Diabetes is a systemic disease affecting almost every cell that metabolises glucose .What begins as a minor functional impairment , worsens gradually and ultimately end up in severe structural changes.The basement membrane of cells face the brunt of the attack . (In the strict sense every cell has a basement but it is well developed only in kidneys ) . We also know , diabetes is able to inflict universal damage by targeting the vascular endothelial cells.
In the kidneys DM makes the glomerulus more porous causing protein leak* and ultimately damages the tubules and end up in CRF. In the retina it excretes the proteinaceous material into the vital layers and result in retinopathy and progressive visual loss.
* Micro/Macro albuminuria
In fact , there is a very close link between eyes and the kidneys Nephrologists hesitate to make a diagnosis of diabetic nephropathy without ocular changes. The peripheral vascular disease and diabetic foot are another expression of this microvascular dysfunction.
What is the impact on cardiac micro-circulation ?
Whenever significant diabetic nephropathy is present there must be a significant cardiac micro- angiopathy as well.This is now a fact than an assumption. We are not recognizing it rather ! (If only we have a cardiac creatinine we can easily identify diabetic myocardial protein leak !)
When kidneys lose protein , cardiac capillaries lose proteins to interstitial space and result in progressive fibrotic reaction . We know extravasaation of high osmolar proteins can play havoc in cardiac interstitium !
Proteins are the particles of life . . . but in wrong places it can transform into deadly molecules in a fraction of time !
Hence , the cardiac protein leak in diabetes can cause any of the following clinico -pathologic entities.
- A mild left ventricular hypertrophy .
- Increase global cardiac mass (Similar to bulky kidneys seen in early diabetic nephropathy )
- Simple diastolic dysfunction.
- Severe restrictive features
- NDCM (Non dilated cardiomyopathy )
- Finally a DCM like transformation
How to recognize cardiac protein leak ?
- Clinically it presents either as angina or early heart failure symptoms ( not both usually ) .Diastolic dysfunction in echo, positive stress test , patchy thallium uptake abnormality often with features of syndrome X is also recognised.
- Many of the low flow or slow flow phenomenon in coronary angiograms might reflect micro-circulatory dysfunction .
- This is recognised by prolonged TIMI frame counts and prolonged coronary sinus filling and emptying time .
What about macro-vascular complications in diabetes ? How is it different from micro-vascular complications ?
Though we expect a direct link between micro and macro vascular complication , the later appears to a patho-genetically independent process . This will be addressed later.