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

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

Association of adiponectin gene single nucleotide polymorphisms with environmental risk factors in type 2 diabetes mellitus: An updated evidence of haplotype-based analysis study.

BACKGROUND AND AIM: Adiponectin (ADIPOQ) gene is considered to be one of the promising players in deciphering the genetic bases of type 2 diabetes. This study investigated the associations between haplotype combinations of three single nucleotide polymorphisms (SNPs) of the ADIPOQ gene and two SNPs of the adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) genes with environmental risk factors for the prediction of T2DM disorder susceptibility in the Iranian population. METHODS: This case-control and cross-sectional study was conducted on 182 patients with T2DM and 155 healthy controls. Genotyping was performed using amplification refractory mutation system-PCR (ARMS-PCR) for rs17300539G/A, rs2241766T/G, and rs1501299G/T of the ADIPOQ gene, rs1342387C/T of the AdipoR1 gene, and rs10773989T/C of the AdipoR2 gene. RESULTS: All polymorphisms met the Hardy-Weinberg equilibrium (p> 0.05). The studied SNPs; rs17300539, rs2241766 of the ADIPOQ gene and rs10773989 of the AdipoR2 gene, were significantly associated with an increased risk of T2DM. Two-way ANOVA analysis indicated that GG carriers of rs2241766T/G had a significantly lower waist-to-hip ratio (P= 0.049) and body mass index (P= 0.011) and higher HbA1c (P= 0.048) compared to TT carriers, while TT genotype carriers of rs2241766T/G showed the higher plasma adiponectin concentration compared to TG and GG carriers (P= 0.009 and P= 0.013, respectively). CC carriers of rs10773989T/C displayed a significantly higher LDL level compared to the TT genotype carries (P= 0.036). Also plasma adiponectin concentrations were significantly lower in AA genotype carriers of rs17300539G/A compared to GG and GA genotypes carriers in the control group only (P= 0.005 and P= 0.016, respectively). According to Combined Haplotype ([rs17300539, rs2241766, rs1501299]/[rs17300539, rs2241766, rs1501299]) analysis, GTT-homozygote carriers displayed the highest plasma adiponectin concentration and in contrast, GGG/GTG, ATG/GTG, and GGG/GGG showed the lowest plasma adiponectin concentration in the controls (p> 0.05). CONCLUSION: The adiponectin gene haplotype combinations were associated with plasma adiponectin concentration in healthy individuals. In T2DM, adiponectin genetic variants displayed less effect on adiponectin plasma concentration.

NLRP3 Inhibitor Alleviates Glycemic Variability-Induced Cognitive Impairment in Aged Rats with Type 2 Diabetes Mellitus.

Glycemic variability (GV) markedly exacerbates cognitive impairment in elderly patients with type 2 diabetes mellitus (T2DM), in part through chronic inflammation. This study investigated the therapeutic efficacy of the NLRP3 inflammasome inhibitor MCC950 in mitigating GV-induced cognitive impairment in an aged rat model of T2DM. Aged Sprague-Dawley rats with induced T2DM were subjected to GV conditions, and the effects of MCC950 were evaluated through measurement of body weight, blood glucose, lipid profiles, insulin level, inflammatory markers, and cognitive function. Transcriptomic analysis was performed on the hippocampus and prefrontal cortex. Treatment with MCC950 significantly alleviated weight loss and hyperglycemia in the GV group compared with the control group. MCC950 also reduced the levels of cholesterol, triglycerides, and pro-inflammatory markers (interleukin-1ß (IL-1ß) and interleukin-18 (IL-18)). Most notably, MCC950 improved spatial learning and memory retention in the GV group. Immunohistochemical analysis indicated a reduction in inflammasome activation and an increase in the expression level of the neuronal marker NeuN in the hippocampus. Transcriptomic analysis revealed that MCC950 altered neuroactive ligand-receptor interaction pathways in the hippocampus and influenced receptor binding and cell adhesion processes in the prefrontal cortex. These findings validated the efficacy of NLRP3 inhibitor in mitigating GV-induced cognitive impairment in elderly rats with T2DM and provided the basis for subsequent clinical studies exploring the broader potential of NLRP3-targeted interventions in addressing diabetes-associated cognitive impairment.

Substituting potatoes with other food groups and type 2 diabetes risk: findings from the Diet, Cancer, and Health Study.

BACKGROUND: While potatoes are considered a dietary staple in some cultures, evidence suggests that their impact on T2D risk is nuanced, with preparation methods and dietary patterns playing crucial roles. Investigating the substitution effects of replacing potatoes with other foods is required to inform dietary recommendations for lowering T2D risk. OBJECTIVE: To investigate associations between the substitution of potatoes (excluding fries/chips) with other food groups (vegetables, wholegrains, refined grains, red meat, processed meat, poultry, fish, and dairy) and the risk of T2D. METHODS: The diet of participants from the prospective Danish Diet, Cancer, and Health study (DCH) was captured at baseline (1993-1997) by a food frequency questionnaire. Participants were followed up for incident T2D from baseline until 2012. Associations between the substitution of potatoes (total, boiled, and mashed) with other food groups and incident T2D was assessed by multivariable Cox-proportional hazards model. RESULTS: In 54,793 DCH study participants, during a median follow-up of 16.3 years, 7,693 incident T2D cases were recorded. A 26% lower risk of T2D was observed when 50 g/day of potatoes were substituted with the same amount of wholegrains [HR and 95% CI: 0.74 (0.70, 0.79)]. Similarly, a lower risk of T2D was observed upon substituting 25 g/day of potatoes with an equivalent amount of green leafy [0.79 (0.74, 0.83)], cruciferous [0.87 (0.83, 0.92)] and yellow/orange/red vegetables [0.97 (0.96, 0.99)]. Conversely, a higher risk of T2D was observed when potatoes were substituted with poultry [1.08 (1.02, 1.15)], red meat [1.06 (1.02, 1.10)] and processed meat [1.17 (1.11, 1.23)]. Replacing boiled potatoes with red meat or poultry was associated with a higher risk of T2D compared to replacing mashed potatoes. CONCLUSIONS: Substituting potatoes with wholegrains and most types of vegetables was associated with a lower risk of T2D while substituting potatoes with poultry, red meat and processed meat was associated with a higher risk.

Prevalence and Predictors of Adverse Events Associated With Dipeptidyl Peptidase-4 (DPP-4) Inhibitors in Type 2 Diabetic Patients: A Cross-sectional Study.

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral hypoglycemic agents widely prescribed in India despite safety concerns. However, studies focused on their safety profile are scarce, especially in South India. Objective: To evaluate the prevalence and predictors of adverse events (AEs) with DPP-4 inhibitors in patients with type 2 diabetes mellitus (T2DM). Research design and methods: This retrospective cross-sectional study analyzed data from medical records of T2DM patients prescribed DPP-4 inhibitors admitted to the medicine department from 2019 to 2021 at a South Indian tertiary care hospital. The causality of AEs was assessed using the WHO-Uppsala Monitoring Centre (WHO-UMC) criteria and the Naranjo scale, and severity using the Modified Hartwig and Seigel scale. We applied a Generalized model with a binary response and logit-link function to understand the factors that best explain the AE. The best-fit models were chosen based on least Akaike's information criterion and highest PseudoR 2 and presented the odds ratio (OR) with a 95% confidence interval. The analyses were performed in R software version 4.2.1. Results: Among the 796 patients included in the study, 26% experienced AEs. A total of 212 AEs were observed, and Saxagliptin-associated AEs were the most prevalent (66.6%). Hepatic AEs were predominant (37.7%), followed by gastrointestinal events (16.5%) and electrolyte imbalances (12.3%). Most AEs were possible based on WHO-UMC criteria (78.7%) and the Naranjo scale (86.7%), with 58% being of moderate severity and 42% mild. In the multivariate analysis, aspartate transaminase [OR: 1.013 (0.006-1.020)], alkaline phosphatase [OR: 1.004 (1.001-1.007)] and patients already on DPP-4 inhibitors [OR 1.191(1.012-1.366)] were significant predictors for AEs with DPP-4 inhibitors. Conclusion: The study highlighted a high prevalence of AEs with DPP-4 inhibitors and identified significant predictors of these AEs. These findings underscore the necessity of vigilant monitoring and risk assessment while prescribing DPP-4 inhibitors to the Indian population.

Introduction: DPP-4 inhibitors are a class of drugs used to manage type 2 diabetes mellitus. These drugs are commonly prescribed regardless of their safety issues in the Indian population. The studies focusing on the side effects or adverse events associated with these drugs and the contributing factors are limited in India. Understanding how common these adverse events are is vital to providing better patient care and management. Aim: To assess the frequency of adverse events with DPP-4 inhibitors and the contributory factors to these events. Method: A retrospective study analyzing the medical records of diabetic patients on DPP-4 inhibitors admitted to a major hospital in South India between 2019 and 2021 was conducted. The frequency, severity and potential causes of adverse events were identified through descriptive analysis. Result: A total of 796 diabetic patients on DPP-4 inhibitors were included in the study, out of which 26% (212 adverse events) experienced adverse events. Most common adverse events were related to liver (37.7%) followed by gastrointestinal (16.5%) and electrolyte imbalance (12.3%). The severity of the events was moderate (58%) and mild (42%). Elevated liver enzymes aspartate transaminase and alkaline phosphatase, and patients already on DPP-4 inhibitors were at high odds of developing adverse events. Conclusion: The study identifies DPP-4 inhibitor-associated adverse events and contributory factors that should be addressed when prescribing these drugs to diabetic patients.

Frequency and factors associated with DPP-4 inhibitor-induced adverse events in diabetic patients.

Fibroblast growth factor 21 improves diabetic cardiomyopathy by inhibiting ferroptosis via ferritin pathway.

BACKGROUND: Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 2 diabetes mellitus, and its mechanisms are complex and poorly understood. Despite growing evidence suggesting that ferroptosis plays a significant role in cardiovascular disease, it has been less extensively studied in DCM. Fibroblast growth factor 21 (FGF21), whose mechanism of action is closely related to ferroptosis, is widely utilized in studies focused on the prevention and treatment of glucolipid metabolism-related diseases and cardiovascular diseases. OBJECTIVE: To confirm the significant role of ferroptosis in DCM and to investigate whether FGF21 improves DCM by inhibiting ferroptosis and elucidating its specific molecular mechanisms. METHODS: The animal DCM models were established through high-fat feeding combined with streptozotocin injection in C57BL/6J mice or by db/db mice, and the diabetic cardiomyocyte injury model was created using high glucose and high fat (HG/HF) culture of primary cardiomyocytes. Intervention modeling of FGF21 were performed by injecting adeno-associated virus 9-FGF21 in mice and transfecting FGF21 siRNA or overexpression plasmid in primary cardiomyocytes. RESULTS: The findings indicated that ferroptosis was exacerbated and played a significant role in DCM. The overexpression of FGF21 inhibited ferroptosis and improved cardiac injury and function, whereas the knockdown of FGF21 aggravated ferroptosis and cardiac injury and function in DCM. Furthermore, we discovered that FGF21 inhibited ferroptosis in DCM by directly acting on ferritin and prolonging its half-life. Specifically, FGF21 binded to the heavy and light chains of ferritin, thereby reducing its excessive degradation in the proteasome and lysosomal-autophagy pathways in DCM. Additionally, activating transcription factor 4 (ATF4) served as the upstream regulator of FGF21 in DCM. CONCLUSIONS: The ATF4-FGF21-ferritin axis mediates the protective effects in DCM through the ferroptosis pathway and represents a potential therapeutic target for DCM.

Glucagon-Like Peptide-1 Receptor Agonist Use is Not Associated with Increased Complications After Total Hip Arthroplasty in Patients Who Have Type-2 Diabetes.

INTRODUCTION: Glucagon-like peptide-1 (GLP-1) agonists have emerged as a powerful diabetic treatment adjunct; however, their effects on outcomes following total hip arthroplasty (THA) are not well known. This study aimed to compare the risk of complications in patients who had type-2 diabetes mellitus (DM) who were on GLP-1 agonists with those who were not on these medications. METHODS: In total, 14,065 patients who had type-2 DM undergoing primary THA between 2016 and 2021 were retrospectively reviewed utilizing a national database. Propensity score matching was employed at a 1:4 ratio to match patients who used GLP-1 agonists (n = 812) to those who did not (n = 3,248). Patients were matched on age, sex, insulin status, presence of other diabetic medications, comorbidities, and smoking status. Multivariable logistic regressions were performed to examine 90-day and 1-year THA outcomes between groups. RESULTS: Patients who were not on GLP-1 agonists exhibited increased rates of extended hospital stays (≥ three days) (OR [odds ratio] 1.25, P = 0.01). Patients who were on GLP-1 agonists exhibited no significant differences in surgical or medical complication rates at 90 days compared to those not on GLP-1 agonists. There were also no significant differences in rates of all-cause revision THA, aseptic revision THA, or PJI during the 1-year postoperative period. CONCLUSION: This study demonstrated that GLP-1 agonists were not associated with increased risks for medical or surgical complications in patients who had DM undergoing THA and were associated with lower rates of extended hospital stays after surgery. This study provides additional evidence regarding the association of GLP-1 agonist use before THA with postoperative outcomes. Given the potential for increased glycemic control and weight loss, more data is needed to delineate the role of GLP-1 agonists in the optimization of patients who have DM before THA to minimize postoperative complications.

ANGPTL3 as a target for treating lipid disorders in type 2 diabetes patients.

Type 2 diabetes mellitus (T2DM) is a globally prevalent metabolic disorder, and cardiovascular disease (CVD) is a significant cause of mortality and morbidity in diabetic individuals. In addition to hyperglycemia, lipid abnormalities associated with T2DM play a crucial role in the development of CVD complications. Diabetic dyslipidemia is characterized by elevated levels of triglyceride (TG)-rich lipoproteins and small dense low-density lipoprotein (LDL) particles, reduced high-density lipoprotein (HDL) cholesterol, and impaired HDL function. Angiopoietin protein-like 3 (ANGPTL3) is a liver-derived protein that plays a crucial role in regulating plasma lipoprotein metabolism by inhibiting lipoprotein lipase and influencing lipid levels. Inhibiting ANGPTL3 has shown promising effects in promoting HDL-mediated cholesterol reverse transport and reducing the levels of TG-rich lipoproteins and LDL cholesterol. Here, we explore the potential of ANGPTL3 as a therapeutic target for lipid management in T2DM patients.

Individuation of a cut-off value of triglyceride-glucose index for incident diabetes mellitus in patients with essential hypertension.

The prevalence of obesity and diabetes, risk factors for atherosclerotic vascular diseases, is increasing worldwide; therefore, it is desirable to early identify them to reduce cardiovascular events. Thus, we investigated whether the triglyceride-glucose index (TyG index), a new marker of insulin resistance, is associated with incident diabetes in patients with newly diagnosed arterial hypertension. We selected 585 patients with newly diagnosed arterial hypertension referred to our tertiary Clinic of Catanzaro University Hospital for the evaluation of their cardiometabolic risk profile. None of the patients had diabetes mellitus at enrollment and took any drug known to affect glucose metabolism. Patients underwent medical history collection, clinical examination and laboratory tests. The TyG index was calculated as the ln [fasting TG (mg/dl) × FPG (mg/dl)/2], as previously suggested. During the follow-up [mean 8.5 years (range 3.1-10.7)], there were 78 new cases of incident diabetes (1.57% patient-year). Patients who developed diabetes mellitus were older and had a higher body mass index (BMI), baseline blood pressure, fasting glucose, insulin, homeostatis model sssessment (HOMA) index, triglyceride, creatinine and hs-CRP mean values, while estimated glomerular filtration rate values were lower. At the Cox regression analysis, covariates significantly associated with incident diabetes were: BMI (HR = 2.842, 95%CI = 2.299-3.514), TyG index (HR = 2.392, 95%CI = 1.745-3.192), age (HR = 1.944, 95%CI = 1.527-2.474), hs-CRP (HR = 1.409, 95%CI = 1.153-1.722), and HOMA (HR = 1.325, 95%CI = 1,079-1.756). The best estimated cut-off value of TyG index in predicting diabetes was 4.71. In addition, we documented a significant relationship between TyG index and HOMA (r = 0.575; p < 0.0001). Present data demonstrate that TyG index, a simple and cost-effective marker of insulin resistance, is useful in predicting incident diabetes in patients with arterial hypertension.

Evaluation of anti-diabetic effects of Glimepiride/metformin cocrystal.

Emerging data suggest that cocrystal of two compounds may have a different pharmacological effect from two compounds alone or their physical combination. Glimepiride (Gli) and metformin (Met) are two types of anti-diabetic drugs. Previously we generated the glimepiride/metformin cocrystal (GM). In this study, we evaluated the anti-diabetic effects of GM and explored the underlying mechanisms. Our result showed that GM reduced the blood glucose and HbA1c levels in db/db mice, and low doses of GM can achieve the hypoglycemic effect as Gli or Met alone, and high dose of GM was better than Gli and Met alone in improving the pathological changes of liver. In vivo studies showed that GM activated AMPK and STAT3 signaling, downregulated TXNIP expression and upregulated MaFA expression. Moreover, GM promoted the secretion of insulin in pancreas of db/db mice and in high glucose-treated INS-1 and MIN-6 cells. Together, GM possesses slightly better anti-diabetic effects than Met or Gli alone in db/db mice, and the mechanism of GM protecting ß-cell dysfunction induced by glucotoxicity may be associated with activation of the AMPK/TXNIP/MaFA pathway.

The Association between Fatty Liver Index and Lower Limb Arterial Calcification in Patients with Type 2 Diabetes Mellitus.

Background: Peripheral arterial calcification is a prevalent condition in patients with type 2 diabetes mellitus (T2DM), resulting in lower-limb amputation and reduced life quality. Non-alcoholic fatty liver disease (NAFLD), which can be simply evaluated using the fatty liver index (FLI), is closely associated with T2DM development. In this study, we aimed to explore the relationship between FLI and lower limb arterial calcification (LLAC) in T2DM patients and to reveal the value of T2DM patients with NAFLD in predicting the occurrence of LLAC. Methods: A total of 77 T2DM patients with LLAC who underwent comprehensive physical and health examinations, serological examinations, as well as lower limb computed tomography imaging at Sun Yat-sen Memorial Hospital of Sun Yat-sen University between January 2018 and January 2019 were enrolled in this study. The FLI was calculated using body mass index, waist circumference, triglycerides, and γ-glutamyl transferase. Additionally, LLAC was evaluated using computed tomography with the Agatston scoring algorithm. The patients were divided into three groups based on their FLI values: Non-liver disease group (FLI <30, n = 29), borderline-liver disease group (30 ≤ FLI < 60, n = 32), and NAFLD group (FLI ≥60, n = 16). Univariate and multivariate binary logistic regression analyses were employed to investigate the association between FLI and LLAC in T2DM patients. Furthermore, differences in LLAC among groups were analyzed using post-hoc multiple comparisons and ordinal logistic regression model analysis. Results: Univariate and multivariate analyses showed that age and FLI influenced LLAC severity in T2DM patients. Moreover, T2DM patients in the NAFLD group had significantly lower LLAC scores than those in the Non-liver disease group. The correlation analysis showed that FLI was negatively associated with LLAC scores (R = -0.31, p = 0.006), while age was positively associated (R = 0.361, p = 0.001). Conclusions: Our study revealed an inverse relationship between FLI and the degree of LLAC. This indicates that, based on evidence in the current research, NAFLD may not be reliable as a predictor of LLAC in T2DM patients.

Dosing Patterns of Dulaglutide and Semaglutide in Patients with Type 2 Diabetes Mellitus in France and Italy: A Retrospective Cohort Study.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a complex metabolic disease with several treatment options. Some glucagon-like peptide 1 receptor agonists (GLP-1 RAs) approved by the European Medicines Agency include dulaglutide, subcutaneous (s.c.) semaglutide, and oral semaglutide. This study examines dulaglutide and semaglutide dosing patterns for T2DM in France and Italy. METHODS: IQVIA Longitudinal Prescription Data identified adults with T2DM prescribed dulaglutide or semaglutide between August 1, 2020 and December 31, 2022. Cohort 1 (incident) and cohort 2 (prevalent) users were followed for 12 months. RESULTS: In France and Italy, 255,571 and 350,853 patients, respectively, received at least one study GLP-1 RA. Most dulaglutide-naïve patients in France (62%) and approximately half in Italy (49%) started on 1.5 mg and remained on this dose for up to 12 months (France: 66% cohort 1, 88% cohort 2; Italy: 73% cohort 1, 87% cohort 2). In cohort 1, s.c. semaglutide users mostly started on 0.25 mg (France, 78%; Italy, 61%). At 12 months, s.c. semaglutide 1.0 mg was most prescribed (France: 58% cohort 1, 75% cohort 2; Italy: 59% cohort 2), with cohort 1 in Italy mostly receiving 0.5 mg (57%). Most oral semaglutide users in Italy started on 3.0 mg (78% cohort 1; 68% cohort 2), which was increased to 7.0 mg (62% cohort 1) and 14.0 mg (48% cohort 2) at 12 months. CONCLUSIONS: GLP-1 RA dosing patterns, although similar between France and Italy, were heterogeneous over time. As oral semaglutide and higher dulaglutide doses are recent to the market, additional real-world evidence is required to evaluate utilization patterns. Graphical abstract available for this article.

Therapeutic Effects of Intermittent Fasting Combined with SLBZS and Prebiotics on STZ-HFD-Induced Type 2 Diabetic Mice.

Purpose: This study aims to assess the therapeutic potential of combining Shen-Ling-Bai-Zhu-San (SLBZS) or prebiotics with intermittent fasting (IF) in type 2 diabetes mellitus (T2DM) mice and to investigate the synergistic effects and underlying mechanisms. Methods: Type 2 diabetic mouse models were induced using high-fat diet (HFD) and streptozotocin (STZ), followed by IF treatment. Mice were then grouped for combined therapy with different doses of SLBZS and prebiotics. Fasting blood glucose (FBG) levels, body weight variations, and oral glucose tolerance tests were assessed to elucidate metabolic alterations. The hepatic and renal parameters were evaluated to determine systemic changes in T2DM mice, while the insulin levels were quantified by ELISA to assess glucose homeostasis. Gut microbiota alterations were examined via 16S rRNA sequencing. Alterations of the genes in relevant signaling pathways were analyzed using RT-qPCR. Results: IF improved FBG, body weight, insulin levels, and other diabetes indicators. Combined IF with SLBZS or prebiotics yielded similar effects. Furthermore, it ameliorated dyslipidemia and mitigated hepatic and renal parameters in T2DM mice. Pancreatic tissue histopathology showed islet cell restoration post-intervention. IF therapy reduced the abnormally elevated GSK-3ß gene expression and increased the abnormally reduced GLUT2 genes. Further analysis indicated that the combination of IF with prebiotics and high doses of SLBZS upregulated the expression of the INSR and IRS1 genes. Gut microbiota analysis revealed restored diversity and structure, with notable changes in specific bacterial families. At the family level, the contents of Akkermansiaceae and Bifidobacteriaceae were restored. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) analysis suggested metabolic pathway alterations. Conclusion: IF improved type 2 diabetic symptoms, with combined SLBZS and prebiotics showing similar effects. IF with high concentration of SLBZS and prebiotics doses upregulated the INSR and IRS1 genes and had superior effects on gut microbiota compared to IF alone.

Contribution of Disease-Specific Distress, Social Support, and Self-Efficacy to Diabetes Self-Management Behaviors in Saudi Adults: A Path Analysis.

Purpose: Disease-specific distress, social support, and self-efficacy have noticeable impacts on diabetes self-management. Although these three concepts are connected, their interplay and subsequent influence on diabetes self-management warrants further research. Patients and Methods: A total of 154 individuals with type 2 diabetes mellitus were recruited to complete a survey, which included questions related to social support, diabetes self-efficacy, diabetes self-management behaviors, and disease-specific stress. The variables were examined with path analysis using Analysis of Moment Structures (AMOS) software. Results: In the final model, diabetes self-efficacy was a significant predictor of increased diabetes self-management behaviors. Lower levels of disease-specific distress were associated with higher levels of self-efficacy. Path analysis indicated that the direct effect of social support on diabetes self-management behaviors was significant, and social support indirectly affected diabetes self-management behaviors through the mediating effect of diabetes self-efficacy. Overall, the study findings indicate that social support can exert an impact on diabetes self-management behaviors through the mediating effect of diabetes self-efficacy. Conclusion: The study's findings support the use of Individual and Family Self-Management Theory to improve diabetes self-management. Further research is needed to better understand how factors related to the family support system influence diabetes self-management behaviors.

Metabolic dysfunction-associated steatotic liver disease-associated fibrosis and cardiac dysfunction in patients with type 2 diabetes.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD), particularly in the presence of liver fibrosis, increases the risk of cardiovascular morbidity and mortality, but the nature of the cardio-hepatic interaction in the context type 2 diabetes mellitus (T2DM) is not fully understood. AIM: To evaluate the changes in cardiac morphology and function in patients with T2DM and MASLD-associated liver fibrosis. METHODS: T2DM patients with MASLD underwent a medical evaluation that included an assessment of lifestyle, anthropometric measurements, vital signs, an extensive laboratory panel, and a standard echocardiography. Liver fibrosis was evaluated using two scores [Fibrosis-4 (FIB4) and Non-alcoholic fatty liver disease-Fibrosis Score (NFS)], and subjects were classified as having advanced fibrosis, no fibrosis, or an indeterminate risk. The correlations between structural and functional cardiac parameters and markers of liver fibrosis were evaluated through bivariate and multiple regression analyses. Statistical significance was set at P < 0.05. RESULTS: Data from 267 T2DM-MASLD subjects with complete assessment was analyzed. Patients with scores indicating advanced fibrosis exhibited higher interventricular septum and left ventricular (LV) posterior wall thickness, atrial diameters, LV end-systolic volume, LV mass index (LVMi), and epicardial adipose tissue thickness (EATT). Their mean ejection fraction (EF) was significantly lower (49.19% ± 5.62% vs 50.87% ± 5.14% vs 52.00% ± 3.25%; P = 0.003), and a smaller proportion had an EF ≥ 50% (49.40% vs 68.90% vs 84.21%; P = 0.0017). Their total and mid LV wall motion score indexes were higher (P < 0.05). Additionally, they had markers of diastolic dysfunction, with a higher E/e' ratio [9.64 ± 4.10 vs 8.44 (2.43-26.33) vs 7.35 ± 2.62; P = 0.026], and over 70% had lateral e' values < 10 cm/second, though without significant differences between groups. In multiple regression analyses, FIB4 correlated with left atrium diameter (LAD; ß = 0.044; P < 0.05), and NFS with both LAD (ß = 0.039; P < 0.05) and right atrium diameter (ß = 0.041; P < 0.01), Moreover, LVMi correlated positively with age and EATT (ß = 1.997; P = 0.0008), and negatively with serum sex-hormone binding protein (SHBP) concentrations (ß = -0.280; P = 0.004). SHBP also correlated negatively with LAD (ß = -0.036; P < 0.05). CONCLUSION: T2DM patients with markers of MASLD-related liver fibrosis exhibit lower EF and present indicators of diastolic dysfunction and cardiac hypertrophy. Additionally, LVMi and LAD correlated negatively with serum SHBP concentrations.

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

We comment on an article by Grubic Rotkvic 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.

A Prospective Cross-Sectional Study on the Correlation of Adenosine Deaminase and HbA1c With Microvascular Complications in Type 2 Diabetes Mellitus at a Tertiary Care Hospital in Central India.

Background Type 2 diabetes mellitus (T2DM) is a prevalent chronic condition characterized by hyperglycemia, which can lead to various microvascular complications, including diabetic nephropathy, neuropathy, and retinopathy. Identifying reliable biomarkers for early detection and risk stratification of these complications is crucial for improving patient outcomes. Adenosine deaminase (ADA) and HbA1c have emerged as potential markers associated with immune function, inflammation, and long-term glycemic control. This study investigates the correlation between ADA and HbA1c levels and microvascular complications in patients with T2DM. Material and methods This prospective observational cross-sectional study involved 150 patients diagnosed with T2DM, focusing on those with diabetic nephropathy, neuropathy, and retinopathy. Clinical data were collected through patient interviews, clinical examinations, and laboratory tests, including measurements of fasting blood glucose, HbA1c, serum creatinine, ADA levels, and urine protein creatinine ratio (UPCR). Fundus examinations and nerve conduction velocity (NCV) tests were performed to assess diabetic retinopathy and neuropathy, respectively. Data were analyzed using SPSS version 25.0 (IBM Corp., Armonk, New York), with statistical tests to evaluate the correlation between ADA and HbA1c levels and microvascular complications. Results The study found a significant correlation between elevated ADA and HbA1c levels and microvascular complications in patients with T2DM. Higher ADA levels were particularly associated with diabetic nephropathy (p=0.003), while HbA1c levels showed a positive correlation with all three complications: nephropathy, neuropathy, and retinopathy. The findings suggest that ADA and HbA1c levels can serve as valuable biomarkers for identifying patients at higher risk of developing these complications. Conclusion This study highlights the potential of ADA and HbA1c as biomarkers for early detection and risk assessment of microvascular complications in T2DM patients. Routine monitoring of these markers could improve the management and prognosis of diabetic patients by enabling timely interventions to prevent or mitigate the progression of complications. Further research is needed to explore the underlying mechanisms linking ADA with diabetic complications and to validate its clinical utility.

Association between sensitivity to thyroid hormones and non-high-density lipoprotein cholesterol levels in patients with type 2 diabetes mellitus.

BACKGROUND: Dyslipidemia and type 2 diabetes mellitus (T2DM) are chronic conditions with substantial public health implications. Effective management of lipid metabolism in patients with T2DM is critical. However, there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population, particularly concerning non-high-density lipoprotein cholesterol (non-HDL-C). AIM: To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM. METHODS: In this cross-sectional study, thyroid hormone sensitivity indices, the thyroid feedback quantile-based index (TFQI), the thyroid-stimulating hormone index (TSHI), the thyrotrophic T4 resistance index (TT4RI), and the free triiodothyronine (FT3)/free thyroxine (FT4) ratio were calculated. Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels. Random forest variable importance and Shapley Additive Explanations (SHAP) summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor. RESULTS: Among the 994 participants, 389 (39.13%) had high non-HDL-C levels. Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI (OR: 1.584; 95%CI: 1.088-2.304; P = 0.016), TSHI (OR: 1.238; 95%CI: 1.034-1.482; P = 0.02), and TT4RI (OR: 1.075; 95%CI: 1.006-1.149; P = 0.032) but was not significantly correlated with the FT3/FT4 ratio. The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex. An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men (OR: 1.331; 95%CI: 1.003-1.766; P = 0.048) but elevated TFQI levels in women (OR: 2.337; 95%CI: 1.4-3.901; P = 0.001). Among the analyzed variables, the average SHAP values were highest for TSHI, followed by TT4RI. CONCLUSION: Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM.

Relationship between hemoglobin glycation index and risk of hypoglycemia in type 2 diabetes with time-in-range in target.

BACKGROUND: In patients with type 2 diabetes mellitus (T2DM), the risk of hypoglycemia also occurs in at a time-in-range (TIR) of > 70%. The hemoglobin glycation index (HGI) is considered the best single factor for predicting hypoglycemia, and offers new perspectives for the individualized treatment of patients with well-controlled blood glucose levels that are easily ignored in clinical settings. AIM: To investigate the relationship between HGI and hypoglycemia and the implications of HGI on hypoglycemia in T2DM with TIR > 70%. METHODS: All participants underwent a 7-days continuous glucose monitoring (CGM) using a retrospective CGM system. We obtained glycemic variability indices using the CGM system. We defined HGI as laboratory hemoglobin A1c minus the glucose management indicator. Patients were categorized into low HGI (HGI < 0.5) and high HGI groups (HGI ≥ 0.5) according to HGI median (0.5). Logistic regression and receiver operating characteristic curve analyses were used to determine the risk factors for hypoglycemia. RESULTS: We included 129 subjects with T2DM (54.84 ± 12.56 years, 46% male) in the study. Median TIR score was 90%. The high HGI group exhibited lower TIR and greater time below range with higher hemoglobin A1c than the low HGI group; this suggests more glycemic excursions and an increased incidence of hypoglycemia in the high HGI group. Multivariate analyses revealed that mean blood glucose, standard deviation of blood glucose and HGI were independent risk factors for hypoglycemia. Receiver operating characteristic curve analysis indicated that the HGI was the best predictor of hypoglycemia. In addition, the optimal cut-off points for HGI, mean blood glucose, and standard deviation of blood glucose in predicting hypoglycemia were 0.5%, 7.2 mmol/L and 1.4 mmol/L respectively. CONCLUSION: High HGI was significantly associated with greater glycemic excursions and increased hypoglycemia in patients with TIR > 70%. Our findings indicate that HGI is a reliable predictor of hypoglycemia in this population.