Insulin resistance: an additional risk factor in the pathogenesis of cardiovascular disease in type 2 diabetes

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Sedentary life style and high calorie dietary habits are prominent leading cause of metabolic syndrome in modern world. Obesity plays a central role in occurrence of various diseases like hyperinsulinemia, hyperglycemia and hyperlipidemia, which lead to insulin resistance and metabolic derangements like cardiovascular diseases (CVDs) mediated by oxidative stress. The mortality rate due to CVDs is on the rise in developing countries. Insulin resistance (IR) leads to micro or macro angiopathy, peripheral arterial dysfunction, hampered blood flow, hypertension, as well as the cardiomyocyte and the endothelial cell dysfunctions, thus increasing risk factors for coronary artery blockage, stroke and heart failure suggesting that there is a strong association between IR and CVDs. The plausible linkages between these two pathophysiological conditions are altered levels of insulin signaling proteins such as IR-β, IRS-1, PI3K, Akt, Glut4 and PGC-1α that hamper insulin-mediated glucose uptake as well as other functions of insulin in the cardiomyocytes and the endothelial cells of the heart. Reduced AMPK, PFK-2 and elevated levels of NADP(H)-dependent oxidases produced by activated M1 macrophages of the adipose tissue and elevated levels of circulating angiotensin are also cause of CVD in diabetes mellitus condition. Insulin sensitizers, angiotensin blockers, superoxide scavengers are used as therapeutics in the amelioration of CVD. It evidently becomes important to unravel the mechanisms of the association between IR and CVDs in order to formulate novel efficient drugs to treat patients suffering from insulin resistance-mediated cardiovascular diseases. The possible associations between insulin resistance and cardiovascular diseases are reviewed here.

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Fig. 2



Angiotensin-converting enzyme


Angiotensin receptor blockers


American Diabetes Association


Advanced glycation end-products


AMP-activated protein kinase


Angiotensin II type I receptor


CCAAT/enhancer binding protein


Cardiac autonomic neuropathy


C-reactive protein


Cardio vascular diseases


Diacyl glycerol


Diabetes mellitus


Endothelial nitric oxide synthase


Estrogen-related nuclear receptors




Fatty acid translocase




Free fatty acid


Glucose transporter 4


High-density lipoprotein


Heme oxygenase-1


Intracellular adhesion molecule-1




Insulin resistance


Insulin receptor β


Insulin receptor substrate-1


Janus kinase


Signal transducer and activator of transcription


Long-chain fatty acid


Low-density lipoprotein


Lipoprotein lipase


Mitogen-activated protein kinase


Macrophage chemo attractant protein-1


Mammalian target of rapamycin


Nicotinamide adenine dinucleotide phosphate


Non-esterified fatty acid


Nuclear factor of activated T cells


Nuclear factor kappa-light-chain-enhancer of activated B cells


Nitric oxide


NADPH oxidases


Nuclear respiratory factor 1


Oxidative phosphorylation


Plasminogen activator inhibitor-1


Phosphofructokinase 2


PPAR-γ coactivator 1α


Pleckstrin homology


Phosphatidylinositol 3-kinase


Protein kinase C


Protein kinase B


Peroxisome proliferator-activated receptors


Phosphatase and tensin homolog


Protein tyrosine phosphatase 1B


Reactive oxygen species


SH2-containing inositol 5′-phosphatase


Suppressors of cytokine signaling


Sterol regulatory element binding protein


Triacyl glycerol

Tfam A:

Mitochondrial transcription factor A


Toll-like receptors


Tumor necrosis factor-α


Uncoupling protein


Visceral adipose tissue


Vascular endothelial growth factor


Very low-density lipoprotein


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Prof. Sarita Gupta was a visiting scientist in Institute of Cardiovascular Sciences. Nathalia Bernardes and Danielle da Silva Dias were exchange students, under the Canada-Brazil Training program. Dr. Pawan Singal is the holder of the Dr. Naranjan S. Dhalla Chair in Cardiovascular Research supported by St. Boniface Hospital and Research Foundation.

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Correspondence to Sarita Gupta.

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Patel, T.P., Rawal, K., Bagchi, A.K. et al. Insulin resistance: an additional risk factor in the pathogenesis of cardiovascular disease in type 2 diabetes. Heart Fail Rev 21, 11–23 (2016) doi:10.1007/s10741-015-9515-6

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  • Insulin resistance
  • CVD
  • Dyslipidemia
  • Metabolic syndrome
  • Oxidative stress
  • Inflammation