Cardiovascular Disease Clinical Trial
Official title:
Factors in Susceptibility to Ischemic Heart Disease in Major Depression: Documentation of Insulin Resistance in Patients With Major Depression Utilizing the Hyperinsulinemic Euglycemic Glucose Clamp
A series of studies in patients with major depression have consistently demonstrated a
doubling of the mortality rate at any age, independent of suicide. In addition, the relative
risk for clinically significant coronary artery disease in patients with major depression is
also 2 or more in studies that independently controlled for risk factors such as smoking,
hypertension, etc. The principal long-term goals of the CNE include the determination of the
mechanisms that underlie enhanced susceptibility to premature ischemic heart disease in
patients with major depression, documenting the age at which demonstrable pathophysiologic or
predictive changes begin to occur, and charting their rate of progression. Our long-term goal
is to use our understanding of underlying mechanisms to enhance our capacity to predict who
with major depression is most likely to develop premature ischemic heart disease, to
determine what the mechanisms underlying this susceptibility are, and to develop improved
means for treatment and prevention.
Depressed patients are known to manifest a variety of neuroendocrine changes that predispose
to coronary artery disease including hypercortisolism, decreased secretion of growth hormone
and a deficiency of sex steroids. A final common denominator of these neuroendocrine
abnormalities is insulin resistance. Insulin resistance promotes several changes that would
favor hypertension and increased coronary artery disease including increased sodium
retention, increased activity of the sympathetic nervous system, proliferation of vascular
smooth muscle and deposition of highly metabolically active visceral fat. The latter induces
additional risk factors for coronary disease, including dyslipidemia, hypercoagulation, and
enhanced inflammation. It is a matter of public health importance to document the frequency
and severity of insulin resistance in patients with major depression compared to a closely
matched group of healthy controls. To accurately quantify insulin resistance in each patient
and control, we will apply the hyperinsulinemic euglycemic glucose clamp procedure. This is
the gold standard method for measuring the insulin sensitivity since it reflects the direct
human body glucose metabolic response to a known insulin infusion. Moreover, it is essential
to use this technique in patients with major depression as data indicate that other
alternative procedures give unreliable results in the context of hypercortisolism.
A series of studies in patients with major depression have consistently demonstrated a
doubling of the mortality rate at any age, independent of suicide. In addition, the relative
risk for clinically significant coronary artery disease in patients with major depression is
also 2 or more in studies that independently controlled for risk factors such as smoking,
hypertension, etc. The principal long-term goals of the CNE include the determination of the
mechanisms that underlie enhanced susceptibility to premature ischemic heart disease in
patients with major depression, documenting the age at which demonstrable pathophysiologic or
predictive changes begin to occur, and charting their rate of progression. Our long-term goal
is to use our understanding of underlying mechanisms to enhance our capacity to predict who
with major depression is most likely to develop premature ischemic heart disease, to
determine what the mechanisms underlying this susceptibility are, and to develop improved
means for treatment and prevention.
Depressed patients are known to manifest a variety of neuroendocrine changes that predispose
to coronary artery disease including hypercortisolism, decreased secretion of growth hormone
and a deficiency of sex steroids. A final common denominator of these neuroendocrine
abnormalities is insulin resistance. Insulin resistance promotes several changes that would
favor hypertension and increased coronary artery disease including increased sodium
retention, increased activity of the sympathetic nervous system, proliferation of vascular
smooth muscle and deposition of highly metabolically active visceral fat. The latter induces
additional risk factors for coronary disease, including dyslipidemia, hypercoagulation, and
enhanced inflammation. It is a matter of public health importance to document the frequency
and severity of insulin resistance in patients with major depression compared to a closely
matched group of healthy controls. To accurately quantify insulin resistance in each patient
and control, we will apply the hyperinsulinemic euglycemic glucose clamp procedure. This is
the gold standard method for measuring the insulin sensitivity since it reflects the direct
human body glucose metabolic response to a known insulin infusion. Moreover, it is essential
to use this technique in patients with major depression as data indicate that other
alternative procedures give unreliable results in the context of hypercortisolism.
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