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.

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.

Antidiabetic Molecule Efficacy in Patients with Type 2 Diabetes Mellitus-A Real-Life Clinical Practice Study.

In this paper, we aim to evaluate the efficacy of antidiabetic cardioprotective molecules such as Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) and Glucagon-like Peptide 1 Receptor Agonists (GLP-1 RAs) when used with other glucose-lowering drugs, lipid-lowering, and blood pressure (BP)-lowering drugs in a real-life setting. A retrospective, observational study on 477 patients admitted consecutively in 2019 to the outpatient clinic of a tertiary care unit for Diabetes Mellitus was conducted. Body mass index (BMI), blood pressure (BP) (both systolic and diastolic), and metabolic parameters, as well as A1c hemoglobin, fasting glycaemia and lipid profile, including total cholesterol (C), HDL-C, LDL-C and triglycerides), were evaluated at baseline and two follow-up visits were scheduled (6 months and 12 months) in order to assess the antidiabetic medication efficacy. Both SGLT-2i and GLP-1 RAs were efficient in terms of weight control reflected by BMI; metabolic control suggested by fasting glycaemia and A1c; and the diastolic component of BP control when comparing the data from the 6 and 12-month visits to the baseline, and when comparing the 12-month visit to the 6-month visit. Moreover, when comparing SGLT-2i and GLP-1 RAs with metformin, there are efficacy data for SGLT-2i at baseline in terms of BMI, fasting glycaemia, and HbA1c. In this retrospective study, both classes of cardioprotective molecules, when used in conjunction with other glucose-lowering, antihypertensive, and lipid-lowering medications, appeared to be efficient in a real-life setting for the management of T2DM.

The Effects of Sodium-Glucose Cotransporter 2-Inhibitors on Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease or Steatohepatitis and Type 2 Diabetes: A Systematic Review of Randomized Controlled Trials.

Type 2 Diabetes Mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are part of metabolic syndrome and share multiple causal associations. Both conditions have an alarmingly increasing incidence and lead to multiple complications, which have an impact on a variety of organs and systems, such as the kidneys, eyes, and nervous and cardiovascular systems, or may cause metabolic disruptions. Sodium-glucose cotransporter 2-inhibitors (SGLT2-i), as an antidiabetic class with well-established cardiovascular benefits, and its class members have also been studied for their presumed effects on steatosis and fibrosis improvement in patients with NAFLD or non-alcoholic steatohepatitis (NASH). The MEDLINE and Cochrane databases were searched for randomized controlled trials examining the efficacy of SGLT2-i on the treatment of NAFLD/NASH in patients with T2DM. Of the originally identified 179 articles, 21 articles were included for final data analysis. Dapagliflozin, empagliflozin, and canagliflozin are some of the most used and studied SGLT2-i agents which have proven efficacy in treating patients with NAFLD/NASH by addressing/targeting different pathophysiological targets/mechanisms: insulin sensitivity improvement, weight loss, especially visceral fat loss, glucotoxicity, and lipotoxicity improvement or even improvement of chronic inflammation. Despite the considerable variability in study duration, sample size, and diagnostic method, the SGLT2-i agents used resulted in improvements in non-invasive markers of steatosis or even fibrosis in patients with T2DM. This systematic review offers encouraging results that place the SGLT2-i class at the top of the therapeutic arsenal for patients diagnosed with T2DM and NAFLD/NASH.

Evaluating the Adipose Tissue Depth as a Predictor Factor for Gestational Diabetes in Later Pregnancy-A Systematic Review.

The increasing prevalence of gestational diabetes mellitus (GDM) requires non-invasive and precise techniques for evaluating the predisposing risk factors such as visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). According to PRISMA, we developed a systematic review and searched after "visceral adipose tissue AND gestational diabetes" and identified 221 articles on the MEDLINE and Word of Science databases. After assessing them for inclusion criteria and two researchers screened them, 11 relevant articles were included. Although evidence is conflicting, more studies favor using US-determined VAT in GDM prediction. VAT may be more valuable than body mass index or SAT in predicting GDM. VAT can represent an additive factor to the prediction tool of the risk of developing GDM when used in conjunction with other anthropometric or biological parameters or maternal risk factors. US measurements are heterogeneous given different evaluation techniques, cut-off values and inter-operator variation. A significant limitation is the lack of a gold standard to identify GDM confidently. Pregnant women may benefit from early monitoring and preventive care if classified as high risk for GDM early in the gestational period. US-measured VAT during the first trimester of pregnancy seems a valuable and inexpensive screening approach to predict GDM development later in pregnancy, either by itself or if used in conjunction with other clinical and biological parameters.

The Effects of Cardioprotective Antidiabetic Therapy on Microbiota in Patients with Type 2 Diabetes Mellitus-A Systematic Review.

As the pathophysiologic mechanisms of type 2 diabetes mellitus (T2DM) are discovered, there is a switch from glucocentric to a more comprehensive, patient-centered management. The holistic approach considers the interlink between T2DM and its complications, finding the best therapies for minimizing the cardiovascular (CV) or renal risk and benefitting from the treatment's pleiotropic effects. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) fit best in the holistic approach because of their effects in reducing the risk of CV events and obtaining better metabolic control. Additionally, research on the SGLT-2i and GLP-1 RA modification of gut microbiota is accumulating. The microbiota plays a significant role in the relation between diet and CV disease because some intestinal bacteria lead to an increase in short-chain fatty acids (SCFA) and consequent positive effects. Thus, our review aims to describe the relation between antidiabetic non-insulin therapy (SGLT-2i and GLP-1 RA) with CV-proven benefits and the gut microbiota in patients with T2DM. We identified five randomized clinical trials including dapagliflozin, empagliflozin, liraglutide, and loxenatide, with different results. There were differences between empagliflozin and metformin regarding the effects on microbiota despite similar glucose control in both study groups. One study demonstrated that liraglutide induced gut microbiota alterations in patients with T2DM treated initially with metformin, but another failed to detect any differences when the same molecule was compared with sitagliptin. The established CV and renal protection that the SGLT-2i and GLP-1 RA exert could be partly due to their action on gut microbiota. The individual and cumulative effects of antidiabetic drugs on gut microbiota need further research.

Non-alcoholic fatty liver disease in diabetes mellitus patients on chronic hemodialysis - A case series addressing cardiovascular and mortality risks.

Non-alcoholic fatty liver disease (NAFLD) has an important role in the pathogenesis of cardiovascular diseases in the population with diabetes and it is highly prevalent in end-stage renal disease (ESRD) patients. This case series describes NAFLD associated factors and survival in type 2 diabetes patients (T2DM) who have ESRD treated with hemodialysis. NAFLD prevalence in patients with T2DM and ESRD is 69.2%. A high number of patients (15 out of 18) have obesity evaluated by calculating body mass index (BMI) and bioimpedance measurements. Patients with NAFLD have higher cardiovascular mortality risk, 13 of 18 patients were already diagnosed with coronary heart disease, 6 of 18 had cerebrovascular disease, and 6 of 18 had peripheral artery disease. Fourteen patients were treated with insulin, two patients with sitagliptin (renal adjusted dose of 25mg/day) and two patients with medical nutrition therapy, with an HbA1c ranging from 4.4 to 9.0%. After one-year follow-up 7 of 18 patients died, the causes having roughly equal proportions: myocardial infarction, SARS-CoV2 infection, and pulmonary edema. In conclusion, our population of type 2 diabetic patients with ESRD in hemodialysis had a prevalence of ultrasound-diagnosed NAFLD of 69.2%. Also, this population had a high death rate at one-year follow-up, cardiovascular causes being among the most common.

Interleukin-8, CXCL10, CXCL11 and their role in insulin resistance in adult females with subclinical hypothyroidism and prediabetes.

In obesity, the hormonal secretion of the thyroid gland switches from homeostasis to type 2 allostasis in order to adapt to persistent modifications of adipose tissue and inflammation. Previous meta-analyses have linked obesity with an increased risk of developing thyroid diseases, prediabetes, and type 2 diabetes mellitus. We designed an observational cross-sectional study including all female patients presenting consecutively in an ambulatory clinic for 16 months. This study aimed to describe the level of serum cytokines and chemokines in relation to TSH, fT4 and insulin resistance (IR) indexes in patients with subclinical hypothyroidism (SCH). The study included 72 women with a median age of 59 ± 17.75 years, and a mean BMI (Body Mass Index) of 31.48 ± 6.75 kg/m2. Modelling homeostasis model assessment of IR indices (HOMA-IR) based on chemokines (IL-8, CXCL10, CXCL11, leptin), C-reactive protein, the presence or absence of SCH, taking into account age, BMI, abdominal circumference, glycated haemoglobin (HbA1c), and anti-thyroid peroxidase antibodies (ATPO) as covariates, identified a single chemokine that was significantly associated with the dependent variable (IL-8). IR indices are negatively associated with IL-8 in female patients with subclinical hypothyroidism, but the effect of the cytokine is minimal. BMI rather than TSH influences the level of CXCL11 in our population. CXCL10 has a tendency to increase in patients with SCH, obesity and prediabetes, with no association with TSH.

Correlations between Diabetes Mellitus Self-Care Activities and Glycaemic Control in the Adult Population: A Cross-Sectional Study.

Although it is well known that lifestyle changes can affect plasma glucose levels, there is little formal evidence for the sustained effectiveness of exercise and diet in diabetes mellitus (DM) management. Self-care in DM refers to the real-life application of the knowledge that the patient gained during the education programmes. The goals are to bring about changes in the patient's behaviour, thus improving glycaemic control. We evaluated the influence of DM self-care activities (SCA) on glycaemic control in a total of 159 patients with DM. Plasma glycated haemoglobin (HbA1c) levels were used to monitor glycaemic control, while SCA were assessed using the standardised Diabetes Self-Management Questionnaire (DSMQ). In our study, 53% of the patients had a HbA1c ≥ 7%. In univariate linear regression models, a statistically significant inverse association was observed between the HbA1c (the dependent variable) and both the DSMQ Dietary Control Score (R2 = 0.037, p = 0.0145) and the DSMQ Sum Score (R2 = 0.06, p = 0.0014). The mean absolute change in the HbA1c% associated with one standard deviation (SD) change in the DSMQ Sum Score, independent of the other significant variables retained in the compacted multivariate regression model, was -0.419% (confidence interval: 95%: from -0.18 to -0.65). Although the impact of the DSMQ Score was modest when compared to the other independent variables in the multivariate model, the findings emphasise the importance of maintaining optimal lifestyle changes to avoid hyperglycaemia and its complications. In conclusion, enhanced self-management of DM is associated with improved glucose control. In patients with chronic diseases such as DM, the role of streamlining SCA encompassing physical activity and proper dietary choices is imperative because of a significantly reduced access to healthcare globally as a result of the COVID-19 pandemic.

Subclinical hypothyroidism has no association with insulin resistance indices in adult females: A case-control study.

Longitudinal studies have indicated an association between thyroid function and insulin resistance (IR) or a neutral relationship. Both the lowest tertile of free thyroxine (fT4) and the highest tertile of free triiodothyronine (fT3) were found to be associated with IR in cross-sectional studies. The aim of the present study was to analyze the association between IR and subclinical hypothyroidism in a female adult population from Bucharest, Romania. This is a retrospective pilot case-control study that included female patients examined by two endocrinologists and a diabetologist in an outpatient clinic. The retrospective follow-up had a one-year duration and included the evaluation of thyroid function tests and IR indices based on fasting insulinemia and C-peptide. The study included 176 women, 91 with subclinical hypothyroidism, with a median age of 60±17 years and a mean body mass index (BMI) of 27.79±4.76 kg/m2. The majority of the population (50%) was diagnosed with autoimmune thyroiditis, and 17.05% with goitre. The univariate logistic regression using hypothyroidism as the explaining variable found no evidence of a significant relationship between a decreased thyroid function and IR (OR 1.32; P=0.36). Metabolic syndrome was probably the most important determinant of IR in the population group studied. Thus, it was not the thyroid function per se, but the coexistence of other elements of this syndrome that prevailed in determining IR. Advantages to the study are the design that permitted evaluation of IR and the thyroid function at different moments in time as well as the uniformity of the blood tests. The multivariate analyses were adjusted for age, lipid profile and treatment; however, one limiting factor was the absence of other hormonal blood tests. In summary, there was no association between the thyroid function tests (TSH, fT4) and IR indices in adult Romanian women in a case-control study with one-year retrospective follow-up.

Diabetic neuropathy: A narrative review of risk factors, classification, screening and current pathogenic treatment options (Review).

Diabetic neuropathy (DN) is a frequent complication of diabetes mellitus (DM) with severe consequences as it progresses and influences all human body systems. This review discusses the risk factors for DN, the main characteristics of the clinical forms of DN, the screening methods and the current therapeutic options. Distal symmetric DN is the primary clinical form, and DM patients should be screened for this complication. The most important treatment of DN remains good glucose control, generally defined as HbA1c ≤7%. Symptomatic treatment improves life quality in diabetic patients. Pharmacological agents such as alpha (α)-lipoic acid and benfotiamine have been validated in several studies since they act on specific pathways such as increased oxidative stress (α-lipoic acid exerts antioxidant effects) and the excessive production of advanced glycosylation products (benfotiamine may inhibit their production via the normalization of glucose). Timely diagnosis of DN is significant to avoid several complications, including lower limb amputations and cardiac arrhythmias.

Weight loss programmes using low carbohydrate diets to control the cardiovascular risk in adolescents (Review).

Cardiovascular risk (CVR) is a broad term that includes traditional factors like hypertension, hyper lipidemia, abdominal obesity, hyperinsulinemia or overt type 2 diabetes mellitus (T2DM), and emerging ones such as hypothyroidism or inflammatory diseases. In epidemiologic studies, all of these factors are associated with atherogenesis and have complex interactions between them. They have in common an increased prevalence in the general population beginning in childhood, and are correlated with endothelial damage as demonstrated by echocardiographic modifications of the left ventricle or carotid intima-media thickness. Adolescence is a transition period where behavioural eating patterns develop and have a major impact on cardiovascular risk. To address these patterns, weight-loss programmes under medical supervision for overweight and obese adolescents are developed. It was observed that those who control the quality and quantity of their carbohydrates, by consuming more fruits and vegetables, associated with increased physical activity reduce their CVR. Some limited studies have shown that low carbohydrate diet (LCD) is safe and effective, but one should take into consideration the limited duration and the structure of the LCD. If there is a proper adherence to this type of nutritional intervention, it results in weight loss, improvement in insulin resistance, lipid profile and subclinical hypothyroidism reversal. We reviewed the literature starting from 2009 by searching all the observational, randomised clinical trials and meta-analyses on MEDLINE and SCOPUS databases regarding obesity and related metabolic diseases (dyslipidemia, type 2 diabetes, hypertension, hypothyroidism, LCD) in adolescents and synthesized the nutritional interventions for this population that could decrease CVR.

Non-alcoholic fatty liver disease: A major challenge in type 2 diabetes mellitus (Review).

Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in type 2 diabetes mellitus (T2DM) patients, being one of the disorders with a relevant global burden. Cross-sectional studies have shown that patients with T2DM and NAFLD have a higher prevalence of liver fibrosis, compared with the general population. Patients with non-alcoholic steatohepatitis (NASH) and T2DM have an increased mortality and morbidity, therefore they generate substantial health care costs. NASH worsens chronic diabetes complications, and T2DM aggravate the NASH progression to fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC). The objectives in NAFLD and NASH therapy are to reduce disease activity, to slow down progression of fibrosis, and to lower the risk factors. Unfortunately, there are no specific validated pharmacological therapies. Several trials have demonstrated that anti-diabetic agents such as thiazolidindiones, sodium-glucose co-transporter inhibitors, glucagon like peptide-1 receptor analogs, or dipeptidyl peptidase-4 inhibitors might have complimentary benefits for patients with NAFLD. Some of the effect on reducing steatosis and fibrosis is explained by the weight loss these treatments produce. A goal in standard care is developing screening tools, early and non-invasive diagnosis methods, studying the pleiotropic effects of drugs, together with newer therapeutic agents, which can target mutual pathogenic mechanisms for diabetes and liver disease.

The efficacy and safety of dipeptidyl peptidase-4 inhibitors compared to other oral glucose-lowering medications in the treatment of type 2 diabetes.

INTRODUCTION: The dipeptidyl peptidase-4 inhibitors (DPP-4is), which belong to the class of incretin-based medications, are recommended as second or third-line therapies in guidelines for the management of type 2 diabetes mellitus. They have a favorable drug tolerability and safety profile compared to other glucose-lowering agents. OBJECTIVE: This review discusses data concerning the use of DPP-4is and their cardiovascular profile, and gives an updated comparison with the other oral glucose-lowering medications with regards to safety and efficacy. Currently available original studies, abstracts, reviews articles, systematic reviews and meta-analyses were included in the review. DISCUSSION: DPP4is are moderately efficient in decreasing the HbA1c by an average of 0.5% as monotherapy, and 1.0% in combination therapy with other drugs. They have a good tolerability and safety profile compared to other glucose-lowering drugs. However, there are possible risks pertaining to acute pancreatitis and pancreatic cancer. CONCLUSION: Cardiovascular outcome trials thus far have proven the cardiovascular safety for ischemic events in patients treated with sitagliptin, saxagliptin, alogliptin, linagliptin and vildagliptin. Data showing increased rate of hospitalisation in the case of saxagliptin did not seem to be a class effect.

No Association between 25-Hydroxyvitamin D and Insulin Resistance or Thyroid Hormone Concentrations in a Romanian Observational Study.

Background and objectives: Vitamin D is involved in insulin resistance through genomic and non-genomic mechanisms. Several observational and randomized studies have discrepant results; some of them showed an improved insulin resistance (IR), and others a neutral effect after vitamin D deficiency is corrected. Materials and Methods: We designed a retrospective observational study that included all women who presented for 33 months in an outpatient clinic in Bucharest, Romania. Results: We analyzed 353 patients with a mean age of 58.5 ± 13.7 years, a mean body mass index (BMI) of 27.36 ± 4.87 kg/m-2, and a mean level of 25-hydroxyvitamin D (25OHD) of 39.53 ± 15.73 ng/mL. There were no differences in the calculated Homeostatic Model Assessment of Insulin Resistance variants 1 and 2 (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI) between women with vitamin D deficit versus normal values. In multivariate analysis, there was no significant relation between 25OHD and the response variables considered by us. Conclusions: We observed a small positive correlation between a higher level of 25OHD and increased glycosylated hemolobin (HbA1c) or IR indices without clinical significance. Other modifiable or non-modifiable factors override 25OHD influence on IR in adult women with a normal serum level and may contribute to the remainder of the variability observed.