The Insulin Resistance Syndrome

The Insulin Resistance Syndrome

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This text is a guide to the Power Point presentation Insulin Resistance Syndrome. Print this document and read it along as you “click” through the Insulin Resistance Syndrome Power Point. Each number corresponds to each slide.

  1. Insulin resistance (IR) is central to this problem, obviously. An older name for the IR Syndrome is Syndrome X and another frequently used name is the Metabolic Syndrome.
  2. To overcome the insulin resistance, the body produces more insulin. In a very insulin resistant person, the insulin level can be more than ten times normal.
  3. The ever decreasing activity level of modern living and the way we eat (highly processed, very energy dense food in large quantities) have both been associated with IR. But some people seem much more prone genetically than others. We all have that friend who never seems to do anything active, eats anything she wants and stays healthy.
  4. Not everyone with IR is overweight, but this often is the case, particularly "around the middle." Waist circumference of >40 inches in men and >35 inches in women is strongly associated with IR. Just why some of us gain fat particularly around the middle (around the abdominal organs, in fact) is not clear. And neither is it clear why this fat is so strongly associated with IR, or for that matter what it is about fat that causes IR. But it has become clear that fat is a very active organ sending out lots of chemical messages to the rest of the body and it is likely that IR results from fat trying to tell the rest of the body - enough already.
  5. There is also some intriguing evidence to suggest that stress of life contributes to central obesity and therefore IR.
  6. So why is IR so bad? Over years, IR makes it more likely that a person will have a heart attack. In fact, IR is now right up there with tobacco smoking as a cause of heart attacks
  7. in genetically susceptible people.
  8. And the link seems to be primarily through elevations of blood triglycerides (we all know about cholesterol, this is the other fat in blood) and the associated low HDL (the good) cholesterol.
  9. In addition, IR is linked to increased tendency of blood to clot and
  10. to increased inflammation in the body, both factors in heart attacks.
  11. And, of course, having high LDL (the bad) cholesterol
  12. and smoking just make matters worse.
  13. In addition, in genetically susceptible people, IR causes the kidney to retain salt and activates the sympathetic (blood pressure controlling) nervous system and therefore IR accounts for about half the cases of high blood pressure,
  14. which is bad for the heart as well.
  15. And then there is type 2 diabetes. Most cases of type 2 diabetes are preceded by IR, often for years (even from childhood).
  16. Some people with IR never get diabetes, but those with genetically "weaker" insulin cells do, perhaps through a process of insulin cell "exhaustion." Remember, initially the body overcomes IR by making more insulin. The insulin cells have to be failing, at least partially, for blood sugars to start increasing.
  17. "On the way" to diabetes, many women will first develop diabetes due to the added stress of pregnancy.
  18. Let's not forget that diabetes is also a risk for heart attacks.
  19. Gout? Yes. Remarkably enough insulin also causes the kidney to retain uric acid, which causes gout. The association between gout and heart disease has been recognized for centuries, but uric acid does not probably directly cause heart disease.
  20. Polycystic Ovary Syndrome (PCOS) is a less understood component of the IR syndrome, but it is very important. In ways that we don't understand, insulin affects the ovaries in genetically susceptible women to make more male hormone than normal. This causes irregular or absent periods, infertility and excess body hair. PCOS is now the leading cause of infertility in the US.
  21. By mechanisms also not fullly understood, IR causes fat to infiltrate the liver, so that IR is now the leading cause of liver function abnormalities in the US. Most of the time this does not cause serious disease, but in some cases liver failure is possible.
  22. The Thrifty Gene Hypothesis - Once upon a time, when we were very active and there was not much food, it was good to have super efficient metabolism, but now this same "efficient" gene set has been overwhelmed by inactivity and out of control eating.

Part of the evidence for this cascade is that improving the situation at any point improves events "downstream." Thus weight loss/less carbohydrate/more activity all improve IR and therefore improve all the steps from that point, as do drugs that improve insulin sensitivity (Metformin/Glucophage/and the so-called TZDs).

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