Diabetes Mellitus, Microalbuminuria, and Subclinical Cardiac Disease: Identification and Monitoring of Individuals at Risk of Heart Failure

Abstract

BackgroundPatients with type 2 diabetes mellitus and elevated urinary albumin:creatinine ratio (ACR) have increased risk of heart failure. We hypothesized this was because of cardiac tissue changes rather than silent coronary artery disease.Methods and ResultsIn a case‐controlled observational study 130 subjects including 50 ACR+ve diabetes mellitus patients with persistent microalbuminuria (ACR >2.5 mg/mol in males and >3.5 mg/mol in females, ≥2 measurements, no previous renin–angiotensin–aldosterone therapy, 50 ACR−ve diabetes mellitus patients and 30 controls underwent cardiovascular magnetic resonance for investigation of myocardial fibrosis, ischemia and infarction, and echocardiography. Thirty ACR+ve patients underwent further testing after 1‐year treatment with renin–angiotensin–aldosterone blockade. Cardiac extracellular volume fraction, a measure of diffuse fibrosis, was higher in diabetes mellitus patients than controls (26.1±3.4% and 23.3±3.0% P=0.0002) and in ACR+ve than ACR−ve diabetes mellitus patients (27.2±4.1% versus 25.1±2.9%, P=0.004). ACR+ve patients also had lower E′ measured by echocardiography (8.2±1.9 cm/s versus 8.9±1.9 cm/s, P=0.04) and elevated high‐sensitivity cardiac troponin T 18% versus 4% ≥14 ng/L (P=0.05). Rate of silent myocardial ischemia or infarction were not influenced by ACR status. Renin–angiotensin–aldosterone blockade was associated with increased left ventricular ejection fraction (59.3±7.8 to 61.5±8.7%, P=0.03) and decreased extracellular volume fraction (26.5±3.6 to 25.2±3.1, P=0.01) but no changes in diastolic function or high‐sensitivity cardiac troponin T levels.ConclusionsAsymptomatic diabetes mellitus patients with persistent microalbuminuria have markers of diffuse cardiac fibrosis including elevated extracellular volume fraction, high‐sensitivity cardiac troponin T, and diastolic dysfunction, which may in part be reversible by renin–angiotensin–aldosterone blockade. Increased risk in these patients may be mediated by subclinical changes in tissue structure and function.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01970319.

Effect of switching from pioglitazone to the sodium glucose co‐transporter‐2 inhibitor dapagliflozin on body weight and metabolism‐related factors in patients with type 2 diabetes mellitus: An open‐label, prospective, randomized, parallel‐group comparison trial

“…Improvement in renal function following SGLT2i treatment may indirectly result in lowering of the cardiovascular risk associated with renal dysfunction (cardiorenal syndrome) in patients with T2DM. Another recent study showed that ACR may represent a useful biomarker to identify patients with diabetes at increased cardiovascular risk from a diffuse cardiac fibrotic process . However, NT‐proBNP has been shown to be affected by renal function, although baseline NT‐proBNP values had no correlation with the baseline ACR in the present trial.…”

“…9 Another recent study showed that ACR may represent a useful biomarker to identify patients with diabetes at increased cardiovascular risk from a diffuse cardiac fibrotic process. 11 However, NT-proBNP has been shown to be affected by renal function, 12 although baseline NT-proBNP values had no correlation with the baseline ACR in the present trial. The significant correlation between change in NT-proBNP and baseline ACR may therefore reflect the therapeutic advantage of DAP administration by reducing excess fluid or sodium levels in patients with nephropathy.…”

Relation of Retinopathy and Microalbuminuria With Diastolic Dysfunction in Subjects With Type 2 Diabetes Mellitus

“…Swoboda PP et al noted that microalbuminuric subjects (ACR+ve) had a lower E′, suggesting more advanced diastolic dysfunction. [19] Shogade et al , in their study of Nigerian normotensive type 2 diabetes subjects, noted that LV diastolic dysfunction (LVDD) showed a stepwise increase from the healthy controls to the normoalbuminuric to the microalbuminuric type 2DM subjects (16.9 vs 61.9 vs 78.9%, respectively) (p < 0.001), while E/A ratio and fractional shortening showed a significant stepwise decrease (both p < 0.001). [20] These findings are comparable with present study.…”

Electronic circular dichroism for the detection of microalbuminuria

“…In the case that the barrier is disrupted because of structural changes within the glomerular membrane, human serum albumin (HSA), the most abundant plasmatic protein, 21 is the first to pass through and appear in urine. [24][25][26] Therefore, it is of the utmost importance to determine the urinary level of albumin with high precision. A slight increase in the urinary level of albumin (30 to 300 mg HSA in 24 hours or~20 to 200 mg/L) is referred to as microalbuminuria (MAU), and its timely detection is crucial, especially in patients with diabetes.…”

“…22,23 This pathological state is regarded as an initial sign of diabetic nephropathy and a predictor of cardiovascular complications, which in the worst case can lead to heart failure. [24][25][26] Therefore, it is of the utmost importance to determine the urinary level of albumin with high precision.…”