JDBT Journal

Introduction

Type 2 Diabetes Mellitus (T2D) is a leading cause of global morbidity and mortality. Its prevalence continues to rise, driven by the ongoing epidemic of obesity, sedentary lifestyles, an aging population, and improved survival due to advances in treatment strategies over recent decades. In Uruguay, the reported prevalence of diabetes is approximately 8.0%, ranging from 6.0% to 8.0% [1,2]. 

Cardiovascular disease is the primary cause of morbidity and mortality among individuals with diabetes, with a 2- to 4-fold increased risk of death from cardiovascular causes compared to non-diabetic individuals. The main contributors to this poor prognosis are Atherosclerotic Cardiovascular Diseases (ASCVD), encompassing coronary, cerebrovascular, and peripheral arterial disease [3,4].

This population also bears a heavy burden of coexisting Cardiovascular Risk Factors (CVRFs), including hypertension, dyslipidemia, obesity, smoking, albuminuria, and Chronic Kidney Disease (CKD), all of which further compound their cardiovascular risk [5].

Multiple international studies have demonstrated that intensive and simultaneous management of these CVRFs is associated with a significant reduction in major cardiovascular events and mortality. Notably, the Steno-2 study showed that multifactorial intervention in T2D patients with microalbuminuria led to meaningful reductions in cardiovascular events and mortality, with long-term gains in cardiovascular disease-free survival [6-8].

More recently, Rawshani et al. analyzed a cohort of 271,174 individuals with T2D compared to 1,355,870 without diabetes. Their findings revealed that patients who maintained the five key CVRFs (HbA1c, LDL-C, blood pressure, smoking status, and albuminuria) within guideline-recommended targets exhibited rates of mortality, myocardial infarction, and stroke comparable to the general population [9].

However, a substantial gap persists between evidence-based recommendations and real-world clinical practice. Several studies have shown that fewer than half of patients with T2D achieve recommended targets for HbA1c, blood pressure, and lipid levels [10]. A recent meta-analysis of 24 studies including 369,251 patients from 20 countries found that the proportion of patients meeting all therapeutic goals remains strikingly low [11].

Furthermore, the presence of CKD-defined by an estimated glomerular filtration rate <60 mL/min/1.73 m² and/or albuminuriasubstantially increases residual cardiovascular risk. For this subgroup, clinical guidelines recommend moderate-intensity statin therapy, even when LDL-C levels are within normal range [12].

In Uruguay, there is a lack of current data on the frequency and degree of CVRF control in patients with T2D receiving routine care. In this context, the aim of this study was to describe the prevalence and control of CVRFs in a cohort of T2D patients followed at the Endocrinology and Metabolism Clinic of the Hospital de Clínicas.

Methodology

A retrospective cross-sectional study was conducted using the medical records of 78 patients with type 2 diabetes mellitus (T2DM) treated in the outpatient Endocrinology Unit of the Hospital de Clinicas, Montevideo, Uruguay. The study period spanned from July to December of 2019. Inclusion criteria: Patients aged 18 years or older, with diagnosis of T2DM for at least one year. In addition, availability of at least one clinical visit and the following laboratory tests within the study period: HbA1c, lipid profile, and renal function parameters. Exclusion criteria included pregnancy, older adults (>65 years) and other type of diabetes. We collected demographic, anthropometric, and clinical data (including blood pressure, BMI, and smoking status), as well as the presence of macrovascular (cardiovascular events, stroke, peripheral arterial disease) and microvascular (nephropathy) complications. Laboratory data included fasting glucose, HbA1c, lipid profile, creatinine, eGFR, albuminuria, and blood pressure levels. The use of pharmacologic treatment for glycemic, lipid, and blood pressure control was also documented. Global cardiovascular risk was estimated using the American Heart Association’s ASCVD Risk Estimator Plus tool (http://tools.acc.org/ASCVDRisk-Estimator-Plus). Achievement of guideline-based control of major cardiovascular risk factors (CVRFs) was assessed according to the 2021 ADA Standards of Care [13].  Metabolic control was defined as HbA1c <7% in most adults, or <8% in those with severe comorbidities or increased hypoglycemia risk. HbA1c values obtained within 6 months prior to the last clinical visit were considered valid. In individuals with low cardiovascular risk (10-year ASCVD risk <15%), the target blood pressure was <140/90 mmHg(10). Lipid targets were defined as follows: LDL <70 mg/dL for patients in secondary prevention or with ASCVD risk >20%, for whom high-intensity statin therapy (atorvastatin 40–80 mg/day or rosuvastatin 20–40 mg/day) is indicated.

Adults ≥40 years without established ASCVD and with 10-year risk <20% were recommended moderate-intensity statins (atorvastatin 10–20 mg/day or rosuvastatin 5–10 mg/day), with a goal LDL <100 mg/dL. In patients <40 years without ASCVD and risk <20%, statins were not indicated provided the target LDL <100 mg/dL was met. A fasting triglyceride goal <150 mg/dL was applied for all participants.

Other CVRFs recorded included: history of smoking (as documented in the medical record), obesity (BMI ≥30 kg/m²), albuminuria >30 mg/g within the previous year, and estimated GFR <60 mL/min/1.73 m² (CKD-EPI equation). Statistical analyses were conducted using R software (version 4.0.4). Descriptive statistics-including means, medians, standard deviations, and proportions-were calculated as appropriate. Inferential analyses were performed based on the type of variable: Student’s t-test was used for comparisons of means, while Chi-square or Fisher’s exact test was applied to assess associations between categorical variables

Results

A total of 78 patients with a diagnosis of Type 2 Diabetes Mellitus (T2DM) were identified from the outpatient records of the Endocrinology and Metabolism Clinic. The majority were female (70.5%), with a mean age of 57 years. The average duration of diabetes was 9.6 years. The main clinical and demographic characteristics of the study population are summarized in (Table 1). Notably, there was a high prevalence of arterial hypertension (68%) and active smoking (13%). Additionally, 11.5% of patients had a documented history of Acute Myocardial Infarction (MI).

Table 1. Demographic characteristics of the patients in the study.

A significantly higher prevalence of smoking was observed among male participants compared to their female counterparts (31.8% vs. 5.5%, p = 0.002). In terms of nutritional status, obesity affected approximately two-thirds of the study population. Although a greater proportion of women were classified as obese compared to men (64.2% vs. 59.1%), this difference was not statistically significant (p = 0.682) (Figure 1).

Figure 1: Obesity and gender.

Regarding overall cardiovascular risk, only male patients presented a 10-year cardiovascular disease (CVD) risk greater than 20%, with approximately one-third of them exceeding this threshold. In contrast, only one patient (1.3%) reported a family history of premature CVD.

Among participants with available renal function data, 20.5% had an estimated glomerular filtration rate (eGFR) below 60 ml/ min/1.73 m². No statistically significant association was found between HbA1c levels and the presence of reduced renal function. In the subgroup of patients over 50 years old with renal impairment (n=67), 90% were receiving statin therapy at either moderate or high intensity.

Macrovascular complications—including myocardial infarction, stroke, and cerebrovascular occlusive conditions—were present in approximately one-quarter of the cohort, with a higher frequency observed among men compared to women (26.1% vs. 18.2%, p = 0.63). However, no association was identified between HbA1c levels and the occurrence of macrovascular complications. Regarding lipid control, only 50% of the patients achieved target levels for both low-density lipoprotein cholesterol (LDL-C) and triglycerides (Table 2).

Table 2: Control of CVD risk factors.

A significantly lower proportion of patients with obesity achieved the target triglyceride (TGL) level of <150 mg/dL compared to their non-obese counterparts (29.8% vs. 53.6%; p = 0.02).

Among patients without terminal illness, one-third achieved an HbA1c level <7%. In contrast, 50% of those with advanced disease reached the recommended target of HbA1c <8%. Regarding blood pressure (BP) control, 68% of the study population had a diagnosis of hypertension, of whom 64.1% maintained BP values within the target range (<140/90 mmHg). Notably, 86.8% of hypertensive patients were receiving treatment with Angiotensin-Converting Enzyme Inhibitors (ACE inhibitors) or Angiotensin Receptor Blockers (ARBs), and 67.4% successfully met the BP target.

In the subgroup without macrovascular disease, 33.8% of patients had an LDL cholesterol level <100 mg/dL, while another 33.8% exceeded this threshold, and LDL values were unavailable for 29.3% of the group.

Among patients with established macrovascular disease, only 25% met the stricter LDL target of <70 mg/dL, whereas nearly half of them failed to achieve this goal (Figure 2).

Figure 2: LDL target in patients with macrovascular complications.

With regard to pharmacological management, approximately 60% of patients were receiving treatment with angiotensinconverting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), as well as statins at moderate doses. However, only a minority of the cohort were prescribed high-intensity statin therapy (Table 3).

Table 3: Frequency of use of medication for cardiovascular risk factors.

Among patients over 40 years of age without macrovascular disease (n = 61), 65.6% were receiving statin therapy. Intermediate doses of atorvastatin predominated (61%), while high-intensity statin use was infrequent (5%). In contrast, among patients with established macroangiopathy, 75% were receiving high-dose statin therapy and aspirin. Overall, suboptimal control of cardiovascular risk factors was observed. Although blood pressure targets (<140/90 mmHg) were achieved in 72% of hypertensive patients, fewer than 40% met the recommended goals for glycemic control (HbA1c), LDL cholesterol, triglyceride levels, and body mass index. Notably, comprehensive control of all major cardiovascular risk factors was achieved in only 5% of the cohort, with no statistically significant differences between sexes (Table 3).

Table 3: Control of modifiable cardiovascular risk factors.

Discussion

This study highlights the suboptimal management of Cardiovascular Risk Factors (CVRFs) in a cohort of 78 patients with type 2 diabetes, despite the well-established elevated cardiovascular risk associated with the disease. Type 2 diabetes is widely recognized as a coronary heart disease risk equivalent, as stated by the U.S. National Cholesterol Education Program (NCEP) and the European guidelines [14,15]. Nonetheless, the achievement of therapeutic goals remains insufficient across several critical domains of cardiovascular risk management. Previous research has demonstrated that patients with type 2 diabetes and no prior Acute Myocardial Infarction (AMI) exhibit a similar risk of cardiovascular events and cardiovascular mortality to that of non-diabetic individuals with prior AMI [16]. The Framingham Heart Study further confirmed this risk, showing that diabetes doubles the risk of cardiovascular disease (CVD) in men and triples it in women, even after adjustment for other risk factors [17]. A meta-analysis including over 530,000 individuals across 102 studies corroborated these findings, reporting a pooled hazard ratio (HR) of 2.0 (95% CI: 1.8-2.2) for coronary heart disease in patients with T2D, with significantly higher rates of non-fatal myocardial infarction and cardiovascular mortality [18]. The overall cardiovascular risk in this population is determined by both the number of risk factors and the degree to which treatment aligns with evidence-based guidelines. In our cohort, the prevalence of CVRFs was notably high: 60.3% of patients were obese (BMI ≥30 kg/m²), a key contributor to atherogenesis [19]. Nearly 70% had hypertension, and about one-fifth exhibited reduced renal function (GFR <60 mL/min/1.73 m²). Additionally, 19.4% had at least one episode of elevated albuminuria, indicating early nephropathy. Interestingly, the prevalence of smoking was relatively low, a finding that may reflect the success of public health tobacco control strategies in Uruguay. This is particularly evident when compared to the 25.9% prevalence reported in the general population by the latest ENFRENT survey [20]. The 10-year cardiovascular risk, estimated using the AHA Risk Estimator Plus, exceeded the 20% threshold only among men in the sample, aligning with findings from original U.S. cohorts. However, studies such as ADVANCEON suggest that, with a similar burden of risk factors, women with T2D may have a higher relative risk of AMI, highlighting the need for gender-sensitive approaches to risk stratification [21].