Surfactant protein-D, diabetes mellitus, oxidative stress, infections and inflammation on the crossroad: A Systematic review.

Objective: To review the association of surfactant protein-D with type 2 diabetes mellitus, infections, oxidative stress and inflammation, and the changes in oxidative stress markers in type 2 diabetes mellitus. METHODS: The systematic review was conducted from April to September 2022, and comprised search on PubMed, Web of Sciences, Scopus, Science Direct and Google Scholar databases for relevant studies published in English language between January 1, 2000, and June 30, 2022. The search was updated in September 2022. After transferring literature to Mendeley, relevant data was extracted from the included studies. Quality assessment for eligible studies was done using Joanna Briggs Institute Critical Appraisal Checklist. Quality of evidences was assessed by using Grading of Recommendations Assessment, Development and Evaluation tool. RESULTS: Of the 203 studies identified, 18(8.9%) were analysed; 16(89%) with humans and 2(11%) with animals as subjects There were 5 (31.25%) studies for SP-D, of which 4 (80%) studies reported lower surfactant protein-D in type 2 diabetes mellitus cases than controls. Its significant negative association with glycated haemoglobin was reported by 1(20%) study and 2(40%) studies with fasting blood glucose levels. Higher surfactant protein-D in type 2 diabetes mellitus cases and its positive association with glycated haemoglobin was reported by 1(20%) study. Recurrent infections were frequent in type 2 diabetes mellitus patients. Malondialdehyde level was higher and superoxide dismutase activity was lower in type 2 diabetes mellitus cases, reflecting oxidative stress. Animal studies also showed that reactive oxygen species generating from hypochlorous acid during oxidative stress promoted the formation of non-disulfide linkages in surfactant protein-D structure, resulting in its decreased functionality. Conclusion: Surfactant protein-D, oxidative stress, inflammation and infections were found to be linked to each other for pathogenesis of infections in type 2 diabetes mellitus.

Physical and Physiological Predictors Determining the Maximal Static Apnea Diving Time of Male Freedivers.

This study aimed to investigate what factors determine freedivers' maximal static apnea dive time. We correlated some physical/physiological factors with male freedivers' maximum apnea diving duration. Thirty-six experienced male freedivers participated in this study. The divers participated in two days of the experiments. On the first day, apnea diving time, blood oxygen saturation (SpO2), heart rate (HR), blood pressure (BP), stress index, and blood parameters were measured before, during, and after the apnea diving in the pool. On the second day, body composition, lung capacity, resting and maximal oxygen consumption (VO2max), and the Wingate anaerobic power were measured in the laboratory. The data were analyzed with Pearson's Correlation using the SPSS 22 program. The correlation coefficient (R) of determination was set at 0.4, and the level of significance was set at p <0.05. There were positive correlations of diving experience, maximum SpO2, and lung capacity with the maximum apnea time R>0.4, P<0.05). There were negative correlations of BMI, body fat percentage, body fat mass, minimum SpO2, stress index, and total cholesterol with the maximum apnea diving time (R>-0.4, P<0.05). No correlations of age, height, weight, fat-free mass, skeletal muscle mass, HR, BP, blood glucose, beta- hydroxybutyrate, lactate, and hemoglobin levels with the maximum apnea diving time were observed (R<0.4, P>0.05). It is concluded that more experience in freediving, reduced body fat, extended SpO2 range, and increased lung capacity are the performance predictors and beneficial for freedivers to improve their maximum apnea diving performance.

Glucose Control and Risk of Symptomatic Intracerebral Hemorrhage Following Thrombolysis for Acute Ischemic Stroke: A SHINE Trial Analysis.

BACKGROUND AND OBJECTIVES: Baseline hyperglycemia is associated with worse outcomes in acute ischemic stroke (AIS), including higher risk of symptomatic intracerebral hemorrhage (sICH) following treatment with thrombolysis. Prospective data are lacking to inform management of post-thrombolysis hyperglycemia. In a prespecified analysis from the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial of hyperglycemic stroke management, we hypothesized that post-thrombolysis hyperglycemia is associated with a higher risk of sICH. METHODS: Hyperglycemic AIS patients <12 hours onset were randomized to intensive insulin (target range 80-130 mg/dL) vs standard sliding scale (80-179 mg/dL) over a 72-hour period, stratified by treatment with thrombolysis. Three board-certified vascular neurologists independently reviewed all sICH events occurring within 7 days, defined by neurologic deterioration of ≥4 points on the NIH Stroke Scale (NIHSS). Associations between blood glucose control and sICH were analyzed using logistic regression accounting for NIHSS, age, systolic blood pressure, onset to thrombolysis time, and endovascular therapy (odds ratios [OR], 95% CI). Additional analysis compared patients in a high-risk group (age older than 60 years and NIHSS ≥8) vs all others. Categorical variables and outcomes were compared using the χ2 test (p < 0.05). RESULTS: Of 1151 SHINE participants, 725 (63%) received thrombolysis (median age 65 years, 46% women, 29% Black, 18% Hispanic). The median NIHSS was 7, baseline blood glucose was 187 (interquartile range 153-247) mg/dL, and 80% were diabetic. Onset to thrombolysis time was 2.2 hours (1.6-2.9). Post-thrombolysis sICH occurred in 3.6% (3.0% intensive vs 4.3% standard glucose control, OR 1.10, 0.60-2.01, p = 0.697). In the first 12 hours, every 10 mg/dL higher glucose increased the odds of sICH (OR 1.08, 1.03-1.14, p = 0.004), and a greater proportion of glucose measures in the normal range (80-130 mg/dL) decreased the odds of sICH (0.89, 0.80-0.99, p = 0.030). These associations were strongest in the high-risk group (age older than 60 years and NIHSS ≥8). DISCUSSION: In this prespecified analysis from the SHINE trial, intensive insulin therapy was not associated with a reduced risk of post-thrombolysis sICH compared with standard sliding scale. However, early post-thrombolysis hyperglycemia was associated with a higher risk of sICH overall, particularly in older patients with more severe strokes. Further prospective research is warranted to address the risk of sICH in hyperglycemic stroke patients undergoing endovascular therapy. TRIAL REGISTRATION INFORMATION: NCT01369069.

In situ anchored ternary hierarchical hybrid nickel@cobaltous sulfide on poly(3,4-ethylenedioxythiophene)-reduced graphene oxide for highly efficient non-enzymatic glucose sensing.

A ternary hierarchical hybrid Ni@CoxSy/poly(3,4-ethylenedioxythiophene)-reduced graphene oxide (Ni@CoxSy/PEDOT-rGO) is rationally designed and in situ facilely synthesized as electrocatalyst to construct a binder-free sensing platform for non-enzymatic glucose monitoring through traditional electrodeposition procedure. The as-prepared Ni@CoxSy/PEDOT-rGO presents unique hierarchical structure and multiple valence states as well as strong and robust adhesion between Ni@CoxSy/PEDOT-rGO and GCE. Profiting from the aforementioned merits, the sensing platform constructed under optimal conditions achieved a wide detection range (0.2 µM ~ 2.0 mM) with high sensitivity (1546.32 µA cm-2 mM-1), a rapid response time (5 s), an ultralow detection limit (0.094 µM), superior anti-interference performance, excellent reproducibility and considerable stability. Furthermore, the sensor demonstrates an acceptable accuracy and appreciable recoveries ranging from 90.0 to 102.0% with less than 3.98% RSD in human blood serum samples, indicating the prospect of the sensor for the real samples analysis. It will provide a strategy to rationally design and fabricate ternary hierarchical hybrid as nanozyme for glucose assay.

Turning the tides: achieving rapid and safe glucose control in adolescents with suboptimally controlled type 1 diabetes using advanced hybrid closed loop systems.

Aim: Many adolescents with T1D experience a decline in metabolic control due to erratic eating habits and subpar adherence to treatment regimens. The objective of our retrospective observational study was to assess the effect of the Tandem Control IQ (CIQ) advanced hybrid closed-loop (AHCL) system on a cohort of adolescents with suboptimal glucose control. Methods: We retrospectively evaluated 20 non-adherent patients with T1D, who were inconsistently using Multiple Daily Injections (MDIs) and flash glucose monitoring and were subsequently started and on CIQ. Glucometrics and the Glucose Risk Index were assessed at baseline and after 2 weeks, 1 month, and 6 months of CIQ use. Results: The study included 20 adolescents with T1D (HbA1c: 10.0% ± 1.7). Time in range (TIR) increased from 27.1% ± 13.7 at baseline to 68.6% ± 14.2 at 2 weeks, 66.6% ± 10.7 at 1 month, and 60.4% ± 13.3 at 6 months of CIQ use. Time above range (TAR) >250 mg/dL decreased from 46.1% ± 23.8 to 9.9% ± 9.5 at 2 weeks, 10.8% ± 6.1 at 1 month, and 15.5% ± 10.5 at 6 months of AHCL use. Mean glucose levels improved from 251 mg/dL ± 68.9 to 175mg/dL ± 25.5 after 6 months of CIQ use. The Glucose Risk Index (GRI) also significantly reduced from 102 to 48 at 6 months of CIQ. HbA1c also improved from 10.0% ± 1.7 at baseline to 7.0% ± 0.7 after 6 months. Two patients experienced a single episode of mild diabetic ketoacidosis (DKA). Conclusions: AHCL systems provide a significant, rapid, and safe improvement in glucose control. This marks a pivotal advancement in technology that primarily benefited those who were already compliant.

Investigating the Effects of Diet-Induced Prediabetes on Skeletal Muscle Strength in Male Sprague Dawley Rats.

Type 2 diabetes mellitus, a condition preceded by prediabetes, is documented to compromise skeletal muscle health, consequently affecting skeletal muscle structure, strength, and glucose homeostasis. A disturbance in skeletal muscle functional capacity has been demonstrated to induce insulin resistance and hyperglycemia. However, the modifications in skeletal muscle function in the prediabetic state are not well elucidated. Hence, this study investigated the effects of diet-induced prediabetes on skeletal muscle strength in a prediabetic model. Male Sprague Dawley rats were randomly assigned to one of the two groups (n = 6 per group; six prediabetic (PD) and six non-pre-diabetic (NPD)). The PD group (n = 6) was induced with prediabetes for 20 weeks. The diet that was used to induce prediabetes consisted of fats (30% Kcal/g), proteins (15% Kcal/g), and carbohydrates (55% Kcal/g). In addition to the diet, the experimental animals (n = 6) were supplied with drinking water that was supplemented with 15% fructose. The control group (n = 6) was allowed access to normal rat chow, consisting of 35% carbohydrates, 30% protein, 15% fats, and 20% other components, as well as ordinary tap water. At the end of week 20, the experimental animals were diagnosed with prediabetes using the American Diabetes Association (ADA) prediabetes impaired fasting blood glucose criteria (5.6-6.9 mmol/L). Upon prediabetes diagnosis, the animals were subjected to a four-limb grip strength test to assess skeletal muscle strength at week 20. After the grip strength test was conducted, the animals were euthanized for blood and tissue collection to analyze glycated hemoglobin (HbA1c), plasma insulin, and insulin resistance using the homeostatic model of insulin resistance (HOMA-IR) index and malondialdehyde (MDA) concentration. Correlation analysis was performed to examine the associations of skeletal muscle strength with HOMA-IR, plasma glucose, HbA1c, and MDA concentration. The results demonstrated increased HbA1c, FBG, insulin, HOMA-IR, and MDA concentrations in the PD group compared to the NPD group. Grip strength was reduced in the PD group compared to the NPD group. Grip strength was negatively correlated with HbA1c, plasma glucose, HOMA-IR, and MDA concentration in the PD group. These observations suggest that diet-induced prediabetes compromises muscle function, which may contribute to increased levels of sedentary behavior during prediabetes progression, and this may contribute to the development of hyperglycemia in T2DM.

The Effect of Sn-2 Palmitate on Blood Glucose, Lipids and Body Composition in Middle-Aged and Elderly Adults: A Randomized, Double-Blinded Controlled Trial.

Sn-2 palmitate is widely used in infant formula. However, little is known about its effects on metabolism and body composition in middle-aged and elderly adults. In a double-blinded, randomized controlled trial, we enrolled Chinese adults aged 45-75 years with self-reported constipation. Individuals were randomly assigned in a 1:1 ratio to a 1,3-dioleoyl-2-palmitoyl-glycerol (OPO)-enriched oil (66% palmitic acid in the sn-2 position) or a control vegetable oil (24% palmitic acid in the sn-2 position) daily for 24 weeks. Skim milk powder was used as the carrier for both fats. Interviews and body composition were performed at baseline, week 4, week 12 and week 24. A fasting blood draw was taken except at week 4. This study was a secondary analysis and considered exploratory. A total of 111 adults (83 women and 28 men, mean age 64.2 ± 7.0 years) were enrolled, of whom 53 were assigned to the OPO group and 57 to the control group. During the intervention, blood glucose, triglyceride, the triglyceride-glucose index, total cholesterol, low-density lipoprotein cholesterol and remnant cholesterol remained stable, while high-density lipoprotein cholesterol decreased in both groups (p = 0.003). No differences in change were observed between the groups (all p > 0.05). From baseline to week 24, the level of visceral fat increased slightly (p = 0.017), while body weight, total body water, protein, soft lean mass, fat-free mass, skeletal muscle and skeletal muscle mass index (SMI) decreased in two groups (p < 0.01). At weeks 4, 12 and 24, the SMI decreased less in the OPO group than in the control group, with a trend towards significance (p = 0.090). A 24-week daily intake of sn-2-palmitate-enriched oil had no adverse impact on fasting blood glucose, lipids and body composition compared with the control vegetable oil in Chinese adults (funded by Chinese Nutrition Society National Nutrition Science Research Grant, National Key Research and Development Program of China and Wilmar (Shanghai) Biotechnology Research & Development Center Co., Ltd.; ChiCTR1900026480).

Glucose control during pregnancy in patients with type 1 diabetes correlates with fetal hemodynamics: a prospective longitudinal study.

BACKGROUND: Maternal diabetes adversely affects fetal cardiovascular system development. Previous studies have reported that the fetuses of mothers with diabetes exhibit both structural and functional changes; nevertheless, prior studies have not examined the association between glucose control and fetal cardiac morphology and performance. Thus, the objective was to determine the association between fetal cardiac morphology and function and maternal glucose control in type 1 diabetes and to compare the differences in measured cardiac parameters between the fetuses of mothers with diabetes and healthy controls. METHODS: In this prospective, longitudinal case-control study - including 62 pregnant women with type 1 diabetes mellitus and 30 healthy pregnant women - fetal cardiac assessment using B-mode, M-mode, and spectral pulsed-wave Doppler was performed in the second and third trimesters. In women with T1DM, glycated hemoglobin and data obtained from glucose sensors - including the percentage of time in, below, and above the range (TIR, TBR, and TAR, respectively), and coefficient of variation (CV) - were analyzed across three time periods: the last menstrual period to 13 (V1), 14-22 (V2), and 23-32 weeks (V3) of gestation. Fetal cardiac indices were compared between groups, and the correlation between glucose control and fetal cardiac indices was assessed. RESULTS: At 28-32 weeks, the fetuses of women with T1DM exhibited increased left ventricular end-diastolic length, relative interventricular septum thickness, right ventricular cardiac output, and pulmonary valve peak systolic velocity compared with healthy controls. At 18-22 weeks, pulmonary and aortic valve diameters, left and right ventricular stroke volumes, and left cardiac output inversely correlated with the CV and glycated hemoglobin levels at V1 and V2. Furthermore, at 28-32 weeks, pulmonary and aortic valve diameters, left ventricular stroke volume, cardiac output, and right/left atrioventricular valve ratio inversely correlated with the TBR at V1, V2, and V3. Moreover, diastolic functional parameters correlated with the TAR and glycated hemoglobin levels, particularly after the first trimester. CONCLUSION: In women with T1DM, maternal hyperglycemia during pregnancy correlates with fetal diastolic function, whereas glucose variability and hypoglycemia inversely correlate with fetal left ventricular systolic function in the second and third trimesters.

The triglyceride glucose index as a sensitive predictor for the risk of MACCEs in patients with diabetic foot ulcers: An ambispective longitudinal cohort study.

The triglyceride glucose (TyG) index has been confirmed a predictive value for type 2 diabetes mellitus (T2DM). However, no research has yet confirmed whether there is a linear correlation between the TyG index and MACCEs in DFUs. The present study aimed to delve into the association between the TyG index and the risk of MACCEs in patients with DFUs. A total of 960 inpatients with DFUs were recruited. All participants were followed up every 6 months for 11 years with a median of 83 months. According to the cut-off value of the TyG index acquired from receiver operating characteristic (ROC) analysis, the subjects were divided into two groups: low-level (<9.12, n = 480) and high-level (≥9.12, n = 480). The relationship between the TyG index and MACCEs was evaluated by the multivariable Cox regression model, restricted cubic spline (RCS) model, stratified analysis and the Kaplan-Meier survival analysis. Out of 960 participants, 271 experienced MACCEs (28.22%), of whom 79 (29.15%) died. ROC analysis got the optimal TyG index cut-off value of 9.12. Multivariable Cox regression analysis combined with the RCS model showed that the TyG index was positively associated with MACCEs in an S-shaped non-linear dose-dependent manner within the range of TyG index 7.5-9.5 (p < 0.001). The Kaplan-Meier survival analysis indicated the higher the TyG index, the greater the cumulative incidence of MACCEs (log-rank, p < 0.001). The study first confirmed an S-shaped non-linear dose-dependent positive relationship between the TyG index and the risk of MACCEs in DFUs. Consequently, lowering the TyG index level aids in improving the prognosis of patients with DFUs.

In-depth correlation analysis between tear glucose and blood glucose using a wireless smart contact lens.

Tears have emerged as a promising alternative to blood for diagnosing diabetes. Despite increasing attempts to measure tear glucose using smart contact lenses, the controversy surrounding the correlation between tear glucose and blood glucose still limits the clinical usage of tears. Herein, we present an in-depth investigation of the correlation between tear glucose and blood glucose using a wireless and soft smart contact lens for continuous monitoring of tear glucose. This smart contact lens is capable of quantitatively monitoring the tear glucose levels in basal tears excluding the effect of reflex tears which might weaken the relationship with blood glucose. Furthermore, this smart contact lens can provide an unprecedented level of continuous tear glucose data acquisition at sub-minute intervals. These advantages allow the precise estimation of lag time, enabling the establishment of the concept called 'personalized lag time'. This demonstration considers individual differences and is successfully applied to both non-diabetic and diabetic humans, as well as in animal models, resulting in a high correlation.

Associations between sleep duration, sleep disturbance and cardiovascular disease biomarkers among adults in the United States.

BACKGROUND: Sleep problems are associated with abnormal cardiovascular biomarkers and an increased risk of cardiovascular diseases (CVDs). However, studies investigating associations between sleep problems and CVD biomarkers have reported conflicting findings. This study examined the associations between sleep problems and CVD biomarkers in the United States. METHODS: Data were from the National Health and Nutrition Examination Survey (NHANES) (2007-2018) and analyses were restricted to adults ≥ 20 years (n = 23,749). CVD biomarkers [C-reactive Protein (CRP), low-density lipoproteins, high-density lipoproteins (HDL), triglycerides, insulin, glycosylated hemoglobin (HbA1c), and fasting blood glucose] were categorized as abnormal or normal using standardized cut-off points. Sleep problems were assessed by sleep duration (short [≤ 6 h], long [≥ 9 h], and recommended [> 6 to < 9 h) and self-reported sleep disturbance (yes, no). Multivariable logistic regression models explored the associations between sleep duration, sleep disturbance, and CVD biomarkers adjusting for sociodemographic characteristics and lifestyle behaviors. RESULTS: The mean sleep duration was 7.1 ± 1.5 h and 25.1% of participants reported sleep disturbances. Compared to participants with the recommended sleep duration, those with short sleep duration had higher odds of abnormal levels of HDL (adjusted odds ratio [aOR] = 1.20, 95% confidence interval [CI] = 1.05-1.39), CRP (aOR = 3.08, 95% CI = 1.18-8.05), HbA1c (aOR = 1.25, 95% CI = 1.05-1.49), and insulin (aOR = 1.24, 95% CI = 1.03-1.51). Long sleep duration was associated with increased odds of abnormal CRP (aOR = 6.12, 95% CI = 2.19-17.15), HbA1c (aOR = 1.54, 95% CI = 1.09-2.17), and blood glucose levels (aOR = 1.45, 95% CI = 1.07-1.95). Sleep disturbance predicted abnormal triglyceride (aOR = 1.18, 95% CI = 1.01-1.37) and blood glucose levels (aOR = 1.24, 95% CI = 1.04-1.49). CONCLUSION: Short and long sleep durations were positively associated with abnormal CRP, HDL, HbA1c, blood glucose, and insulin levels, while sleep disturbance was associated with abnormal triglyceride and blood glucose levels. Since sleep is a modifiable factor, adopting healthy sleeping habits may create a balanced metabolism and reduce the risk of developing a CVD. Our study may provide insights into the relationship between sleep duration, sleep disturbance, and CVD risk.

Triglyceride-glucose-waist circumference index predicts the incidence of cardiovascular disease in Korean populations: competing risk analysis of an 18-year prospective study.

BACKGROUND: The triglyceride and glucose-waist circumference (TyG-WC) index demonstrated a strong association with insulin resistance, especially in Asian population. However, evidence on the association between TyG-WC index and the occurrence of cardiovascular disease (CVD) is limited. This study aimed to verify association between the TyG-WC index and the occurrence of CVD by considering all-cause mortality as a competing risk. METHODS: The study included 7482 participants divided into four groups based on the TyG-WC index quartiles. Kaplan-Meier curves illustrated cumulative incidence rates of CVD and all-cause mortality during the follow-up period. Log-rank tests determined group differences. The Cox proportional hazard spline curve demonstrates the dose-dependent relationship between the TyG-WC index and incident CVD. Modified Cox regression (Fine and Gray) estimated hazard ratios (HRs) with 95% CIs for incident CVD, treating death as a competing risk. Death event after incident CVD was excluded from the death count. RESULTS: During the median 15.94 year of follow-up period, a total of 691 (9.24%) new-onset CVD cases and 562 (7.51%) all-cause mortality cases were confirmed. Cox proportional hazard spline curves suggested that TyG-WC index exhibited a dose-dependent positive correlation with incident CVD. The cumulative incidence rate of CVD was significantly higher in the groups with higher TyG-WC index quartiles in Kaplan-Meier curves. The adjusted HR (95% CI) for incident CVD in Q2-Q4, compared with Q1, was 1.47 (1.12-1.93), 1.91 (1.44-2.54) and 2.24 (1.63-3.07), respectively. There was no significant association between TyG-WC index and all-cause mortality. Specifically, angina and stroke were significantly associated with the TyG-WC index, in contrast to myocardial infarction and peripheral artery disease. CONCLUSIONS: The TyG-WC index was positively associated with incident CVD even considering all-cause mortality as a competing risk. Therefore, TyG-WC index may be a valuable marker for predicting the occurrence of CVD.

A Combined Measure of the Triglyceride Glucose Index and Trimethylamine N-Oxide in Risk Stratification of ST-Segment Elevation Myocardial Infarction Patients with High-Risk Plaque Features Defined by Optical Coherence Tomography: A Substudy of the OCTAMI Registry Study.

Background and Aim: An elevated triglyceride-glucose (TyG) level is associated with increased risk of mortality in patients with CAD. Trimethylamine N-oxide (TMAO) has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is correlated with adverse outcomes. However, the incremental prognostic value of TMAO and TyG in the cohort of optical coherence tomography (OCT)-defined high-risk ST-segment elevation myocardial infarction (STEMI) patients is unknown. Methods: We studied 274 consecutive aged ≥18 years patients with evidence of STEMI and detected on pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019. Outcomes: There were 22 (22.68%), 27 (27.84%), 26 (26.80%), and 22 (22.68%) patients in groups A-D, respectively. The baseline characteristics according to the level of TMAO and TyG showed that patients with higher level in both indicators were more likely to have higher triglycerides (p < 0.001), fasting glucose (p < 0.001) and higher incidence of diabetes (p = 0.008). The group with TMAO > median and TyG ≤ median was associated with higher rates of MACEs significantly (p = 0.009) in fully adjusted analyses. During a median follow-up of 2.027 years, 20 (20.6%) patients experienced MACEs. To evaluate the diagnostic value of the TyG index combined with TMAO, the area under the receiver operating characteristic curve for predicting MACEs after full adjustment was 0.815 (95% confidence interval, 0.723-0.887; sensitivity, 85.00%; specificity, 72.73%; cut-off level, 0.577). Among the group of patients with TMAO > median and TyG ≤ median, there was a significantly higher incidence of MACEs (p=0.033). A similar tendency was found in the cohort with hyperlipidemia (p=0.016) and diabetes mellitus (p=0.036). Conclusion: This study demonstrated the usefulness of combined measures of the TyG index and TMAO in enhancing risk stratification in STEMI patients with OCT-defined high-risk plaque characteristics. Trial Registration: This study was registered at ClinicalTrials.gov as NCT03593928.

Is polyethylene glycol loxenatide 100 µg the preferred glucagon-like peptide-1 receptor agonist for type 2 diabetes mellitus? A meta-analysis and trial sequential analysis.

OBJECTIVE: This study aimed to systematically evaluate the efficacy, safety and optimal dose of polyethylene glycol loxenatide (PEX168) for treating type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Clinical trials of PEX168 for T2DM were identified in 8 databases, with a build time limit of January 2023. Included studies were subjected to meta-analysis and trial sequential analysis (TSA). RESULTS: On the efficacy endpoint, the meta-analysis showed that PEX168 100 µg significantly reduced 0.86% glycated hemoglobin type A1c (HbA1c) (MD -0.86, 95% CI -1.02 - -0.70,  p<0.00001), 1.11 mmol/L fasting plasma glucose (FPG) (MD -1.11, 95% CI -1.49 - -0.74, p<0.00001) and 1.91 mmol/L 2h postprandial glucose (PPG) (MD -1.91, 95% CI -3.35 - -0.46, p=0.01) compared with placebo. The TSA showed that all these benefits were conclusive. On safety endpoints, total adverse events (AEs), gastrointestinal (GI) AEs, serious AEs, and hypoglycemia were comparable to placebo for PEX168 100 µg (p>0.05). In the dose comparison, the HbA1c, FPG, and 2h PPG of PEX168 200 µg were comparable to 100 µg (p>0.05), while GI AEs were significantly higher than 100 µg (RR=2.84, 95% CI 1.64-4.93,  p=0.0002). CONCLUSIONS: PEX168 100 µg can significantly lower blood glucose and does not increase the risk of total AEs, GI AEs, and hypoglycemia, which may be a preferred glucagon-like peptide-1 receptor agonist for type 2 diabetes mellitus.

Current barriers to initiating insulin therapy in individuals with type 2 diabetes.

Insulin is an essential drug in the treatment of diabetes, often necessary for managing hyperglycemia in type 2 diabetes mellitus (T2DM). It should be considered in cases of severe hyperglycemia requiring hospitalization, after the failure of other treatments, in advanced chronic kidney disease, liver cirrhosis, post-transplant diabetes, or during pregnancy. Moreover, in specific patient subgroups, early initiation of insulin is crucial for hyperglycemia control and prevention of chronic complications. Clinical guidelines recommend initiating insulin when other treatments fail, although there are barriers that may delay its initiation. The timing of initiation depends on individual patient characteristics. Typically, insulinization starts by adding basal insulin to the patient's existing treatment and, if necessary, progresses by gradually introducing prandial insulin. Several barriers have been identified that hinder the initiation of insulin, including fear of hypoglycemia, lack of adherence, the need for glucose monitoring, the injection method of insulin administration, social rejection associated with the stigma of injections, weight gain, a sense of therapeutic failure at initiation, lack of experience among some healthcare professionals, and the delayed and reactive positioning of insulin in recent clinical guidelines. These barriers contribute, among other factors, to therapeutic inertia in initiating and intensifying insulin treatment and to patients' non-adherence. In this context, the development of once-weekly insulin formulations could improve initial acceptance, adherence, treatment satisfaction, and consequently, the quality of life for patients. Currently, two once-weekly basal insulins, insulin icodec and basal insulin BIF, which are in different stages of clinical development, may help. Their longer half-life translates to lower variability and reduced risk of hypoglycemia. This review addresses the need for insulin in T2DM, its positioning in clinical guidelines under specific circumstances, the current barriers to initiating and intensifying insulin treatment, and the potential role of once-weekly insulin formulations as a potential solution to facilitate timely initiation of insulinization, which would reduce therapeutic inertia and achieve better early control in people with T2DM.

U-shaped relationship between fasting blood glucose and urinary albumin-to-creatinine ratio in the general United States population.

Objective: The current controversy surrounding the association between fasting blood glucose (FBG) and albuminuria necessitates further investigation. Hence, the primary objective of this study was to examine the relationship between FBG and urinary albumin-to-creatinine ratio (UACR). Methods: A cohort of complete data from National Health and Nutrition Examination Survey (NHANES) participants (1999-2020) was analyzed. Linear regression analyses and a generalized additive model explored the association between FBG and UACR. Furthermore, the stability of this relationship across different populations was assessed. Results: The study involved a total of 20,264 participants who were identified as U.S. citizens. By employing linear regression analysis, a statistically significant relationship was observed between elevated FBG levels and an increase in UACR (P<0.0001). Additionally, using a generalized additive model analysis, a U-shaped correlation between FBG and UACR was identified. Further examination using threshold effect analysis indicated a turning point for FBG at 5.44 mmol/L. A noteworthy finding in multiple populations is the consistent U-shaped association between FBG and UACR, except for individuals with serum uric acid levels ≥420 µmol/L and those who refrain from alcohol consumption. Conclusion: The general U.S. population has a U-shaped nonlinear relationship between FBG and UACR.

Blood glucose monitoring devices for type 1 diabetes: a journey from the food and drug administration approval to market availability.

Blood glucose monitoring constitutes a pivotal element in the clinical management of Type 1 diabetes (T1D), a globally escalating metabolic disorder. Continuous glucose monitoring (CGM) devices have demonstrated efficacy in optimizing glycemic control, mitigating adverse health outcomes, and augmenting the overall quality of life for individuals afflicted with T1D. Recent progress in the field encompasses the refinement of electrochemical sensors, which enhances the effectiveness of blood glucose monitoring. This progress empowers patients to assume greater control over their health, alleviating the burdens associated with their condition, and contributing to the overall alleviation of the healthcare system. The introduction of novel medical devices, whether derived from existing prototypes or originating as innovative creations, necessitates adherence to a rigorous approval process regulated by the Food and Drug Administration (FDA). Diverse device classifications, stratified by their associated risks, dictate distinct approval pathways, each characterized by varying timelines. This review underscores recent advancements in blood glucose monitoring devices primarily based on electrochemical sensors and elucidates their regulatory journey towards FDA approval. The advent of innovative, non-invasive blood glucose monitoring devices holds promise for maintaining stringent glycemic control, thereby preventing T1D-associated comorbidities, and extending the life expectancy of affected individuals.

Restoration of gut dysbiosis through Clostridium butyricum and magnesium possibly balance blood glucose levels: an experimental study.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by an elevated level of blood glucose due to the absence of insulin secretion, ineffectiveness, or lack of uptake of secreted insulin in the body. The improperly diagnosed and poorly managed DM can cause severe damage to organs in the body like the nerves, eyes, heart, and kidneys. This study was aimed at investigating the effect of Clostridium butyricum (probiotic) with magnesium supplementation to evaluate the effect on gut microbial dysbiosis and blood glucose levels. In the laboratory, 6-8 weeks old 24 male albino rats weighing 200-250 g were given free access to water and food. Diabetes was induced using streptozotocin (60 mg/kg) in overnight fasted rats. Diabetic rats were randomly divided into four groups (n = 6, 6 replicates in each group). Metformin (100 mg/kg/day) with a standard basal diet was provided to control group (G0), Clostridium butyricum (1.5 × 105 CFU/day) with standard basal diet was provided to treatment group (G1), magnesium (500 mg/kg/day) was provided to group (G2). Clostridium butyricum (1.5 × 105 CFU/day) and magnesium (300 mg/kg/day) in combination with a standard basal diet was provided to group (G3). Blood Glucose, Magnesium blood test and microbial assay were done. Random blood glucose levels were monitored twice a week for 21 days and were represented as mean of each week. The results conclude that Clostridium butyricum (1.5 × 105 CFU) is very effective in balancing random blood glucose levels from 206.6 ± 67.7 to 85.1 ± 3.8 (p = 0.006) compared to other groups (p > 0.005). The results of stool analysis showed that Clostridium butyricum as probiotic restores microbial dysbiosis as evident by the 105 CFU Clostridium butyricum load in G1, which was higher than G0, G2 and G3 which were 103 and 104 CFU respectively. The findings of this study conclude that Clostridium butyricum supplementation improved blood glucose levels and intestinal bacterial load in type II diabetes mellitus.

Nephro-protective effects of alpha-lipoic acid in type I diabetes.

Type 1 diabetes (T1D) is an insulin-dependent autoimmune condition. Short chain fatty acids (SCFAs) are volatile fatty acids with 1-6 carbon atoms that influence glucose storage in the body and can reduce appetite, potentially decreasing T1D risk. Alpha-lipoic acid (α-LA), a type of SCFA, has previously been used to treat diabetic neuropathy and inflammation due to its antioxidant properties. This study aims to assess α-LA's protective effects against T1D and associated kidney damage in rats induced with streptozotocin. Diabetic rats were treated with α-LA orally for 15 days, resulting in improved blood glucose (56% decrease) and kidney function markers like blood urea nitrogen, creatinine and uric acid. α-LA also showed significant antioxidant effects by decreasing LPO as well as improving activities of antioxidant enzymes like superoxide dismutase, catalase and glutathione-S transferase and alleviated kidney damage caused by diabetes. Docking experiments suggest that α-LA may regulate diabetes-related changes at the epigenetic level through interactions with the SIRT1 protein, indicating its potential as a target for future antidiabetic drug development.

Efficacy and safety of bexagliflozin compared with dapagliflozin as an adjunct to metformin in Chinese patients with type 2 diabetes mellitus: A 24-week, randomized, double-blind, active-controlled, phase 3 trial.

BACKGROUND: Bexagliflozin and dapagliflozin are sodium-glucose cotransporter-2 (SGLT2) inhibitors. No direct comparison of SGLT2 inhibitors in a randomized controlled trial has been reported to date. METHODS: This was a multicenter, randomized, double-blind, active-controlled trial comparing bexagliflozin to dapagliflozin for the treatment of type 2 diabetes mellitus in adults with disease inadequately controlled by metformin. Subjects (n = 406) were randomized to receive bexagliflozin (20 mg) or dapagliflozin (10 mg) plus metformin. The primary endpoint was noninferiority of bexagliflozin to dapagliflozin for the change in glycated hemoglobin (HbA1c) from baseline to week 24. Secondary endpoints included intergroup differences in fasting plasma glucose (FPG), 2-h-postprandial glucose (PPG), body weight, and systolic blood pressure (SBP) from baseline to week 24. The trial also evaluated the safety profiles. RESULTS: The model-adjusted mean change from baseline to week 24 HbA1c was -1.08% for bexagliflozin and -1.10% for dapagliflozin. The intergroup difference of 0.03% (95% confidence interval [CI] -0.14% to 0.19%) was below the prespecified margin of 0.4%, confirming the noninferiority of bexagliflozin. The changes from baseline in FPG, PPG, body weight, and SBP were -1.95 mmol/L, -3.24 mmol/L, -2.52 kg, and -6.4 mm Hg in the bexagliflozin arm and -1.87 mmol/L, -3.07 mmol/L, -2.22 kg, and -6.3 mm Hg in the dapagliflozin arm. Adverse events were experienced in 62.6% and 65.0% and serious adverse events affected 4.4% and 3.5% of subjects in the bexagliflozin and dapagliflozin arm, respectively. CONCLUSIONS: Bexagliflozin showed nearly identical effects and a similar safety profile to dapagliflozin when used in Chinese patients on metformin.