, lipoprotein profiling, blood glucose, glucagon, insulin secretion, NT-proBNP, angiotensins, oxidative stress biomarkers, serum, urine, and fecal metabolomics. Differences between BAS1 and BAS2 were analyzed using non-parametric Wilcoxon signed-rank testing. The isocaloric WD model induced significant variations in several markers of MetS, including elevated BP, increased glucose concentrations, and reduced HDL-cholesterol. It also caused an increase in circulating NT-proBNP levels, a decrease in serum bicarbonate, and significant changes in general metabolism, lipids, and biogenic amines. Short-term, isocaloric feeding with a WD in dogs replicated key biological features of MetS while also causing low-grade metabolic acidosis and elevating natriuretic peptides. These findings support the use of the WD canine model for studying the metabolic effects of new antidiabetic therapies independent of obesity.

Higher fasting glucose is associated with poorer survival in non-diabetic subjects having ischemia with non-obstructive coronary arteries.

Subjects who have ischemia with non-obstructive coronary arteries (INOCA) experience angina pectoris with evidence of myocardial ischemia but without coronary stenosis. Few studies have investigated factors associated with its survival, especially insulin resistance. In this study, subjects with angina pectoris, without known diabetes mellites (DM), and with non-invasive tests showing myocardial ischemia were admitted for coronary angiography (CAG). Those whose CAG did not reveal stenosis and agreed to receive an oral glucose tolerance test (OGTT) 2 weeks after hospital discharge were enrolled for analysis. All-cause mortality was recorded, which served as the outcome of the study. A total of 587 subjects with INOCA, without known DM, and with OGTT data were analyzed. After OGTT and HbA1c tests, 86 subjects (14.7%) were newly diagnosed with DM and 59.8% had pre-DM. The median duration of follow-up was 7.03 years. Thirty-nine subjects died during the follow-up period. The incidence rate of mortality was 9.9 /1000 person-year. Those who died had a higher fasting glucose (101 ± 17 vs. 94 ± 13 mg/dl, p = 0.003) but a lower estimated glomerular filtration rate (eGFR) (54 ± 22 vs. 87 ± 30 ml/min, p < 0.001). In the Cox survival analysis, a higher fasting glucose (hazard ratio 1.053, p = 0.007) was associated with worse mortality for INOCA without DM (N = 501). On the contrary, a higher eGFR (hazard ratio 0.967, p = 0.012) was protective of better survival for non-diabetic INOCA (N = 501). In conclusion, for non-diabetic INOCA, higher fasting glucose was associated with worse mortality and higher eGFR was protective for better survival.

Association of atherogenic index of plasma and triglyceride glucose-body mass index and sarcopenia in adults from 20 to 59: a cross-sectional study.

Background: The relationship between atherogenic index of plasma (AIP) and triglyceride glucose-body mass index (TyG-BMI) and sarcopenia has not been studied in the United States (US) population. Methods: This research included 4,835 people from the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018. The relationship between sarcopenia and TyG-BMI, as well as the AIP index, was examined through the utilization of restricted cubic spline (RCS) analysis, subgroup analysis, and multivariate logistic regression analysis. Diagnostic value of AIP and TyG-BMI for sarcopenia was compared by receiver operating characteristic (ROC) curves. Results: In this research, 428 people with sarcopenia were identified among the 4,835 subjects that were included in the experiment. AIP and sarcopenia were positively associated with an odds ratio (OR) of 1.58 and a 95% confidence interval (CI) of (1.07, 2.34) on fully adjusted multivariate logistic regression analysis. Similarly, TyG-BMI and sarcopenia were positively associated with an OR of 8.83 and a 95% CI of (5.46, 14.26). AIP and sarcopenia had a non-linear positive connection (P-value<0.001, P-Nonlinear=0.010), while TyG-BMI and sarcopenia had a linear positive correlation (P-value<0.001, P-Nonlinear=0.064), according to RCS analysis. Subgroup analyses showed a significant interaction between TyG-BMI and sarcopenia due to gender (P = 0.023). ROC curves showed that TyG-BMI (AUC:0.738, 95% CI: 0.714 - 0.761) was more useful than AIP (AUC:0.648, 95% CI: 0.622 - 0.673) in diagnosing sarcopenia. Conclusion: In US adults aged 20-59 years, our study revealed a correlation between elevated AIP and TyG-BMI levels and heightened sarcopenia risk. Moreover, TyG-BMI has better diagnostic validity than AIP.

Mice lacking ASIC2 and ßENaC are protected from high-fat-diet-induced metabolic syndrome.

Introduction: Degenerin proteins, such as ßENaC and ASIC2, have been implicated in cardiovascular function. However, their role in metabolic syndrome have not been studied. To begin to assess this interaction, we evaluated the impact of a high fat diet (HFD) on mice lacking normal levels of ASIC2 (ASIC2-/-) and ßENaC (ßENaCm/m). Methods: Twenty-week-old male and female mice were placed on a 60% HFD for 12 weeks. Body weight was measured weekly, and body composition by non-invasive ECHO MRI and fasting blood glucose were measured at 0, 4, 8 and 12 weeks. A glucose tolerance test was administered after 12 weeks. Differences between ASIC2-/-/ßENaCm/m and WT groups were compared using independent t-tests or ANOVA where appropriate within each sex. Data are presented as mean ± SEM and ASIC2-/-/ßENaCm/m vs. WT. Results: At 20 weeks of age, ASIC2-/-/ßENaCm/m mice (n=9F/10M) weighed less and gained less weight than WT (n=12F/16M). Total body fat and lean body masses were reduced in female and male ASIC2-/-/ßENaCm/m mice. Total body fat and lean body masses as % control were identical at the end of 12 weeks. Fasting blood glucoses were lower in female and male ASIC2-/-/ßENaCm/m vs. WT mice after 12 weeks HFD. The area under the curve for the glucose tolerance test was reduced in female and tended (p=.079) to decrease in male ASIC2-/-/ßENaCm/m. Plasma leptin and insulin were reduced in female and male ASIC2-/-/ßENaCm/m vs. WT mice. Plasma insulin in female ASIC2-/-/ßENaCm/m mice remained unchanged throughout the HFD period. Liver and liver fat masses, as well as percent liver fat, were reduced in both female and male ASIC2-/-/ßENaCm/m mice after HFD. Plasma triglycerides, cholesterol, LDL- and HDL-cholesterols were markedly improved in male and/or female ASIC2-/-/ßENaCm/m following the HFD. Discussion: These novel findings suggest that loss of ASIC2 and ßENaC offer a significant protection against HFD-induced metabolic syndrome.

Exploring the Effect of Exercise versus Metformin on Insulin Resistance amongst Nigerians with Pre-diabetes: A Randomised Controlled Trial.

BACKGROUND: Pre-diabetes is an important risk factor for the development of type 2 diabetes and is common in Nigeria. Effective intervention can reverse the underlying pathogenesis of insulin resistance in pre-diabetes. This study aimed to determine and compare the impact of moderate exercise and metformin interventions on insulin resistance among participants with pre-diabetes. MATERIALS AND METHODS: Using a randomised placebo-controlled design, 54 Nigerians with pre-diabetes were selected using simple random sampling. They were offered metformin, moderate exercise or placebo treatment and followed up for 12 weeks. Insulin resistance was assessed before and after the interventions and the outcome was compared. RESULTS: Forty-nine participants with pre-diabetes completed the study. Participants in both the exercise and metformin groups had significantly decreased insulin resistance compared to placebo after 12 weeks of intervention. However, there was a decrease in insulin resistance by 77.3% (homeostasis model assessment-insulin resistance [HOMA-IR]) and an increase in insulin sensitivity by 81.2% (quantitative insulin sensitivity check index [QUICKI]) in the exercise group. In comparison, participants in the metformin group had a decrease in insulin resistance by 66.3% (HOMA-IR) and an increase in insulin sensitivity by 76.2% (QUICKI). CONCLUSION: Amongst Nigerians with pre-diabetes, both moderate exercise and metformin have significantly higher efficacy than placebo in improving insulin resistance. However, moderate exercise improved insulin resistance more than the metformin intervention. Participants in this study need to be followed up for a longer period to assess the long-term effects of these interventions.

Non-linear relationship between TyG index and the risk of prediabetes in young people: a 5-year retrospective cohort study in Chinese young adults.

Objective: Given the limited evidence on the relationship between the triglyceride-glucose (TyG) index and the risk of prediabetes among young adults, our study aimed to investigate the potential impact of the TyG index on the future development of prediabetes in young individuals. Methods: This retrospective cohort study included 125,327 healthy adults aged 20 to 45 years. We utilized Cox proportional hazards regression models, combined with cubic spline functions and smooth curve fitting, to assess the relationship between baseline TyG index and the risk of prediabetes among young adults, exploring its non-linear association. A series of sensitivity analyses and subgroup analyses were conducted to ensure the robustness of our findings. Results: After adjusting for covariates, the study found a positive correlation between the TyG index and the risk of prediabetes (HR=1.81, 95%CI: 1.54-2.13, p<0.0001). The risk of prediabetes increased progressively across quartiles of the TyG index (Q1 to Q4), with Q4 showing a significantly higher risk compared to Q1 (adjusted HR=2.33, 95% CI=1.72-3.16). Moreover, a non-linear relationship was identified between the TyG index and the risk of prediabetes, with an inflection point at 9.39. To the left of the inflection point, the HR was 2.04 (95% CI: 1.69 to 2.46), while to the right, the HR was 0.89 (95% CI: 0.48 to 1.65). Conclusion: Our study reveals a non-linear relationship and a saturation effect between the TyG index and the development of prediabetes among young individuals in China, with an inflection point at 9.39. Understanding this non-linear relationship can assist clinicians in identifying young individuals at high risk and implementing targeted interventions to reduce their risk of progressing to diabetes.

Uncovering novel regulatory variants in carbohydrate metabolism: a comprehensive multi-omics study of glycemic traits in the Indian population.

Clinical biomarkers such as fasting glucose, HbA1c, and fasting insulin, which gauge glycemic status in the body, are highly influenced by diet. Indians are genetically predisposed to type 2 diabetes and their carbohydrate-centric diet further elevates the disease risk. Despite the combined influence of genetic and environmental risk factors, Indians have been inadequately explored in the studies of glycemic traits. Addressing this gap, we investigate the genetic architecture of glycemic traits at genome-wide level in 4927 Indians (without diabetes). Our analysis revealed numerous variants of sub-genome-wide significance, and their credibility was thoroughly assessed by integrating data from various levels. This identified key effector genes, ZNF470, DPP6, GXYLT2, PITPNM3, BEND7, and LORICRIN-PGLYRP3. While these genes were weakly linked with carbohydrate intake or glycemia earlier in other populations, our findings demonstrated a much stronger association in the Indian population. Associated genetic variants within these genes served as expression quantitative trait loci (eQTLs) in various gut tissues essential for digestion. Additionally, majority of these gut eQTLs functioned as methylation quantitative trait loci (meth-QTLs) observed in peripheral blood samples from 223 Indians, elucidating the underlying mechanism of their regulation of target gene expression. Specific co-localized eQTLs-meth-QTLs altered the binding affinity of transcription factors targeting crucial genes involved in glucose metabolism. Our study identifies previously unreported genetic variants that strongly influence the diet-glycemia relationship. These findings set the stage for future research into personalized lifestyle interventions integrating genetic insights with tailored dietary strategies to mitigate disease risk based on individual genetic profiles.

A hybrid Transformer-LSTM model apply to glucose prediction.

The global prevalence of diabetes is escalating, with estimates indicating that over 536.6 million individuals were afflicted by 2021, accounting for approximately 10.5% of the world's population. Effective management of diabetes, particularly monitoring and prediction of blood glucose levels, remains a significant challenge due to the severe health risks associated with inaccuracies, such as hypoglycemia and hyperglycemia. This study addresses this critical issue by employing a hybrid Transformer-LSTM (Long Short-Term Memory) model designed to enhance the accuracy of future glucose level predictions based on data from Continuous Glucose Monitoring (CGM) systems. This innovative approach aims to reduce the risk of diabetic complications and improve patient outcomes. We utilized a dataset which contain more than 32000 data points comprising CGM data from eight patients collected by Suzhou Municipal Hospital in Jiangsu Province, China. This dataset includes historical glucose readings and equipment calibration values, making it highly suitable for developing predictive models due to its richness and real-time applicability. Our findings demonstrate that the hybrid Transformer-LSTM model significantly outperforms the standard LSTM model, achieving Mean Square Error (MSE) values of 1.18, 1.70, and 2.00 at forecasting intervals of 15, 30, and 45 minutes, respectively. This research underscores the potential of advanced machine learning techniques in the proactive management of diabetes, a critical step toward mitigating its impact.

Impact of blood glucose on cognitive function in insulin resistance: novel insights from ambulatory assessment.

BACKGROUND/OBJECTIVES: Insulin resistance (IR)-related disorders and cognitive impairment lead to reduced quality of life and cause a significant strain on individuals and the public health system. Thus, we investigated the effects of insulin resistance (IR), and blood glucose fluctuations on cognitive function under laboratory and free-living conditions, using ecological momentary assessment (EMA). SUBJECTS/METHODS: Baseline assessments included neuropsychological tests and blood analysis. Individuals were classified as either insulin-sensitive (<2) or insulin-resistant (≥2), based on their Homeostatic Model Assessment (HOMA-IR) values. Continuous glucose monitoring (CGM) using a percutaneous sensor was performed for 1 week. Using multiple linear regression, we examined the effects of HOMA-IR and CGM metrics on cognitive domains. Working memory (WM) performance, which was assessed using EMA, 4 times a day for 3 consecutive days, was matched to short-term pre-task CGM metrics. Multilevel analysis was used to map the within-day associations of HOMA-IR, short-term CGM metrics, and WM. RESULTS: Analyses included 110 individuals (mean age 48.7 ± 14.3 years, 59% female, n = 53 insulin-resistant). IR was associated with lower global cognitive function (b = -0.267, P = 0.027), and WM (b = -0.316; P = 0.029), but not with executive function (b = -0.216; P = 0.154) during baseline. EMA showed that higher HOMA-IR was associated with lower within-day WM performance (ß = -0.20, 95% CI -0.40 to -0.00). CGM metrics were not associated with cognitive performance. CONCLUSIONS: The results confirm the association between IR and decrements in global cognitive functioning and WM, while no effects of CGM metrics were observed, making IR a crucial time point for intervention. Targeting underlying mechanisms (e.g., inflammation) in addition to glycemia could be promising to minimize adverse cognitive effects. Registered under https://drks.de/register/de identifier no. DRKS00022774.

Blood PAI-1 and cardiovascular and metabolic risk factors among the middle-aged women from SWAN study.

The research on the role of plasminogen activator inhibitor-1 (PAI-1) in cardiovascular and metabolic diseases is insufficient. We aimed to explore whether elevated blood PAI-1 levels are significantly related to increased cardiovascular and metabolic risk factors in a midlife women population. Data were obtained from baseline characteristics in Study of Women's Health Across the Nation (SWAN) study. Multivariable linear regression models were performed to examine for the trends of associations between PAI-1 and cardiovascular and metabolic risk factors (systolic BP, diastolic BP, fasting blood glucose, insulin, HDL-C, LDL-C, TG and TC), respectively. Smooth curve demonstrated gradual upward trends on associations of blood PAI-1 levels with LDL-C, TG, TC, fasting blood glucose, insulin, systolic BP and diastolic BP (all P < 0.05) and a gradual downward trend of PAI-1 levels with HDL-C (P < 0.05). Multivariable linear regression models still indicated that increased blood PAI-1 levels were associated with higher cardiovascular and metabolic risk after confounding factors including age, race/ethnicity, ever smoked regularly, alcohol in last 24 h, menopausal status, total family income and BMI were controlled for. Moreover, we observed that the independent associations between blood levels of PAI-1 and cardiovascular and metabolic risk factors examined by stratified analysis were not influenced by age, smoking status, menopausal status and BMI, respectively. Our analysis showed that increased blood PAI-1 levels were associated with higher level for cardiovascular and metabolic risk factors which mainly causes to higher possibility of cardio-cerebrovascular diseases in a large-sample midlife women subjects.

Triglyceride-glucose index correlates with the occurrence and prognosis of acute myocardial infarction complicated by cardiogenic shock: data from two large cohorts.

BACKGROUND: Triglyceride-glucose (TyG) index, a dependable indicator of insulin resistance, has been identified as a valid marker regarding multiple cardiovascular diseases. Nevertheless, the correlation of TyG index with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains uncertain. Our study aims for elucidating this relationship by comprehensively analyzing two large-scale cohorts. METHODS: Utilizing records from the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care IV, the link between TyG and the incidence and prognosis of AMICS was assessed multicentrally and retrospectively by logistic and correlation models, as well as restricted cubic spline (RCS). Propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting (OW) were employed to balance the potential confounders. Subgroup analyses were performed according to potential modifiers. RESULTS: Overall, 5208 AMI patients, consisting of 375 developing CS were finally included. The TyG index exhibited an apparently higher level in AMI populations developing CS than in those who did not experienced CS [9.2 (8.8-9.7) vs. 9.0 (8.5-9.5)], with a moderate discrimination ability to recognize AMICS from the general AMI (AUC: 0.604). Logistic analyses showed that the TyG index was significantly correlated with in-hospital and ICU mortality. RCS analysis demonstrated a linear link between elevated TyG and increased risks regarding in-hospital and ICU mortality in the AMICS population. An increased mortality risk remains evident in PSM-, OW- and IPTW-adjusted populations with higher TyG index who have undergone CS. Correlation analyses demonstrated an apparent link between TyG index and APS score. Subgroup analyses presented a stable link between elevated TyG and mortality particularly in older age, females, those who are overweight or hypertensive, as well as those without diabetes. CONCLUSIONS: Elevated TyG index was related to the incidence of CS following AMI and higher mortality risks in the population with AMICS. Our findings pointed a previously undisclosed role of TyG index in regard to AMICS that still requires further validation.