When the word “insulin” comes up, most of us think it has something to do with sugar, but insulin also has to do with the way fat is used by the body.
In 1992 Denis McGarry, PhD, published an article in Science called “What if Minkowski Had Been Ageusic? An Alternative Angle on Diabetes.” Oskar Minkowski was the researcher who pinpointed the role of the pancreas in diabetes. Ageusic refers to lacking the sense of taste.
McGarry wrote, “Legend has it that on a momentous day in 1889 Oskar Minkowski noticed that urine collected from his pancreatectomized dog attracted an inordinate number of flies. He is said (by some) to have tasted the urine and to have been struck by its sweetness. From this simple but astute observation he established for the first time that the pancreas produced some entity essential for control of the blood sugar concentration, which, when absent, resulted in diabetes mellitus.”
If Minkowski couldn’t taste the sweetness of urine then he might have instead noticed the smell of acetone, McGarry surmised. Acetone is a molecule produced from the breakdown of fat into ketone bodies, and it often smells metallic or a little like nail polish remover. “He would surely have concluded that removal of the pancreas causes fatty acid metabolism to go awry.”
McGarry thought that the scientific fixation on abnormal glucose metabolism had masked the crucial importance of abnormal lipid (fat, cholesterol) metabolism especially in the case of type II diabetes, because it begins with insulin resistance. I agree and think that the relationship between insulin resistance and cardiovascular disease emerges more clearly when taking this into consideration.
First, normal energy metabolism, the balance between the use of carbohydrates and stored fat for energy needs must be understood.
Carbohydrates are simply chains of sugar molecules. They are broken down during digestion, causing blood glucose levels to rise after a meal. The rise in blood glucose summons the secretion of insulin from the pancreas. Glucose tells the pancreas, “Energy is here! Please secrete insulin to assist me in entering cells.” The cells then have no problem taking up glucose when insulin signals them to open their gates. That’s normal glucose tolerance.
If too much energy (calories), especially in the form of carbohydrates are consumed, the body says, “I’m good, really. What the heck am I going to do with all this energy? My cellular machinery is running just fine with what you gave me.” Insulin will then cause the liver and muscles to store all the glucose they can in a branched form called glycogen, the human equivalent of what starch is to plants.
The liver and muscle together can only store about several hundred grams of glycogen. Fat cells on the other hand, can store huge amounts of energy in the form of triglycerides (fatty acids bound to a modified glucose molecule called glycerol) under the direction of insulin.
During periods of fasting—the gap between breakfast and lunch, lunch and dinner, dinner and breakfast—blood sugar levels are maintained by the release of stored energy, the breakdown of glycogen from the liver. During periods of prolonged fasting triglycerides are broken down for mainly alternative energy sources like fatty acids and ketones and the liver produces glucose to maintain stable blood sugar levels.
These energy stores are tapped into during periods of fasting because blood sugar levels go down, which means insulin levels come down. Insulin in high amounts, inhibits enzymes that break down glycogen and triglycerides.
Here’s where energy metabolism goes awry:
When cells are insulin resistant, insulin levels are higher than normal, but it’s almost like it’s not there. Insulin wants the cells to store or use energy, however, in this situation insulin can’t stop the liver cells from making and releasing glucose, contributing to elevated fasting blood sugar levels. Insulin cannot efficiently keep triglycerides stored in fat cells. Triglycerides are continually broken down into free fatty acids and they spill into the bloodstream, constantly circulating through the liver.
The liver, overwhelmed with fatty acids, is stimulated to synthesize them back into triglycerides and export them as part of VLDLs, very low density lipoproteins. Lipoproteins are a kind of protein-fat hybrid molecule. Protein, with its ability to travel through blood, is the medium of transport for triglycerides and other lipids like cholesterol, hydrophobic substances that can’t travel in the blood alone.
This is also why high carbohydrate diets raise triglycerides and most likely precipitate insulin resistance in the first place. They are broken down into glucose and when they are eaten in excess and the body can’t burn all of that glucose, fatty acids are produced. These fatty acids are then linked, as I mentioned in the preceding section, to glycerol to form triglycerides.
As VLDLs travel in the blood, the triglycerides are broken down, delivering fatty acids back to the adipose tissue, contributing to abdominal (visceral) obesity, and to tissues like muscle, causing fat to build up inside muscle cells. Fat can even accumulate in the beta islet cells of the pancreas leading to their destruction. McGarry thought that the build-up of fat inside of these tissues exacerbated insulin resistance by interfering with glucose metabolism.
When the liver is very overwhelmed with large influxes of fatty acids it can begin doing a third thing, storing the excess triglycerides causing fatty liver to develop.
HDL (high density lipoprotein) is a complicated story that isn’t completely understood. What is important to understand is that with insulin resistance, triglyceride concentrations rise while the cholesterol content of HDL drops.
It is possible that since the liver is in a compromised state, it is not able to synthesize HDL adequately, lowering the levels of this protective lipoprotein in the blood. HDL also strips triglycerides from VLDL, a process that forms LDL (low density lipoprotein) from VLDL. When excess triglycerides are constantly churned from the liver the production of smaller sized LDL goes into high gear.
What does this have to do with cardiovascular disease?
Cardiovascular disease is not the result of a simple accumulation of cholesterol along the artery wall. There’s a lot more to the story of LDL that has come to light in recent years. The LDL test most of us get at the doctor’s office is a measurement of the total cholesterol in LDL (LDL-C). The more telling test is to know the actual number of LDL particles (LDL-P). The more you have, the worse off you are.
Small LDL particles are more likely to undergo oxidative modification—a stress for the vascular walls—because they hang out in the blood stream too long due to their small size, and are less efficiently cleared from the circulation. They crash the artery walls and build up underneath them, just like a pimple does underneath the skin.
The body’s inflammatory response involves sending white blood cells and other chemical messengers to the damaged area, further adding to the build up. The plaque keeps building inside the arterial wall and becomes like a huge inflamed zit that can suddenly erupt one day, clogging the lumen of an artery.
For example, if this happens in an important artery such as the coronary artery and the heart is starved of oxygen, that’s a heart attack. In the brain, a stroke.
Is the answer to these problems drugs? What about stents and other invasive procedures? Stents aren’t that effective as they only address individual blockages, and they cost the healthcare system a whopping $30,000 to $50,000 each. Inflammation is a systemic problem.
McGarry postulated that disordered lipid metabolism precipitated insulin resistance, while other scientists have argued that it begins with disordered glucose metabolism usually stemming from the heavy intake of processed foods. This is the chicken or the egg question. Regardless of which comes first disordered glucose and lipid metabolism probably drive each other in the worsening of insulin resistance, which roughly 100 million Americans are estimated to have according to the American Diabetes Association.
No matter the exact biochemical cause of insulin resistance, for most of us insulin sensitivity can be restored—even after a diagnosis of type II diabetes—and the threat of heart disease eliminated with the curbing of processed food intake and weight loss if necessary.
In my next post I will discuss how my lipid profile used to look before I changed my diet and regained insulin sensitivity and how it looks today. I will give specific examples of the types of foods that I eat.
For more reading on insulin resistance and impaired fat metabolism: “Insulin Resistance and Lipid Disorders”