diabetes is most prevalent disease in asia, incidence of heart failure is also increasing in diabetic population, understanding the pathophysiology is very important to deal with these cases.

1. Pathophysiology of diabetic
cardiomyopathy
DR MAHENDRA
CARDIOLOGY, JIPMER

2.  Cardiovascular disease is a common complication of diabetes
responsible for 80% of the mortality.
 1972 for the fist time , the description of 4 patients with
diabetes and heart failure but without arterial hypertension or
coronary artery disease appeared.
 anatomical dissection of their hearts revealed LV hypertrophy and
fibrosis without evidence of coronary artery atheroma or another
substrate pathology responsible for these findings.

3.  defined as cardiovascular damage characterized by myocardial
dilatation and hypertrophy, decrease systolic and diastolic
function of LV independent of IHD or HTN.

4. Pathogenesis of diabetic
cardiomyopathy
1) HYPERGLYCEMIA –
 Excess AGE and Reactive Oxygen Species(ROS)
formation with deactivation of NO.
 Myocardial collagen deposition and fibrosis.

7. 2) FATTY ACIDS
 Impaired glycolysis, pyruvate oxidation, lactate uptake results
in apoptosis.
 Alteration of myocardial bioenergetics and
contraction/relaxation coupling.

8. 3) PROTEIN KINASE C
 Activation of DAG/PKC signal transduction pathway
 Reduction in tissue blood flow.
 Increased vascular permeability.
 Alterations in neovascularization.
 Enhanced extracellular matrix deposition.

9. 4) RENIN ANGIOTENSIN SYSTEM(RAS)
 Activation of stretch receptors in heart activates RAS and the SNS 
Cardiomyocyte hypertrophy and apoptosis.
5) ALDOSTERONE INDUCED FIBROSIS-
 Existence of local cardiac renin-angiotensin-aldosterone system have been
demonstrated.
 Myofibroblast growth with interstitial and focal perivascular accumulation
of collagen.

10. 6) ENDOTHELIAL DYSFUNCTION
 Impaired endothelial NO production.
 Increased-
 vasoconstrictor prostaglandins
 glycated proteins
 endothelium adhesion molecules
 platelet and vascular growth factors
 enhance vasomotor tone and vascular permeability and limit
growth and remodeling.

11. 7) AUTONOMIC NEUROPATHY
 Decreased sympathetic/parasympathetic myocardial
innervation with impaired coronary resistance vessel
vasodilator response .
 Impaired ventricular diastolic filling.

12. Gene expression
 Enhanced myocardial gene expression for muscle carnitine
palmitoyltransferase 1–8.
 Significant depression of the Na+/K+ ATPase α1-subunit mRNA.
 increase in Na+/Ca2+ exchanger mRNA in the ventricular myocardium.
 Enhanced arrhythmogenicity, associated with a decrease of repolarizing
K+ currents.
 down-regulation of αMHC (fast) isoform (contains 3–4 times enzymic
activity of βMHC.
Screening and analysis of early cardiopathology-related gene in type 2 diabetes mellitus. Zhonghua Nei. Ke. Za. Zhi. 41, 530–533

13. Diabetic cardiomyopathy: mild myocardial interstitial fibrosis
stained in blue with Masson trichrome (white arrow) in a patient
with long-duration type 1 diabetes mellitus at autopsy, with
perivascular fibrosis (A) and mild fibrosis between myocytes (B).

14. Fibrotic infiltration in the myocardium with Masson's trichrome
staining. Area stained blue represent fibrotic infiltration.
Magnification at 200×, scale bar is 100 μm.
B) Quantitative analysis of fibrosis. The collagen volume fraction
was higher in the diabetic group than in the control group

17. Stages of diabetic cardiomyopathy
STAGES CHARACTERISTICS FUNCTIONAL
FEATURES
STRUCTURAL
FEATURES
METHODS
Early stage Depletion of GLUT4
Increased FFA
Carnitine deficiency
Ca2 homeostasis changes
Insulin resistance
No overt functional
abnormalities or
possible
overt diastolic
dysfunction
but normal ejection
fraction
Normal LV size, wall
thickness, and mass
Sensitive
methods such as
strain, strain rate,
and
myocardial tissue
velocity
Middle stage Apoptosis and necrosis
Increased AT II
Reduced IGF-I
Increased TGF-1
Mild CAN
Abnormal diastolic
dysfunction and
normal or
slightly decreased
ejection
fraction
Slightly increased LV
mass,
wall thickness, or size
Conventional
echocardiograph
y or
sensitive
methods such as
strain, strain rate,
and
myocardial tissue
velocity
Late stage Microvascular changes
Hypertension
CAD
Severe CAN
Abnormal diastolic
dysfunction and
ejection
fraction
Significantly increased
LV
size, wall thickness,
and
mass
Conventional
echocardiograph
y

18. Functional change in heart

21. Summary
 belief is widely held that the increase in cardiovascular mortality is a
consequence of accelerated atherosclerosis
 Studies showing diabetes mellitus increases the risk for cardiac dysfunction
and heart failure independently of other risk factors such as coronary
disease and hypertension
 down-regulation of SERCA2a, mitochondrial dysfunction, and defects in
cytoprotective signaling appear to be leading cause for cardiomyopathy.
 Novel therapy is required to counteract above failure mechanism.