The effect of duration of medication with metformin and sulfonylurea (SUs) on cardiovascular diseases (CVD) and mortality events by duration of type 2 diabetes (DM) is unclear. This study aimed to investigate the effect of duration of treatment with metformin and SUs on CVD and mortality events based on DM duration in newly diagnosed DM patients. Data from three prospective cohorts of Tehran Lipid and Glucose Study (TLGS), Multi-Ethnic Study of Atherosclerosis (MESA), and Atherosclerosis Risk in Communities (ARIC) including 4108 newly diagnosed type 2 diabetes individuals (mean age, 59.4 ± 0.66 years) were pooled. Exposure was defined as the duration of metformin alone, SUs alone, and a combination of both since drug initiation. The Cox proportional hazards (CPH) model adjusted for confounders, including statin, aspirin, and anti-hypertensive, was used to estimate the hazard ratio (HR) (95% CI) for the outcomes. Cumulative exposure for metformin, SUs, aspirin, statin, and anti-hypertensive medication was calculated using the same method. The median follow-up was 20.33 ± 0.45 years. Cardiovascular events, all-cause mortality (ACM), and CVD mortality occurred in 767, 913, and 439 newly diagnosed DM patients, respectively. Metformin alone reduced the hazard of cardiovascular events, ACM, and CV-mortality by 7%, 4%, and 6%, respectively, for each year of use, respectively (p < 0.05); the corresponding values for SUs alone were 4%, 3%, and 4%, respectively (p < 0.05). The effect of metformin on reducing cardiovascular events, ACM, and CVD mortality continued until approximately 8, 10, and 5 years after the start of treatment, respectively, and then reached Plato. The effect of SUs on cardiovascular events, ACM, and CVD mortality continued to decline or reach Plato until approximately 6, 5, and 8 years after initiation of therapy and then was ineffective or reversed. The effect of the combination therapy on the reduction of cardiovascular events continued until 11 years after therapy initiation. Among newly diagnosed DM patients, metformin, with and without SUs, was associated with a reduced risk of cardiovascular events, ACM, and CVD mortality for up to about one decade. The combined effect of metformin + sulfonylurea was superior to the single effect of metformin or sulfonylurea alone. The combination therapy of Metformin and SUs can still be used with good safety, especially in the first years of diabetes diagnosis.

Atrial fibrillation (AF) is the most common sustained arrhythmia, contributing to significant morbidity and healthcare burden worldwide. This review evaluates the role of early risk factor modification and timely catheter ablation in preventing AF progression and improving patient outcomes. A comprehensive literature search was conducted using PubMed, MEDLINE, and Google Scholar, focusing on studies published after the ESC 2020 guidelines for the diagnosis and management of AF up to the release of the updated ESC 2024 guidelines for the management of AF. Keywords included "atrial fibrillation", "catheter ablation", "risk factor management", and "psychological stress". Relevant clinical trials, randomized controlled trials, systematic reviews, and meta-analyses were included, with particular emphasis on novel studies contributing to the ESC 2024 updated recommendations. Traditional risk factors such as obesity, hypertension, diabetes, sleep apnea, alcohol consumption, and physical exertion are well established in AF progression. Early evidence also suggests a role for psychological stress and mood disorders, including depression and post-traumatic stress disorder (PTSD), in increasing AF susceptibility. Psychological stress and mood disorders are linked to AF primarily through behavioral changes such as poor medication adherence, unhealthy lifestyle choices, and increased substance use. Recent guidelines recommend early catheter ablation in selected patients to reduce AF burden, prevent atrial remodeling, and improve quality of life, particularly in those resistant to antiarrhythmic drugs or individuals with AF-induced cardiomyopathy. Furthermore, we highlight the importance of a patient-centered, multidisciplinary approach, integrating electrophysiologists, cardiologists, and primary care providers with structured risk factor interventions and shared decision-making. Despite these advances, gaps remain in defining optimal timing, patient selection, and long-term benefits of catheter ablation in persistent AF, necessitating the need for further research. By integrating early intervention, personalized treatment strategies, and collaborative care models, we may usher in a paradigm shift in AF management, improving long-term cardiovascular outcomes and patient quality of life.

Prior research has demonstrated an association between sodium-glucose cotransporter 2 (SGLT2) inhibitor and a reduced incidence of atrial fibrillation (AF). Given the established link between mitochondrial dysfunction and AF, this study aimed to explore the impact of SGLT2 inhibitors on AF burden and plausible antiarrhythmic mechanisms in patients with cardiovascular implantable electronic devices (CIEDs). Patients with atrial high-rate episodes (AHREs) detected by CIEDs were randomized to receive either 10 mg of dapagliflozin or a placebo for 3 months. AF burdens were quantified via CIEDs interrogations as AHREs duration, percentage, and number of episodes at baseline and after 3 months of treatment. Mitochondrial parameters, cellular oxidative stress, and norepinephrine levels were measured in peripheral blood mononuclear cells (PBMCs). A total of 54 patients with CIEDs were enrolled in the study. Among them, 36 patients (66.7%) had a history of clinical AF, and 9 patients (16.7%) had diabetes mellitus. After 3 months of the assigned treatment, the median longest AHRE duration decreased similarly in both the dapagliflozin and placebo groups (-77.0 vs. -162.0 min, p = 0.442). Clinical AF, as opposed to subclinical AF, was independently linked to decreased basal respiration and adenosine triphosphate (ATP) production. Although the changes in AHREs burden over the 3 months did not significantly differ between the dapagliflozin and placebo groups, dapagliflozin significantly decreased the number of AHREs per month by 2.2 episodes among patients with clinical AF, whereas the placebo group experienced an increase of 0.6 episodes (p = 0.048). Additionally, dapagliflozin significantly reduced cellular oxidative stress (from 26840 to 18164 arbitrary units, p = 0.049) and improved mitochondrial spare respiratory capacity (SRC) percentage (from 166 to 202%, p = 0.016) in patients with clinical AF. Dapagliflozin did not significantly reduce the longest AHRE duration in patients with CIED. However, in the subgroup of patients with clinical AF, dapagliflozin reduced the number of AHREs potentially via reduction of cellular oxidative stress and enhancement of mitochondrial function.The study protocol was registered at the Thai Clinical Trials Registry (TCTR identification number TCTR20210315003) on March 15, 2021.

Atrial fibrillation (AF) is a continually growing health-care burden that often presents together with metabolic disorders, including diabetes mellitus and obesity. Current treatments often fall short of preventing AF and its adverse outcomes. Accumulating evidence suggests that metabolic disturbances can promote the development of AF through structural and electrophysiological remodelling, but the underlying mechanisms that predispose an individual to AF are aetiology-dependent, thus emphasizing the need for tailored therapeutic strategies to treat AF that target an individual's metabolic profile. AF itself can induce changes in glucose, lipid and ketone metabolism, mitochondrial function and myofibrillar energetics (as part of a process referred to as 'metabolic remodelling'), which can all contribute to atrial dysfunction. In this Review, we discuss our current understanding of AF in the setting of metabolic disorders, as well as changes in atrial metabolism that are relevant to the development of AF. We also describe the potential of available and emerging treatment strategies to target metabolic remodelling in the setting of AF and highlight key questions and challenges that need to be addressed to improve outcomes in these patients.

Diabetes mellitus (DM) confers an increased risk of sudden cardiac death (SCD) independent of its associated cardiovascular comorbidities. DM induces adverse structural, electrophysiologic, and autonomic cardiac remodeling that can increase one's risk of ventricular arrhythmias and SCD. Although glycemic control and prevention of microvascular and macrovascular complications are cornerstones in the management of DM, they are not adequate for the prevention of SCD. In this narrative review, we describe the contribution of DM to the pathophysiologic mechanism of SCD beyond its role in atherosclerotic cardiovascular disease and heart failure. On the basis of this pathophysiologic framework, we outline potential preventive and therapeutic strategies to mitigate the risk of SCD in this population of high-risk patients.

Metformin is an orally effective anti-hyperglycemic drug that despite being introduced over 60 years ago is still utilized by an estimated 120 to 150 million people worldwide for the treatment of type 2 diabetes (T2D). Metformin is used off-label for the treatment of polycystic ovary syndrome (PCOS) and for pre-diabetes and weight loss. Metformin is a safe, inexpensive drug with side effects mostly limited to gastrointestinal issues. Prospective clinical data from the United Kingdom Prospective Diabetes Study (UKPDS), completed in 1998, demonstrated that metformin not only has excellent therapeutic efficacy as an anti-diabetes drug but also that good glycemic control reduced the risk of micro- and macro-vascular complications, especially in obese patients and thereby reduced the risk of diabetes-associated cardiovascular disease (CVD). Based on a long history of clinical use and an excellent safety record metformin has been investigated to be repurposed for numerous other diseases including as an anti-aging agent, Alzheimer's disease and other dementias, cancer, COVID-19 and also atrial fibrillation (AF). AF is the most frequently diagnosed cardiac arrythmia and its prevalence is increasing globally as the population ages. The argument for repurposing metformin for AF is based on a combination of retrospective clinical data and in vivo and in vitro pre-clinical laboratory studies. In this review, we critically evaluate the evidence that metformin has cardioprotective actions and assess whether the clinical and pre-clinical evidence support the use of metformin to reduce the risk and treat AF.

The effects of metformin on atrial fibrillation (AF) in type 2 diabetes patients remain unclear. We aimed to explore the effects of metformin on AF, including new-onset AF and AF burden, in type 2 diabetes patients with pacemakers.

This retrospective study included a total of 227 patients. Based on the presence of paroxysmal AF, the patients were divided into a paroxysmal AF group (n = 80) and a non-AF group (n = 147). In the non-AF group, a significant association was observed between metformin use and a lower risk of new-onset AF in multivariable Cox hazards models (hazard ratio [HR]: 0.36; 95 % confidence interval [CI]: 0.14-0.91; p = 0.0311*) when adjusted for age, sex, body mass index (BMI), drinking, smoking, left atrial dimension, creatinine, complications, and drugs. In the paroxysmal AF group, univariable analysis indicated no association between the AF burden and metformin use (p = 0.817). Furthermore, when adjusted for metformin use, age, sex, BMI, drinking, smoking, cardiovascular disease, myocardial infarction, heart failure, stroke, and ejection fraction in multivariable Cox hazards models, we found a lower proportion of major adverse cardiovascular events (MACEs) both in the total (HR: 0.28; 95 % CI: 0.1-0.82; p = 0.0202*) and the non-AF group (HR: 0.19; 95 % CI: 0.05-0.79; p = 0.0223*) compared to that in the AF group (HR: 0.31; 95 % CI: 0.02-4.41; p = 0.3879).

In type 2 diabetes patients with pacemakers, metformin reduced the probability of new-onset AF instead of addressing the AF burden. Furthermore, metformin therapy decreased the incidence of MACEs in type 2 diabetes patients without AF.

Atrial fibrillation/flutter (AF) is a major public health problem and is associated with stroke, heart failure, dementia, and death. It is estimated that 20%-30% of Americans will develop AF at some point in their life. Current medications to prevent AF have limited efficacy and significant adverse effects. Newer and safer therapies to prevent AF are needed. Ventricular arrhythmias are less prevalent than AF but may have significant consequences including sudden cardiac death. Metformin is the most prescribed, first-line medication for treatment of diabetes mellitus (DM). It decreases hepatic glucose production but also reduces inflammation and oxidative stress. Experimental studies have shown that metformin improves metabolic, electrical, and histologic risk factors associated with AF and ventricular arrhythmias. Furthermore, in large clinical observational studies, metformin has been associated with a reduced risk of AF in people with DM. These data suggest that metformin may have antiarrhythmic properties and may be a candidate to be repurposed as a medication to prevent cardiac arrhythmias. In this article, we review the clinical observational and experimental evidence for the association between metformin and cardiac arrhythmias. We also discuss the potential antiarrhythmic mechanisms underlying this association. Repurposing a well-tolerated, safe, and inexpensive medication to prevent cardiac arrhythmias has significant positive public health implications.

Dapagliflozin exerts cardioprotective effects in Type 2 Diabetes Mellitus (T2DM). However, whether these effects prevent electrocardiographic changes associated with T2DM altogether remain unknown. Our aim was to investigate the prophylactic effect of dapagliflozin pretreatment on the rat ECG using a high-fat, high-fructose (HFHf) diet and a low dose streptozotocin (STZ) model of T2DM.

Twenty-five (25) rats were randomized into five (5) groups: normal control receiving a normal diet while the other groups received an 8-week HFHf and 40mg/kg STZ on day 42, and either: saline for the diabetic control (1 mg/kg/d), low dose (1.0 mg/kg/d) and high dose dapagliflozin (1.6 mg/kg/d), or metformin (250 mg/kg/d). Oral glucose tolerance (OGT), electrocardiograms (ECGs), paracardial adipose mass, and left ventricular fibrosis were determined. Data were analyzed using GraphPad version 9.0.0.121, with the level of significance at p < 0.05.

Compared to the diabetic control group, a high dose of dapagliflozin preserved the OGT (p = 0.0001), QRS-duration (p = 0.0263), QT-interval (p = 0.0399), and QTc intervals (p = 0.0463). Furthermore, the high dose dapagliflozin group had the lowest paracardial adipose mass (p = 0.0104) and fibrotic area (p = 0.0001). In contrast, while metformin showed favorable effects on OGT (p = 0.0025), paracardial adiposity (p = 0.0153) and ventricular fibrosis (p = 0.0291), it did not demonstrate significant antiarrhythmic effects.

Pretreatment with higher doses of Dapagliflozin exhibits prophylactic cardioprotective characteristics against diabetic cardiomyopathy that include antifibrotic and antiarrhythmic qualities. This suggests that higher doses of dapagliflozin could be a more effective initial therapeutic option in T2DM.

Acute myocardial infarction (AMI) ranks among the top contributors to sudden death and disability worldwide. It should be noted that current therapies always cause increased reperfusion damage. Evidence suggests that humanin (HN) reduces mitochondrial dysfunction to have cardio-protective effects against MI-reperfusion injury. In this context, we hypothesized that HN may attenuate MI-reperfusion injury by alleviating lymphatic endothelial cells dysfunction through the regulation of mitophagy.

In this study, primary lymphatic endothelial cells were selected as the experimental model. Cells were maintained under 1% O2 to induce a hypoxic phenotype. For in vivo experiments, the left coronary arteries of C57/BL6 mice were clamped for 45 min followed by 24 h reperfusion to develop MI-reperfusion injury. The volume of infarcted myocardium in MI-reperfusion injury mouse models were TTC staining. PCR and western blot were used to quantify the expression of autophagy-, mitophagy- and mitochondria-related markers. The fibrosis and apoptosis in the ischemic area were evaluated for Masson staining and TUNEL respectively. We also used western blot to analyze the expression of VE-Cadherin in lymphatic endothelial cells.

We firstly exhibited a specific mechanism by which HN mitigates MI-reperfusion injury. We demonstrated that HN effectively reduces such injury in vivo and also inhibits dysfunction in lymphatic endothelial cells in vitro. Importantly, this inhibitory effect is mediated through BNIP3-associated mitophagy.

In conclusion, HN alleviates myocardial infarction-reperfusion injury by inhibiting lymphatic endothelial cells dysfunction, primarily through BNIP3-mediated mitophagy.

Brugada phenocopy (BrP) is a clinical condition characterized by transient ECG changes of Brugada syndrome (BrS), which can be due to various clinical conditions. We describe a case report of BrP due to psychotic drugs.

Type 2 diabetes mellitus (T2DM) is a leading risk factor for cardiovascular complications around the globe and one of the most common medical conditions. Atrial fibrillation (AF) is the most common supraventricular arrhythmia, with a rapidly increasing prevalence. T2DM has been closely associated with the risk of AF development, identified as an independent risk factor. Regarding cardio-vascular complications, both AF and T2DM have been linked with high mortality. The underlying pathophysiology has not been fully determined yet; however, it is multifactorial, including structural, electrical, and autonomic pathways. Novel therapies include pharmaceutical agents in sodium-glucose cotransporter-2 inhibitors, as well as antiarrhythmic strategies, such as cardioversion and ablation. Of interest, glucose-lowering therapies may affect the prevalence of AF. This review presents the current evidence regarding the connection between the two entities, the pathophysiological pathways that link them, and the therapeutic options that exist.

Trastuzumab, a potent anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody, is conditionally reimbursed by the Taiwan National Health Insurance (NHI) for HER2-positive breast cancer (BC). Trastuzumab-induced cardiotoxicity studies have well characterized heart failure (HF) but fewer addressed arrhythmia, particularly the association of potential life threatening atrial fibrillation (Af) is poorly characterized. We aimed to study the trastuzumab-related risk of Af and HF using the claimed data of Taiwan NHI.

A nationwide retrospective cohort of patients with BC from the Taiwan NHI reimbursement database from January 2007 to December 2016 was analyzed. Propensity score matching and competing risk model analysis were used for adjusting confounding concurrent medication or comorbidities and competing events. The HF study was used to validate the method used.

For Af, 12,472 trastuzumab users were matched with 12,472 non-trastuzumab users. For HF, 12,241 trastuzumab users and 12,241 non-users were enrolled. We found that trastuzumab users had significantly worse HF-free survival but not Af-free survival than non-trastuzumab users. In the competing risk analysis, the use of trastuzumab did not increase the risk of Af (hazard ratio [HR] 0.76, P = 0.0006) but was associated with HF (HR 1.19, P = 0.0052). The risk trends among stratifications by comorbidities and concurrent medication remained in similar directions for both Af and HF.

Trastuzumab in real-world practice was associated with an increased risk of HF, but was not associated with an increased risk of Af in BC patients. Trastuzumab-induced arrhythmogenic effects may be masked by concurrent heart-protecting measures, more prominent roles of comorbidities or concurrent medications under real-world settings. Further studies are required.

Background Commonly prescribed diabetic medications such as metformin and sulfonylurea may be associated with different arrhythmogenic risks. This study compared the risk of ventricular arrhythmia or sudden cardiac death between metformin and sulfonylurea users in patients with type 2 diabetes. Methods and Results Patients aged ≥40 years who were diagnosed with type 2 diabetes or prescribed antidiabetic agents in Hong Kong between January 1, 2009, and December 31, 2009, were included and followed up until December 31, 2019. Patients prescribed with both metformin and sulfonylurea or had prior myocardial infarction were excluded. The study outcome was a composite of ventricular arrhythmia or sudden cardiac death. Metformin users and sulfonylurea users were matched at a 1:1 ratio by propensity score matching. The matched cohort consisted of 16 596 metformin users (47.70% men; age, 68±11 years; mean follow-up, 4.92±2.55 years) and 16 596 sulfonylurea users (49.80% men; age, 70±11 years; mean follow-up, 4.93±2.55 years). Sulfonylurea was associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin hazard ratio (HR, 1.90 [95% CI, 1.73-2.08]). Such difference was consistently observed in subgroup analyses stratifying for insulin usage or known coronary heart disease. Conclusions Sulfonylurea use is associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin in patients with type 2 diabetes.

: A growing body of evidence suggests that diabetes mellitus (DM) is associated with an increased risk of new-onset atrial fibrillation (AF) and contributes to suboptimal arrhythmia control and poor prognosis in patients with AF. The high prevalence of AF among patients with DM is primarily attributed to common risk factors, shared pathophysiological mechanisms, and associated atrial remodeling and autonomic dysfunction.

: This comprehensive review covers the current data on the role of DM in the development and prognosis of AF. In addition, we review the impact of anti-DM medications on AF prevention and the role of anticoagulation in patients with coexisting DM and AF.

: DM is independently associated with new-onset AF, and the coexistence of these two conditions contributes to poor outcomes, from reduced quality of life to increased risks of thromboembolic events, heart failure, and mortality. Despite this strong link, the current evidence is insufficient to recommend routine screening for AF in patients with DM. Although some observations exist on preventing AF with anti-DM medications, randomized controlled trials are warranted to explore the proposed benefits of novel anti-DM medicines in reducing the risk of incident AF.

Diabetes mellitus (DM) is a health condition characterized by glucose dysregulation and affects millions of people worldwide. The presentation of heart failure in diabetic cardiomyopathy extends over a wide phenotypic spectrum, commencing from asymptomatic, subclinical structural abnormalities to severely symptomatic biventricular dysfunction with increased mortality risk. Similarly, the spectrum of systolic dysfunction in diabetic-induced heart failure is diverse. DM leads also to cardiac electrical remodeling reacting on various targets. Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce glucagon and blood glucose levels by raising levels of the endogenous hormones glucagon-like-peptide 1 and glucose-dependent insulinotropic peptide and constitute a safe and effective glucose lowering treatment option in patients with type 2 DM. Despite DPP-4 inhibitors' efficacy regarding glycemic control, their effect on cardiovascular outcomes (myocardial infarction, stroke, hospitalization for heart failure, hospitalization for unstable angina, hospitalization for coronary revascularization, and cardiovascular death) in diabetic patients has been neutral. The potential correlation between atrial flutter and DPP-4 inhibitors administration needs further investigation.

Cardiovascular disease (CVD) remains the leading cause of death worldwide. Therefore, exploring the mechanism of CVDs and critical regulatory factors is of great significance for promoting heart repair, reversing cardiac remodeling, and reducing adverse cardiovascular events. Recently, significant progress has been made in understanding the function of protein kinases and their interactions with other regulatory proteins in myocardial biology. Protein kinases are positioned as critical regulators at the intersection of multiple signals and coordinate nearly every aspect of myocardial responses, regulating contractility, metabolism, transcription, and cellular death. Equally, reconstructing the disrupted protein kinases regulatory network will help reverse pathological progress and stimulate cardiac repair. This review summarizes recent researches concerning the function of protein kinases in CVDs, discusses their promising clinical applications, and explores potential targets for future treatments.

Ventricular arrhythmias and sudden cardiac death (SCD) occur most frequently in the setting of coronary artery disease, cardiomyopathy and heart failure, but are also increasingly observed in individuals suffering from diabetes mellitus and obesity. The incidence of these metabolic disorders is rising in Western countries, but adequate prevention and treatment of arrhythmias and SCD in affected patients is limited due to our incomplete knowledge of the underlying disease mechanisms. Here, an overview is presented of the prevalence of electrophysiological disturbances, ventricular arrhythmias and SCD in the clinical setting of diabetes and obesity. Experimental studies are reviewed, which have identified disease pathways and associated modulatory factors, in addition to pro-arrhythmic mechanisms. Key processes are discussed, including mitochondrial dysfunction, oxidative stress, cardiac structural derangements, abnormal cardiac conduction, ion channel dysfunction, prolonged repolarization and dysregulation of intracellular sodium and calcium homeostasis. In addition, the recently identified pro-arrhythmic effects of dysregulated branched chain amino acid metabolism, a common feature in patients with metabolic disorders, are addressed. Finally, current management options are discussed, in addition to the potential development of novel preventive and therapeutic strategies based on recent insight gained from translational studies.

The sinoatrial node (SAN) is composed of highly specialized cells that mandate the spontaneous beating of the heart through self-generation of an action potential (AP). Despite this automaticity, the SAN is under the modulation of the autonomic nervous system (ANS). In diabetes mellitus (DM), heart rate variability (HRV) manifests as a hallmark of diabetic cardiomyopathy. This is paralleled by an impaired regulation of the ANS, and by a pathological remodeling of the pacemaker structure and function. The direct effect of diabetes on the molecular signatures underscoring this pathology remains ill-defined. The recent focus on the electrical currents of the SAN in diabetes revealed a repressed firing rate of the AP and an elongation of its tracing, along with conduction abnormalities and contractile failure. These changes are blamed on the decreased expression of ion transporters and cell-cell communication ports at the SAN (i.e., HCN4, calcium and potassium channels, connexins 40, 45, and 46) which further promotes arrhythmias. Molecular analysis crystallized the RGS4 (regulator of potassium currents), mitochondrial thioredoxin-2 (reactive oxygen species; ROS scavenger), and the calcium-dependent calmodulin kinase II (CaMKII) as metabolic culprits of relaying the pathological remodeling of the SAN cells (SANCs) structure and function. A special attention is given to the oxidation of CaMKII and the generation of ROS that induce cell damage and apoptosis of diabetic SANCs. Consequently, the diabetic SAN contains a reduced number of cells with significant infiltration of fibrotic tissues that further delay the conduction of the AP between the SANCs. Failure of a genuine generation of AP and conduction of their derivative waves to the neighboring atrial myocardium may also occur as a result of the anti-diabetic regiment (both acute and/or chronic treatments). All together, these changes pose a challenge in the field of cardiology and call for further investigations to understand the etiology of the structural/functional remodeling of the SANCs in diabetes. Such an understanding may lead to more adequate therapies that can optimize glycemic control and improve health-related outcomes in patients with diabetes.