Predictors and prevention of diabetic cardiomyopathy

Figures & data

Figure 1 Different risk factors associated with diabetic cardiomyopathy.

Note: “↑” indicates increased levels.
Abbreviations: AGE, advanced glycation end product; DCM, diabetic cardiomyopathy; FFA, free fatty acid; miRNA, micro-RNA; RAGE, receptor for AGE; ROS, reactive oxygen species.

Figure 2 (A) Different pathways associated with increased free fatty acid mediated diabetic cardiomyopathy and (B) different pathways associated with hyperglycemia mediated diabetic cardiomyopathy.

Notes: “↑” indicates increased levels and “↓” indicates decreased levels.
Abbreviations: AGE, advanced glycation end product; AKT-1, serine/threonine kinase; DCM, diabetic cardiomyopathy; ECM, extracellular matrix; FFA, free fatty acid; GAPDH, glyceraldehyde phosphate dehydrogenase; GLUT, glucose transporter; GSK-3β, glycogen synthase kinase-3β; K-ATP, ATP sensitive potassium channel; miRNA, micro-RNA; MMP9, matrix metalloprotinease 9; mTOR, mammalian target of rapamycin; PARP, poly(ADP ribose) polymerase; PKC, protein kinase C; PPAR, peroxisome proliferator-activated receptor; ROS, reactive oxygen species; RyR, ryanodine receptor; SERCA2, sarco-endoplasmic reticulum-calcium ATPase 2; TNF-α, tumor necrosis factor-α.

Figure 3 Effect of high fat diet, type 1 diabetes, and type 2 diabetes on cardiac remodeling leading to diabetic cardiomyopathy.

Abbreviations: DCM, diabetic cardiomyopathy; E-M, endothelial-myocytes; T1D, type 1 diabetes; T2D, type 2 diabetes.

Table 1 The phenotype and functional impairment in different stages of diabetic cardiomyopathy

Stage	Cellular mechanism	Structural change	Functional change
Early	Increased FFA; altered Ca^2+ homeostasis; depleted GLUT-1 and GLUT-4	Slightly increased LV size, wall thickness, and mass	Possible diastolic dysfunction, normal ejection fraction
Middle	Insulin resistance; AGE formation; increased RAAS and TGF-β1; reduced IGF-1; apoptosis; necrosis; fibrosis; mild CAN	Increased LV size, wall thickness, and mass, dilatation, fibrosis	Diastolic dysfunction, ejection fraction is <50%
Late	Hypertension; microvascular changes; severe CAN; CAD	Increased LV size, wall thickness, and mass, dilatation, fibrosis, micro-angiopathy	Systolic and diastolic dysfunction

Abbreviations: AGE, advanced glycation end product; CAN, cardiovascular autonomic neuropathy; CAD, coronary artery disease; FFA, free fatty acid; GLUT, glucose transporter; IGF-1, insulin growth factor-1; TGF-β1, transforming growth factor-β1; LV, left ventricle; RAAS, renin-angiotensin-aldosterone system.

Table 2 Predictors of and preventative measures for diabetic cardiomyopathy

Predictors		Preventative measures
1. Serological markers		Early DCM
a. Increased levels of N-terminal pro-brain natriuretic peptide (NT proBNP)	Heart failure	Lifestyle modification
b. Increased levels of BNP		a. Exercise
c. Hyperglycemia	Diabetes	b. Controlled diet (less glucose)
d. Elevated Hb1c		Middle DCM
e. Troponins infrequent or positive necrosis		1. Lifestyle modification
f. Elevated MMPs (especially MMP9)	Fibrosis	a. Exercise
g. Decreased TIMPs		b. Diet with less glucose
h. Altered levels of circulating miRNAs		2. Treatments
2. Morphology		a. Metformin (T2D)
a. Hypertrophy		b. Insulin (T1D)
b. Dilatation		c. Pioglitazone (mitigates diastolic dysfunction)
c. Micro- and macro-angiopathy		d. Beta-blocker (decreases hypertension)
3. Echocardiography		Late DCM
a. Mitral valve E/E′		3. Lifestyle modification
b. Transmitral E/A ratio		a. Exercise
c. % fractional shortening		b. Diet with less glucose
4. Magnetic resonance imaging		4. Treatments
a. LV mass, volume and function		a. Metformin (T2D)
b. Systolic and diastolic dysfunction		b. Insulin (T1D)
5. Heart catherisation		c. Pioglitazone (mitigates diastolic dysfunction)
a. LV end diastolic pressure (>15 mmHg)		d. Beta-blocker (decreases hypertension)
b. Mean pulmonary wedge pressure (>15 mmHg)		e. Angioplasty (for microangiopathy and coronary stenosis
6. Coronary angiography		f. miRNA treatment?
a. Coronary artery stenosis: micro-angiopathy		g. Stem cell therapy?

Abbreviations: BNP, B-type natriuretic peptide; DCM, diabetic cardiomyopathy; E/E′, ratio between mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E′); E/A, ratio between early (E) and late (atrial - A) ventricular filling velocity; Hb_1c, glycosylated haemoglobin; LV, left ventricle; miRNA, micro-RNA; MMP, matrix metalloproteinase; TIMP, tissue inhibitor of metalloproteinase; T1D, type 1 diabetes; T2D, type 2 diabetes.