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The liver is the primary manufacturing site for taking in fats and repackaging them in the form of lipoproteins for delivery to peripheral tissues. Insulin resistance disrupts this lipid repackaging process. Triglyceride levels rise, high-density cholesterol levels decrease, and low-density lipoproteins become smaller, more dense, and more atherogenic (more likely to increase the formation of plaques in the arteries). All of these risk factors increase the likelihood of developing cardiovascular disease. The reason that these small dense LDL particles are atherogenic is that it appears they are more easily oxidized in the blood. This is why the levels of oxidized LDL are far more predictive of future heart disease than total LDL levels are. As insulin resistance (really cellular inflammation) spreads to the muscle, the glucose in the blood stays elevated, increasing the production of more glycosylated proteins (AGE) that increase inflammation throughout the body. The best way to measure insulin resistance is by using a euglycemic insulin clamp, which is an extremely complex procedure done only under research conditions. The best surrogate marker of insulin resistance is the ratio of triglycerides (TG) to high-density lipoprotein (HDL) cholesterol in the blood. The higher the TG/HDL ratio, the greater the level of insulin resistance in the liver. So what are good levels of the TG/HDL ratio? These are shown below: Ideal Fair Poor At risk <1 1–2 3.5 >3.5 You usually find a TG/HDL ratio of less than one in elite athletes or people who follow the Mediterranean Zone. The average American has a TG/HDL ratio of 3.5, indicative of developing widespread insulin resistance. By the time the TG/HDL is greater than 4, you have metabolic syndrome (pre-diabetes) or fully developed type 2 diabetes. An alternative method of determining insulin resistance is the levels of fasting insulin. This is a more expensive test than the TG/HDL ratio so insurance companies don’t like to reimburse it. If you are able to get such a test, here are the numbers you are looking for in terms international units per ml (IU/ml). Ideal Fair Poor At risk <5 5–10 10–15 >15 Since insulin resistance is the result of cellular inflammation, by following a strict Mediterranean Zone dietary program supplemented with purified omega-3 fatty acids and polyphenols, you can expect to see significant changes within thirty days. Once you are in the Zone, your challenge is to stay there for a lifetime. These markers of wellness will provide continued clinical sentinels in the blood to alert you if you are moving out of the Zone. The correction to get back into the Zone is easy. Just follow the dietary instructions in this book.