Skin Autofluorescence as a Potential Adjunctive Marker for Cardiovascular Risk Assessment in Type 2 Diabetes: A Systematic Review.

Diabetes mellitus (DM), due to its long-term hyperglycemia, leads to the accumulation of advanced glycation end-products (AGEs), especially in the vessel walls. Skin autofluorescence (SAF) is a non-invasive tool that measures AGEs. DM patients have a rich dietary source in AGEs, associated with high oxidative stress and long-term inflammation. AGEs represent a cardiovascular (CV) risk factor, and they are linked with CV events. Our objective was to assess whether SAF predicts future CV events (CVE) by examining its association with other CV risk factors in patients with type 2 DM (T2DM). Additionally, we assessed the strengths and limitations of SAF as a predictive tool for CVE. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology, we conducted a systematic review with CRD42024507397 protocol, focused on AGEs, T2DM, SAF, and CV risk. We identified seven studies from 2014 to 2024 that predominantly used the AGE Reader Diagnostic Optic tool. The collective number of patients involved is 8934, with an average age of 63. So, SAF is a valuable, non-invasive marker for evaluating CV risk in T2DM patients. It stands out as a CV risk factor associated independently with CVE. SAF levels are influenced by prolonged hyperglycemia, lifestyle, aging, and other chronic diseases such as depression, and it can be used as a predictive tool for CVE.

Assessment of Cardiovascular Risk Categories and Achievement of Therapeutic Targets in European Patients with Type 2 Diabetes.

Background: Individuals diagnosed with type 2 diabetes mellitus (T2DM) are more prone to experiencing severe cardiovascular (CV) events, often occurring at a younger age, due to a complex interplay of risk factors. T2DM diagnosis inherently classifies patients as belonging to a higher CV risk group. In light of the increased susceptibility to severe CV outcomes, our study aims to assess the distribution of CV risk categories and the attainment of therapeutic targets among Romanian patients diagnosed with T2DM. Methods: A cross-sectional analysis was performed, including 885 patients diagnosed with T2DM who were consecutively admitted to a secondary care hospital unit between January and July 2019. Data collection included demographics, lipid profile, glycated hemoglobin (HbA1c), blood pressure (BP), estimated glomerular filtration rate (eGFR), and medication specifics for T2DM and associated conditions. Patients were stratified into CV risk categories based on the ESC/EAS guidelines, encompassing moderate, high, and very high risk categories. The rationale for selecting these guidelines for CV risk categories was that they were current and provided best practice recommendations for T2DM patients during the cross-sectional evaluation. We assessed therapeutic target achievement rates for LDL-C, HbA1C, and BP for each CV risk category. Additionally, we examined utilization rates of statins and novel cardio- and reno-protective, non-insulin antidiabetic medications. Results: The group's average age was 62.9 ± 7.7 years and comprised 53.7% females. An average HbA1c level of 7.1 ± 1.3% was observed in the group. Within the cohort, 83% had hypertension, with a mean systolic BP of 132 ± 16.2 mm Hg and mean diastolic BP of 80 ± 9.6 mm Hg. Additionally, 64.6% of patients were obese, with a mean body mass index of 32.3 ± 5.3 kg/m2. Mean LDL-C levels varied across the different CV risk categories: 106.6 ± 35.6 mg/dL in the very high risk category, 113 ± 39.3 mg/dL in the high risk category, and 124.3 ± 38.3 mg/dL in the moderate risk category. Most treatment schemes included metformin (87.0%) and statins (67.0%), with variable use rates for other glucose-lowering and CV risk-modifying therapies. The percentage of patients using GLP-1 RAs was 8.1%, while 3.9% used SGLT2 inhibitors. Conclusions: Most Romanian patients with T2DM are at very high or high CV risk. Despite reaching glycemic control targets, most patients are not achieving the composite target, which includes, besides glycemic control, BP values and lipid profile. Many patients with T2DM are not benefiting from DM therapies with additional cardiorenal benefits or statins.

Associations between Skin Autofluorescence Levels with Cardiovascular Risk and Diabetes Complications in Patients with Type 2 Diabetes.

Advanced Glycation End Products (AGEs) contribute to the pathophysiology of type 2 diabetes mellitus (T2DM) and cardiovascular (CV) diseases (CVDs), making their non-invasive assessment through skin autofluorescence (SAF) increasingly important. This study aims to investigate the relationship between SAF levels, cardiovascular risk, and diabetic complications in T2DM patients. We conducted a single-center, cross-sectional study at Consultmed Hospital in Iasi, Romania, including 885 T2DM patients. The assessment of SAF levels was performed with the AGE Reader™, (Diagnoptics, Groningen, The Netherlands). CVD prevalence was 13.9%, and according to CV risk category distribution, 6.1% fell into the moderate-risk, 1.13% into the high-risk, and 92.77% into the very-high-risk category. The duration of DM averaged 9.0 ± 4.4 years and the mean HbA1c was 7.1% ± 1.3. After adjusting for age and eGFR, HbA1c values showed a correlation with SAF levels in the multivariate regression model, where a 1 SD increase in HbA1c was associated with a 0.105 SD increase in SAF levels (Nagelkerke R2 = 0.110; p < 0.001). For predicting very high risk with an SAF cut-off of 2.35, sensitivity was 67.7% and specificity was 56.2%, with an AUC of 0.634 (95% CI 0.560-0.709, p = 0.001). In T2DM, elevated SAF levels were associated with higher CV risk and HbA1c values, with 2.35 identified as the optimal SAF cut-off for very high CV risk.

To What Extent Does Cardiovascular Risk Classification of Patients with Type 2 Diabetes Differ between European Guidelines from 2023, 2021, and 2019? A Cross-Sectional Study.

Background and Objectives: Type 2 Diabetes (T2DM) is intricately associated with an increased cardiovascular (CV) risk, highlighting the imperative for tailored intervention in the prevention and management of CV diseases. To assess the CV risk and subsequent interventions in patients with diabetes, the European Society of Cardiology (ESC) has been consistently developing and updating specific guidelines for risk assessment and patient management since 2019. The 2023 risk classification method has significantly changed, introducing a novel probability-based assessment through the implementation of SCORE2-Diabetes instrument. This marks a shift from the risk factor-based classification employed in the 2019 and 2021 methods, representing an innovative approach in risk assessment for individuals with T2DM. This study aims to evaluate the differences in the CV risk classification among hospitalized patients with T2DM using the three proposed methods within the Romanian population, a European population considered to be at very high cardiovascular risk. Materials and Methods: in a consecutive-case, population-based study design, 70 patients hospitalized with T2DM from a European population characterized by very high CV risk were assessed for CV risk using the three proposed methods. The differences between these classifications were subsequently analyzed. Results: In the study group, according to 2023 classification, one patient (1.4%) was classified with moderate CV risk, eight (11.4%) with high cardiovascular risk, and sixty-one (87.2%) with very high cardiovascular risk. A total of 36 patients (51.4%) were classified differently compared to 2021 criteria, the differences being statistically significant (p = 0.047), while 13 (18.6%) were different compared to 2019 criteria, the differences being statistically non-significant (p = 0.731). By comparing the 2021 to the 2019 ESC Guidelines recommendations, 40 patients had a one-step decrease in cardiovascular risk category, from very high to high risk. Conclusions: Most patients included in the analysis were classified as very high CV risk (87.2%). Within a European population characterized by very high CV risk, the SCORE2-Diabetes instrument proves to be a valuable tool, contributing to most step-ups in CV risk classes within the 2023 classification. In a very-high-risk demographic, the 2023 algorithm resulted in different classifications in contrast to the 2021 method but similar classifications observed with the 2019 method.

To What Extent Is HbA1c Associated with Glycemic Variability in Patients with Type 1 Diabetes? A Retrospective, Noninterventional Study.

BACKGROUND: Glycemic variability (GV) is a novel parameter used in evaluating the quality of diabetes management. Current guidelines recommend the use of GV indexes alongside the traditional parameter to evaluate glycemic control: hemoglobin A1c (HbA1c). This study aims to evaluate the extent to which HbA1c explains the GV phenomena in patients with Type 1 diabetes (T1DM). METHODS: In 147 patients with T1DM, associations between HbA1c and several GV indexes were analyzed. RESULTS: Patients with an HbA1c < 7% had a lower median standard deviation of glycemia (60 vs. 48; p < 0.001), a lower coefficient of variation (34.1 vs. 38.0; p < 0.001), and a significantly increased median time in range (78 vs. 58; p < 0.001). HbA1c was positively correlated with the coefficient of variation (r = 0.349; p < 0.001) and the standard deviation (r = 0.656; p < 0.001) but reversely correlated with a lower time in range (r = -0.637; p < 0.001). CONCLUSIONS: HbA1c only partially explains the GV phenomena in patients with T1DM. The HbA1c value is associated more strongly with the time in range and standard deviation than with the coefficient of variation.

A Systematic Review Assessing the Impact of Vitamin D Levels on Adult Patients with Lymphoid Malignancies.

Vitamin D deficiency has been correlated with various conditions, including the risk of developing lymphoid malignancies. This systematic review aimed to assess the association between vitamin D levels at diagnosis of lymphoid malignancies, patient outcomes, and survival. A systematic review was conducted, encompassing 15 studies published until January 2023, involving 4503 patients, examining the relationship between vitamin D and lymphoid cancers. The median age of the patients was 56.5 years, with a median follow-up duration of approximately 36 months across studies. The overall median vitamin D level at initial measurement was 20.4 ng/mL, while a <20 ng/mL threshold was used to define vitamin D insufficiency. The results demonstrated significant associations between vitamin D levels and patient outcomes in several lymphoid malignancies, with a pooled risk in disease progression of 1.93 and a pooled hazard ratio of 2.06 for overall survival in patients with 25-(OH)D levels below the normal threshold of 20 ng/mL. Among findings, it was demonstrated that supplemental vitamin D improves the chemosensitivity of tumors by reducing the rate of tumor growth compared with vitamin D or chemotherapy alone. Vitamin D had a protective effect for patients with DLBCL under R-CHOP treatment, while vitamin D insufficiency was associated with the impairment of rituximab treatment and showed worse clinical outcomes in chimeric antigen receptor T-cell (CAR-T) recipients. Although one study found no association between vitamin D deficiency and the cause of death, most associated vitamin D insufficiency with early clinical failure and lower survival probability. In conclusion, his systematic review highlights the importance of vitamin D levels in the prognosis and survival of patients with lymphoid malignancies. Further research is needed to better understand the underlying mechanisms and explore the potential benefits of vitamin D supplementation in managing these cancers.

How to Measure Glycemic Variability? A Literature Review.

Optimal glycemic control without the presence of diabetes-related complications is the primary goal for adequate diabetes management. Recent studies have shown that hemoglobin A1c level cannot fully evaluate diabetes management as glycemic fluctuations are demonstrated to have a major impact on the occurrence of diabetes-related micro- and macroangiopathic comorbidities. The use of continuous glycemic monitoring systems allowed the quantification of glycemic fluctuations, providing valuable information about the patients' glycemic control through various indicators that evaluate the magnitude of glycemic fluctuations in different time intervals. This review highlights the significance of glycemic variability by describing and providing a better understanding of common and alternative indicators available for use in clinical practice.

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.

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.