Insulin sensitivity in the pathogenesis of hypertension and hypertensive complications
Insulin is the hormone that the pancreas produces to regulate the metabolization of carbohydrates. When we consume foods that contain carbohydrate energy (which makes up the bulk of most diets), our body turns it into simple glucides or sugars that are efficient sources of energy. These enter the blood, whereupon insulin is released to stimulate muscle cells to bring the glucose inside and store it as an energy reserve. When a body’s cells fail to respond adequately to the signals of insulin, an individual is said to be insulin resistant. Often, to compensate for the reduced action of glucose, the pancreas will produce more of it than would normally be necessary, and it will linger in the blood in higher concentrations. This is known as hyperinsulinemia. These two conditions, which tend to go together, are often but not always precursors of diabetes, which could be described as chronic dysfunction of glucose metabolism.
Study after study has revealed an unusually high prevalence of both conditions among people with high blood pressure, and particularly among hypertensive people who are also overweight. Insulin is also linked to myocardial infarction (the most common form of heart attack) and microalbuminuria (the wastage of proteins in urine, a common kidney complication of hypertension as well as diabetes).
Even lean normotensive offspring of hypertensive parents show high levels of insulin and decreased insulin sensitivity, suggesting that it is hyperinsulinemia and insulin resistance that promote hypertension, and not the other way around. As if to confirm the causative link, experiments in lowering insulin levels and insulin resistance have succeeded in lowering blood pressure, while experimental lowering of blood pressure has not lowered insulin levels.
Insulin may not only cause hypertension to appear, but also promote hypertensive complications and other cardiovascular diseases. Hyperinsulinemia tends to lower levels of beneficial high-density lipoproteins and raise levels of harmful triglycerides — both well-documented risk factors for heart disease. Hyperinsulinemia with high blood pressure is also associated with the loss of proteins in urine, a sign of kidney damage.
The mechanism by which insulin exerts this effect is less clear. There appears to be some role for the sympathetic nervous system, the collective term for the channels through which any two organs or parts of the body communicate with each other. The consumption of food in healthy persons causes a temporary disinhibition of neurons that stimulate the sympathetic nervous system; this stimulation can be seen in heart activity. In an insulin-resistant individual, hyperinsulinemia mimics the conditions of digestion when the body is not actually consuming food, promoting sympathetic nervous stimulation all of the time. This becomes evident when urine is analyzed for the presence of norepinephrine, a chemical which is secreted during sympathetic nervous activity. Urinary norepinephrine and insulin levels were both related to each other and to hypertension during the Normative Aging Study in Boston, which looked at metabolic changes in the elderly. Insulin suppression, on the other hand, has been shown to cause decreases in both norepinephrine levels and blood pressure.
It has been suggested that sympathetic stimulation is more than just a pathway through which insulin affects blood pressure; some see it as the actual cause of both insulin resistance and hypertension. Such chicken-and-egg arguments are not uncommon in the study of metabolic effects, but a convincing case can be made for insulin resistance as the prime culprit in hypertension mediated by sympathetic activity. Insulin resistant hypertensive patients remain insulin resistant even when their sympathetic nervous system is suppressed with drugs. In experiments looking at hypertension caused by obesity, insulin sensitivity tends to go down even before blood pressure goes up. Both of these facts suggest that insulin resistance has a primary, causative role in the metabolic changes that lead to hypertension.
The other likely mechanism by which insulin causes hypertension is sodium reabsorption by the kidneys. It has long been known that high levels of insulin in the body mean low levels of sodium in urine; the kidneys are retaining more sodium than they should, and the sodium is returned to the blood, driving pressure up. These mechanisms (sodium reabsorption and nervous stimulation) may both operate at the same time, linking insulin resistance very directly to hypertension.
Is there a way to reduce insulin resistance, and thereby lower blood pressure? Exercise both diminishes sympathetic nervous activity and increases sensitivity to insulin, leading directly to drops in blood pressure. Drugs can also have a role; newer antidiabetic drugs such as thiazolidinediones increase insulin sensitivity, so the body produces less. Troglitazone, a member of this drug family, cuts blood pressure and insulin levels together.
Heredity probably plays a strong role in the development of insulin resistance and hyperinsulinemia, though obesity also is often a factor. The effects of insulin resistance on the metabolism are many, and all of them are bad. They are almost certainly mediated in part by the sympathetic nervous system, though other mechanisms may also exist. Fortunately, even given genetic predisposition, insulin resistance can usually be reduced by the great defence against all cardiovascular problems: regular, healthy exercise.
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