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Diabetes is a prime risk factor for car- knowledge related to CVD in patients
diovascular disease (CVD). Vascular with diabetes.
disorders include retinopathy and However, managing cardiovascular
Betsy B. Dokken, PhD, NP, CDE
nephropathy, peripheral vascular risk factors in patients with diabetes
disease (PVD), stroke, and coronary does not eradicate these complica-
artery disease (CAD). Diabetes also tions. We are only just beginning to
affects the heart muscle, causing both understand the complex and multi-
systolic and diastolic heart failure. The factorial etiology of CVD in diabetes.
etiology of this excess cardiovascular This review will attempt to provide an
morbidity and mortality is not com- explanation of the current scientific
knowledge in this field, from defects
pletely clear. Evidence suggests that
in the large blood vessels (macrovas-
although hyperglycemia, the hallmark
culature) and the small blood vessels
of diabetes, contributes to myocar- (microvasculature) to the less well-
dial damage after ischemic events, it understood cellular and molecular
is clearly not the only factor, because mechanisms of CVD in patients with
both pre-diabetes and the presence of diabetes.
the metabolic syndrome, even in nor-
moglycemic patients, increase the risk Macrovasculature
of most types of CVD.14 Atherosclerosis is the major threat
In 2002, a survey of people in the to the macrovasculature for patients
United States with diagnosed diabe- with and without diabetes. The gen-
tes found that, surprisingly, 68% of eral pathogenesis of atherosclerosis
patients did not consider themselves has been reviewed elsewhere,7 but
at risk for heart attack or stroke.5 In several factors specific to diabetes are
addition, only about half of patients worth mentioning here. Clinically,
surveyed reported that their health dyslipidemia is highly correlated
care providers discussed the high risk with atherosclerosis, and up to 97%
of patients with diabetes are dyslipi-
of CVD in diabetes and what steps
demic.8 In addition to the characteristic
they could take to reduce that risk. 5
pattern of increased triglycerides and
Fortunately, we are now making the decreased HDL cholesterol found in
link. Health care providers are now the plasma of patients with diabetes,
focused on decreasing cardiovascu- abnormalities are seen in the structure
lar risk in patients with diabetes by of the lipoprotein particles. In diabetes,
treating dyslipidemia and hypertension the predominant form of LDL choles-
and by improving glycemic control.6 terol is the small, dense form. Small
Moreover, the American Diabetes LDL particles are more atherogenic
Association/American College of than large LDL particles because they
Cardiology Make the Link public can more easily penetrate and form
awareness campaign has improved stronger attachments to the arterial
160 Diabetes Spectrum Volume 21, Number 3, 2008
wall, and they are more susceptible to deficiency and insulin resistance pro- which may partially explain the high
diabetes. In the Strong Heart Study, factors in patients with type 2 diabetes. Am Regensteiner JG: Skeletal muscle deoxygen-
which included 1,299 adults with type Fam Phys 62:26332642, 26452646, 2002 ation after the onset of moderate exercise
2 diabetes, those with left ventricu- 7
Libby P, Theroux P: Pathophysiology suggests slowed microvascular blood flow
of coronary artery disease. Circulation kinetics in type 2 diabetes. Diabetes Care
lar hypertrophy had higher levels of 30:28802885, 2007
111:34813488, 2005
fibrinogen and C-reactive protein (both
markers of chronic inflammation) and 8
Fagot-Campagna A, Rolka DB, Beckles GL, 25
Tooke JE: Microcirculation and diabetes.
Gregg EW, Narayan KM: Prevalence of lipid British Med Bull 45:206223, 1989
urinary albumin independent of tra- ablormalities, awareness, and treatment in US
ditional cardiovascular risk factors.64 Weir M: Microalbuminuria and cardio-
26
adults with diabetes [Abstract]. Diabetes 49 vascular disease. Clin J Am Soc Nephrol
In addition, fibrinogen and C-reactive (Suppl. 1):A78, 2000 2:581590, 2007
protein levels were independently and 9
Rosenson RS: Clinical role of LDL and HDL
significantly higher in subjects with left
27
Pickup JC, Mattock MB, Chusney GD, Burt
subclasses and apolipoprotein measurement.
D: NIDDM as a disease of the innate immune
ventricular hypertrophy among those ACC Curr J Rev May, 2004, p. 3337
system: association of acute-phase reactants
without pathological albuminuria, sug- Chan AC: Vitamin E and atherosclerosis. J
10
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164 Diabetes Spectrum Volume 21, Number 3, 2008
28
Festa A, DAgostino Jr R, Howard G, of diabetes mellitus and its complications. stolic dysfunction as an early manifestation of
Mykknen L, Tracy RP, Haffner SM: Chronic Antiox Redox Sig 9:343353, 2007 diabetic cardiomyopathy. Cardiol 98:3339,
Endothelin-1 is induced by cytokines in in the coronary microcirculation early in Marinescu V, Schroeder J, Larkin D, Yamada
human vascular smooth muscle cells: evidence reperfusion following ischemia [Abstract]. J E, Raffel DM, Stevens MJ: Sympathetic
for intracellular endothelin-converting Diabetes Comp 14:96107, 2000 dysfunction in type 1 diabetes: association
enzyme. Mol Pharmacol 55:902909, 1999 with impaired myocardial blood flow reserve
44
Freedman SF, Hatchell DL: Enhanced and diastolic dysfunction. J Am Coll Cardiol
Chung KF, Barnes PJ: Cytokines in asthma.
31
superoxide radical production by stimulated 44:23682374, 2004
Thorax 54:825857, 1999 polymorphonuclear leukocytes in a cat model
of diabetes [Abstract]. Exp Eye Res 55:767 Galderisi M, Cicala S, Caso P, De Simone
57
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45
diastolic dysfunction in arterial hypertension.
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Galderisi M: Diastolic dysfunction and dia-
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Weyrich AS, Prescott SM, Zimmerman J Am Coll Cardiol 48:15481551, 2006
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1997 signaling in the vascular play book. Matthews DR, Manley SE, Cull CA, Hadden
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51