An etiologic model proposing that non-insulin-dependent diabetes mellitus is chronic hypoxic stress hyperglycemia

Abstract

This etiologic model equates non-insulin-dependent diabetes mellitus (NIDDM) to chronic hypoxic stress hyperglycemia produced by increased stimulation of the sympathetic nervous system and hypothalamic–pituitary–adrenal axis. In the initial stages of the disease, hypoxia is believed to result from hemodilutional anemia precipitated by a reduction in vascular smooth muscle tone. The reduction increases lumen diameter necessitating an increased blood volume to maintain pressure. Increased lumen diameter may also trigger atherosclerotic changes that characterize the later stages of NIDDM. The increased diameter decreases the shear stress experienced by endothelial cells and they respond by releasing endothelin, a smooth muscle constrictor and mitogen. The constricting action is hypothesized to be relatively ineffective in NIDDM leading to long-term endothelin release and activation of its mitogenic properties. The resulting increase in the number of smooth muscle cells may explain the intimal thickening of atherosclerosis. Restoration of vascular muscle tone is proposed as a treatment strategy for mild NIDDM.