Diabetes, Vol 38, Issue 2 141-145, Copyright © 1989 by American Diabetes Association
Importance of small intestine in diabetic hypercholesterolemia
KR Feingold
Department of Medicine, University of California, San Francisco.
Numerous studies have demonstrated that poor glycemic control is associated
with elevated plasma cholesterol levels in diabetic patients. Experiments
have shown that cholesterol synthesis is increased in the small intestine
of various diabetic animals. This increase is a generalized phenomenon
occurring in all segments of the small intestine. Insulin therapy that
normalizes blood glucose levels markedly decreases intestinal cholesterol
synthesis in diabetic animals to a level similar to that observed in
control animals. Studies have suggested that the hyperphagia that
accompanies poorly controlled diabetes is the chief stimulus for the
increase in intestinal cholesterol synthesis. However, the direct contact
of the intestinal mucosa with nutrients is not the sole trigger for
increasing cholesterol synthesis in the small intestine, suggesting that
circulating and/or neurological factors play a role. The transport of newly
synthesized cholesterol, most of which is in the chylomicron lipoprotein
fraction, from the intestines to the circulation is increased in diabetic
rats. The sterols associated with these chylomicrons are rapidly cleared
from the circulation and delivered to the liver. The increased transport of
chylomicrons from the intestine to the circulation in diabetic patients
could potentially result in several alterations in lipid metabolism that
may increase the risk of atherosclerotic vascular disease.