Association between the triglyceride glucose index and short-term mortality in septic patients with or without obesity: a retrospective cohort study.

BACKGROUND: Sepsis is a significant contributor to both intensive care unit (ICU) admissions and mortality among patients in ICU, with a rising prevalence of obesity. There is a lack of extensive research on the correlation between TyGI and findings in patients with sepsis, especially in obese patients. METHODS: This study used a retrospective cohort design and included patients with sepsis (≥18 years) from the Medical Information Mart for Intensive Care IV database. The association between TyGI and outcome was examined using multivariable logistic regression analysis. RESULTS: 8,840 patients with sepsis were included in the analysis. The in-ICU mortality rate was 9.7%. Non-survivors exhibited significantly greater TyGI levels than survivors [9.19(8.76-9.71) vs. 9.10(8.67-9.54), p < 0.001]. The adjusted multivariate regression model showed that elevated TyGI values were linked to a greater likelihood of death in ICU (odds ratio [OR] range 1.072-1.793, p < 0.001) and hospital (OR range 1.068-1.445, p = 0.005). Restricted Cubic Spline analysis revealed a nonlinear association between TyGI and in-ICU and in-hospital mortality risks within specified ranges. Subgroup analysis revealed interaction effects in the general obesity, abdominal obesity, and impaired fasting glucose subgroups (p = 0.014, 0.016, and < 0.001, respectively). CONCLUSION: TyGI was associated with an increased sepsis-related short-term mortality risk and adverse outcomes after ICU admission.

A moderately higher time-in-range threshold improves the prognosis of type 2 diabetes patients complicated with COVID-19.

Objective: After fully lifting coronavirus disease 2019 (COVID-19) pandemic control measures in mainland China in 12/2022, the incidence of COVID-19 has increased markedly, making it difficult to meet the general time-in-range (TIR) requirement. We investigated a more clinically practical TIR threshold and examined its association with the prognosis of COVID-19 patients with type 2 diabetes(T2D). Research design and methods: 63 T2D patients complicated with COVID-19 were evaluated. Patients were divided into favorable outcome group and adverse outcome group according to whether achieving composite endpoint (a >20-day length of stay, intensive care unit admission, mechanical ventilation use, or death). TIR, the time-below-range (TBR) and the time-above-range (TAR) were calculated from intermittently scanned continuous glucose monitoring. Logistic regression analysis and other statistical methods were used to analyze the correlation between glucose variability and prognosis to establish the appropriate reference range of TIR. Results: TIR with thresholds of 80 to 190 mg/dL was significantly associated with favorable outcomes. An increase of 1% in TIR is connected with a reduction of 3.70% in the risk of adverse outcomes. The Youden index was highest when the TIR was 54.73%, and the sensitivity and specificity were 58.30% and 77.80%, respectively. After accounting for confounding variables, our analysis revealed that threshold target ranges (TARs) ranging from 200 mg/dL to 230 mg/dL significantly augmented the likelihood of adverse outcomes. Conclusion: The TIR threshold of 80 to 190 mg/dL has a comparatively high predictive value of the prognosis of COVID-19. TIR >54.73% was associated with a decreased risk of adverse outcomes. These findings provide clinically critical insights into possible avenues to improve outcomes for COVID-19 patients with T2D.

Perceptions of Emerging Adults With Type 1 Diabetes Mellitus on How the Condition Influences Sleep Quality: A Qualitative Study.

Background: Emerging adulthood is a phase characterized by exploration which potentially affecting sleep quality. While many emerging adults are healthy, the effects of chronic diseases such as Type 1 Diabetes Mellitus (T1DM) on sleep may be underestimated. Considering the frequency of nocturnal glycemic alterations that cause awakenings, this study explored the perceptions of emerging adults in Andalusia on the influence of T1DM on their sleep quality. Methods: A qualitative approach was used for this study. Purposive sampling through diabetes associations was initially utilized, supplemented by snowball sampling, in order to conduct semistructured interviews with 73 emerging adults (aged 18-29) diagnosed with T1DM, to explore their perceptions of the influence of T1DM on sleep quality. Interpretative Phenomenological Analysis was used for data analysis. Results: Sleep disruptions caused by overnight hyperglycemia and hypoglycemia were identified as significant factors. However, 62% of participants did not perceive the influence of diabetes on their sleep quality, despite experiencing frequent overnight glycemic alterations (reported by 40.9%). Conclusions: Perception of the impact of T1DM on sleep quality does not always align with the frequency of disruptions. Nonetheless, promoting healthy sleep and systematically assessing sleep quality can benefit both sleep and glycemic outcomes, regardless of individual perceptions.

Prevalence of type 2 diabetes mellitus and hypertension in patient's visiting the conservative dentistry and endodontics department: a cross-sectional study in Surabaya City.

Background: This descriptive cross-sectional study focuses on the prevalence of hypertension (HTN) and type 2 diabetes mellitus (T2DM) amongst patients who visited the Conservative Dentistry and Endodontics department. Recognizing these incidence statistics is critical for improving endodontic therapy delivery and assuring high-quality dental care with positive treatment outcomes. Methods: In advance of getting dental care, all patients visiting the department were advised to get their blood sugar and blood pressure levels checked at random. Measurements were taken with digital equipment, and individuals with high levels were encouraged to seek medical advice before undergoing dental procedures. The obtained data was imported into Excel and analyzed with IBM SPSS software (version 21). Results: The investigation had 1,100 participants (55.8% female and 44.2% male), with an average age of 44.58 ± 12.77 years. Of the individuals, 40.6% were referred for type 2 diabetes, 12.6% for hypertension, and 24.0% for both diseases. There was a significant correlation (p < 0.05) between referral status and gender. The average blood pressure and random blood sugar readings were 141.02 mmHg ± 56.28 mmHg (systolic), 79.83 mmHg ± 10.68 mmHg (diastolic), and 126.68 mg/dL ± 15.36 mg/dL, respectively. There was a substantial (p < 0.05) difference in mean systolic blood pressure between men and women. Furthermore, age was strongly connected with random blood sugar levels (p < 0.05) and systolic and diastolic blood pressure (p < 0.05). There were significant (p < 0.05) variations in mean blood pressure and blood sugar levels between referred and non-referred individuals. Conclusion: Age had a relationship with higher random blood sugar levels, systolic blood pressure, and diastolic blood pressure. Dentists should consider patient age while planning treatment, as type 2 diabetes mellitus and hypertension require unique techniques to emphasize patient safety and produce excellent outcomes.

ALLOPURINOL TREATMENT IMPROVES INSULIN RESISTANCE IN NON-DIABETIC PATIENTS WITH RENAL STONE.

Hyperuricemia is an objective risk factor of derangement of fasting serum glucose and type 2 diabetes (T2D), yet whether hyperuricemia has a causative influence on insulin resistance is still debatable. In this study, we tested the hypothesis that lowering uric acid in hyperuricemic nondiabetic subjects might improve insulin resistance. Patients with renal stone and hyperuricemia (n=15) were recruited from the private clinic of Ib-Sina Local Teaching Hospital in Mosul city and prospectively placed on allopurinol (300mg/day) for 6 months. Serum uric acid (SUA), fasting serum glucose (FSG), fasting insulin, and C-peptide were measured using commercial kits. Results confirmed that allopurinol has significantly (P<0.05) reduced c-peptide and insulin together with a non-significant (p>0.05) reduction of serum glucose levels. In conclusion, allopurinol has improved insulin level and glycemic control in a healthy individual, these findings could be used as a template for using allopurinol in diabetic patients to improve glycemic control or future studies could be directed toward structural modification of allopurinol which hopefully might lead to innovation of new antidiabetic drugs.

GENDER DIFFERENCES IN THYROIDECTOMY-INDUCED WEIGHT LOSS AND IMPAIRED GLUCOSE LEVELS: ROLE OF L-THYROXINE.

Thyroxine, a key regulator of metabolic pathways, plays a pivotal role in glucose metabolism and the maintenance of glucose homeostasis. In clinical practice, L-thyroxine replacement therapy is commonly prescribed for patients with hypothyroidism. However, the specific effects of L-thyroxine and thyroidectomy (TX) on glucose levels remain an area of interest and investigation. In this study, 20 rats were divided into two groups (n=10 per group). The TX group (male and female rats) underwent thyroidectomy for 4 weeks. After 4 weeks, male and female thyroidectomized rats received L-thyroxine (10 µg/100 g/day, intraperitoneally) for 4 weeks. The rats' weights were monitored weekly post-surgery. Compared to the initial level, thyroidectomy resulted in weight loss, whereas L-thyroxine replacement therapy normalized the weight loss induced by thyroidectomy. Additionally, thyroidectomy led to impaired glucose levels, which were restored to normal levels with L-thyroxine treatment. These findings underscore the impact of thyroid function on glucose metabolism and highlight the potential therapeutic role of L-thyroxine.

INfluenza VaccInation To mitigate typE 1 Diabetes (INVITED): a study protocol for a randomised, double-blind, placebo-controlled clinical trial in children and adolescents with recent-onset type 1 diabetes.

INTRODUCTION: Children and adolescents with recent-onset type 1 diabetes (T1D) commonly maintain a certain level of insulin production during the remission phase, which can last months to years. Preserving ß-cell function can reduce T1D complications and improve glycaemic control. Influenza vaccination has pleiotropic effects and administration of the vaccine during the early phases of T1D may offer ß-cell protection. This study aims to assess the effect of influenza vaccination on preserving ß-cell function in children and adolescents with recent-onset T1D. METHODS AND ANALYSIS: The INfluenza VaccInation To mitigate typE 1 Diabetes trial is a randomised, double-blind, placebo-controlled, multicentre trial in paediatric patients with recent-onset T1D aged 7-17 years. 100 participants will be randomised in a 1:1 ratio to receive either a standard inactivated quadrivalent influenza vaccine or a placebo within 14 days of diagnosis. The primary outcome is a difference in mean change (from baseline to 12 months) in C-peptide level between groups during a 2-hour mixed-meal tolerance test. Secondary outcomes include mean change (from baseline to 6 months) in C-peptide levels, haemoglobin A1c, ambulatory glucose profiles and insulin requirements. Exploratory outcomes are diabetes-related autoantibodies, inflammatory markers and serum haemagglutinin inhibition antibody titres against the influenza viruses. The current treatment for T1D is largely symptomatic, relying on insulin administration. There is a pressing need for novel pharmacological approaches aimed at modulating the immune system to preserve residual ß-cell function. Existing immunotherapies are cost-prohibitive and associated with multiple side effects, whereas influenza vaccination is inexpensive and generally well tolerated. A positive outcome of this study holds potential for immediate implementation into standard care for children and adolescents with recent-onset T1D and may guide future research on immune modulation in T1D. ETHICS AND DISSEMINATION: Ethical approval was obtained from Danish Health Authorities prior to participant enrollment. The trial results will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05585983 and EudraCT Number 2022-500906-17-01.

[Expert consensus on stroke prevention and blood glucose management in patients with type 2 diabetes].

Abnormal glucose metabolism is closely related to stroke and has adverse effects on the occurrence, development, and prognosis of stroke. Ideal glycemic control is of great significance in improving the prognosis of stroke. Some hypoglycemic drugs can reduce the risk of stroke occurrence and recurrence in patients with type 2 diabetes. Furthermore, such patients with stroke should strengthen their blood pressure and blood lipid control and use antiplatelet drugs reasonably. The expert consensus group finally established this consensus after discussions pertaining to evidence-based medicine and clinical practice, with the aim to provide a reference for clinical practice.

First-trimester hemoglobin, haptoglobin genotype, and risk of gestational diabetes mellitus in a retrospective study among Chinese pregnant women.

BACKGROUND: This study aimed to assess whether the Haptoglobin (Hp) genotype influences the relationship between hemoglobin (Hb) levels and the development of gestational diabetes mellitus (GDM). Additionally, it sought to evaluate the interaction and joint association of Hb levels and Hp genotype with GDM risk. METHODS: This retrospective study involved 358 women with GDM and 1324 women with normal glucose tolerance (NGT). Peripheral blood leukocytes were collected from 360 individuals at 14-16 weeks' gestation for Hp genotyping. GDM was diagnosed between 24-28 weeks' gestation. Interactive moderating effect, joint analysis, and mediation analysis were performed to evaluate the crosslink of Hb levels and Hp genotype with GDM risk. RESULTS: Women who developed GDM had significantly higher Hb levels throughout pregnancy compared to those with NGT. Increase first-trimester Hb concentration was associated with a progressive rise in GDM incidence, glucose levels, glycosylated hemoglobin levels, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) values, cesarean delivery rates, and composite neonatal outcomes. Spline regression showed a significant linear association of GDM incidence with continuous first-trimester Hb level when the latter exceeded 122 g/L. Increased first-trimester Hb concentration was an independent risk factor for GDM development after adjusting for potential confounding factors in both the overall population and a matched case-control group. The Hp2-2 genotype was more prevalent among pregnant women with GDM when first-trimester Hb exceeded 122 g/L. Significant multiplicative and additive interactions were identified between Hb levels and Hp genotype for GDM risk, adjusted for age and pre-pregnancy BMI. The odds ratio (OR) for GDM development increased incrementally when stratified by Hb levels and Hp genotype. Moreover, first-trimester Hb level partially mediated the association between Hp genotype and GDM risk. CONCLUSION: Increased first-trimester Hb levels were closely associated with the development of GDM and adverse pregnancy outcomes, with this association moderated by the Hp2-2 genotype.

Life's Essential 8 is inversely associated with high-sensitivity C-reactive protein.

Life's Essential 8 (LE8) is a score that includes modifiable risk factors for cardiovascular disease. Four health behaviors (diet, physical activity, nicotine exposure and sleep health) and four health factors (non-HDL cholesterol, blood glucose, blood pressure and body mass index) are included. These modifiable risk factors promote inflammation, and inflammation is one of the biological mechanisms of cardiovascular disease development. Thus, we examined the relationship between cardiovascular health measured by LE8 and low-grade inflammation measured by high-sensitivity C-reactive protein (hs-CRP) in the cross-sectional population-based Swedish CArdioPulmonary bioImage Study (SCAPIS). The study consisted of 28,010 participants between 50 and 64 years (51.5% women, mean age 57.5 years). All individual LE8 components were assigned a score between 0 (unhealthy) and 100 (healthy) points, and a global score was calculated. The association between LE8 scores and high-risk hs-CRP (defined as > 3.0 mg/L) was analyzed using adjusted logistic regression with spline analyses. There was a strong, dose response and inverse association between LE8 scores and levels of hs-CRP. Thus, those with a low LE8 score (= 50.0 points) had 5.8 higher (95% confidence interval [CI] 5.2-6.4) odds ratio (OR) of having high hs-CRP as compared to those with a high LE8 score (= 80.0 points). In conclusion, our findings show strong inverse associations between LE8 scores and levels of hs-CRP.

Impaired GK-GKRP interaction rather than direct GK activation worsens lipid profiles and contributes to long-term complications: a Mendelian randomization study.

BACKGROUND: Glucokinase (GK) plays a key role in glucose metabolism. In the liver, GK is regulated by GK regulatory protein (GKRP) with nuclear sequestration at low plasma glucose level. Some GK activators (GKAs) disrupt GK-GKRP interaction which increases hepatic cytoplasmic GK level. Excess hepatic GK activity may exceed the capacity of glycogen synthesis with excess triglyceride formation. It remains uncertain whether hypertriglyceridemia associated with some GKAs in previous clinical trials was due to direct GK activation or impaired GK-GKRP interaction. METHODS: Using publicly available genome-wide association study summary statistics, we selected independent genetic variants of GCKR and GCK associated with fasting plasma glucose (FPG) as instrumental variables, to mimic the effects of impaired GK-GKRP interaction and direct GK activation, respectively. We applied two-sample Mendelian Randomization (MR) framework to assess their causal associations with lipid-related traits, risks of metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular diseases. We verified these findings in one-sample MR analysis using individual-level statistics from the Hong Kong Diabetes Register (HKDR). RESULTS: Genetically-proxied impaired GK-GKRP interaction increased plasma triglycerides, low-density lipoprotein cholesterol and apolipoprotein B levels with increased odds ratio (OR) of 14.6 (95% CI 4.57-46.4) per 1 mmol/L lower FPG for MASLD and OR of 2.92 (95% CI 1.78-4.81) for coronary artery disease (CAD). Genetically-proxied GK activation was associated with decreased risk of CAD (OR 0.69, 95% CI 0.54-0.88) and not with dyslipidemia. One-sample MR validation in HKDR showed consistent results. CONCLUSIONS: Impaired GK-GKRP interaction, rather than direct GK activation, may worsen lipid profiles and increase risks of MASLD and CAD. Development of future GKAs should avoid interfering with GK-GKRP interaction.

Nonpharmacological interventions on glycated haemoglobin in youth with type 1 diabetes: a Bayesian network meta-analysis.

The available evidence on the impact of specific non-pharmacological interventions on glycaemic control is currently limited. Consequently, there is a need to determine which interventions could provide the most significant benefits for the metabolic health of young individuals with type 1 diabetes mellitus. The aim of this study was to identify optimal nonpharmacological interventions on glycaemic control, measured by glycated haemoglobin (HbA1c), in children and adolescents with type 1 diabetes. Systematic searches were conducted in PubMed, Web of Science, Scopus, and SPORTDiscus from inception to July 1, 2023. Randomised clinical trials (RCT) investigating nonpharmacological interventions (e.g., physical activity, nutrition, and behavioural therapies) were included. Primary outcome was change in HbA1c levels. Secondary outcome was change in daily insulin dose requirement. Seventy-four RCT with 6,815 participants (49.43% girls) involving 20 interventions were analysed using a network meta-analysis. Most interventions showed greater efficacy than standard care. However, multicomponent exercise, which includes aerobic and strength training (n = 214, standardised mean difference [SMD] =- 0.63, 95% credible interval [95% CrI] - 1.09 to - 0.16) and nutritional supplements (n = 146, SMD =- 0.49, - 0 .92 to - 0.07) demonstrated the greatest HbA1c reductions. These interventions also led to the larger decreases in daily insulin needs (n = 119, SMD =- 0.79, 95% CrI -  1.19 to - 0.34) and (n = 57, SMD =- 0.62, 95% CrI -  1.18 to - 0.12, respectively). The current study underscores non-pharmacological options such as multicomponent exercise and nutritional supplements, showcasing their potential to significantly improve HbA1c in youth with type 1 diabetes. Although additional research to confirm their efficacy is required, these approaches could be considered as potential adjuvant therapeutic options in the management of type 1 diabetes among children and adolescents.

The effect of a split-dose intravenous dexamethasone and a single high-dose on postoperative blood glucose after total joint arthroplasty: a randomized double-blind placebo-controlled trial.

BACKGROUND: In patients undergoing total joint arthroplasty (TJA), the administration of dexamethasone may contribute to perioperative blood glucose (BG) disturbances, potentially resulting in complications, even in patients without diabetes. This study aimed to demonstrate the impact of different administration regimens of dexamethasone in postoperative BG levels. METHODS: In this randomized, controlled, double-blind trial, 136 patients without diabetes scheduled for TJA were randomly assigned to three groups: two perioperative saline injections (Group A, placebo); a single preoperative injection of 20 mg dexamethasone and a postoperative saline injection (Group B), and two perioperative injections of 10 mg dexamethasone (Group C). Primary outcomes were the postoperative fasting blood glucose (FBG) levels. Secondary outcome parameters were the postoperative postprandial blood glucose (PBG) levels. Postoperative complications within 90 days were also recorded. Risk factors for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl were investigated. RESULTS: Compared to Group A, there were transient increases in FBG and PBG on postoperative days (PODs) 0 and 1 in Groups B and C. Statistical differences in FBG and PBG among the three groups were nearly absent from POD 1 onward. Both dexamethasone regimens did not increase the risk for postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl. Elevated preoperative HbA1c levels may increase the risk of postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl, respectively. CONCLUSION: Perioperative intravenous high-dose dexamethasone to patients without diabetes has transient effects on increasing BG levels after TJA. However, no differences were found between the split-dose and single high-dose regimens. The elevated preoperative HbA1c, but not the dexamethasone regimens were the risk factor for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl. TRIAL REGISTRATION: Chinese Clinical Trail Registry, ChiCTR2300069473. Registered 17 March 2023, https://www.chictr.org.cn/showproj.html?proj=186760 .

Can the postload-fasting glucose gap be used to determine risk of developing diabetes in chinese adults: A prospective cohort study.

OBJECTIVE: To evaluate the relationship between fasting plasma glucose (FPG) and 2-hour postload plasma glucose (2hPG) measured during an oral glucose tolerance test, and the risk of developing diabetes in Chinese adults. METHODS: We followed 3,094 participants without diabetes, categorizing them based on their oral glucose tolerance test (OGTT) results into low post load (2hPG ≤ FPG) and high post load (2hPG > FPG) at baseline. We monitored the incidence of diabetes, incidence of prediabetes, disease progression from prediabetes to diabetes and disease reversal from prediabetes to normal glucose tolerance (NGT) over an average of 3.2 years of follow-up. After the Schoenfeld residual test, Cox's time-varying covariate (Cox-TVC) models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) to compare the different clinical events between low and high post load groups. RESULTS: In the cohort study, of the 3,094 participants, 702 (22.7 %) had low post load (2hPG ≤ FPG, mean postload-fasting gap: -0.8 ± 0.7 mmol/L) and 2,392 (77.3 %) had high post load (2hPG > FPG, mean postload-fasting gap: 1.8 ± 1.2 mmol/L). Over 3.2 ± 0.2 years of follow-up, 282 (9.1 %) developed diabetes. In the low post load group, the incidence rates per 1,000 person-years were: diabetes was 7.9, prediabetes was 70.0, disease progression from prediabetes to diabetes was 23.4 and disease reversal to NGT was 327.2. For the high post load group, incidence rates for diabetes was 13.9, prediabetes was 124.3, disease progression was 59.5 and disease reversal was 238.6 per 1,000 person-years. Participants with high post load showed higher incidence rates of diabetes, prediabetes, and progression from prediabetes to diabetes compared to those with low post load. HRs were significantly higher for incident diabetes and prediabetes, and disease progression from prediabetes to diabetes, whereas disease reversal was lower. CONCLUSION: The risk of developing prediabetes/diabetes after 3.2 years of follow-up was higher in the participants with high post load. It suggested that postload-fasting gap may be a simple tool to predict the risk of developing prediabetes, diabetes or reversal to NGT.

Metabolic score for insulin resistance (METS-IR) predicts all-cause and cardiovascular mortality in the general population: evidence from NHANES 2001-2018.

BACKGROUND: The prevalence of obesity-associated insulin resistance (IR) is increasing along with the increase in obesity rates. In this study, we compared the predictive utility of four alternative indexes of IR [triglyceride glucose index (TyG index), metabolic score for insulin resistance (METS-IR), the triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and homeostatic model assessment of insulin resistance (HOMA-IR)] for all-cause mortality and cardiovascular mortality in the general population based on key variables screened by the Boruta algorithm. The aim was to find the best replacement index of IR. METHODS: In this study, 14,653 participants were screened from the National Health and Nutrition Examination Survey (2001-2018). And TyG index, METS-IR, TG/HDL-C and HOMA-IR were calculated separately for each participant according to the given formula. The predictive values of IR replacement indexes for all-cause mortality and cardiovascular mortality in the general population were assessed. RESULTS: Over a median follow-up period of 116 months, a total of 2085 (10.23%) all-cause deaths and 549 (2.61%) cardiovascular disease (CVD) related deaths were recorded. Multivariate Cox regression and restricted cubic splines analysis showed that among the four indexes, only METS-IR was significantly associated with both all-cause and CVD mortality, and both showed non-linear associations with an approximate "U-shape". Specifically, baseline METS-IR lower than the inflection point (41.33) was negatively associated with mortality [hazard ratio (HR) 0.972, 95% CI 0.950-0.997 for all-cause mortality]. In contrast, baseline METS-IR higher than the inflection point (41.33) was positively associated with mortality (HR 1.019, 95% CI 1.011-1.026 for all-cause mortality and HR 1.028, 95% CI 1.014-1.043 for CVD mortality). We further stratified the METS-IR and showed that significant associations between METS-IR levels and all-cause and cardiovascular mortality were predominantly present in the nonelderly population aged < 65 years. CONCLUSIONS: In conjunction with the results of the Boruta algorithm, METS-IR demonstrated a more significant association with all-cause and cardiovascular mortality in the U.S. population compared to the other three alternative IR indexes (TyG index, TG/HDL-C and HOMA-IR), particularly evident in individuals under 65 years old.

Bridging the gap between GLP1-receptor agonists and cardiovascular outcomes: evidence for the role of tirzepatide.

Tirzepatide is a new drug targeting glucagon-like peptide 1(GLP1) and gastric inhibitory polypeptide (GIP) receptors. This drug has demonstrated great potential in improving the clinical outcomes of patients with type 2 diabetes. It can lead to weight loss, better glycemic control, and reduced cardiometabolic risk factors. GLP1 receptor agonists have been proven effective antidiabetic medications with possible cardiovascular benefits. Even though they have been proven to reduce the risk of major adverse cardiovascular events, their effectiveness in treating heart failure is unknown. Unlike traditional GLP1 receptor agonists, tirzepatide is more selective for the GIP receptor, resulting in a more balanced activation of these receptors. This review article discusses the possible mechanisms tirzepatide may use to improve cardiovascular health. That includes the anti-inflammatory effect, the ability to reduce cell death and promote autophagy, and also its indirect effects through blood pressure, obesity, and glucose/lipid metabolism. Additionally, tirzepatide may benefit atherosclerosis and lower the risk of major adverse cardiac events. Currently, clinical trials are underway to evaluate the safety and efficacy of tirzepatide in patients with heart failure. Overall, tirzepatide's dual agonism of GLP1 and GIP receptors appears to provide encouraging cardiovascular benefits beyond glycemic control, offering a potential new therapeutic option for treating cardiovascular diseases and heart failure.

Diabetes, glycemic profile and risk of vitiligo: A Mendelian randomization study.

BACKGROUD: Previous observational studies have shown that vitiligo usually co-manifests with a variety of dysglycemic diseases, such as Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM). Mendelian randomization (MR) analysis was performed to further evaluate the causal association between fasting plasma glucose, glycosylated hemoglobin (HbA1c), T1DM, T2DM and vitiligo. MATERIALS AND METHODS: We used aggregated genome-wide association data from the Integrative Epidemiology Unit (IEU) online database of European adults vitiligo; HbA1c data were from IEU. Fasting blood glucose data were obtained from the European Bioinformatics Institute (EBI). T1DM and T2DM data were from FinnGen. We used bidirectional two-sample and multivariate MR analyses to test whether dysglycemic measures (fasting blood glucose, HbA1c), diabetes-related measures (T1DM, T2DM) are causatively associated with vitiligo. Inverse variance weighting (IVW) method was used as the main test method, MR-Egger, Weighted mode and Weighted median were used as supplementary methods. RESULTS: We found no statistically significant evidence to support a causal association between dysglycemic traits and vitiligo, but in the correlation analysis of diabetic traits, our data supported a positive causal association between T1DM and vitiligo (p = 0.018). In the follow-up multivariate MR analysis, our results still supported this conclusion (p = 0.016), and suggested that HbA1c was not a mediator of T1DM affecting the pathogenesis of vitiligo. No reverse causality was found in any of the reverse MR Analyses of dysglycemic traits and diabetic traits. CONCLUSIONS: Our findings support that T1DM is a risk factor for the development of vitiligo, and this conclusion may explain why the co-presentation of T1DM and vitiligo is often seen in observational studies. Clinical use of measures related to T1DM may be a new idea for the prevention or treatment of vitiligo.

Termite Fungus Comb Polysaccharides Alleviate Hyperglycemia and Hyperlipidemia in Type 2 Diabetic Mice by Regulating Hepatic Glucose/Lipid Metabolism and the Gut Microbiota.

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia and dyslipidemia. The termite fungus comb is an integral component of nests of termites, which are a global pest. Termite fungus comb polysaccharides (TFCPs) have been identified to possess antioxidant, anti-aging, and immune-enhancing properties. However, their physicochemical characteristics and their role in fighting diabetes have not been previously reported. In the current study, TFCPs were isolated and structurally characterized. The yield of TFCPs was determined to be 2.76%, and it was found to be composed of a diverse array of polysaccharides with varying molecular weights. The hypoglycemic and hypolipidemic effects of TFCPs, as well as their potential mechanisms of action, were investigated in a T2D mouse model. The results demonstrated that oral administration of TFCPs could alleviate fasting blood glucose levels, insulin resistance, hyperlipidemia, and the dysfunction of pancreatic islets in T2D mice. In terms of mechanisms, the TFCPs enhanced hepatic glycogenesis and glycolysis while inhibiting gluconeogenesis. Additionally, the TFCPs suppressed hepatic de novo lipogenesis and promoted fatty acid oxidation. Furthermore, the TFCPs altered the composition of the gut microbiota in the T2D mice, increasing the abundance of beneficial bacteria such as Allobaculum and Faecalibaculum, while reducing the levels of pathogens like Mailhella and Acetatifactor. Overall, these findings suggest that TFCPs may exert anti-diabetic effects by regulating hepatic glucose and lipid metabolism and the composition of the gut microbiota. These findings suggest that TFCPs can be used as a promising functional ingredient for the prevention and treatment of T2D.