Modern life subjects modern humans to stresses our ancestors did not encounter. Early humans (who contributed our genetic background) evolved in an environment where starvation and predation were the predominant hazards to survival. Their lifestyles were characterized by chronic caloric restriction and high levels of physical activity. The world in which we live today is quite different-we have essentially unlimited caloric access and make physical inactivity a high priority. The chronic imbalance between energy intake and energy expenditure creates oxidative and inflammatory stress that has led to an epidemic of "metabolic disease". The resultant abnormal regulation of cell signaling pathways has led to increased rates of many forms of cancer. In the brain and central nervous system we see neurodegenerative diseases such as Alzheimer's dementia and Parkinson's disease. In the blood vessels these changes contribute to atherosclerosis. In adipose tissue (fat), liver and skeletal muscle they lead to resistance to insulin action (insulin resistance) and what is commonly known as the metabolic syndrome. Resistance to insulin in peripheral tissues eventually leads to the failure of pancreatic cells to make insulin-this causes diabetes. By all accounts we are in the midst of an epidemic of diabetes in the Western world.
The "metabolic syndrome" is also known as the dysmetabolic syndrome, Reaven's syndrome (after the Stanford cardiologist who first tied the pieces together), syndrome X or insulin resistance syndrome. Different criteria have been used to define metabolic syndrome. The World Health Organization, American Diabetes Association and other health care organizations have used different definitions. All of them, however, include high blood pressure as a major criteria for the diagnosis. Other features include obesity, particularly central or truncal obesity (apple shaped body habitus), low levels of HDL cholesterol ("good" cholesterol), high levels of the blood fats called triglycerides, and generally some abnormality of glucose metabolism. Some definitions include elevated levels of uric acid, the product of protein metabolism that causes gout and is also associated with hypertension and vascular diseases.
Why do patients with insulin resistance develop high blood pressure? The short answer is that we don't know for certain. Theories abound and there are probably many mechanisms. Oxidative stress and inflammation can both cause hypertension. Fat cells release enzymes that raise blood pressure. Insulin itself can cause salt retention which also raises blood pressure. Recent studies have focused on the role of the brain both in the control of glucose and fat metabolism and also in determining blood pressure in patients with insulin resistance.
Why is this important? How does insulin resistance change our approach to treating hypertension? Physicians should be aware of the high prevalence of insulin resistance in patients with high blood pressure. Over half of hypertensive patients over 50 years are insulin resistant. They should be screened for the other metabolic abnormalities associated with insulin resistance. The abnormal blood fats contribute to the increased risk for heart attack and stroke. Optimal drug treatment can depend on the presence of insulin resistance. For instance, there is evidence that some beta blockers and diuretics can worsen insulin sensitivity and that drugs that act on the renin-angiotensin system ("ACE" inhibitors and "ARBs") might have beneficial effects. There is increasing evidence that our blood pressure and cholesterol targets should be lower in insulin resistant patients to better protect them from stroke, heart attack and chronic kidney disease. Most importantly, patients should realize that changing the "energy in/energy out" equation is a powerful tool to not just lower blood pressure but reduce risk for vascular disease.
Published On: November 24, 2008