Insulin (as Villain) and Hypertension
A Direct Relationship
Insulin resistance refers to the (lack of) effect of insulin on carbohydrate (glucose) metabolism.
Only 1/2 (50%) of hypertensives have insulin values similar to the normal population and hence are not insulin resistant. Not all hypertensives are insulin resistant and not all insulin resistant people (like Mexican-Americans) are hypertensive.
It is believed that the key to understanding the relationship between hypertension and high insulin values is to understand that even though the effective of insulin on body glucose-carbohydrate metabolism may be impaired, other insulin functions are not impaired such as:
- The effect of insulin in increasing renal sodium retention.
- Insulin resistance may involve glucose-carbohydrate metabolism but may not affect lipid or potassium metabolism. The resistance is in "the non-oxidative pathways of intracellular glucose disposal."
Insulin resistance is selective (involving glucose metabolism although occasionally amino acid, or fatty-acid metabolism). It may be tissue-specific predominantly affecting skeletal muscle although it may affect fat cells, white cells, and the liver. It may be pathway specific affecting only glycogen except during EEA. Hence, hypertension may develop depending on how much insulin resistance occurs in a given tissue (kidneys) or pathway (amino acid-protein metabolism), etc. Because muscles may be resistant to the effect of insulin, excess insulin may be produced which then would give an excess stimulation to the kidneys and 3ympathetic nervous system, which still are normally sensitive to the effects of insulin. This could result in retaining of sodium-salt, increased sympathetic reactivity, either of which may result in the development of hypertension.
Insulin and insulin-like growth factors are "mitogens" capable of stimulating smooth muscle proliferation such as in blood vessels (vascular smooth muscle hypertrophy may narrow the lumen of resistance vessels and aid in the development of hypertension). Moreover the hyperinsulinemla can stimulate the nervous system, which then causes sympathetic nervous system excess function resulting in increase in heart rate, blood pressure, plasma norepinephrine, and even the recently available technique of measured Increased sympathetic nerve activity.
Insulin resistance, high serum insulin levels (hyperinsulinemia) or both, can cause chronic sodium retention directly through the effect of insulin on the renal tubules and indirectly through stimulation of the sympathetic nervous system which augments angiotensin Il-mediated aldosterone secretion.
There is information to suggest a direct relationship between sodium-sensitlvity and insulin resistance. It may be that insulin resistance is a marker for sodium sensitive hypertension.
Weight gain causes selective Insulin resistance. Upper body "ANDROID" fat distribution is associated with hypertension, glucose intolerance and hyperlipidemia.
The abnormal lipids of insulin resistance is increased tryglicerides, decreased HDL cholesterol and occasionally an increase in LDL. There is an increased rate of Apo-protein I (the main HDL cholesterol lipoprotein) destruction. Vasodilators like ACE inhibitors calcium-channel blockers and alpha blockers are neutral or improve insulin resistance whereas diuretics and beta blockers worsen insulin resistance and lipoprotein metabolism. Exercise and weight loss are the cornerstones of hypertension management. (This is an abstract of the article "How Does Insulin Influence Hypertension," by Albert P. Rocchini, of the University of Minnesota Medical School in Choices In Cardiology, 6:165168, 1992)
H. Robert Silverstein, MD