Interactions between Gut Microbiota and Oral Antihyperglycemic Drugs: A Systematic Review.

The intestinal microbiota refers to the collection of microorganisms that exist in the human gut. It has been said that bacteria influence the development of metabolic diseases, such as diabetes mellitus, as they have roles in immunomodulation, protection against pathogens, blood vessel growth, repairing the intestinal wall, and the development of the neurological system. In this review, we look at the latest research regarding interactions between gut microbiota and oral antihyperglycemic drugs and we present data suggesting that the microbiome may help counteract the reduced glucose tolerance and insulin resistance associated with metabolic disorders. We found that antidiabetic drugs can have significant impacts on gut microbiota composition and function, potentially influencing both the efficacy and side effects of these medications. Additionally, we discovered that microbial-based therapeutics, including probiotics, prebiotics, and postbiotics, and fecal microbiota can be considered when discussing preventive measures and personalized treatment options for type 2 diabetes mellitus. Understanding how antidiabetic drugs modulate gut microbiota composition and function is essential for optimizing their therapeutic efficacy and minimizing potential adverse effects. The relationship between the gut microbiota and glycemic agents, not fully understood, is currently the subject of increasing research and discussion. It has been proven that the microbiome can impact the effectiveness of the medications, but further research in this field may uncover novel therapeutic strategies for diabetes and other metabolic disorders by targeting the gut microbiota.

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.

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.

A Critical View over the Newest Antidiabetic Molecules in Light of Efficacy-A Systematic Review and Meta-Analysis.

The increase in life expectancy without a decrease in the years lived without disability leads to the rise of the population aged over 65 years prone to polypharmacy. The novel antidiabetic drugs can improve this global therapeutic and health problem in patients with diabetes mellitus (DM). We aimed to establish the efficacy (A1c hemoglobin reduction) and safety of the newest antidiabetic drugs (considered so due to their novelty in medical practice use), specifically DPP-4i, SGLT-2i, GLP-1 Ra, and tirzepatide. The present meta-analysis followed the protocol registered at Prospero with the CRD42022330442 registration number. The reduction in HbA1c in the DPP4-i class for tenegliptin was 95% CI -0.54 [-1.1, 0.01], p = 0.06; in the SGLT2-iclass for ipragliflozin 95% CI -0.2 [-0.87, 0.47], p = 0.55; and for tofogliflozin 95% CI 3.13 [-12.02, 18.28], p = 0.69, while for tirzepatide it was 0.15, 95% CI [-0.50, 0.80] (p = 0.65). The guidelines for treatment in type 2 DM are provided from cardiovascular outcome trials that report mainly major adverse cardiovascular events and data about efficacy. The newest antidiabetic non-insulinic drugs are reported to be efficient in lowering HbA1c, but this effect depends between classes, molecules, or patients' age. The newest antidiabetic drugs are proven to be efficient molecules in terms of HbA1c decrease, weight reduction, and safety, but more studies are needed in order to characterize exactly their efficacy and safety profiles.

Clinical Study of Serum Serotonin as a Screening Marker for Anxiety and Depression in Patients with Type 2 Diabetes.

Over time, studies have shown the importance of determining serotonin levels to diagnose somatic and psychiatric disorders. There are theoretical premises and practical ways to achieve a subtle correlation between the existence of comorbid psychiatric disorders and somatic diseases caused by the changes observed in serotonin levels. The present study, classified as retrospective and quantitative, provides evidence for determining the serotonin levels in patients with diabetes and anxiety or depression. A total of 48 patients with diabetes type 2 were enrolled in the study. Blood glucose level, glycated haemoglobin, and serum serotonin were noted, and they completed Hamilton A and Beck Depression Inventory questionnaires. We found robust correlations between serum serotonin and blood glucose (Sig. = 0.008), serum serotonin and HbA1c (Sig. = 0.007), serum serotonin and anxiety (Sig. = 0.000), and serum serotonin and depression (Sig. = 0.000). It is also noteworthy that women recorded extreme values higher than men for glycated haemoglobin (95% confidence interval: 6.92-7.79 in women and 6.30-7.23 in men). In conclusion, using serotonin as a marker of the mentioned diseases in clinical practice is of significant utility, considering the benefits in terms of the evolution and prognosis of comorbidities in patients with type 2 diabetes and anxiety and depressive symptoms.

An Update on the Current and Emerging Use of Thiazolidinediones for Type 2 Diabetes.

Guidelines have increasingly stressed the concept that adequate glycemic control is required to prevent or decrease the macro- and microvascular complications of type 2 diabetes mellitus (T2DM). PPAR-gamma agonists ("glitazones") are no longer prioritized due to their effects on heart failure. However, the association between these drugs and innovative therapies could be a valuable tool to attenuate the risk factors of the metabolic syndrome. Glitazones are used for the treatment of diabetes and associated comorbidities. There is substantial scientific evidence demonstrating the effect of glitazones at a cardiometabolic level, as well as on hematological and neurological pathologies that point to their usefulness. The use of glitazones has always been controversial both for the type of patients who must take these drugs and for the side effects associated with them. Unfortunately, the recent guidelines do not include them among the preferred drugs for the treatment of hyperglycemia and rosiglitazone is out of the market in many countries due to an adverse cardiovascular risk profile. Even though real-life studies have proven otherwise, and their pleiotropic effects have been highlighted, they have been unable to achieve primacy in the choice of antihyperglycemic drugs. It would be appropriate to demonstrate the usefulness of pioglitazone and its therapeutic benefit with further cardiovascular safety studies.

Novel Therapeutical Approaches to Managing Atherosclerotic Risk.

Atherosclerosis is a multifactorial vascular disease that leads to inflammation and stiffening of the arteries and decreases their elasticity due to the accumulation of calcium, small dense Low Density Lipoproteins (sdLDL), inflammatory cells, and fibrotic material. A review of studies pertaining to cardiometabolic risk factors, lipids alterations, hypolipidemic agents, nutraceuticals, hypoglycaemic drugs, atherosclerosis, endothelial dysfunction, and inflammation was performed. There are several therapeutic strategies including Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) inhibitors, inclisiran, bempedoic acid, Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RAs), and nutraceuticals that promise improvement in the atheromatous plaque from a molecular point of view, because have actions on the exposure of the LDL-Receptor (LDL-R), on endothelial dysfunction, activation of macrophages, on lipid oxidation, formations on foam cells, and deposition extracellular lipids. Atheroma plaque reduction both as a result of LDL-Cholesterol (LDL-C) intensive lowering and reducing inflammation and other residual risk factors is an integral part of the management of atherosclerotic disease, and the use of valid therapeutic alternatives appear to be appealing avenues to solving the problem.

Low-density lipoprotein cholesterol lowering treatment: the current approach.

In the last 50 years, several clinical and epidemiological studies during have shown that increased levels of low-density lipoprotein cholesterol (LDLc) are associated with the development and progression of atherosclerotic lesions. The discovery of ß-Hydroxy ß-methylglutaryl-CoA reductase inhibitors (statins), that possess LDLc-lowering effects, lead to a true revolution in the prevention and treatment of cardiovascular diseases. Statins remain the cornerstone of LDLc-lowering therapy. Lipid-lowering drugs, such as ezetimibe and bile acid sequestrants, are prescribed either in combination with statins or in monotherapy (in the setting of statin intolerance or contraindications to statins). Microsomal triglyceride transfer protein inhibitors and protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are other drug classes which have been investigated for their potential to decrease LDLc. PCSK9 have been approved for the treatment of hypercholesterolemia and for the secondary prevention of cardiovascular events. The present narrative review discusses the latest (2019) guidelines of the European Atherosclerosis Society/European Society of Cardiology for the management of dyslipidemia, focusing on LDLc-lowering drugs that are either already available on the market or under development. We also consider "whom, when and how" do we treat in terms of LDLc reduction in the daily clinical practice.

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.

Polypharmacy in Type 2 Diabetes Mellitus: Insights from an Internal Medicine Department.

BACKGROUND AND OBJECTIVES: Polypharmacy heavily impacts the quality of life of patients worldwide. It is a necessary evil in many disorders, and especially in type 2 diabetes mellitus, as patients require treatment both for this condition and its related or unrelated comorbidities. Thus, we aimed to evaluate the use of polypharmacy in type 2 diabetes mellitus vs. non-diabetes patients. MATERIALS AND METHODS: A cross-sectional retrospective observational study was conducted. We collected the medical records of patients hospitalized in the Internal Medicine Clinic of the Clinical Emergency Hospital of Bucharest, Romania, for a period of two months (01/01/2018-28/02/2018). Patients diagnosed with type 2 diabetes mellitus were included in the study group, whereas patients who were not diabetic were used as controls. RESULTS: The study group consisted of 63 patients with type 2 diabetes mellitus (mean age 69.19 ± 9.67 years, range 46-89 years; 52.38% males). The control group included 63 non-diabetes patients (mean age 67.05 ± 14.40 years, range 42-93 years, 39.68% males). Diabetic patients had more comorbidities (10.35 ± 3.09 vs. 7.48 ± 3.59, p = 0.0001) and received more drugs (7.81 ± 2.23 vs. 5.33 ± 2.63, p = 0.0001) vs. non-diabetic counterparts. The mean number of drug-drug and food-drug interactions was higher in type 2 diabetes mellitus patients vs. controls: 8.86 ± 5.76 vs. 4.98 ± 5.04, p = 0.0003 (minor: 1.22 ± 1.42 vs. 1.27 ± 1.89; moderate: 7.08 ± 4.08 vs. 3.54 ± 3.77; major: 0.56 ± 0.74 vs. 0.37 ± 0.77) and 2.63 ± 1.08 vs. 2.19 ± 1.42 (p = 0.0457), respectively. CONCLUSIONS: Polypharmacy should be an area of serious concern also in type 2 diabetes mellitus, especially in the elderly. In our study, type 2 diabetes mellitus patients received more drugs than their non-diabetes counterparts and were exposed to more drug-drug and food-drug interactions.

Treatment with Statins in Elderly Patients.

Elderly patients are a special category of patients, due to the physiological changes induced by age, the great number of comorbidities and drug treatment and last, but not least, to the cognitive dysfunction frequently encountered in this population. Cardiovascular disease is the most important cause of morbidity and mortality in elderly individuals worldwide. The rate of cardiovascular events increases after 65 years in men and after 75 years in women. Myocardial infarction and stroke are the leading disorders caused by atherosclerosis, that lead to death or functional incapacity. Elderly people have a greater risk to develop atherosclerotic cardiovascular disease. The incidence and prevalence of atherosclerosis increase with age and the number of cardiovascular events is higher in elderly patients. The most efficient treatment against atherosclerosis is the treatment with statins, that has been shown to decrease the risk both of stroke and coronary artery disease in all age groups. The advantages of the treatment become evident after at least one year of treatment. Primary prevention is the most important way of preventing cardiovascular disease in elderly individuals, by promoting a healthy lifestyle and reducing the risk factors. Secondary prevention after a stroke or myocardial infarction includes mandatory a statin, to diminish the risk of a recurrent cardiovascular event. The possible side effects of statin therapy are diabetes mellitus, myopathy, and rhabdomyolysis, hepatotoxicity. The side effects of the treatment are more likely to occur in elderly patients, due to their multiple associated comorbidities and drugs that may interact with statins. In elderly people, the benefits and disadvantages of the treatment with statins should be put in balance, especially in those receiving high doses of statins.

Metabolic dysfunction-associated fatty liver disease: current therapeutic strategies.

The definition of "Metabolic Associated Fatty Liver Disease - MAFLD" has replaced the previous definition of Nonalcoholic Fatty Liver Disease (NAFLD), because cardiometabolic criteria have been added for the prevention of cardiological risk in these patients. This definition leads to an in-depth study of the bidirectional relationships between hepatic steatosis, Type 2 Diabetes Mellitus (T2DM), Cardiovascular Disease (CVD) and/or their complications. Lifestyle modification, which includes correct nutrition combined with regular physical activity, represents the therapeutic cornerstone of MAFLD. When therapy is required, there is not clear accord on how to proceed in an optimal way with nutraceutical or pharmacological therapy. Numerous studies have attempted to identify nutraceuticals with a significant benefit on metabolic alterations and which contribute to the improvement of hepatic steatosis. Several evidences are supporting the use of silymarin, berberine, curcumin, Nigella sativa, Ascophyllum nodosum, and Fucus vesiculosus, vitamin E, coenzyme Q10 and Omega-3. However, more evidence regarding the long-term efficacy and safety of these compounds are required. There is numerous evidence that highlights the use of therapies such as incretins or the use of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors or other similar therapies which, by assisting existing therapies for pathologies such as diabetes, hypertension, insulin resistance, have given a breakthrough in prevention and the reduction of cardiometabolic risk. This review gave an overview of the current therapeutic strategies that are expected to aid in the treatment and prevention of MAFLD.

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.

New-Onset Diabetes Mellitus in COVID-19: A Scoping Review.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic became superimposed on the pre-existing obesity and diabetes mellitus (DM) pandemics. Since COVID-19 infection alters the metabolic equilibrium, it may induce pathophysiologic mechanisms that potentiate new-onset DM, and we evaluated this issue. METHOD: A systematic review of the literature published from the 1 January 2020 until the 20 July 2023 was performed (PROSPERO registration number CRD42022341638). We included only full-text articles of both human clinical and randomized controlled trials published in English and enrolling adults (age > 18 years old) with ongoing or preceding COVID-19 in whom hyperglycemia was detected. The search was based on the following criteria: "(new-onset diabetes mellitus OR new-onset DM) AND (COVID-19) AND adults". RESULTS: Articles on MEDLINE (n = 70) and the Web of Science database (n = 16) were included and analyzed by two researchers who selected 20 relevant articles. We found evidence of a bidirectional relationship between COVID-19 and DM. CONCLUSIONS: This link operates as a pathophysiological mechanism supported by epidemiological data and also by the clinical and biological findings obtained from the affected individuals. The COVID-19 pandemic raised the incidence of DM through different pathophysiological and psychosocial factors.

Comparative evaluation of LDL-CT, non-HDL/HDL ratio, and ApoB/ApoA1 in assessing CHD risk among patients with type 2 diabetes mellitus.

BACKGROUND: Research proved the importance of dosing apolipoprotein B (ApoB) over LDL cholesterol as a predictor of cardiovascular events. In this study, we aimed to observe the input apolipoprotein A1 (ApoA1) and ApoB, primarily if its ratio could provide in patients with type 2 diabetes mellitus (T2DM) without known atherosclerotic events regarding the coronary heart disease (CHD) risk. METHODS: We enrolled 83 patients with T2DM who attended the National Institute of Diabetes (Bucharest) between March 2022 and December 2022. A blood sample was taken from all patients to measure the different lipid parameters, including ApoA1 and ApoB. Spearman's correlation test for correlation between variables was used, and a multivariate regression analysis was performed to determine whether there are associations between CHD and the ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios. Values of p < 0.05 were considered significant. RESULTS: Correlation analyses revealed that LDL-C was moderately associated with CHD (r = 0.199, p = 0.067). The non-HDL-C/HDL-C ratio exhibited a stronger, significant correlation with CHD (r = 0.366, p = 0.001). Evaluating apolipoproteins, ApoA1 levels negatively correlated with CHD (r = -0.233, p = 0.035), whereas ApoB levels showed a positive association (r = 0.292, p = 0.008). Notably, the severity of CHD risk increased with the ApoB/ApoA1 ratio (r = 0.530, p < 0.001). Similar trends in correlation coefficients were observed for fatal CHD and ASCVD, albeit with varied significance levels. CONCLUSIONS: Among patients with T2DM, the ApoB/ApoA1 ratio exhibited the strongest correlation with CHD risk, surpassing traditional LDL-C and even the non-HDL-C/HDL-C ratio, suggesting its potential utility as a more reliable marker for cardiovascular risk assessment in this population.

The Bidirectional Relationship between Periodontal Disease and Diabetes Mellitus-A Review.

Periodontitis is a chronic inflammatory disease caused by the presence of a bacterial biofilm known as dental plaque. This biofilm affects the supporting apparatus of the teeth, especially the periodontal ligaments and the bone surrounding the teeth. Periodontal disease and diabetes seem to be interrelated and in a bidirectional relationship, and have been increasingly studied in recent decades. For example, diabetes mellitus has a detrimental effect on periodontal disease, increasing its prevalence, extent, and severity. In turn, periodontitis negatively affects glycemic control and the course of diabetes. This review aims to present the most recently discovered factors that contribute to the pathogenesis, therapy, and prophylaxis of these two diseases. Specifically, the article focuses on microvascular complications, oral microbiota, pro- and anti-inflammatory factors in diabetes, and periodontal disease. As presented in this review, these two diseases require specific/ complementary therapeutic solutions when they occur in association, with new clinical trials and epidemiological research being necessary for better control of this interdependent pathogenic topic.

Effect of Semaglutide on Subclinical Atherosclerosis and Cardiometabolic Compensation: A Real-World Study in Patients with Type 2 Diabetes.

BACKGROUND: Semaglutide is a recently approved glucagon-like peptide-1 receptor agonist. Several trials reported the protective effect of injectable semaglutide on cardiovascular (CV) risk by reducing major adverse cardiovascular events in type 2 diabetes patients. Strong preclinical evidence supports the CV benefits of semaglutide through an effect on atherosclerosis. However, scant evidence is available about the protective mechanisms of semaglutide in clinical practice. METHODS: A retrospective observational study was conducted among consecutive type 2 diabetes patients treated with injectable semaglutide in Italy between November 2019 and January 2021 when the drug was first available in the country. The primary aims were the assessment of the carotid intima-media thickness (cIMT) and hemoglobin A1c (HbA1c) levels. The secondary aims were the evaluation of anthropometric, glycemic, and hepatic parameters and plasma lipids, including the assessment of the triglyceride/high-density lipoprotein ratio as an indirect marker of atherogenic small, dense low-density lipoprotein particles. RESULTS: Injectable semaglutide reduced HbA1c and cIMT. An improvement in CV risk factors and the triglyceride/high-density lipoprotein ratio was reported. Moreover, through correlation analyses, we found that hepatic fibrosis and steatosis indices and the anthropometric, hepatic, and glycemic parameters, as well as plasma lipids, were unrelated to the variations in cIMT and HbA1c. CONCLUSIONS: Our findings suggest the effect of injectable semaglutide on atherosclerosis as a key CV protective mechanism. Considering the favorable effects on atherogenic lipoproteins and hepatic steatosis indices, our results support the pleiotropic effect of semaglutide beyond glycemic control.

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.

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.