Euglycemic Ketoacidosis Associated with SGLT-2 Inhibitors in Non-diabetic Patients-A Narrative Review.

Euglycemic ketoacidosis is an acute, life-threatening emergency that is characterized by euglycemia, metabolic acidosis, and ketonemia. It is a well-recognized adverse event in diabetic patients taking sodium-glucose cotransporter-2 inhibitor (SGLT-2 inhibitor). However, there is limited data on SGLT-2 inhibitor-related euglycemic ketoacidosis in non-diabetic patients. The mechanism behind SGLT-2 inhibitor-associated euglycemic ketoacidosis involves a general state of starvation or relative insulin deficiency, which exacerbates the mild baseline ketonemia caused by this class of medications while normoglycemia is maintained. The incidence of euglycemic ketoacidosis will likely increase with the increasing use of SGLT-2 inhibitors for various indications in addition to diabetes mellitus type 2, predominantly for congestive heart failure (CHF). Recognizing the signs and symptoms of this life-threatening condition is essential to treat it effectively. Our objective is to comprehensively revisit the pathophysiology of euglycemic ketoacidosis associated with SGLT-2 inhibitors and the risk factors for the condition, review the available data, and summarize the reported cases of euglycemic ketoacidosis in non-diabetic patients on SGLT-2 inhibitors. Our literature search identified five articles with six cases of euglycemic ketoacidosis in non-diabetic patients who were on SGLT-2 inhibitors for heart failure with reduced ejection fraction. The common risk factor in five out of the six cases was decreased oral intake due to acute illness, fasting, or a perioperative state.

Randomized study of the effects of empagliflozin and topiramate dual therapy on anthropometric and metabolic indices in non-diabetic individuals with overweight/obesity on a calorie-restricted diet.

OBJECTIVES: The objective of this study was to evaluate the effectiveness of the combined use of empagliflozin (EMPA) and topiramate (TPM) versus a placebo in overweight/obese individuals without diabetes on a calorie-restricted diet. METHODS: In this study, 44 non-diabetic and overweight/obese subjects who were on a calorie restricted diet were randomly assigned into 2 groups: (1) Participants received a 10 mg EMPA tablet daily plus TPM tablet (at the 1st week 25 mg once a day and from the second week 25 mg twice a day); (2) Participants received an empagliflozin placebo (daily) plus a topiramate placebo (as mentioned for topiramate tablet in group 1), for 12 weeks. At baseline and weeks 4, 8, 12, weight, height, body mass index (BMI), waist circumference (WC), and body composition were evaluated. Before and after the intervention, blood pressure, C reactive protein, and glucose and lipid profile parameters were measured. RESULTS: The EMPA/TPM group, compared to placebo, had a greater percent change of weight at week 12 (- 8.92 ± 1.80 vs. - 4.93 ± 1.17). The intervention group had a greater percent change of fat mass and fat percent at week 12 (P < 0.05). However, there was no difference in the percent of change in fat-free percent between the two groups at week 12 (P = 0.577). Within-group analysis found a significant reduction in SBP, DBP, FBS, insulin, HOMA-IR, TC, LDL, HDL, TG, and CRP in both groups (P < 0.05). At week 12, no statistically significant difference was observed between the two groups in any of mentioned variables (P > 0.05). CONCLUSION: In non-diabetic overweight/obese individuals, the combination of EMPA/TPM and calorie restriction led to a notable decrease in body weight and was generally well-tolerated. Further research is required to evaluate the potential advantages of utilizing this combination for sustained weight management in the long run. LEVEL I: Randomized clinical trial.

The role of kidney biopsy in deciphering diabetic versus non-diabetic origin of kidney disease among patients with type 2 diabetes mellitus and nephrotic range proteinuria: A retrospective study.

Background: Diabetes mellitus (DM) is tightly associated with the increased prevalence of diabetic kidney disease (DKD). Nonetheless, severe renal function impairment and/or nephrotic range-proteinuria could also result from non-diabetic renal disease (non-DRD) among patients with DM. The 'Gold standard' for the differential diagnosis between DKD and non-DRD is kidney biopsy, although no real consensus exists. Thus, this study intends to associate the clinical and biochemical profile of patients with DM and renal disease with the histopathological data of kidney biopsy.In addition, we aimed to evaluate the role of kidney biopsy, especially when other causes, other than DM, are highly suspected among patients with DM and kidney disease. Methods: Thirty two patients with T2DM and nephrotic range levels of proteinuria or with co-existing factors pointing towards a non-diabetic origin of kidney disease were studied, retrospectively. All 32 patients underwent kidney biopsy and were classified according to histopathological findings into 3 groups: a) isolated diabetic kidney disease (DKD), b) non-diabetic kidney disease (NDKD) and c) mixed kidney disease (MKD). Results: Fifteen out of the 32 patients had findings of an isolated DKD, while 17 out of 32 patients suffered from NDKD (13 patients) or MKD (4 patients). DKD patients were younger (p = 0.016) and had a higher HbA1c value (p = 0.069, borderline statistical significance), while the NDKD patients had significantly shorter disease duration (p = 0.04). Furthermore, the incidence of diabetic retinopathy (DR) was lower among the NDKD patients (p < 0.001), who had also significantly less interstitial fibrosis (p = 0.02). Finally, the presence of DR, higher levels of interstitial fibrosis and longer T2DM duration were recognized as factors, which were positively associated with DKD. Conclusion: This study advocates the usefulness of kidney biopsy in patients with T2DM and nephrotic range levels of proteinuria, especially when DR is absent and shorter disease duration is observed.

Evaluation of alveolar bone loss among diabetic patients with class II amalgam restorations.

The relationship between Class II amalgam restorations and alveolar bone loss among diabetic and non-diabetic patients is evaluated at the Faculty of Dentistry, Najran University, KSA. Hence, we compared type 2 diabetic (n = 32) and non-diabetic patients (n=32) using clinical assessments and imaging techniques. Parameters such as bone loss rate, extent, age, and periodontal condition (plaque index and Gingival Index) were analyzed. Analysis of data shows that diabetic patients on average have higher bone loss.

Association Between Glycated Hemoglobin (HbA1c) Levels in Patients With Iron Deficiency Anemia in a Tertiary Care Hospital in Central India.

Background Iron deficiency anemia (IDA) and diabetes are prevalent health concerns, especially in regions like India. While previous studies have explored the relationship between glycated hemoglobin (HbA1c) levels and IDA, there is still inconsistency in the findings, particularly in the Indian population. Understanding this association is crucial for accurate diagnosis and management of both conditions. Materials and methods A case-control study was conducted at the Department of General Medicine at Acharya Vinoba Bhave Rural Hospital (AVBRH), Wardha, India, from May 2022 to October 2022. A total of 141 non-diabetic patients with IDA (study group) and 141 age- and gender-matched non-anemic controls were included. HbA1c levels were measured at baseline and after three months of IDA treatment. Statistical analysis was performed using SPSS software, including the Kolmogorov-Smirnov test, Chi-square test, Mann-Whitney test, and Pearson correlation coefficient. Results In the study group, HbA1c levels significantly increased from a mean of 4.63% at baseline to 5.82% after IDA treatment (p < 0.0001). However, there was no significant correlation between changes in hemoglobin (Hb) levels and HbA1c levels post-correction (r = 0.056, p = 0.510). In addition, all cases and controls were labeled non-diabetic based on a cutoff HbA1c level of 6%. After three months of IDA treatment, 80.85% of cases recovered from IDA. Conclusion The study highlights that HbA1c levels are lower in patients with IDA and may increase with the correction of IDA. However, there is no significant direct correlation between IDA correction and HbA1c increase. Therefore, when interpreting HbA1c levels, clinicians must consider the presence of IDA, especially in regions with high prevalence rates of both IDA and diabetes, like India. This understanding can improve management strategies for both conditions, ensuring better patient health outcomes.

Comparison of glucagon-like peptide-1 receptor agonists vs. placebo on any cardiovascular events in overweight or obese non-diabetic patients: a systematic review and meta-analysis.

Introduction: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) have been extensively used to treat obesity in recent years. These novel drugs are effective at reducing body weight and also the risk of major adverse cardiovascular events in individuals with type 2 diabetes. However, the data of its efficacy in reducing cardiovascular events in individuals without type 2 diabetes is not as robust. We aim to update and conduct a systematic review and meta-analysis to assess the same. Methods: The study was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guideline. Researchers searched PubMed, EMBASE, and Clinicaltrails.gov for English literature from inception to 2024. Randomized Controlled trails enrolling adult participants (age ≥ 18 years) who are overweight or obese (BMI > 25 Kg/m2) with a comparison of all cardiovascular events between patients taking GLP1-RA and placebo were included. The analysis was done by Revman version 5.4. Results: A total of 17 RCTs among 34,419 participants were included in the analysis. The pooled risk ratio from 17 studies illustrated that patients with GLP-1 RA had a significantly lower risk of cardiovascular events compared to patients who had a placebo (RR = 0.75; 95% confidence interval 0.64-0.89, p-value = 0.0008). Semaglutide was found to have a statistically significant greatest risk reduction than other drug types. Conclusions: This meta-analysis found that GLP-1 RA significantly reduced all types of cardiovascular events in overweight and obese patients without diabetes. Semaglutide was found to be superior to others in CV event reductions. But still, the results of ongoing trials are needed. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=553048, PROSPERO (CRD42024553048).

Effect of Semaglutide in Individuals With Obesity or Overweight Without Diabetes.

This systematic review evaluates the efficacy and safety of semaglutide in individuals with obesity or overweight without diabetes. Obesity is a significant public health concern, associated with various comorbidities and reduced quality of life. Semaglutide, a glucagon-like peptide-1 receptor agonist, has emerged as a promising pharmacological intervention for weight management. This review synthesizes findings from multiple clinical trials, highlighting the impact of semaglutide on weight loss, metabolic parameters, and overall health outcomes in non-diabetic populations. The review also addresses methodological considerations, including study design, participant selection, and outcome measures, to assess the robustness of the evidence. Ethical considerations and potential conflicts of interest are discussed to ensure transparency in the research process. The findings indicate that semaglutide is associated with significant weight reduction and improvement in obesity-related health markers, suggesting its potential as a valuable treatment option for individuals struggling with obesity. Limitations of the current literature and recommendations for future research directions are also presented, emphasizing the need for further studies to explore the long-term effects and generalizability of semaglutide treatment in diverse populations.

Histological Analysis of Platelet-Rich Fibrin in Diabetics, Non-diabetics, and Smokers Suffering with Chronic Periodontitis: An In Vitro Study.

Aim: The present study was aimed at evaluating the variations in fibrin network patterns of the platelet-rich fibrin (PRF) procured from diabetics, non-diabetics, and smokers suffering from chronic periodontitis. Materials and Methods: Five milliliters of blood were drawn using a syringe from 60 participants (systemically healthy non-diabetics, diabetics, and smokers) who were diagnosed with chronic periodontitis. Five milliliters of blood were transferred to a dry glass tube. The clot (PRF) obtained after centrifugation from the glass tube was processed for light microscopy analysis. Results: The PRF samples have demonstrated the presence of both dense and loose fibrin networks. There is an increase in cellular content in diabetic participants compared to systemically healthy and smoker participants. Smoker participants demonstrated a higher amount of loose fibrin content, which was arranged irregularly. Conclusion: A significantly greater increase in cellular content and loose fibrin network is seen in diabetics and smokers, respectively, compared to systemically healthy individuals. As compared to the systemically healthy participants, there is a variation in the fibrin network pattern and distribution of cellular structures in diabetic and smoker participants.

Classic ketogenic diet-induced ketoacidosis in the treatment of pyruvate dehydrogenase deficiency: a case report and literature review.

BACKGROUND: As a rare mitochondrial disorder, the pyruvate dehydrogenase complex (PDC) deficiency is a rare inborn disease characterized with glucose metabolism defects, which leads to neurological dysfunction, serum lactic acid buildup and a resultant trend of metabolic acidosis. Although the ketogenic diet (KD) is the first-line treatment for PDC deficiency, there is currently no widely accepted consensus on specific implementation of KD for this condition. Due to the combined effect of pre-existing hyperlactacidemia and KD-induced ketoacidosis that can further exacerbate metabolic disturbances, maintaining metabolic homeostasis should be prioritized during the implementation of KD. CASE PRESENTATION: Herein, the authors present a 6-year-old boy with lactic acidosis, ataxia, hypotonia and neuromotor development retardation. The KD was started after the patient was diagnosed with PDC deficiency based on genetic testing. The initiation with classic KD resulted in severe non-diabetic ketoacidosis with elevated anion gap, which was promptly alleviated by dextrose supplementation and dietary modification to a less-restrictive KD. Long-term supervision demonstrated the efficacy of a modified KD in improving both clinical course and metabolic acidosis of the patient. CONCLUSIONS: This rare case adds to the limited evidence of KD application in PDC deficiency, and provides valuable insights into the importance of reasonably lowering the ketogenic ratio of KD at the start of treatment to reduce the risk of metabolic acidosis.

A Study on the Incidence and Impact of Dysglycemia in Non-diabetic Sepsis Patients.

Context Dysglycemia is common in severe sepsis and is associated with a poor prognosis. There is a limited amount of research on stress-induced dysglycemia in non-diabetic sepsis patients. Aim This study aims to estimate the incidence of dysglycemia among non-diabetic patients presenting with sepsis at the Emergency Department and to determine its correlation with gender, age, APACHE II (Acute Physiology and Chronic Health Evaluation) scores, diagnosis, and duration of hospital stay. Materials and methods The study was conducted at a medical college hospital in Kochi from January 1, 2023, to December 31, 2023. A minimum sample size of 77 was derived after a pilot study, with a 95% confidence interval and 10% allowable error. A total of 100 non-diabetic sepsis patients meeting the inclusion and exclusion criteria were analyzed with regard to gender, age, diagnosis, glycemic status (hypo/hyper/normoglycemic), APACHE II scores, and hospital stay duration. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, New York) software. Categorical variables were expressed as frequency and percentage. Continuous variables were presented as mean ± SD (standard deviation) and median (Q1-Q3). To test the statistical significance of the association between the presence of various factors (gender, age, diagnosis) and dysglycemia, the chi-square test was used. To test the statistical significance of the difference in the mean age and APACHE II score values with dysglycemia, an independent sample t-test was used. To test the statistical significance of the difference in the median hospital stay with dysglycemia, the Whitney U test was used. Data were represented as mean ± SD, and a p-value of <0.05 was considered to be statistically significant. Results The incidence of dysglycemia in the inclusion group was 49% (hypoglycemia in 16% and hyperglycemia in 33% of cases), and it increased with age (p=0.002). The majority of the dysglycemic patients fell into the age group >40 years. Dysglycemia was 54.8% in pneumonia and 66.7% in gastrointestinal sepsis ( p=0.138). Dysglycemia increased with an increase in APACHE II scores (p=0.017). The median hospital stay was almost the same in both normoglycemics and dysglycemics. Conclusion Dysglycemia is a frequent complication in non-diabetic patients with sepsis. It increased with age and APACHE II score, but it does not prolong the duration of hospital stay, nor is it associated with the diagnosis.

Independent risk factors of left ventricular hypertrophy in non-diabetic individuals in Sierra Leone - a cross-sectional study.

BACKGROUND: Left ventricular hypertrophy (LVH) is a critical factor in heart failure and cardiovascular event-related mortality. While the prevalence of LVH in diabetic patients is well-documented, its occurrence and risk factors in non-diabetic populations remain largely unexplored. This study addresses this issue by investigating the independent risk factors of LVH in non-diabetic individuals. METHODS: This cross-sectional study, conducted meticulously, utilized data from a robust and comprehensive source, DATADRYAD, in the Sierra Leone database, collected between October 2019 and October 2021, including LVH and various variables. All variables were described and screened using univariate analysis, Spearman correlation, and principal component analysis (PCA). The lipid profile, including total cholesterols (TC), triglycerides (TG), high-density lipoprotein (HDL-C), non-high-density lipoprotein (Non-HDL-C), and low-density lipoprotein cholesterol (LDL-C), TC/HDL-C ratio, TG/HDL-C ratio, Non-HDL-C /HDL-C ratio and LDL-C/HDL-C ratio, which quartiles were treated as categorical variables, with the lowest quartile serving as the reference category. Three adjusted models were constructed to mitigate the influence of other variables. To ensure the robustness of the model, receiver operating characteristic (ROC) curves were used to calculate the cutoff values by analyzing the ROC curves. A sensitivity analysis was performed to validate the findings further. RESULTS: The dataset encompasses information from 2092 individuals. After adjusting for potential factors that could influence the results, we found that TC (OR = 2.773, 95%CI: 1.805-4.26), Non-HDL-C (OR = 2.74, 95%CI: 1.7723-4.236), TC/HDL-C ratio (OR = 2.237, 95%CI: 1.445-3.463), Non-HDL-C/HDL-C ratio (OR = 2.357, 95%CI: 1.548-3.588), TG/HDL-C ratio (OR = 1.513, 95%CI: 1.02-2.245) acts as independent risk factors of LVH. ROC curve analysis revealed the predictive ability of blood lipids for LVH, with Non-HDL-C exhibiting area under the curve (AUC = 0.6109), followed by TC (AUC = 0.6084). CONCLUSIONS: TC, non-HDL-C, TC/HDL-C ratio, Non-HDL-C/HDL-C ratio, and TG/HDL-C ratio were independent risk factors of LVH in non-diabetic people. Non-HDL-C and TC were found to be essential indicators for predicting the prevalence of LVH.

Correlation between retinal vascular geometric parameters and pathologically diagnosed type 2 diabetic nephropathy.

Background: Diabetic nephropathy (DN) and diabetic retinopathy (DR) are common microvascular complications of diabetes. The purpose of this study was to investigate the correlation between retinal vascular geometric parameters and pathologically diagnosed type 2 DN and to determine the capacity of retinal vascular geometric parameters in differentiating DN from non-diabetic renal disease (NDRD). Methods: The study participants were adult patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease who underwent a renal biopsy. Univariate and multivariable regression analyses were performed to evaluate associations between retinal vessel geometry parameters and pathologically diagnosed DN. Multivariate binary logistic regression analyses were performed to establish a differential diagnostic model for DN. Results: In total, 403 patients were examined in this cross-sectional study, including 152 (37.7%) with DN, 157 (39.0%) with NDRD and 94 (23.3%) with DN combined with NDRD. After univariate logistic regression, total vessel fractal dimension, arteriolar fractal dimension and venular fractal dimension were all found to be associated with DN. In multivariate analyses adjusting for age, sex, blood pressure, diabetes, DR and other factors, smaller retinal vascular fractal dimensions were significantly associated with DN (P < .05). We developed a differential diagnostic model for DN combining traditional clinical indicators and retinal vascular geometric parameters. The area under the curve of the model established by multivariate logistic regression was 0.930. Conclusions: Retinal vessel fractal dimension is of great significance for the rapid and non-invasive differentiation of DN. Incorporating retinal vessel fractal dimension into the diagnostic model for DN and NDRD can improve the diagnostic efficiency.

Insulin Autoimmune Syndrome: A Case Report Highlighting Diagnostic Pitfalls.

Insulin autoimmune syndrome (IAS) is characterized by spontaneous hyperinsulinemic hypoglycemia and the presence of insulin autoantibodies in high titers without exogenous insulin use. The C-peptide level during a hypoglycemia episode is useful for differentiating spontaneous hypoglycemia. Generally, low C-peptides are suspicious for exogenous insulin administration. We report a 47-year-old male nurse who presented with an initial episode of hypoglycemia. Despite the pattern of hyperinsulinemic hypoglycemia and low C-peptide, he was diagnosed with IAS based on the presence of insulin autoantibodies. This case underscores the importance of suspecting IAS in non-diabetic adults with hypoglycemia, even in the setting of low C-peptide levels.

Age- and deprivation-related inequalities in identification of people at high risk of type 2 diabetes in England.

BACKGROUND: Early detection of intermediate hyperglycaemia, otherwise known as non-diabetic hyperglycaemia (NDH) is crucial to identify people at high risk of developing type 2 diabetes mellitus (T2DM) who could benefit from preventative interventions. Failure to identify NDH may also increase the risks of T2DM-related complications at the time of T2DM diagnosis. We investigate sociodemographic inequalities in identification of NDH in England. METHODS: We used nationwide data from the English National Health Service (NHS) National Diabetes Audit, which includes all people who were newly identified with NDH (N = 469,910) or diagnosed with T2DM (N = 222,795) between 1st April 2019 and 31st March 2020. We used regression models to explore inequalities in the under identification of NDH by area-level deprivation and age group. RESULTS: Of those with a new T2DM diagnosis, 67.3% had no previous record of NDH. The odds of no previous NDH being recorded were higher amongst people living in more deprived areas (Odds ratio (OR) 1.15 (95% confidence intervals (CI) [1.12, 1.19]) most deprived (Q1) compared to least deprived (Q5) quintile) and younger individuals (OR 4.02 (95% CI [3.79, 4.27] under 35s compared to age 75-84)). Deprivation-related inequalities persisted after stratification by age group, with the largest inequalities amongst middle and older age groups. People living in more deprived areas and younger people also had shorter recorded NDH duration before progression to T2DM, and higher T2DM severity at the time of diagnosis. CONCLUSIONS: There is under identification of NDH relative to diagnosis of T2DM amongst people living in more deprived areas and particularly amongst younger people, resulting in missed opportunities for targeted T2DM prevention efforts and potentially contributing to inequalities in T2DM prevalence and severity. More active NDH case-finding amongst these groups may be an important first step in helping to reduce inequalities in T2DM.

Postoperative hyperglycemia among adult non-diabetic surgical patients at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia.

BACKGROUND: Postoperative hyperglycemia is associated with morbidity and mortality in non-diabetic surgical patients. However, there is limited information on the extent and factors associated with postoperative hyperglycemia. This study assessed the magnitude and associated factors of postoperative hyperglycemia among non-diabetic adult patients who underwent elective surgery at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. METHODS: A facility-based cross-sectional study was conducted among 412 adult patients who underwent elective surgery at University of Gondar Comprehensive Specialized Hospital from April 14 to June 30, 2022 All consecutive postoperative non-diabetic elective surgical patients who were admitted to PACU during the data collection period and who fulfilled inclusion criteria were included in the study until the intended minimum sample size was achieved. And data were collected through interviews using a pretested semi-structured questionnaire. Postoperative hyperglycemia was defined as a blood glucose level of ≥ 140 mg/dl. Multivariable logistic regression was performed to identify the association between postoperative hyperglycemia and independent variables. Variables with a p-value less than 0.05 and a 95% confidence interval (CI) were considered statistically significant. RESULTS: A total of 405 patients' data were evaluated with a response rate of 98.3%. The median (IQR) age was 40 (28-52) years. The prevalence of postoperative hyperglycemia was 34.1% (95% CI: 29.4-39.0). Factors significantly associated with postoperative hyperglycemia included being overweight (AOR = 5.45, 95% CI: 2.46-12.0), American Society of Anesthesiologists (ASA) classification II and III (AOR = 2.37, 95% CI: 1.17-4.79), postoperative low body temperature (AOR = 0.18, 95% CI: 0.069-0.48), blood loss ≥ 500 ml (AOR = 2.33, 95% CI: 1.27-4.27), long duration of surgery, mild pain (AOR = 5.17, 95% CI: 1.32-20.4), and moderate pain (AOR = 7.63, 95% CI: 1.811-32.20). CONCLUSION AND RECOMMENDATION: One-third of the study participants had postoperative hyperglycemia. Weight, ASA classification, postoperative body temperature, duration of surgery, intraoperative blood loss, and postoperative pain were identified as a modifiable risk factors. Maintaining normal body temperature throughout the procedure, treating postoperative pain, and monitoring and controlling blood glucose level in patients at risk of hyperglycemia is crucial.

Maxillary Mucormycotic Osteonecrosis as a Manifestation of Post-COVID-19 Infection in Non-diabetic Patients: Report of Two Cases.

Mucormycosis is a rare, opportunistic fungal infection prevalent in the elderly, especially in patients with uncontrolled diabetes or a compromised immune system. However, the outbreak of the pandemic declared by the World Health Organization in late 2019 increased the incidence of mucormycosis cases in COVID-19 patients due to increased steroid usage that resulted in an immunocompromised state. The current report presents two cases of oral mucormycotic osteomyelitis in patients who developed diabetes post-COVID infection, along with a review and relevant literature.

Empagliflozin and dapagliflozin decreased atrial monoamine oxidase expression and alleviated oxidative stress in overweight non-diabetic cardiac patients.

The sodium-glucose-cotransporter 2 inhibitors (SGLT2i) are the blockbuster antidiabetic drugs that exert cardiovascular protection via pleiotropic effects. We have previously demonstrated that empagliflozin decreased monoamine oxidase (MAO) expression and oxidative stress in human mammary arteries. The present study performed in overweight, non-diabetic cardiac patients was aimed to assess whether the two widely prescribed SGLT2i decrease atrial MAO expression and alleviate oxidative stress elicited by exposure to angiotensin 2 (ANG2) and high glucose (GLUC). Right atrial appendages isolated during cardiac surgery were incubated ex vivo with either empagliflozin or dapagliflozin (1, 10 µm, 12 h) in the presence or absence of ANG2 (100 nm) and GLUC (400 mg/dL) and used for the evaluation of MAO-A and MAO-B expression and ROS production. Stimulation with ANG2 and GLUC increased atrial expression of both MAOs and oxidative stress; the effects were significantly decreased by the SGLT2i. Atrial oxidative stress positively correlated with the echocardiographic size of heart chambers and negatively with the left ventricular ejection fraction. In overweight patients, MAO contributes to cardiac oxidative stress in basal conditions and those that mimicked the renin-angiotensin system activation and hyperglycemia and can be targeted with empagliflozin and dapagliflozin, as novel off-target class effect of the SGLT2i.

Effectiveness and safety of finerenone in Chinese CKD patients without diabetes: a retrospective, real-world study.

BACKGROUND: Finerenone, a non-steroidal mineralocorticoid receptor antagonist, has previously demonstrated its efficacy and safety in chronic kidney disease (CKD) associated with diabetes mellitus. Given its therapeutic potential, finerenone has been preliminarily explored in clinical practice for non-diabetic CKD patients. The effectiveness and safety in this population require further investigation in a real-world setting. METHODS: This retrospective, real-world analysis included non-diabetic CKD patients receiving finerenone. The main clinical outcomes assessed were changes in urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Serum potassium (sK+) levels were also monitored. Data were collected at baseline, and then at 1 month and 3 months following treatment initiation. RESULTS: Totally, 16 patients were included. There was a notable decrease in UACR from 1-month post-treatment, with a further reduction at 3 months, resulting in a median reduction of 200.41 mg/g (IQR, 84.04-1057.10 mg/g; P = 0.028; percent change, 44.52% [IQR, 31.79-65.42%]). The average eGFR at baseline was 80.16 ml/min/1.73m2, with no significant change after 1 month (80.72 ml/min/1.73m2, P = 0.594) and a slight numerical increase to 83.45 ml/min/1.73m2 (P = 0.484) after 3 months. During the 3-month follow-up, sK+ levels showed only minor fluctuations, with no significant differences compared to baseline, and remained within the normal range throughout the treatment period. No treatment discontinuation or hospitalization due to hyperkalemia was observed. CONCLUSION: In non-diabetic CKD patients, finerenone showed good effectiveness and safety within a 3-month follow-up period. This study provides valuable real-world evidence supporting the use of finerenone in non-diabetic CKD and highlights the need for future large-scale prospective research to further validate its efficacy.

Non-diabetic elderly populations: the MHR as a protective factor against bone abnormalities.

Objectives: In China, osteoporosis has become a major health concern among elderly population, imposing significant burden on the country's social and economic systems. The monocyte to high-density lipoprotein ratio (MHR) has been currently recommended as a novel marker of inflammation and oxidative stress associated with osteoporosis in type 2 diabetes mellitus (T2DM). However, its reliability in non-diabetic elderly populations remains unclear. The present study was to evaluate the association between MHR and osteoporosis in a non-diabetic elderly population. Methods: The clinical data of 240 non-diabetic elderly subjects (115 in the osteoporosis group and 125 in the normal bone group) were retrospectively analyzed and all statistical analyses were performed by using SPSS 26.0. Results: Differences in age, neutrophils, lymphocytes, monocytes, MHR, uric acid, creatinine, triglycerides,and high-density lipoprotein cholesterol were found to be statistically significant between the two groups. A binary logistic regression model was conducted by including age, MHR, UA and Cr as variables. The results showed that age was an independent risk factor and MHR was an independent protective factor for bone abnormality in the non-diabetic elderly population. The ROC analysis showed that the area under the curve for the predictive effect of MHR, age and their combined test on osteoporosis in non-diabetic elderly populations was 0.623, 0.728 and 0.761, respectively; the correlation analysis showed that MHR was positively correlated with lumbar and hip BMD, and negatively associated with femoral neck stress ratio, femoral intertrochanteric stress ratio, and femoral stem stress ratio, showing statistically significant differences (P<0.05). Conclusions: For the non-diabetic elderly population: the MHR is a protective factor against bone abnormalities and was significantly higher in the normal bone group than in the abnormal bone group.

Shifting the Paradigm: How Stress Hyperglycemia Alters the Landscape of Heart Failure Management.

Background Acute decompensated heart failure (ADHF) significantly contributes to global morbidity. Stress hyperglycemia (SHGL), although commonly observed in non-diabetic ADHF patients, remains underexplored. This study investigates the predictive value of SHGL for major adverse cardiac events (MACEs) and its impact on coronary intervention outcomes. Methods In this prospective observational study at a tertiary care center, 650 non-diabetic ADHF patients admitted for coronary intervention between April 2021 and April 2022 were assessed. SHGL was defined by random blood sugar levels >140 mg/dl. We monitored the incidence of MACEs, including cardiac death, non-fatal myocardial infarction, and heart failure rehospitalization, alongside the success rates of coronary revascularizations over 12 months. Results SHGL was present in 54% of patients (n=352) and was significantly associated with increased MACEs (p<0.001), higher rehospitalization rates (p<0.01), and lower success in revascularization (p<0.05). Using logistic regression, SHGL, age >65, and prior heart failure hospitalization were identified as independent predictors of MACEs. Statistical analyses were performed using two-tailed Mann-Whitney U tests, with significance levels set at p<0.05 for noteworthy findings and p<0.01 or p<0.001 for highly significant findings. Conclusions SHGL significantly impacts coronary intervention outcomes and the future prognosis of heart failure in non-diabetic ADHF patients, identifying it as a critical, modifiable risk factor. These findings advocate integrating SHGL management into ADHF care, emphasizing the need for further research to develop standardized treatment protocols. Proper management of SHGL could potentially improve patient outcomes, highlighting the importance of metabolic control in heart failure management.