Suppose that Alice, a nondiabetic, arises in the morning and has a mixed breakfast, that is, one that contains both carbohydrate and protein. On the carbohydrate side, she has toast with jelly and a glass of orange juice; on the protein side, she has a boiled egg. Her basal (i.e., before-meals) insulin secretion has kept her blood sugar steady during the night, inhibiting gluconeogenesis. Shortly after the sugar in the juice or jelly hits her mouth, or the starchy carbohydrates in the toast reach certain enzymes in the saliva and intestines, glucose begins to enter her bloodstream. The mere presence of food in her gut as well as the sugar her pancreas to release the granules of insulin it has stored in order to offset a jump in blood sugar This rapid release of stored insulin is called phase I insulin response. It quickly corrects the initial blood sugar increases and can prevent further increase from the ingested carbohydrate. As the pancreas runs out of stored insulin, it manufactures more, but it has to do so from scratch. The insulin known as the phase II insulin response, and it’s secreted much more slowly. As she eats her boiled egg, the small amount of insulin of phase II can cover the glucose that, over a period of hours, is slowly produced from the protein egg.
Insulin acts in the nondiabetic as the means to admit glucose-fuel-into the cells. It does this by activating the movement of glucose “transporters” within the cells. These specialized protein molecules protrude from the cytoplasm of the cells and their outer surfaces to grab glucose from the blood and bring it to the interiors of the cells. Once inside the cells, glucose can be utilized to power energy-requiring functions. Without insulin, the cells can absorb only a very small amount of glucose, not enough to sustain the body. As glucose continues to enter Alice’s blood, and the beta cells in her pancreas continue to release insulin, some of her blood sugar is transformed to glycogen, a starchy substance stored in the muscles and liver. Once glycogen storage sites in the muscles and liver are filled, excess glucose remaining in the bloodstream is converted to and stored as saturated fat. Later, as lunchtime nears but before Alice eats, if her blood sugar drops slightly low, the alpha cells of her pancreas will release another pancreatic hormone, glucagon, which will “instruct” her liver and muscles to begin converting glycogen to glucose, to raise blood sugar. When she eats again, her store of glycogen will be replenished. This pattern of basal, phase I, then phase II insulin secretion is perfect for keeping Alice’s blood glucose levels in a safe range. Her body is nourished, and things work according to design. Her mixed meal is handled beautifully. This is not, however, how things work for either the type 1 of type 2 diabetic.
The Type 1 Diabetic
Let’s look at what would happen to me, a type 1 diabetic, if I had the same breakfast as Alice, our nondiabetic. Unlike Alice, because of a condition peculiar to diabetics, if I take a long-acting insulin at bedtime, I might awaken with a normal blood sugar, but if I spend some time awake before breakfast, my blood sugar may rise, even I haven’t had anything to eat. Ordinarily, the liver is constantly removing some insulin from the bloodstream, but during the first few hours after waking from a full night’s sleep, it clears insulin out of the blood at an accelerated rate. This dip is the level of my previously injected insulin is called the dawn phenomenon. Because of it, my blood glucose can rise even though I haven’t eaten. A nondiabetic just makes more insulin to offset the increased insulin clearance. Those of us who are severely diabetic have to track the dawn phenomenon carefully by monitoring blood glucose levels, and can learn how to use injected insulin to prevent its effect upon blood sugar. As with Alice, the minute the meal hits my mouth, the enzymes in m saliva begin to break down the sugars in the toast and juice, and almost immediately my blood sugar would begin to rise. Even if the toast had no jelly, the enzymes in my saliva and intestines and acid in my stomach would begin to transform the toast rapidly into glucose shortly after ingestion. Since my beta cells no longer produce detectable amounts of insulin, there is no stored insulin to be released by my pancreas, so I have no phase I insulin response. My blood sugar (in the absence of injected insulin) will rise while I digest my meal. None of the glucose will be converted to fat, nor will any be converted to glycogen. Eventually much will be filtered out by my kidneys and passed out through the urine, but not before my body has endured damagingly high blood sugar levels-which won’t kill me on the spot but will do so over a period of days if I don’t inject insulin. The natural question is, wouldn’t injected insulin “cover” the carbohydrate in such a breakfast? Not adequately! This is a common misconception-even by those in the health care professions. Injected insulin (even with an insulin pump) doesn’t work the same as insulin created naturally in the body. Conventional insulin/diet therapy resulting in high blood sugar after meals is a guaranteed slow, incremental, “silent” death from the rages of diabetic complications. Norma phase I insulin is almost instantly in the bloodstream. Rapidly it begins to hustle blood sugar off to where it’s needed. Injected insulin, on the other hand, is injected either into fat or muscle (not usually into a vein) and absorbed slowly. The fastest insulin we have starts to work in about 20 minutes, but its full effect is drawn out over a number of hours, not nearly fast enough to prevent a damaging upswing in blood sugars if fast-acting carbohydrate, like bread, is consumed. This is the central problem for type 1 diabetics-the carbohydrate and the drastic surge it causes in blood sugar. Because I know my body produces essentially no insulin, I have a shot of insulin before every meal. But I no longer eat meals with fast-acting or large amounts of carbohydrate, because the blood sugar swings they cause were what brought about my long-term complications. Even injection by means of an insulin pump (see the discussion near the end of chapter 19 “Intensive Insulin Regimens”) cannot automatically fine-tune the level of glucose in my blood the way a nondiabetic’s body does naturally. Now, if I ate only the protein portion of the meal, my blood sugar wouldn’t have the huge, and potentially toxic surge that carbohydrates cause. It would rise less rapidly, and a small dose of insulin could act quickly enough to cover the glucose that’s slowly derived from the protein. My body would not have to endure wide swings in blood sugar levels. (Dietary fat, by the way, has no direct effect on blood sugar levels, except that it can slightly slow the digestion of carbohydrate. In a sense, you could look at my insulin shot before eating only the protein portion of the meal as mimicking the nondiabetic’s phase II response. This is much easier to accomplish than trying to mimic phase I, because of the much lower levels of dietary carbohydrate (only the slow-acting kind) and injected insulin that I use.
The Type 2 Diabetic
Let’s say Bob, a type 2 diabetic, is 6 feet tall and weighs 300 pounds, much of which is centered around his midsection. Remember, at least 80 percent of type 2 diabetics are overweight. If Bob weighed only 170 pounds, he might well be nondiabetic, but because he’s insulin-resistant, Bob’s body no longer produces enough excess insulin to keep his blood sugar levels normal. The overweight tend to be insulin-resistant as a group, a condition that’s not only hereditary but also directly related to the ratio of visceral and total body fat to lean mass (muscle). The higher this ratio, the more insulin-resistant a person will be. Whether or not an overweight individual is diabetic his weight, intake of carbohydrates, and insulin resistance all tend to make him produce considerably more insulin than a slender person of similar age and height (See Figure 1-3). Many athletes because of their low fat mass and high percentage of muscle, tend as a group to require and make less insulin than nonathletes. An overweight type 2 diabetic like Bob, on the other had, typically makes two to three times as much insulin as the slender nondiabetic. In Bob’s case, from many years of having to overcompensate, his pancreas has partially burned out, his ability to store insulin is diminished or gone, and his phase I insulin response is attenuated. Despite his huge output of insulin, he no longer can keep his blood sugars within normal ranges. ***talks about his patients*** Let’s take another look at that mixed breakfast and see how it affects a type 2 diabetic. Bob has the same toast and jelly and juice and boiled egg that Alice, our nondiabetic, and I had. Bob’s blood sugar levels at waking may be normal. **Since he has bigger appetite than either Alice or I, he has two glasses of juice, four pieces of toast, and two eggs. Almost as soon as the toast and juice hit his mouth, his blood sugar begins to rise. Unlike mine, Bob’s pancreas eventually releases insulin, but he has very little or no stored insulin (his pancreas works hard just to keep his basal insulin level), so he has impaired phase I secretion. His phase II insulin response, however, may be partially intact. So, very slowly, his pancreas will struggle to produce enough insulin to bring his blood sugar down toward the normal range. Eventually it may get there, but not until hours after his meal, and hours after his body has been exposed to high blood sugars. Insulin is not only the major fat-building hormone; it also serves to stimulate the centers in the brain responsible for feeding behavior. Thus, in all likelihood, Bob will grow even more overweight, as demonstrated by the cycle illustrated in Figure 1-1. Since he’s resistant to insulin, his pancreas has to work that much harder to produce insulin to enable him to utilize the carbohydrate he consumes. Because of insulin’s fat-building properties, his body stores away some of his blood sugar as fat and glycogen; but his blood sugar continues to rise, since his cells are unable to utilize all of the glucose derived from his meal. Bob, therefore, still feels hungry. As he eats more, his beta cells work harder to produce more insulin. The excess insulin and the “hungry” cells in his brain prompt him to want yet more food. He has just one more piece of toast with a little more jelly on it, hoping that it will be enough to get him through until lunch. Meanwhile, his blood sugar goes even higher, his beta cells work harder, and perhaps a few burn out. **Even after all this food, he still may feel many of the symptoms of hunger. His blood sugar, however, will probably not go anywhere near as high as mine would if I took no insulin. In addition, his phase II insulin response could even bring his blood sugar down to normal after many hours without more food. Postprandial (after-eating) blood sugar levels that I would call unacceptably high – 140 mg/dl, or even 200 mg/dl – may be considered by other physicians to be unworthy of treatment because the patient still produces adequate insulin to bring them down periodically down to normal or “acceptable,” ranges. If Bob, our type 2 diabetic, had received intensive medical intervention before the beta cells of his pancreas began to burn out, he would have slimmed down, brought his blood sugars into line, and ease the burden on his pancreas. He might even have “cured” his diabetes by slimming down, as I’ve seen in several patients. But many doctors might decide such “mildly” abnormal blood sugars are only impaired glucose tolerance (IGT) and do little more than “watch” them. Again, it’s my belief that aggressive treatment at an early stage can save most patients considerable lost time and personal agony by preventing complications that will occur if blood sugar levels are left unchecked. Such intervention can make subsequent treatment of what can remain – a mild disease – elegantly simple.