Diastolic Dysfunction and Pulmonary Hypertension in T2DM With Microalbuminuria

Type 2 diabetes mellitus (T2DM) is associated with subclinical cardiac abnormalities that often precede overt heart failure. Diabetic cardiomyopathy is characterized early by impaired left ventricular relaxation and increased filling pressures, detectable echocardiographically as left ventricular diastolic dysfunction (LVDD), frequently before any drop in ejection fraction. Pulmonary hypertension (PH) is increasingly recognized as a comorbid finding in diabetic populations, potentially arising secondary to diastolic dysfunction, microvascular disease, or both.

Albuminuria is a graded marker of generalized microvascular endothelial dysfunction in diabetes, classified by KDIGO 2024 criteria into normal-to-mildly-increased, moderately increased (microalbuminuria), and severely increased (macroalbuminuria) categories, corresponding to progressive cardiovascular and renal risk. While microalbuminuria in isolation has been linked to adverse cardiopulmonary outcomes, the relationship between the full albuminuria spectrum and echocardiographic indices of diastolic dysfunction and PH has not been well characterized, particularly against a non-diabetic control benchmark, in an Upper Egyptian population.

This protocol compares standard transthoracic echocardiographic markers of diastolic dysfunction and PH, alongside glycemic control (HbA1c) and diabetes duration, across four groups: healthy controls and T2DM patients with normal albuminuria, microalbuminuria, and macroalbuminuria.

Inclusion criteria

• Four groups will be recruited: (1) healthy, non-diabetic controls, age- and sex-matched to the diabetic groups; (2) T2DM with normal albuminuria (KDIGO A1, urine ACR <30 mg/g); (3) T2DM with microalbuminuria (KDIGO A2, ACR 30-300 mg/g); (4) T2DM with macroalbuminuria (KDIGO A3, ACR >300 mg/g). Diabetic groups: adult patients (≥18 years) with an established diagnosis of type 2 diabetes mellitus. Control group: adults (≥18 years) without diabetes (confirmed by fasting glucose/HbA1c), age- and sex-matched to the diabetic groups. All groups: willingness and ability to provide informed consent.

Exclusion criteria

Type 1 diabetes or secondary forms of diabetes; known primary valvular heart disease (moderate or greater); prior myocardial infarction or established coronary artery disease with regional wall motion abnormality; reduced ejection fraction (EF < 50%) on screening echocardiography; chronic kidney disease stage ≥4 or dialysis dependence; known chronic lung disease or other secondary causes of pulmonary hypertension unrelated to left heart disease; atrial fibrillation or other rhythm disturbance precluding reliable diastolic assessment; pregnancy. Note: systemic hypertension is not an exclusion criterion, given its high prevalence as a diabetes comorbidity; it will instead be recorded and analyzed as a covariate.

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