Obesity Causes
Subclinical Atherosclerosis in Type 2 Diabetes
Patients
Obesity may
mediate early stages of subclinical
atherosclerotic disease in patients with type 2
diabetes, whereas hyperglycemic and insulin
resistance may contribute to the progression of
later stages.
Cardiovascular disease is the leading cause of
death for patients with type 2 diabetes. The
pathogenesis of macrovascular disease has been
attributed to a number of metabolic risk factors
associated with type 2 diabetes, but it was
previously uncertain how these factors interact
to produce clinical manifestations.
To better understand the pathogenesis of
macrovascular disease in these individuals,
Refaat A.F. Hegazi, MD, PhD, from the University
of Pittsburgh, Pennsylvania, and colleagues
examined the relationship between obesity,
insulin resistance, and 5 different measures of
subclinical atherosclerosis in 52 obese
individuals with type 2 diabetes (mean age=51;
65% females). The study focused on subclinical
vascular disease because it is known to be one
of the strongest predictors of clinically
symptomatic vascular disease among patients with
type 2 diabetes.
All participants in the study had type 2
diabetes of relatively short known duration
(less than 5 years) and did not have any
clinical manifestations of large vessel
pathology. Insulin resistance was measure by
hyperinsulinaemic euglycaemic clamp, and body
composition was measure by DXA and computed
tomography. Subclinical vascular disease was
assessed by measures of arterial stiffness by
pulse wave velocity (PWV), carotid artery
intimal-medial thickness (IMT) and plaque index
by ultrasound, and extent of coronary and aortic
calcification using electron beam computed
tomography.
The measures of subclinical vascular disease
were chosen to represent different stages of
disease progression. Arterial stiffness is a
measure of early functional changes of loss of
elasticity and compliance within the vascular
system. In contrast, IMT and plaque measure a
later phase of structural changes involving
hyperplasia of arterial smooth muscle and the
subintimal deposition of cholesterol plaques.
Coronary calcium represents a relatively
advanced phase of atherosclerotic plaques.
The researchers found a significant correlation
between PWV and several measures of adiposity,
including BMI, abdominal subcutaneous fat, thigh
fat, and hepatic fat. In contrast, IMT
measurements correlated with age, plasma
glucose, HbA1c, and low-density lipoprotein
cholesterol, but not adiposity. HbA1c and plasma
activator inhibitor-1 significantly correlated
with plaque index. Coronary and aortic calcium
were significantly correlated with age, and
coronary calcium was also correlated with
interleukin-6 and negatively correlated to an
insulin sensitivity index (P < .05 for
all).
"Obesity acts as a determinant of the early
functional changes of the arterial tree as
measured by arterial stiffness, whereas
hyperglycemia and insulin resistance act as
determinants of later structural and atherotic
changes as measured by carotid IMT and coronary
calcification," the researchers conclude. Obes
Res 2003 Dec;11:12:1597-605
