Diabetes mellitus (DM) is a chronic and complex metabolic disorder and also an important cause of cardiovascular (CV) disease (CVD). Patients with type 2 DM (T2DM) and obesity show a greater ...propensity for visceral fat deposition (and excessive fat deposits elsewhere) and the link between adiposity and CVD risk is greater for visceral than for subcutaneous (SC) adipose tissue (AT). There is growing evidence that epicardial AT (EAT) and pericardial AT (PAT) play a role in the development of DM-related atherosclerosis, atrial fibrillation (AF), myocardial dysfunction, and heart failure (HF). In this review, we will highlight the importance of PAT and EAT in patients with DM. We also consider therapeutic interventions that could have a beneficial effect in terms of reducing the amount of AT and thus CV risk. EAT is biologically active and a likely determinant of CV morbidity and mortality in patients with DM, given its anatomical characteristics and proinflammatory secretory pattern. Consequently, modification of EAT/PAT may become a therapeutic target to reduce the CV burden. In patients with DM, a low calorie diet, exercise, antidiabetics and statins may change the quantity of EAT, PAT or both, alter the secretory pattern of EAT, improve the metabolic profile, and reduce inflammation. However, well-designed studies are needed to clearly define CV benefits and a therapeutic approach to EAT/PAT in patients with DM.
Diabetes mellitus (DM) is also a cause of cardiovascular (CV) disease (CVD). Addressing the atherosclerotic CVD (ASCVD) burden in DM should reduce premature death and improve quality of life. ...Diabetes mellitus–associated ASCVD can lead to complications in all vascular beds (carotids as well as coronary, lower extremity, and renal arteries). This narrative review considers the diagnosis and pharmacological treatment of noncardiac atherosclerotic vascular disease (mainly in patients with DM). Based on current knowledge and the fact that modern DM treatment guidelines are based on CV outcome trials, it should be noted that patients with noncardiac CVD may not have the same benefits from certain drugs compared with patients who predominantly have cardiac complications. This leads to the conclusion that in the future, consideration should be given to conducting well-designed trials that will answer which pharmacological treatment modalities will be of greatest benefit to patients with noncardiac ASCVD.
The obesity pandemic is accompanied by increased risk of developing metabolic syndrome (MetS) and related conditions: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), ...type 2 diabetes mellitus (T2DM) and cardiovascular (CV) disease (CVD). Lifestyle, as well as an imbalance of energy intake/expenditure, genetic predisposition, and epigenetics could lead to a dysmetabolic milieu, which is the cornerstone for the development of cardiometabolic complications. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs promote positive effects on most components of the “cardiometabolic continuum” and consequently help reduce the need for polypharmacy. In this review, we highlight the main pathophysiological mechanisms and risk factors (RFs), that could be controlled by GLP-1 and dual GIP/GLP-1 RAs independently or through synergism or differences in their mode of action. We also address the evidence on the use of GLP-1 and dual GIP/GLP-1 RAs in the treatment of obesity, MetS and its related conditions (prediabetes, T2DM and NAFLD/NASH). In conclusion, GLP-1 RAs have already been established for the treatment of T2DM, obesity and cardioprotection in T2DM patients, while dual GIP/GLP-1 RAs appear to have the potential to possibly surpass them for the same indications. However, their use in the prevention of T2DM and the treatment of complex cardiometabolic metabolic diseases, such as NAFLD/NASH or other metabolic disorders, would benefit from more evidence and a thorough clinical patient-centered approach. There is a need to identify those patients in whom the metabolic component predominates, and whether the benefits outweigh any potential harm.
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,
= 0.06; in the SGLT2-iclass for ipragliflozin 95% CI -0.2 -0.87, 0.47,
= 0.55; and for tofogliflozin 95% CI 3.13 -12.02, 18.28,
= 0.69, while for tirzepatide it was 0.15, 95% CI -0.50, 0.80 (
= 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.
The prevalence of non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases, is rising. About 25% of adults worldwide are probably affected by NAFLD. Insulin resistance (IR) ...and fat accumulation in the liver are strongly related. The association between NAFLD, metabolic syndrome (MetS) and IR is established, but an independent impact of NAFLD on vascular risk and progression of cardiovascular (CV) disease (CVD) still needs to be confirmed. This narrative review considers the evidence regarding the link between NAFLD, IR and CVD risk. There is strong evidence for a “concomitantly rising incidence” of NAFLD, IR, MetS and CVD but there is no definitive evidence regarding whether NAFLD is, or is not, an independent and significant risk factor the development of CVD. There are also considerations that type 2 diabetes mellitus (T2DM) may be a common link between NAFLD/non-alcoholic steatohepatitis (NASH) and CVD. NAFLD may be associated with widespread abnormal peri-organ or intra-organ fat (APIFat) deposition (e.g. epicardial adipose tissue) which may further contribute to CV risk. It is clear that NAFLD patients have a greater CV risk (independent or not) which needs to be addressed in clinical practice.
•IR and NAFLD are strongly related.•NAFLD may be associated with widespread APIFat deposition.•An adverse vascular risk profile may account for the link between NAFLD and CVD.•Antidiabetic agents have beneficial effects on NAFLD and CVD.•Urgent research is needed in this field because NAFLD/NASH is highly prevalent.
Diabetes mellitus (DM) can lead to the development of macro- and microvascular complications. Homocysteine (Hcy) may play a role in the development of cardiovascular (CV) diseases (CVDs). The role of ...Hcy in the development of the vascular complications associated with DM is not clearly defined. Despite a strong initial assumption regarding the importance of Hcy in DM and its complications, over time “enthusiasm has waned” because several studies showed unconvincing and occasionally contradictory results. A universal conclusion is not easy to draw given the diversity of studies (e.g. number of patients, design, folic acid and vitamin B status, ethnic differences, genetic background). For some complications, most results encourages further investigation. Impaired renal function is a major independent determinant of high total Hcy (tHcy) levels. However, the role of hyperhomocysteinaemia (HHcy) in the development of diabetic kidney disease (DKD) has yet to be determined. Hcy-lowering therapies can significantly decrease Hcy levels but their effects on CVD risk reduction are conflicting. Further studies are needed to determine the influence of Hcy-lowering therapy on CVD risk reduction, especially in patients with DM.
•Homocysteine metabolism may be modulated by insulin and glucose.•The regulation of enzymes involved in homocysteine metabolism in diabetes is complex.•Homocysteine as a risk factor in diabetes requires reassessment.
•NAFLD is the most common liver disease in children.•“Obesity-induced insulin resistance” in T1DM children could be a “driver” for NAFLD development.•There is an urgent need for more research in the ...field of NAFLD in childhood.
Genetic testing is increasingly becoming a common consideration in the clinical approach of dyslipidemia patients. Advances in research in last decade and increased recognition of genetics in ...biological pathways modulating blood lipid levels created a gap between theoretical knowledge and its applicability in clinical practice. Therefore, it is very important to define the clinical justification of genetic testing in dyslipidemia patients.
Clinical indications for genetic testing for most dyslipidemias are not precisely defined and there are no clearly established guideline recommendations. In patients with severe low-density lipoprotein cholesterol (LDL-C) levels, the genetic analysis can be used to guide diagnostic and therapeutic approach, while in severe hypertriglyceridemia (HTG), clinicians can rely on triglyceride level rather than a genotype along the treatment pathway. Genetic testing increases diagnostic accuracy and risk stratification, access and adherence to specialty therapies, and cost-effectiveness of cascade testing. A shared decision-making model between the provider and the patient is essential as patient values, preferences and clinical characteristics play a very strong role.
Genetic testing for lipid disorders is currently underutilized in clinical practice. However, it should be selectively used, according to the type of dyslipidemia and when the benefits overcome costs.
Type 2 diabetes mellitus (T2DM) is associated with increased prevalence of cardiovascular (CV) disease (CVD). Optimal anti-hyperglycemic agents should include control of multiple CV risk factors (RF) ...to improve macrovascular and microvascular complications, as well as glycemia.
In this narrative review, the authors focus on the effects of glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose transport protein 2 inhibitors (SGLT2i) on blood pressure (BP) and the lipid profile, two well-established CV RF.
Results from recent CV outcome trials (CVOTs), showed the impact of GLP-1 RA and SGLT2i on BP and lipid levels. These classes of medication can alter cardiac function by affecting the process of atherosclerosis and/or hemodynamic status. The results of published GLP1-RA and SGLT2i CVOTs have shown multifactorial benefits; in addition to the main effects on glycemia and body weight (BW), there are also positive but moderate effects on BP and lipid levels. Full advantage of the pleiotropic benefit of these agents should be taken to prevent CV events.
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