Lower Blood Glucose Research Articles

SGLT2 inhibition improves coronary flow velocity reserve and contractility: role of glucagon signaling.

SGLT2 inhibitors, a T2DM medication to lower blood glucose, markedly improve cardiovascular outcomes but the underlying mechanism(s) are not fully understood. SGLT2i's produce a unique metabolic pattern by lowering blood glucose without increasing insulin while increasing ketone body and glucagon levels and reducing body weight. We tested if glucagon signaling contributes to SGLT2i induced improvement in CV function. Cardiac contractility and coronary flow velocity reserve (CFVR) were monitored in ob/ob mice and rhesus monkeys with metabolic syndrome using echocardiography. Metabolic status was characterized by measuring blood ketone levels, glucose tolerance during glucose challenge and Arg and ADMA levels were measured. Baysian models were developed to analyse the data. Dapagliflozin improved CFVR and contractility, co-application of a glucagon receptor inhibitor (GcgRi) blunted the effect on CFVR but not contractility. Dapagliflozin increased the Arg/ADMA ratio and ketone levels and co-treatment with GcgRi blunted only the Dapagliflozin induced increase in Arg/ADMA ratio but not ketone levels. Since GcgRi co-treatment only reduced the Arg/ADMA increase we hypothesize that dapagliflozin via a glucagon-signaling dependent pathway improves vascular function through the NO-signaling pathway leading to improved vascular function. Increase in ketone levels might be a contributing factor in SGLT2i induced contractility increase and does not require glucagon signaling.

Abstract 4119744: Evaluation of Neuropsychological development and Factors Affecting it in Children With Cyanotic and Acyanotic Congenital Cardiac Disease After Surgical Treatment

Objective: To evaluate neuropsychological development in children with cyanotic and acyanotic congenital heart diseases (CHDs) after surgical treatment and analyze the risk factors. Methods: 89 children who received follow-up in Fuwai Hospital after surgical treatment of CHDs were recruited in this study and 90 normal children were recruited as the control group. The children with CHDs were divided into cyanotic CHDs group and acyanotic CHDs group. Neuropsychological development was assessed according to Pediatric-psychological mental test scale and statistical analysis was employed. Results: The acyanotic CHDs group achieved better distribution of development quotient than cyanotic CHDs group (p < 0.05) but worse than the normal control group (p = 0.004). The proportion in cyanotic CHDs group with developmental quotient below the moderate level was higher than that of the normal control group (p < 0.001), but there was no significant difference between the cyanotic CHDs group and acyanotic CHDs group (p = 0.055). Multivariate regression analysis indicated that for cyanotic CHDs group, younger age at cardiac surgery, lower body mass, lower preoperative blood glucose level, lower BIS level, and prolonged duration of tracheal intubation after surgery were linked with lower scores in the test scale (p < 0.05); for acyanotic CHDs group, younger age at cardiac surgery, lower body mass, lower temperature during surgery and prolonged duration of tracheal intubation after surgery were linked with lower scores in the test scale(p < 0.05). Conclusion: Distinct neuropsychological impairment could be present in children with cyanotic CHDs. Younger age at cardiac surgery, body mass, preoperative blood glucose level, BIS level during surgery, temperature during surgery and duration of tracheal intubation after surgery were perioperative factors that could influence long-time neuropsychological development in children with CHDs.

Effects of Soluble and Insoluble Fibre on Glycolipid Metabolism and Gut Microbiota in High-Fat-Diet-Induced Obese Mice

Background: Dietary fibre can alleviate or reduce the risk of obesity and obesity-induced abnormalities in glycolipid metabolism. However, the effects of different types of dietary fibre or their combinations on obesity remain unclear. Here, we explored the effects of different ratios of inulin soluble dietary fibre (ISDF) and barley leaf insoluble dietary fibre (BLIDF) on the body weight, glycolipid metabolism and gut microbiota of obese mice. Methods: Seven experimental groups were treated with different combinations of soluble and insoluble fibre, comprising HFD (high-fat diet without dietary fibre), BLIDF, ISDF, I3S1DF (insoluble/soluble = 3:1), I2S2DF (insoluble/soluble = 1:1), I1S3DF (insoluble/soluble = 1:3) and MIX (inulin, BLIDF and matcha powder fibre; insoluble/soluble = 3.6:1) groups. Results: Our results showed that the BLIDF, ISDF and MIX treatments decreased the body weight gain of the HFD mice significantly after eight-week interventions. All the fibre intervention groups except the MIX group displayed lower fasting blood glucose and glycosylated serum protein levels than the HFD group. BLIDF, ISDF, I3S1DF and I2S2DF improved the glucose tolerance of the mice. Moreover, none of the dietary fibre interventions affected the liver lipid metabolism, while I3S1DF and I1S3DF improved the abnormal serum lipid metabolism. BLIDF, ISDF, I3S1DF and I2S2DF reduced the serum IL-6 levels, and BLIDF and I1S3DF increased SOD activity significantly. Additionally, all the dietary fibre interventions decreased the Firmicutes to Bacteroidota (F/B) ratio and increased the abundance of beneficial gut microbes differently. Conclusions: In short, our results suggest that different ratios of soluble and insoluble dietary fibre have unique impacts on mice body weight, glycolipid metabolism, inflammation and gut microbiota. The ratio of soluble to insoluble dietary fibre intake should be considered for specific health goals in the future.

Association between the oxidative balance score with metabolic syndrome traits in US adults

ObjectiveTo explore the association between the Oxidative Balance Score (OBS), which represents the balance of multiple oxidative stress-related dietary and lifestyle exposures, and the risk of metabolic syndrome (MetS).MethodsA population-based cross-sectional study design was adopted and 16,850 participants in NHANES database were included in the statistics analysis stage. The OBS was constructed by combining information from 20 a priori selected pro- and antioxidant factors. Weighted logistic regression and restricted cubic splines (RCS) were used to estimate the association between OBS and MetS.ResultsParticipants in the highest OBS quartile, indicating low oxidative stress (OS) levels, exhibited a significantly lower risk of MetS (odds Ratio [OR] = 0.55, 95% confidence Interval [CI]: 0.47–0.64) compared to the lowest quartile. Specifically, higher OBS was inversely associated with abdominal obesity (OR = 0.61, 95% CI: 0.54–0.69), hypertension (OR = 0.69, 95% CI: 0.58–0.83), elevated triglycerides (OR = 0.68, 95% CI: 0.57–0.82), low high-density lipoprotein cholesterol (HDL-C) levels (OR = 0.60, 95% CI: 0.50–0.70) and fasting blood glucose (FBG) levels (OR = 0.74, 95% CI: 0.62–0.88). The observed inverse association between OBS and hypertension or FBG levels appeared to primarily influenced by BMI. The association between dietary OBS intervals and elevated FBG levels was not statistically significant in men, whereas the risk was lower by 25% in women.ConclusionsA higher OBS, representing a balance of multiple oxidative stress-related dietary and lifestyle exposures, is associated with a lower risk of MetS. Therefore, adhering to an antioxidant diet and lifestyle may help prevent the occurrence of metabolic disorders.

Empagliflozin Attenuates High-Glucose-Induced Astrocyte Activation and Inflammation via NF-κB Pathway

Sodium-glucose cotransporter-2 (SGLT2) inhibitors regulate blood glucose levels in patients with type 2 diabetes mellitus and may also exert anti-inflammatory and anti-atherosclerotic effects by promoting M2 macrophage polarization. Although SGLT2 is expressed in brain regions that influence glucose balance and cognitive function, its roles in the central nervous system are unclear. This study investigated the effects of empagliflozin (EMPA), an SGLT2 inhibitor, on hypothalamic inflammation associated with metabolic diseases. Mice were subjected to a high-fat diet (HFD) for varying durations (3 d, 3 weeks, and 16 weeks) and treated with EMPA for 3 weeks (NFD, NFD + EMPA, HFD, HFD + EMPA; n = 5/group). EMPA regulated the expression of astrocyte markers and pro-inflammatory cytokine mRNA in the hypothalamus of HFD-induced mice, which was linked to regulation of the NF-κB pathway. Under hyperglycemic conditions, EMPA may mitigate hypothalamic inflammation by modulating astrocyte activation via the NF-κB pathway. Our findings demonstrated that EMPA possesses therapeutic potential beyond merely lowering blood glucose levels, opening new avenues for addressing inflammation and providing neuroprotection in metabolic disease management.

Randomized trial of early exercise rehabilitation and its effects on patients with acute coronary syndrome

To assess the psychological and physiological benefits of early exercise rehabilitation in patients with acute coronary syndrome (ACS). Among 559 ACS-diagnosed patients at Fuzhou University Affiliated Provincial Hospital from January to December 2021, 200 eligible participants were assigned to two groups. The control group received standard care, while the experimental group received early exercise rehabilitation in addition to standard care. The outcomes measured included changes in depression levels (PHQ-9), fasting blood glucose, and troponin I (TnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Data were analyzed using SPSS, with t tests and chi-square tests for group comparisons. In comparison to the control group, the experimental group demonstrated significant improvements in PHQ-9 scores (P < 0.001) and lower fasting blood glucose levels before discharge (P = 0.046). Additionally, the experimental group had notably reduced TnI levels at 72 h after admission (P = 0.001), especially among non-diabetic NSTEMI patients over 60 years old, who showed decreased TnI levels at the 48-hour mark (P = 0.016). However, there were no significant differences in NT-ProBNP change values between the two groups (P > 0.05). Subgroup analysis revealed enhanced outcomes in the intervention group for ACS patients without smoking or drinking history and no heart failure (P = 0.025,P = 0.014,P = 0.018). Early exercise rehabilitation has notable benefits for ACS patients, including reduced depression, improved blood glucose control, and enhanced myocardial protection, especially in nondiabetic NSTEMI patients aged 60 and above.

Administration of a diabetes-specific formula can improve postprandial glycemic control and delay insulin use in gestational diabetes mellitus: a randomized controlled trial from two centers

Background and AimsThere have been limited studies on the application of a diabetes-specific formula in gestational diabetes mellitus (GDM), the role of which has not been well studied. We explored the effect of a diabetes-specific formula on blood glucose levels, insulin use and pregnancy outcomes in GDM patients. MethodsIn this randomized controlled study, 112 GDM patients were randomly assigned to the intervention group (56) and the control group (56). Both groups received individualized dietary counseling. The intervention group consumed a soy-protein-based, high-monounsaturated-fatty-acid, and multi-fiber diabetes-specific formula as milk replacement for breakfast and an extra meal after dinner. All participants were followed up every two weeks until delivery. The blood glucose levels, insulin use and pregnancy outcomes between the groups were compared. ResultsCompared to the control group, the intervention group had significantly lower 2h postprandial blood glucose levels after breakfast (5.84±0.56 vs. 6.15±0.44mmol/L, p=0.008), and exhibited higher postprandial time in range values (83.80% vs. 78.95%, p=0.045). The intervention group used insulin later (33 vs. 28 weeks, p=0.015) and for fewer days (36 vs 78 days, p=0.024), but no differences in the proportion, dose or frequency of insulin use between the groups. There were no significant differences in pregnancy outcomes between the groups. ConclusionsThe diabetes-specific formula significantly decreased postprandial blood glucose levels and improved postprandial glycemic control in GDM patients. Moreover, it delayed the initiation of insulin use and reduced the duration of insulin therapy. Our findings may offer a potential new approach for achieving better personalized blood glucose control in GDM patients. Registration number of Clinical TrialNCT03957603 (registered at ClinicalTrials.gov).

Organophosphorus Flame Retardants and Metabolic Disruption: An in Silico, in Vitro, and in Vivo Study Focusing on Adiponectin Receptors.

Environmental chemical exposures have been associated with metabolic outcomes, and typically, their binding to nuclear hormone receptors is considered the molecular initiating event (MIE) for a number of outcomes. However, more studies are needed to understand the influence of such exposures on cell membrane-bound adiponectin receptors (AdipoRs), which are critical metabolic regulators. We aimed to clarify the potential interactions between AdipoRs and environmental chemicals, specifically organophosphorus flame retardants (OPFRs), and the resultant effects. Employing in silico simulation, cell thermal shift, and noncompetitive binding assays, we screened eight OPFRs for interactions with AdipoR1 and AdipoR2. We tested two key events underlying AdipoR modulation upon OPFR exposure in a liver cell model. The Toxicological Prioritization Index (ToxPi)scoring scheme was used to rank OPFRs according to their potential to disrupt AdipoR-associated metabolism. We further examined the inhibitory effect of OPFRs on AdipoR signaling activation in mouse models. Analyses identified pi-pi stacking and pi-sulfur interactions between the aryl-OPFRs 2-ethylhexyl diphenyl phosphate (EHDPP), triphenyl phosphate (TPhP), and tricresyl phosphate (TCP) and the transmembrane cavities of AdipoR1 and AdipoR2. Cell thermal shift assays showed a rightward shift in the AdipoR proteins' melting curves upon exposure to these three compounds. Although the binding sites differed from adiponectin, results suggest that aryl-OPFRs noncompetitively inhibited the binding of the endogenous peptide ligand ADP355 to the receptors. Analyses of key events underlying AdipoR modulation revealed that glucose uptake was notably lower, whereas lipid content was higher in cells exposed to aryl-OPFRs. EHDPP, TCP, and TPhP were ranked as the top three disruptors according to the ToxPi scores. A noncompetitive binding between these aryl-OPFRs and AdipoRs was also observed in wild-type (WT) mice. In db/db mice, the finding of lower blood glucose levels after ADP355 injection was diminished in the presence of a typical aryl-OPFR (TCP). WT mice exposed to TCP demonstrated lower AdipoR1 signaling, which was marked by lower phosphorylated AMP-activated protein kinase (pAMPK) and a higher expression of gluconeogenesis-related genes. Moreover, WT mice exposed to ADP355 demonstrated higher levels of pAMPK protein and peroxisome proliferator-activated receptor- messenger RNA. This was accompanied by higher glucose disposal and by lower levels of long-chain fatty acids and hepatic triglycerides; these metabolic improvements were negated upon TCP co-treatment. In silico, in vitro, and invivo assays suggest that aryl-OPFRs act as noncompetitive inhibitors of AdipoRs, preventing their activation by adiponectin, and thus function as antagonists to these receptors. Our study describes a novel MIE for chemical-induced metabolic disturbances and highlights a new pathway for environmental impact on metabolic health. https://doi.org/10.1289/EHP14634.

Inhibitory mechanism of apigenin, quercetin, and phloretin on α-glucosidase

Flavonoids present promising potential as α-glucosidase inhibitors, with potential benefits in lowering blood glucose levels. In our previous study, apigenin, quercetin, and phloretin obtained from whole-grain highland barley demonstrated notable efficacy as α-glucosidase inhibitors. Therefore, in this study, we used enzyme kinetics, fluorescence spectroscopy, circular dichroism, and molecular docking to explore the interactions between apigenin, quercetin, and phloretin, and α-glucosidase. With the addition of three flavonoids, the inhibitory effect of all the flavonoids on α-glucosidase activity was reversible and exhibited a mixed-type pattern. Molecular docking analysis revealed that the three flavonoids predominantly bind to yeast-derived α-glucosidase mainly through hydrophobic interactions and van der Waals forces, whereas the interaction with human-derived α-glucosidase involved hydrophobic interactions. Further experiments revealed that the flavonoids quenched the fluorescence of α-glucosidase due to the complex formation between the flavonoids and α-glucosidase, leading to changes in the protein secondary structure and conformational changes, which was further supported by molecular dynamics simulations. These results provided insights into the mechanism of the flavonoid inhibition of α-glucosidase. These findings could promote the consumption of whole-grain highland barley and the development of hypoglycemic foods rich in flavonoids.

Anti-diabetic and anti-inflammatory activities of Marrubiin isolated from Marrubium vulgare: Indications of its interaction with PPAR γ

BackgroundThe aerial parts of Marrubium vulgare L. were used for many ailments like catarrh to diabetes in many parts of Latin America and Asia. PurposeIdentifying the active principle responsible for anti-diabetic activity of methanol extract of M. vulgare leaves and to predict the possible targets. Study designAll the activity investigations were conducted simultaneously for the extract, fraction, and isolated compounds to decipher the activity profile in comparison to each other which allowed the identification of an active principle followed by use of in silico methods to identify the possible target/s. MethodsThe aerial parts of M. vulgare were extracted using methanol. A chloroform fraction was prepared. Marrubiin and marrubinone B were isolated from this fraction. The anti-hyperglycemic, hypoglycemic, and postprandial blood glucose lowering activities were investigated using streptozotocin-induced diabetic and non-diabetic rat models. Pro-inflammatory cytokine inhibitory potential was investigated using LPS induced acute-inflammatory mouse model and RAW 264.7 cells. Further, antioxidant activity was investigated using a DPPH assay. The in silico analysis, using the Swiss-target prediction tool, was carried out to predict the probable targets of the isolated molecules. ResultsMarrubiin exhibited anti-hyperglycemic effect in diabetic rats followed by hypoglycemia, and postprandial blood glucose lowering in non-diabetic rats. Methanol extract (Mv extract) and chloroform fraction (Mv fraction) showed anti-hyperglycemic and hypoglycemic effects. Moderate inhibition of IL-1β, TNF-α, and IL-6 was observed for marrubiin, marrubinone B, Mv extract, and Mv fraction, in vitro and in vivo. Neither marrubiin nor marrubinone B could quench the DPPH free radicals while Mv extract and Mv fraction could show 80 % suppression. In silico analysis has predicted that marrubiin can interact with PPAR γ but not marrubinone B. ConclusionsMarrubiin and marrubinone B were responsible for the anti-inflammatory effect of Mv extract and Mv fraction while not contributing to the antioxidant effect. Marrubiin was found to be responsible for the anti-diabetic activity of Mv extract. The predicted interaction propensity of marrubiin with PPAR γ could explain its dual activity observed in the experimental setup.

Sexual Dimorphism in the Immunometabolic Role of Gpr183 in Mice.

Excessive eating and intake of a Western diet negatively affect the intestinal immune system, resulting in compromised glucose homeostasis and lower gut bacterial diversity. The G protein-coupled receptor GPR183 regulates immune cell migration and intestinal immune response and has been associated with tuberculosis, type 1 diabetes, and inflammatory bowel diseases. We hypothesized that with these implications, GPR183 has an important immunometabolic role and investigated this using a global Gpr183 knockout mouse model. Wild-type (WT) and Gpr183-deficient (Gpr183-/-) mice were fed a high-fat, high-sucrose diet (HFSD) for 15 weeks. We investigated changes in weight, body composition, fecal immunoglobulin A (IgA) levels, fecal microbiome, and glucose tolerance before and after the diet. Macrophage infiltration into visceral fat was determined by flow cytometry, and hepatic gene expression was measured. A sexual dimorphism was discovered, whereby female Gpr183-/- mice showed adverse metabolic outcomes compared to WT counterparts with inferior glucose tolerance, lower fecal IgA levels, and increased macrophage infiltration in visceral fat. In contrast, male Gpr183-/- mice had significantly lower fasting blood glucose after diet than male WT mice. Liver gene expression showed reduced inflammation and macrophage markers in Gpr183-/- livers, regardless of sex, while the pancreatic islet area did not differ between the groups. No conclusive differences were found after microbiome sequencing. Gpr183 maintains metabolic homeostasis in female but not in male mice independent of diet. If confirmed in humans, future therapy targeting GPR183 should consider this sexual dimorphism.

Effects of Ovariectomy on Kidney Injury in SDT Fatty Rats

Postmenopausal women are at a higher risk of developing diabetes, and estrogen can lower blood glucose levels. The purpose of this study was to investigate the effect of ovariectomy (OVX) on the pathology of diabetic nephropathy. Female SD rats and SDT fatty rat underwent bilateral OVX or sham treatment at 6 weeks of age, and their blood and kidneys were collected at 40 weeks of age for blood biochemical and histopathological analyses. OVX treatment resulted in a decrease in blood estradiol levels at 24 and 40 weeks of age. Histopathological analysis revealed that Sham-treated SDT fatty rats showed glomerular atrophy, adhesions, enlargement, mesangial cell proliferation, regenerated tubules, hyaline casts, Armani-Ebstein lesions, tubular dilatation, interstitial inflammatory cell infiltration, and fibrosis. OVX treatment slightly reduced glomerular atrophy and enlargement, renal tubular dilatation, and interstitial inflammatory cell infiltration, while slightly increased or exacerbated mesangial cell hyperplasia, tubular regeneration, and Armani-Ebstein lesions. The above findings suggest that SDT fatty rats are not a practical model to study postmenopausal diabetic nephropathy.

Hypoglycaemia Prevention, Awareness of Symptoms, and Treatment (HypoPAST): protocol for a 24-week hybrid type 1 randomised controlled trial of a fully online psycho-educational programme for adults with type 1 diabetes

BackgroundManagement of type 1 diabetes (T1D) requires the use of insulin, which can cause hypoglycaemia (low blood glucose levels). While most hypoglycaemic episodes can be self-treated, all episodes can be sudden, inconvenient, challenging to prevent or manage, unpleasant and/or cause unwanted attention or embarrassment. Severe hypoglycaemic episodes, requiring assistance from others for recovery, are rare but potentially dangerous. Repeated exposure to hypoglycaemia can reduce classic warning symptoms (‘awareness’), thereby increasing risk of severe episodes. Thus, fear of hypoglycaemia is common among adults with T1D and can have a negative impact on how they manage their diabetes, as well as on daily functioning, well-being and quality of life. While advances in glycaemic technologies and group-based psycho-educational programmes can reduce fear, frequency and impact of hypoglycaemia, they are not universally or freely available, nor do they fully resolve problematic hypoglycaemia or associated worries. This study aims to determine the effectiveness of a fully online, self-directed, scalable, psycho-educational intervention for reducing fear of hypoglycaemia: the Hypoglycaemia Prevention, Awareness of Symptoms, and Treatment (HypoPAST) programme.MethodsA 24-week, two-arm, parallel-group, hybrid type 1 randomised controlled trial, conducted remotely (online and telephone). Australian adults (≥ 18 years) with self-reported T1D and fear of hypoglycaemia will be recruited, and allocated at random (1:1) to HypoPAST or control (usual care). The primary outcome is the between-group difference in fear of hypoglycaemia (assessed using HFS-II Worry score) at 24 weeks. A sample size of N = 196 is required to detect a 9-point difference, with 90% power and allowing for 30% attrition. Multiple secondary outcomes include self-reported psychological, behavioural, biomedical, health economic, and process evaluation data. Data will be collected at baseline, 12 and 24 weeks using online surveys, 2-week ecological momentary assessments, website analytics and semi-structured interviews.DiscussionThis study will provide evidence regarding the effectiveness, cost-effectiveness and acceptability of a novel, online psycho-educational programme: HypoPAST. Due to the fully online format, HypoPAST is expected to provide an inexpensive, convenient, accessible and scalable solution for reducing fear of hypoglycaemia among adults with T1D.Trial registrationAustralian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623000894695 (21 August 2023).

The relationship between daily blood glucose fluctuation and readmission in patients with acute coronary syndrome

Abstract Background Although the comprehensive diagnos and treatment of patients with acute coronary syndrome(ACS) has been greatly improved,the morbidity and mortality are still high. Previous literature has reported that about 70-75% of patients diagnosed with acute coronary syndrome have abnormal blood glucose metabolism1,and there existed gender differences. At present, most research results showed that elevated blood glucose is related to the prognosis of ACS. However, further intervention studies indicated that simply strengthen the reducement of blood glucose did not improve prognosis of these patients2. Glucose fluctuations, another dimension of blood glucose, reflect acute changes in blood glucose. However, there are few studies on the effect of blood glucose fluctuation on the prognosis of patients with ACS. Purpose This study aimed to explore the relationship between seven daily fluctuations of blood glucose and readmission in ACS patients. Methods In this study, a total of 664 patients admitted to our University from January 1, 2019 to December 31, 2019 were included and their blood glucose was monitored seven times a day during their hospitalization. The coefficient of variation of blood glucose (CV) was calculated from the results of seven daily blood glucose monitoring to represent the daily fluctuation of blood glucose. Univariate and multivariate regression analyses were performed to determine whether CV was an independent risk factor for re-hospitalization. In addition, the area under the curve (AUC) was used to evaluate the predictive efficacy of CV for outcome events. Finally, we performed a subgroup analysis based on gender and diabetes status to assess the association between CV and readmission in each subgroup. Results After a median follow-up of 21 months, the rate of readmission was 38.4%. Unstable angina pectoris (71.4%) and heart failure (16.4%) were the most common reasons for readmission. Patients with greater CV levels typically exhibited lower fasting blood glucose, higher post breakfast blood glucose, and higher admission blood glucose.The readmission rate increased with the increasing blood glucose variability after the cox regression analysis. Moreover, independent of glycated hemoglobin,CV could predict the risk of readmission in patients with ACS.When using 26.66% as the cutoff point of CV, the study population was divided into two groups and showed a significant differentiation for rehospitalization.In subgroup analysis, there was no significant association between seven daily blood glucose fluctuations and readmission in female and non-diabetes mellitus patients with acute coronary syndrome. Conclusions Besides some normal blood glucose index,seven daily fluctuations of blood glucose was associated with readmission in ACS patients. ACS patients who were male and combined with diabetes were more likely to be readmitted if their CV levels were greater.

A real-world data analysis investigating the cardioprotective effects of glucagon-like peptide-1 receptor agonists among people with type 2 diabetes in England

Abstract Background Cardiovascular disease (CVD) is a common and major complication of type 2 diabetes (T2D). Anti-diabetic therapy aims to lower blood glucose, with primary clinical trial endpoints for new antidiabetic entrants focused on HbA1c. Research suggests some glucose-lowering drugs, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), can have a cardioprotective effect in people with T2D.1,2 Purpose To compare the real-world risk of major adverse cardiovascular event (MACE) in people with T2D treated with GLP-1 RAs compared to dipeptidyl peptidase-4 (DPP-4) inhibitors or basal insulin. Methods We conducted a retrospective cohort study using linked primary care data from the Clinical Practice Research Datalink Aurum, secondary care Hospital Episode Statistics and Office for National Statistics death registrations. We included patients aged ≥18 years with T2D at high-risk or very-high-risk of CVD (as defined by the European Society of Cardiology) who had ≥2 prescriptions of either GLP-1 RA (dulaglutide, liraglutide, and semaglutide), DPP-4 inhibitor (as part of line 4 therapy) or basal insulin from 01/01/2014-31/12/2018. We excluded those pregnant at therapy initiation or with type 1 diabetes. Follow-up started at second prescription of relevant therapy and ended at the earliest of two years later, pregnancy, death, end of primary care record, or 31/12/2019. We used data from patients’ medical histories to define baseline characteristics. We calculated the incidence of MACE per 100,000 person-years (PY), defined as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. We used Cox proportional hazards regression, using LASSO to select confounding clinical variables including BMI, prior MACE and intercurrent antidiabetic treatments, to estimate risk difference of MACE among those treated with 1) GLP1-RA and DPP-4 inhibitor and 2) GLP1-RA and basal insulin. Results We included 63,237 patients, among whom the patients treated with GLP1-RA were younger and a higher proportion were obese or severely obese than those treated with DPP-4 inhibitor or basal insulin (Table 1). The incidence of MACE was highest in those treated with DPP-4 inhibitor (high-risk 1,503.0/100,000 PY; very-high-risk 6,000.7/100,000 PY) followed by basal insulin (high-risk 1,396.9/100,000 PY; very-high-risk 5,707.1/100,000 PY), and lowest in those treated with GLP1-RA (high-risk 377.1/100,000 PY; very-high-risk 1,946.1/100,000 PY). After adjustment, the risk of MACE among patients treated with GLP1-RA was still significantly lower than those treated with either DPP-4 inhibitor (high-risk aHR: 0.42, 95% CI 0.21-0.86 and very-high-risk aHR: 0.65, 95% CI 0.58-0.73) or those treated with basal insulin (high-risk aHR: 0.36, 95% CI 0.18-0.72 and very-high-risk aHR: 0.72, 95% CI 0.64-0.81). Conclusion(s) Our study supports clinical trial and other observational research studies which find a cardioprotective effect of GLP-1 RA use in people with T2D.

The Triglycerides - Glucose Index: An independent predictor of late subclinical cardiotoxicity in adult survivors of childhood, adolescent and young adult cancer

Abstract Introduction The Triglycerides - Glucose index (TyG index) has been identified as a reliable alternative for estimating insulin resistance (IR). Numerous recent studies have provided strong statistical evidence suggesting that this index is associated with the development and prognosis of cardiovascular pathologies. Objectives The aim of this study was to investigate the predictive role of the TyG index on the decrease in left ventricular longitudinal global strain (GLS) assessed on two-dimensional echocardiography in asymptomatic adult survivors of childhood, adolescent and young adult cancer. Methods The study included patients aged 18 years and older, asymptomatic cardiovascular survivors of childhood, adolescent and young adult cancer treated with anthracyclines with or without mediastinal radiotherapy. Anthropometric characteristics, cardiovascular risk factors and cancer treatment-related characteristics were collected. The TyG index was calculated using the formula: ln [fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. GLS was assessed and expressed as an absolute value. A GLS equal to 17.3% was retained as the threshold value after calculation in a referent group matched to patients according to age and gender. Cardiac biomarkers GDF 15, ultra-sensitive troponin I and NT-proBNP levels were measured in addition to fasting blood glucose and lipid profiles. Multivariate analysis using linear regression was performed to identify associations between these different parameters. Results A total of 105 cancer survivors from childhood, adolescence and young adulthood were included. The sex ratio was 1.3. The mean age of the patients was 25 years, the mean time since completion of cancer treatment was 10.6 years, the mean cumulative doses of anthracyclines and mediastinal radiotherapy were successively 245.75 ± 75.14 mg/m2 and 34.6 ± 6.19 Gy. Mean GLS was 18.5 ± 2.83%, mean LVEF 60.6 ± 5.69%. None of the patients had any known diabetes or treatment to lower blood glucose or triglyceride levels. No patient had a history of cardiovascular disease. In the univariate study, the factors associated with lower GLS were patient age at recruitment (p = 0.03), mean time since completion of cancer treatment when this was greater than ten years (p = 0.005), dyslipidemia (p = 0.012), obesity (p = 0.037) and TyG (p = 0.037). In multivariate analysis, lower GLS was related to mean time since completion of cancer treatment (p = 0.015) and TyG index (p = 0.002). Conclusion Our results suggest that the TyG index, as a simple and inexpensive marker of insulin resistance, could help identify cancer survivors from childhood, adolescence and young adulthood who would be at risk of subclinical cardiac dysfunction. Prospective studies with larger numbers are needed to confirm these findings.

Effectiveness and mechanisms of sodium-dependent glucose transporter 2 inhibitors in type 2 diabetes and heart failure patients.

We comment on an article by Grubić Rotkvić et al published in the recent issue of the World Journal of Cardiology. We specifically focused on possible factors affecting the therapeutic effectiveness of sodium-dependent glucose transporter inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM) and their impact on comorbidities. SGLT2i inhibits SGLT2 in the proximal tubules of the kidneys, lowering blood glucose levels by inhibiting glucose reabsorption by the kidneys and causing excess glucose to be excreted in the urine. Previous studies have demonstrated a role of SGLT2i in cardiovascular function in patients with diabetes who take metformin but still have poor glycemic control. In addition, SGLT2i has been shown to be effective in anti-apoptosis, weight loss, and cardiovascular protection. Accordingly, it is feasible to treat patients with T2DM with cardiovascular or renal diseases using SGLT2i.

Novel Phenoxyalkanoic Acid Derivatives as Free Fatty Acid Receptor 4 Agonists for Treating Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) is a common metabolic disease that poses a severe threat to human health. Despite a range of therapeutic approaches, there remains a lack of effective and safe therapies with the existing drugs. Therefore, there is an urgent need to develop novel, effective, and safe therapeutic strategies for DM. Free fatty acid receptor 4 (FFAR4), also known as GPR120, is a member of the G protein-coupled receptor family, which has received considerable attention as an attractive new therapeutic target for treating DM. In the present study, based on the structure of TUG-891, which has excellent activity and selectivity, a series of novel FFAR4 agonists was designed by replacing the phenylpropanoic acid β position carbon atom with an oxygen atom, while replacing the linking oxymethylene with an amide-linking group. The target compounds were evaluated for FFAR4 agonistic activity, and the preferred compounds were evaluated for selectivity, oral glucose tolerance in normal ICR mice, antidiabetic activity in diet-induced obese (DIO) mice, pharmacokinetic properties in ICR mice and molecular modeling studies. The results showed that compound 10f possessed excellent FFAR4 agonistic activity and selectivity, significantly improved glucose tolerance in normal ICR mice, lowered blood glucose and promoted insulin secretion in a dose-dependent manner in DIO mice, and showed favorable pharmacokinetic properties. These results indicate that compound 10f may be a promising compound that deserves further structure-activity relationship and pharmacological studies for the development of antidiabetic drugs.

A Study of the Role of Statins in the Treatment of Coronary Heart Disease

Statins, as hydroxymethylglutaryl coenzyme A reductase inhibitors, have a significant effect on lowering cholesterol, and are widely used in the clinical treatment of cardiovascular and cerebrovascular diseases, and are potent drugs for the prevention and treatment of coronary heart disease. Recent studies have shown that statins also have other effects, such as lowering blood pressure, lowering blood glucose, stabilizing atherosclerotic plaques, slowing down the proliferation and migration of smooth muscle cells, anti-inflammatory and antihypertensive, etc., which are very significant. This paper addresses the physicochemical properties, pharmacological effects, adverse effects, and therapeutic applications of statins in the treatment of cardiovascular diseases (coronary heart disease).

Exploring the Cardiorenal Benefits of SGLT2i: A Comprehensive Review

The history of sodium-glucose cotransporter 2 inhibitors (SGLT2i) is so long and started in 1835 when Petersen extracted a compound called phlorizin from apple tree bark. About fifty years later, von Mering discovered its glucosuric properties. In the 1980s, it was discovered that the glucosuria resulted from inhibition by phlorizin of glucose reabsorption by the renal tubules, which lowered blood glucose levels in diabetic rats. Nowadays, beyond their glucose-lowering effects, growing evidence suggests significant cardiorenal benefits associated with SGLT2i therapy. Indeed, several clinical trials, including landmark studies such as EMPA-REG OUTCOME, CANVAS Program, and DECLARE-TIMI 58, have demonstrated robust reductions in cardiovascular events, particularly heart failure hospitalizations and cardiovascular mortality, among patients treated with SGLT2i. However, subsequent trials showed that SGLT2i benefits extend beyond the diabetic population, encompassing individuals with and without diabetes. Additionally, SGLT2i exhibit nephroprotective effects, manifesting as a slowing of the progression of chronic kidney disease and a reduction in the risk of end-stage kidney disease. The mechanisms underlying the cardiorenal benefits of SGLT2i are multifactorial and include improvements in glycemic control, reduction in arterial stiffness, modulation of inflammation and oxidative stress, reduction of intraglomerular pression and promotion of natriuresis and diuresis through inhibition of SGLT2 in the luminal brush border of the first segments of the proximal kidney tubule. This narrative review aims to explore the cardiorenal outcomes of SGLT2i, encompassing their mechanisms of action, clinical evidence, safety profile, and implications for clinical practice.