The Pathophysiology of Cardiovascular Disease and Diabetes: Beyond Blood Pressure and Lipids

In Brief The pathophysiology of the link between diabetes and cardiovascular disease (CVD) is complex and multifactorial. Understanding these profound mechanisms of disease can help clinicians identify and treat CVD in patients with diabetes, as well as help patients prevent these potentially devastating complications. This article reviews the biological basis of the link between diabetes and CVD, from defects in the vasculature to the cellular and molecular mechanisms specific to insulin-resistant states and hyperglycemia. It concludes with a discussion of heart failure in diabetes, a clinical entity that demonstrates many of the mechanisms discussed.

[1]  E. Abel,et al.  Mitochondrial uncoupling: a key contributor to reduced cardiac efficiency in diabetes. , 2006, Physiology.

[2]  K. Petersen,et al.  Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. , 2004, The New England journal of medicine.

[3]  C. Nielson,et al.  Blood glucose and heart failure in nondiabetic patients. , 2005, Diabetes care.

[4]  A. C. Chan.  Vitamin E and atherosclerosis. , 1998, The Journal of nutrition.

[5]  K. Maehara,et al.  A comparison of ultrastructural changes on endomyocardial biopsy specimens obtained from patients with diabetes mellitus with and without hypertension , 2007, Heart and Vessels.

[6]  G. Tognoni,et al.  Prevention of cardiovascular disease in type-2 diabetes: How to improve the clinical efficacy of aspirin , 2004, Thrombosis and Haemostasis.

[7]  B. Howard,et al.  Relation of left ventricular hypertrophy to inflammation and albuminuria in adults with type 2 diabetes: the strong heart study. , 2003, Diabetes care.

[8]  J. Pickup,et al.  NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X , 1997, Diabetologia.

[9]  E. Antman,et al.  ACC/AHA PRACTICE GUIDELINES ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary , 2002 .

[10]  S. Smith,et al.  Cardiac autonomic dysfunction in patients with diabetic retinopathy , 1981, Diabetologia.

[11]  P. Libby,et al.  Pathophysiology of Coronary Artery Disease , 2005, Circulation.

[12]  M. Taşkıran,et al.  Decreased myocardial perfusion reserve in diabetic autonomic neuropathy. , 2002, Diabetes.

[13]  J. Kips,et al.  Cytokines in asthma , 2001, European Respiratory Journal.

[14]  M. Harris,et al.  Mortality in Adults With and Without Diabetes in a National Cohort of the U.S. Population, 1971–1993 , 1998, Diabetes Care.

[15]  K. Chung,et al.  Cytokines in asthma , 1999, Thorax.

[16]  Vilmundur Gudnason,et al.  The association between glucose abnormalities and heart failure in the population-based Reykjavik study. , 2005, Diabetes care.

[17]  B. Horne,et al.  Effect of fasting glucose levels on mortality rate in patients with and without diabetes mellitus and coronary artery disease undergoing percutaneous coronary intervention. , 2003, American heart journal.

[18]  T. Marwick,et al.  Diabetic heart disease. , 2006, Heart.

[19]  R. Baggott.  DISEASE , 1947, Social Policy & Administration.

[20]  J. Buse,et al.  Physician attitudes and practices and patient awareness of the cardiovascular complications of diabetes. , 2002, Journal of the American College of Cardiology.

[21]  D. Bell,et al.  Diabetic Cardiomyopathy: A unique entity or a complication of coronary artery disease? , 1995, Diabetes Care.

[22]  R. Rosenson.  Clinical role of LDL and HDL subclasses and apolipoprotein measurement , 2004 .

[23]  Douglas W Mahoney,et al.  Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. , 2003, JAMA.

[24]  M. Carr.  Diabetes mellitus: a hypercoagulable state. , 2001, Journal of diabetes and its complications.

[25]  A. Weyrich,et al.  Platelets, endothelial cells, inflammatory chemokines, and restenosis: complex signaling in the vascular play book. , 2002, Circulation.

[26]  J. Oram,et al.  Nonenzymatic Glycosylation of HDL and Impaired HDL-Receptor–Mediated Cholesterol Efflux , 1991, Diabetes.

[27]  E. Araki,et al.  Impact of mitochondrial ROS production in the pathogenesis of diabetes mellitus and its complications. , 2006, Antioxidants & redox signaling.

[28]  T Nakamura,et al.  Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. , 1999, Biochemical and biophysical research communications.

[29]  S. Haffner,et al.  Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). , 2000, Circulation.

[30]  R. Pop-Busui,et al.  Sympathetic dysfunction in type 1 diabetes: association with impaired myocardial blood flow reserve and diastolic dysfunction. , 2004, Journal of the American College of Cardiology.

[31]  R. Bucala,et al.  Lipid advanced glycosylation: pathway for lipid oxidation in vivo. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[32]  J. Pickup,et al.  Activation of the innate immune system as a predictor of cardiovascular mortality in Type 2 diabetes mellitus , 2003, Diabetic medicine : a journal of the British Diabetic Association.

[33]  B. Howard,et al.  Impact of diabetes on cardiac structure and function: the strong heart study. , 2000, Circulation.

[34]  C. Bauters,et al.  [Pathophysiology of coronary artery disease]. , 2008, La Revue du praticien.

[35]  M. Quon,et al.  Inflammatory markers and the metabolic syndrome: insights from therapeutic interventions. , 2005, Journal of the American College of Cardiology.

[36]  B. Strauer,et al.  Left Ventricular Diastolic Dysfunction as an Early Manifestation of Diabetic Cardiomyopathy , 2002, Cardiology.

[37]  Oreste de Divitiis,et al.  Coronary flow reserve and myocardial diastolic dysfunction in arterial hypertension. , 2002, The American journal of cardiology.

[38]  M. Quon,et al.  The union of vascular and metabolic actions of insulin in sickness and in health. , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[39]  B. Halliwell,et al.  Relationships between plasma measures of oxidative stress and metabolic control in NIDDM , 1997, Diabetologia.

[40]  E. Feskens,et al.  Glucose tolerance and mortality: comparison of WHO and American Diabetic Association diagnostic criteria , 1999, The Lancet.

[41]  J. Copeland,et al.  Diabetes enhances leukocyte accumulation in the coronary microcirculation early in reperfusion following ischemia. , 2000, Journal of diabetes and its complications.

[42]  T. Warner,et al.  Endothelin-1 is induced by cytokines in human vascular smooth muscle cells: evidence for intracellular endothelin-converting enzyme. , 1999, Molecular pharmacology.

[43]  P Trayhurn,et al.  Signalling role of adipose tissue: adipokines and inflammation in obesity. , 2005, Biochemical Society transactions.

[44]  Michael Brownlee,et al.  The pathobiology of diabetic complications: a unifying mechanism. , 2005, Diabetes.

[45]  Maurizio Galderisi,et al.  Diastolic dysfunction and diabetic cardiomyopathy: evaluation by Doppler echocardiography. , 2006, Journal of the American College of Cardiology.

[46]  R. Holman,et al.  Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study , 2000, BMJ : British Medical Journal.

[47]  J. Tooke.  Microcirculation and diabetes. , 1989, British medical bulletin.

[48]  D. Celermajer,et al.  Endothelial dysfunction: does it matter? Is it reversible? , 1997, Journal of the American College of Cardiology.

[49]  Farris K. Timimi,et al.  Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. , 1998, Circulation.

[50]  Joshua A. David,et al.  Abstract , 1996, Journal of the Neurological Sciences.

[51]  M. Shipley,et al.  Type 2 (non-insulin-dependent) diabetes mellitus and cardiovascular disease — putative association via common antecedents; further evidence from the whitehall study , 1988, Diabetologia.

[52]  M. Brownlee.  Biochemistry and molecular cell biology of diabetic complications , 2001, Nature.

[53]  Daniel G Blanchard,et al.  Diastolic heart failure: challenges of diagnosis and treatment. , 2004, American family physician.

[54]  P. Poirier,et al.  Diastolic dysfunction in normotensive men with well-controlled type 2 diabetes: importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy. , 2001, Diabetes care.

[55]  D. Hatchell,et al.  Enhanced superoxide radical production by stimulated polymorphonuclear leukocytes in a cat model of diabetes. , 1992, Experimental eye research.

[56]  S. Tyagi,et al.  The central role of vascular extracellular matrix and basement membrane remodeling in metabolic syndrome and type 2 diabetes : the matrix preloaded , 2015 .

[57]  D. Mikhailidis,et al.  Inflammatory markers and the metabolic syndrome. , 2005, Atherosclerosis.

[58]  M. Triggiani,et al.  Glycosylation enhances oxygen radical-induced modifications and decreases acetylhydrolase activity of human low density lipoprotein , 1997, Basic Research in Cardiology.

[59]  D. Ewing,et al.  The natural history of diabetic autonomic neuropathy. , 1980, The Quarterly journal of medicine.

[60]  J. Regensteiner,et al.  Skeletal Muscle Deoxygenation Following the Onset of Moderate Exercise Suggests Slowed Microvascular Blood Flow Kinetics in Type 2 Diabetes , 2007 .

[61]  C. Szabó.  PARP as a Drug Target for the Therapy of Diabetic Cardiovascular Dysfunction. , 2002, Drug news & perspectives.

[62]  M. Weir.  Microalbuminuria and cardiovascular disease. , 2007, Clinical journal of the American Society of Nephrology : CJASN.

[63]  R. S. Sohal,et al.  Hydrogen peroxide release by mitochondria increases during aging , 1991, Mechanisms of Ageing and Development.