The Renoprotective Mechanisms of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i)-A Narrative Review.

Chronic kidney disease (CKD) is a noncommunicable condition that has become a major healthcare burden across the globe, often underdiagnosed and associated with low awareness. The main cause that leads to the development of renal impairment is diabetes mellitus and, in contrast to other chronic complications such as retinopathy or neuropathy, it has been suggested that intensive glycemic control is not sufficient in preventing the development of diabetic kidney disease. Nevertheless, a novel class of antidiabetic agents, the sodium-glucose cotransporter-2 inhibitors (SGLT2i), have shown multiple renoprotective properties that range from metabolic and hemodynamic to direct renal effects, with a major impact on reducing the risk of occurrence and progression of CKD. Thus, this review aims to summarize current knowledge regarding the renoprotective mechanisms of SGLT2i and to offer a new perspective on this innovative class of antihyperglycemic drugs with proven pleiotropic beneficial effects that, after decades of no significant progress in the prevention and in delaying the decline of renal function, start a new era in the management of patients with CKD.

Lipid Disorders Management Strategies (2024) in Prediabetic and Diabetic Patients.

Dyslipidaemia is a modifiable risk factor commonly associated with diabetes mellitus and prediabetes, with a major impact on the early development of atherosclerotic cardiovascular disease. Various studies have tried to identify the key treatment targets, their optimal values according to patients' CV risk, and the most efficient yet safe therapeutic agents which, alongside lifestyle changes, would improve lipid levels and reduce cardiovascular mortality and morbidity. Currently, there are multiple pharmacologic options that can be used in the management of dyslipidaemia, such as statins, ezetimibe, bempedoic acid, PCSK9 inhibitors, n-3 polyunsaturated fatty acids or fibrates, to name only a few, while many other are under development. In the current setting of a continuously increasing population of patients with metabolic disorders, this review aims to summarise current knowledge regarding lipid disorders and the recommendations of recent guidelines in treating dyslipidaemia in patients with diabetes mellitus or prediabetes.

Sport as Medicine for Dyslipidemia (and Other Risk Factors).

PURPOSE OF REVIEW: Dyslipidemia is a common condition characterized by abnormal lipid levels in the blood, which can increase the risk of cardiovascular disease. Physical activity and participation in sports have been shown to have a positive impact on lipid profiles and reduce the risk of dyslipidemia. Additionally, regular physical activity can lead to weight loss and improved insulin sensitivity, both of which are associated with improved lipid profiles. This review aims to provide an overview on the utility of physical activity in the management of dyslipidemia. RECENT FINDINGS: Improvements in lipid profiles were observed across both short- and long-term durations of high-intensity interval training (HIIT) and moderate intensity interval training (MIIT). However, it seems that more significant improvements in lipid profiles can be achieved with longer periods of physical activity and more intense exercise regimens. Several studies have investigated the relationship between aerobic exercise and HDL cholesterol (HDL-C), and the results suggest that HDL-C levels are more responsive to aerobic exercise compared to LDL cholesterol (LDL-C) and triglycerides (TG). Although findings on the effect of aerobic exercise on LDL-C levels have been inconsistent, there may still be beneficial changes in LDL-C subfractions that could provide cardiovascular protection. One such subfraction is plasma Lp(a), which contains Apo(a). However, unlike other LDL subfractions, Lp(a) is determined by genetics and is not influenced by physical activity. Therefore, it cannot be improved through exercise. Exercise is commonly believed to lead to a decrease in plasma TG concentrations. However, it is important to note that the baseline TG level may play a crucial role in determining the effect of exercise on the TG response. Factors such as individual variability and metabolic differences can influence the response of TG levels to exercise. Overall, exercise plays a crucial role in improving lipid profiles and promoting cardiovascular health. In conclusion, sport can be considered a form of medicine for dyslipidemia. Regular physical activity and participation in sports can improve lipid profiles, reduce the risk of cardiovascular disease, and improve overall health. It is essential to incorporate exercise and a healthy lifestyle into one's daily routine to prevent and manage dyslipidemia effectively.

Validation and Cross-Cultural Adaptation of the Diabetes Self-Management Questionnaire (DSMQ) and the Social Phobia Inventory (SPIN) in Romanian Patients with Diabetes Mellitus.

Background and Objectives: Anxiety disorders are common in individuals with diabetes mellitus (DM) and have a negative impact on diabetes-related self-management and, therefore, on patients' evolution and prognosis. In this context, it becomes necessary to accurately and easily assess anxiety and self-management behaviours. Thus, the aim of this research was translation and cultural adaptation for Romanian patients and validation of two instruments used for assessing diabetes self-management and anxiety, namely the Diabetes Self-Management Questionnaire (DSMQ) and the Social Phobia Inventory (SPIN). Materials and Methods: The Summary of Diabetes Self-Care Activities Questionnaire (SDSCA) and the DSMQ instruments for assessing diabetes self-management, as well as the Generalised Anxiety Disorder Scale (GAD-7) and the SPIN instruments for assessing anxiety, have been administered to 117 patients from Timisoara, Romania, previously diagnosed with DM. Results: The SPIN has proven to have good internal consistency, excellent acceptability of its questions without non-responders and a median completion time of 3 min and 10 s, an excellent test−retest performance (Spearman's rho = 0.971, p < 0.001 between two administrations of the test) and good validity in comparison with the GAD-7, a previously validated and comprehensive instrument. The DSMQ has also proven to have acceptable internal consistency, excellent acceptability of its questions without non-responders and a median completion time of 2 min and 28 s; however, it has shown a weak, positive correlation without statistical significance in comparison with the SDSCA, a previously validated questionnaire. Conclusions: The SPIN, translated in Romanian and culturally adapted, is a valid tool for the screening of social phobias in individuals with DM. The DSMQ requires additional data for its validation in DM patients from Romania.

Comparison of Composite Lipid Indices in Patients with Obstructive Sleep Apnoea.

Purpose: Obstructive sleep apnoea (OSA) is a recognised risk factor for cardiovascular disease. However, it is difficult to evaluate the risk of cardiovascular disease in patients with OSA due to multiple shared risk factors. Composite lipid indices, such as atherogenic index of plasma (AIP), visceral adiposity index (VAI) and lipid accumulation product (LAP) have been shown to predict cardiovascular disease better than their individual lipid components. This study aimed to evaluate these indices in patients with OSA. Patients and Methods: Six hundred sixty-seven (667) patients with OSA and 139 non-OSA control volunteers participated in the study. Fasting serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C) levels were measured, and AIP, LAP and VAI were calculated following cardiorespiratory polygraphy. The relationship between lipid parameters, OSA and its comorbidities was evaluated using receiver operating curve (ROC) analysis. Results: We found a significant difference in all lipid parameters between OSA patients and controls. Comparing ROCs, LAP was significantly more strongly associated with OSA compared to all the other parameters. The optimal cut-off value for LAP to detect OSA was 76.4, with a sensitivity of 63% and a specificity of 76%. In addition, LAP was the best parameter to predict hypertension and diabetes in patients with OSA, and it was predictive for ischaemic heart disease together with HDL-C. Conclusion: Our results support the use of LAP in clinical practice when evaluating cardiovascular risk in patients with OSA. However, the optimal cut-off value should be determined in large-scale follow-up studies.

Factors Influencing the Desirability, Acceptability, and Adherence of Patients with Diabetes to Telemedicine.

Background and Objectives: Telemedicine solutions have proven their value and efficacy in augmenting diabetes care. In addition to the availability of tools needed to implement telemedicine solutions for patients with diabetes, the patients' desirability, acceptance, and adherence represent major burdens in implementing them. The main aim of this research is to evaluate which factors are influencing the desirability, acceptance, and adherence of patients with diabetes to telemedicine interventions in diabetes care. Materials and Methods: QTelemeDiab, a previously validated instrument for assessing patients' desirability, acceptance, and adherence to telemedicine in diabetes care, was used on 114 enrolled patients with diabetes mellitus, in parallel with demographic, socio-economic, disease history, and psychometric data from all patients. Results: Left-skewed score distributions were observed for the QTelemeDiab total score (median = 166; skewness = −1.738), as well as all its components, thus denoting a high desirability, acceptance, and adherence towards telemedicine use. The presence of severe depression was associated with significant decreases in the QTelemeDiab score (148 vs. 167; p < 0.001), as well as on the desirability sub-score (101 vs. 115; p < 0.001) and adherence sub-score (30 vs. 35; p < 0.001). The presence of severe anxiety was associated with significant decreases in QTelemeDiab score (150 vs. 166), as well as the desirability sub-score (104 vs. 114; p = 0.008) and adherence sub-score (30 vs. 34; p = 0.012). Conclusions: There is a high desirability, acceptance, and adherence to the use of telemedicine interventions in patients with diabetes, both in special and in normal epidemiological settings. The presence of severe anxiety decreases the patient's desirability, acceptance, and adherence, while the presence of severe depression decreases the patient's desirability and adherence to the use of telemedicine interventions in diabetes care.

Instrument for Assessing Patients' Desirability, Acceptability, and Adherence to Telemedicine in Diabetes: Development, Validity, and Reliability.

PURPOSE: To develop, test, and validate an instrument for assessing patients' desirability, acceptability, and adherence to telemedicine in diabetes. PATIENTS AND METHODS: A group of six experts defined the components that needed to be assessed when developing telemedicine platforms aimed at improving the care of patients with diabetes. The resulting instrument was tested for reliability and construct validity of 114 patients with diabetes and re-tested for reproducibility and consistency on a sub-group of 34 patients. Based on the analysis, the questionnaire's syntax, phrasing, and flow were improved to obtain optimal assessment results. RESULTS: The resulting questionnaire has three major sections: one for the main evaluated component (acceptability, desirability, and adherence to telemedicine in diabetes), one for collecting socio-economic and demographical information, and one for diabetes history-related data, respectively. The corresponding data for these sections are collected using 29 questions. The developed instrument has a good reliability (Cronbach's alpha = 0.890), reproducibility (Total score 164 vs 166 points at re-test vs test; Mann-Whitney U p-value = 0.394) and external validity (Spearman's rho = -0.580; p < 0.001 for correlation with Patient's Health Questionnaire -9; and Spearman's rho = -0.516; p < 0.001 for correlation with Generalized Anxiety Disorder - 7). CONCLUSION: The developed questionnaire is a valid and reliable instrument in assessing the patients' acceptability, desirability, and adherence to telemedicine use in diabetes care. In addition, the use of this instrument in the development of telemedicine platforms may improve and optimize their usage by providing valuable information regarding patients' preferences and specific needs.

Triglyceride-Glucose Index in Non-Diabetic, Non-Obese Patients with Obstructive Sleep Apnoea.

Obstructive sleep apnoea (OSA) is associated with increased insulin resistance. Triglyceride-glucose index (TyG) is a simple marker of insulin resistance; however, it has been investigated only by two studies in OSA. The aim of this study was to evaluate TyG in non-diabetic, non-obese patients with OSA. A total of 132 patients with OSA and 49 non-OSA control subjects were included. Following a diagnostic sleep test, fasting blood was taken for the analysis of the lipid profile and glucose concentrations. TyG was calculated as ln(triglyceride [mg/dL] × glucose [mg/dL]/2). Comparison analyses between OSA and control groups were adjusted for age, gender, body mass index (BMI) and smoking. TyG was higher in men (p < 0.01) and in ever-smokers (p = 0.02) and it was related to BMI (ρ = 0.33), cigarette pack-years (ρ = 0.17), apnoea-hypopnoea index (ρ = 0.38), oxygen desaturation index (ρ = 0.40), percentage of total sleep time spent with oxygen saturation below 90% (ρ = 0.34), and minimal oxygen saturation (ρ = -0.29; all p < 0.05). TyG values were significantly higher in OSA (p = 0.02) following adjustment for covariates. OSA is independently associated with higher TyG values which are related to disease severity in non-obese, non-diabetic subjects. However, the value of TyG in clinical practice should be evaluated in follow-up studies in patients with OSA.

The Impact Of Hyperuricemia On Cardiometabolic Risk Factors In Patients With Diabetes Mellitus: A Cross-Sectional Study.

PURPOSE: Hyperuricemia (HUA) is linked to a variety of non-communicable diseases such as atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD) and hypertension, with evidence showing its role in the development of diabetes mellitus (DM). Our study's main aim was to explore the associations of HUA with other traditional risk factors in Romanian patients with DM and to assess the impact of the increase of serum UA on DM complications and HbA1c. PATIENTS AND METHODS: In this cross-sectional, non-interventional study, we enrolled, according to a population-based, consecutive-case principle, 133 patients previously diagnosed with DM. HbA1c, uric acid, lipid profile, urinary albumin/creatinine ratio, glomerular filtration rate, TSH and FT4 measurements were performed, while the diagnosis of retinopathy and of diabetic neuropathy was established using standardized methods. RESULTS: An increased uric acid level was associated with a significant increase in the risk for development of stroke (OR=1.526; p=0.004). A weak, positive and statistically significant correlation can also be observed between the BMI and the presence of hyperuricemia (r=0.131; p=0.034), and between the triglyceride levels and hyperuricemia (r= 0.173; p=0.004). Glomerular filtration rate was correlated to hyperuricemia in a strong and negative manner, having an important statistical significance (r=-0.818; p=0.003). In our study, UA levels and HbA1c were negatively correlated, without reaching statistical significance. CONCLUSION: Serum UA is strongly correlated with the BMI, triglyceride level and GFR in Romanian patients with DM and HUA is significantly associated with a higher risk of stroke in these individuals.

Preliminary data of familial hypercholesterolemia (FH) patients in Romania.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is one of the most frequent monogenic cholesterol disorders. Its prevalence varies in adults between 1/500-1/217 individuals in the heterozygous form. The objective of this study was to uncover the FH prevalence in Romania to perform an adequate prevention for high risk individuals. METHODS: We have conducted an epidemiological study between January 2015 and January 2018 by recruiting patients from the CardioPrevent Foundation based on their FH score (taking into account their low density lipoprotein cholesterol (LDLc) levels, clinical characteristics such as premature coronary artery disease (CAD), and their family history of premature cardiovascular disease). We have calculated the probability of FH using the Dutch Lipid Clinic Network (DLCN) criteria and we have included patients with a score over 3 points. RESULTS: We have enrolled 59 patients, out of whom 61% were females. 8.4% of the patients recruited had a first degree relative with premature coronary artery disease and 5% had a relative with LDLc >190 mg/dl (without statin treatment). 10.16% of the patients had coronary artery disease and 15.25% peripheral vascular disease. 91.52% of the patients had a possible FH, while 6.7% had a probable FH and 1.6% a definite FH diagnosis. Based on this data, the prevalence of FH in Romania is: 1:213. CONCLUSIONS: To raise the suspicion for FH is easy at the level of the general practitioners, based on the analysis of LDLc levels and premature CAD occurrence. Diagnosis can be further refined using an available online free software.

Decreased serum arylesterase activity in autism spectrum disorders.

The PON1 gene, previously found associated with autism spectrum disorders (ASDs), encodes a serum protein responsible for the detoxification of organophosphates (OPs) and able to exert several enzymatic activities. PON1 arylesterase, but not diazoxonase activity, was significantly decreased in 174 ASD patients compared to 175 first-degree relatives and 144 controls (P=2.65×10⁻¹6). First degree relatives displayed intermediate activities, closer to patient than to control levels. Differences between patients, first-degree relatives and controls were especially evident among 164 Italians compared to 329 Caucasian-Americans, because arylesterase activity was significantly higher in Italian controls, compared to Caucasian-American controls (P=2.84×10⁻¹6). Arylesterase activity and PON protein concentrations were not significantly correlated, supporting a functional inhibition of arylesterase activity in ASD patients over quantitative changes in protein amounts. Serum arylesterase activity, in combination with PON1 genotypes at two single nucleotide polymorphisms (SNPs) known to influence protein amounts (rs705379: C-108T) and substrate specificity (rs662: Q192R), was able to discriminate ASD patients from controls with elevated sensitivity and specificity, depending on genotype and ethnic group. Serum arylesterase activity and genotyping at these two SNPs could thus represent an informative biochemical/genetic test, able to aid clinicians in estimating autism risk in ethnic groups with higher baseline arylesterase activity levels.