Sometimes, even when you think you’re doing everything right, your blood sugars may not respond as you expect. Often this will be due to one or more of the biologic curiosities that affect diabetics. The purpose of this chapter is to acquaint you with some real phenomena that can confound your plans, but which you can frequently circumvent if you are aware of them.
Figure 1-2 illustrates the normal, nondiabetic blood insulin response to a meal containing carbohydrate and protein. When glucose from dietary carbohydrate enters the bloodstream, beta cells of the pancreas respond—or should respond—immediately by releasing stored insulin granules. These granules may have been stored for many hours in anticipation of what is known as a glucose challenge. This rapid release is called phase I insulin response.
The nondiabetic body will utilize this immediate release of insulin to prevent blood sugar from increasing significantly. As we discussed in Chapter 1, “Diabetes: The Basics,” one of the hallmarks of type 2 diabetes is the diminished ability to do this. Therefore, blood sugars will shoot up after eating (carbohydrates in particular) and will be brought back into line only slowly by phase II insulin response (the release of newly manufactured insulin). This blood sugar rise can be minimized, primarily by dietary manipulation, but for some diabetics by diet and/or oral agents or injected insulin.
A possible but unproven explanation for diminished or absent phase I insulin response in diabetics is that the beta cells are still capable of making insulin but not capable of storing it. In this model, insulin would be released almost as soon as it is made. This inability to store insulin could also explain the inappropriate release of insulin that often occurs when blood sugar is already low in very early type 2 diabetes. Such individuals may experience blood sugars that are both too high and too low in the same day—even without medication. An alternative explanation is that the sensitivity of the beta cells to changes in blood sugar diminishes, so that they respond inadequately to such changes.
You may begin to notice as you regularly monitor your blood sugars that your fasting blood glucose on waking in the morning is considerably higher than it was when you went to bed, even though you didn’t get up for a midnight snack. There are three common causes for this: gluconeogenesis, the dawn phenomenon, and gastroparesis (delayed stomach-emptying).
Gluconeogenesis, which we discussed briefly in Chapter 1, is the mechanism by which the liver (and, to a lesser degree, the kidneys and intestines) converts amino acids into glucose. Dietary protein is not the only source of amino acids. The proteins of your muscles and other tissues continually receive amino acids from and return them to the bloodstream. This constant flux ensures that amino acids are always available in the blood for conversion to glucose (gluconeogenesis) by the liver or to protein by the muscles and vital organs. Some diabetics still make adequate insulin to prevent gluconeogenesis. However, once your insulin production drops below a certain level, your liver (and your kidneys and intestines) will inappropriately produce glucose and thus raise your blood sugar even while you’re fasting.
In all likelihood, you won’t be able to control this phenomenon by diet alone, particularly if you’re a type 1 diabetic or a type 2 making far too little insulin to offset your insulin resistance. For type 2s, appropriate weight loss and vigorous exercise may be most helpful in improving the sensitivity of the liver and muscles to whatever insulin remains. The most reliable treatments will involve medication, either certain oral agents or insulin. If you’re obese, however, large doses of insulin can make you more obese and more resistant to insulin. So a major goal should be to bring your weight into line.
As you know, I’m a type 1 diabetic. I may no longer make any insulin at all. If I decide to fast for 24 hours—eat absolutely nothing—I will need to inject 4 units of long-acting insulin in the morning to prevent gluconeogenesis for 18 hours. If I check my blood sugar every few hours, it will remain constant, confirming that the insulin is suppressing gluconeogenesis.
If, 18 hours after my first injection—and while still fasting—I inject another 4 units of insulin, common sense would maintain that this second dose should suppress gluconeogenesis overnight. In reality it doesn’t. I must set an alarm for 4 hours later and then insert another 4 units.
So I go to sleep and awaken 9–10 hours later. On arising, I check my blood sugar. Instead of being constant, as it was during my waking hours, it’s now 20–100 mg/dl higher than it was at bedtime.
If I were to try the same experiment a week later, I’d experience about the same overnight rise in blood sugar. Why?
Although the mechanics of the dawn phenomenon aren’t yet entirely clear, research suggests that the liver deactivates more circulating insulin during the early morning hours than at other times of the day. It doesn’t matter whether you made the insulin yourself or injected it; the liver has no preference. With inadequate circulating insulin to prevent gluconeogenesis, your blood sugars may be higher in the morning than they were at bedtime.* This isn’t a problem for a nondiabetic, because a body with fully functional pancreatic beta cells will just make more insulin.
Investigators have actually measured blood sugar every hour throughout the night. They have found that the entire blood sugar increase occurs about 8–10 hours after bedtime for most people who are so affected. That doesn’t mean, however, that you should sleep only 7 hours a night to try to avoid it. Both the time it takes for blood sugar to increase and the amount of the increase vary from one person to another. An increase may be negligible in some and profound in others. This is one of many reasons why any truly workable program for blood sugar normalization must be tailored to the individual.
Though it is more apparent in type 1 diabetics, many type 2 diabetics also show signs of the dawn phenomenon. As you will see, the treatments described in this book enable us to circumvent this blood sugar rise.
This condition has a chapter all its own (Chapter 22, “Delayed Stomach-Emptying”), and we will discuss it there in detail. However, it’s important to mention it in any list of factors that can lead to puzzling blood sugar readings.
Most people who’ve had long-standing diabetes develop some degree of damage to the nerves that govern the muscles of the stomach and intestines. Gastroparesis diabeticorum (the weak or paralyzed stomach of diabetics) is caused by many years of elevated blood sugars. If you’re a type 1, or a type 2 who isn’t making significant amounts of insulin, it can have unpredictable effects on blood sugar.
Like diabetes itself, gastroparesis can be mild to severe. In extreme cases, people may walk around for days with constipation, belching or vomiting, midchest burning, and bulging stomachs. Much more common, however, is mild gastroparesis in which physical symptoms are not apparent but blood sugars are erratic.
The big problems with gastroparesis arise if you’re taking insulin. If you take your insulin before a meal to prevent a subsequent rise in blood sugar but the meal remains in your stomach and glucose doesn’t enter the bloodstream as predicted, the insulin can take your blood sugar dangerously low. I know three individuals who experienced daily episodes of unconsciousness and seizures from time to time after meals for several years before I met them and diagnosed this condition.
There are, however, ways of greatly improving blood sugars in spite of the unpredictability of this condition, and these are discussed in Chapter 22.
For years, many physicians have been blaming emotional stress for the frequent unexplained blood sugar variations that many patients experience. This is an evasive and possibly self-serving diagnosis. It puts the responsibility for unexplained variations in blood sugar on the patient’s shoulders and leaves the physician with no obligation to examine the treatment regimen. Certainly there is no question that stress can have adverse effects upon your health. I have reviewed more than a million blood sugar entries from many patients, including myself. One common feature of all this data is that most prolonged emotional stress rarely has a direct effect upon blood sugar. This kind of stress can, however, have a secondary effect by precipitating overeating, binge eating, or indulgence in kinds of eating that will increase blood sugar.
I know many diabetics who’ve been involved in stressful marriages, divorces, loss of a business, slow death of a close relative, and the countless other sustained stresses of life we all must endure. These stresses have one thing in common: they aren’t sudden but usually last days, or even years. I have yet to see such a situation directly cause blood sugar to increase—or, for that matter, decrease. An important thing to remember during sustained periods of life when everything seems out of control is that at least you can control one thing: your blood sugar.
Many patients have reported sudden blood sugar spurts after brief episodes of severe stress. Examples have included an automobile accident without physical injury; speaking in front of a large audience; taking very important exams in school; and having arguments that nearly become violent. I am occasionally interviewed on television, and I always check—and, if necessary, adjust—my blood sugar immediately before and after such appearances. Until I eventually became accustomed to this, my blood sugar would inevitably increase 75–100 mg/dl, even though on the surface I might have appeared relaxed. As a rule of thumb, from personal experience and from observing my patients, I would say that if an acute event is stressful enough to start your epinephrine (adrenaline) flowing, as indicated by rapid heart rate and tremors, it is likely to raise your blood sugar. Epinephrine is one of the counterregulatory hormones that cause the liver to convert stored glycogen to glucose. This is part of what is often called the “fight or flight” response, your body’s attempt to provide you with enough extra energy either to overcome an enemy or run like heck to get away. Type 2 diabetics who make a lot of insulin are less likely to have their blood sugar reflect acute stress than are those who make little or none.
An occasional blood sugar increase after a very stressful event may well have been brought on by the event. On the other hand, unexplained blood sugar increases extending for days or weeks can rarely be properly attributed to stress. I know of no instances where prolonged emotional stress caused abnormal blood sugars in diabetic or nondiabetic individuals. Therefore, if you experience a prolonged unexplained change in your blood sugar levels after extended periods of normal blood sugars, it is wise to seek out a cause other than emotional stress.
If not treated with special dosing of insulin, type 1 and most type 2 diabetics with previously level, normal blood sugars may experience a blood sugar increase during surgery that is accompanied by general anesthesia.
There are at least five causes of insulin resistance—inheritance, dehydration, infection, obesity, and high blood sugars. Insulin’s ability to facilitate the transport of glucose from the blood into liver, muscle, fat, and other cells is impaired as blood sugar rises. This reduced effectiveness of insulin, known as insulin resistance, has been attributed to a phenomenon called postreceptor defects in glucose utilization. If, for example, 1 unit of injected or self-made insulin will usually lower blood sugar from 130 to 90 mg/dl, someone with insulin resistance caused by elevated blood sugars may require 3 units to lower it from 430 to 390 mg/dl.
Consider what might happen if I, a type 1 diabetic, am fasting and inject just enough long-acting insulin to keep my blood sugar at 90 mg/dl for 18 hours. If I eat 8 grams of glucose—enough to raise my blood sugar to 130 mg/dl—the chances are that, because of the elevated blood sugar, my blood sugar won’t just rise to 130 mg/dl and remain there. It will continue to rise slowly throughout the day, so that 12 hours after I consumed the glucose, my blood sugar might actually be 165 mg/dl. Insulin resistance, at least for type 1 diabetics, occurs as blood sugar increases, and so elevated blood sugar should be corrected as soon as it’s feasible. Delay will only permit it to rise higher. Because type 2s still produce some insulin, their bodies are more likely to eventually correct the blood sugar rise automatically.
We will discuss dehydration as a cause of insulin resistance in Chapter 21. Infections are discussed at the end of this chapter and also in Chapter 21.
Many years ago a patient asked me why her blood sugar went from 90 mg/dl up to 300 mg/dl every afternoon after she went swimming. I asked what she ate before the swim. “Nothing, just a freebie,” she replied. As it turned out, the “freebie” was lettuce. When I asked her just how much lettuce she was eating before her swims, she replied, “A head.”
A head of lettuce contains about 10 grams of carbohydrate, which can raise a type 1 adult’s blood sugar about 50 mg/dl at most. So what accounts for the other 160 mg/dl rise in her blood sugar?
The explanation lies in what I call the Chinese restaurant effect. Often Chinese restaurant meals contain large amounts of protein or slow-acting, low-carbohydrate foods, such as bean sprouts, bok choy, mushrooms, bamboo shoots, and water chestnuts, which can make you feel full.
How can these low-carbohydrate foods affect blood sugar so dramatically?
The upper part of the small intestine contains cells that release hormones into the bloodstream when they are stretched, as after a meal. These hormones signal the pancreas to produce some insulin to prevent the blood sugar rise that might otherwise follow the digestion of a meal. Large meals will cause greater stretching of the intestinal cells, which in turn will secrete proportionately larger amounts of these “incretin” hormones. Since a very small amount of insulin released by the pancreas can cause a large drop in blood sugar, the pancreas simultaneously produces the less potent hormone glucagon to offset the potential excess effect of the insulin. If you’re diabetic and deficient in producing insulin, you might not be able to release insulin, but you will still release glucagon, which will cause gluconeogenesis and glycogenolysis and thereby raise your blood sugar. Thus, if you eat enough to feel stuffed, your blood sugar can go up by a large amount, even if you eat something indigestible, such as sawdust. Even a small amount of an indigestible substance will cause a blood sugar increase in type 1 diabetics if not covered by an insulin injection.
Complicating matters further, pancreatic beta cells also make a hormone called amylin. Amylin inhibits the effectiveness of glucagon and works on the brain to cause satiety. It also slows stomach-emptying to discourage overeating. With few or no beta cells, diabetics don’t make enough amylin, and consequently they tend to remain hungry after eating and show an exaggerated Chinese restaurant effect. Since the first edition of this book, amylin substitutes have become available and have found an important use in the prevention of overeating (see here).
The first lesson here is: Don’t stuff yourself. The second lesson is: There’s no such thing as a freebie.* Any solid food that you eat can raise your blood sugar.† If you can’t control your overeating, see here.
Exercise can have varying effects upon blood sugar, depending upon a number of variables, including the type of exercise, how vigorously it’s performed, when it is performed, and what type of medication you are using, if any. These effects are too varied and numerous to discuss in this brief space. Please see Chapter 14, “Using Exercise to Enhance Insulin Sensitivity and Slow Aging,” if you are embarking on an exercise program or find your blood sugars unpredictably affected by your existing exercise program.
At the time they are diagnosed, type 1 diabetics usually have experienced very high blood sugars that cause a host of unpleasant symptoms, such as weight loss, frequent urination, and severe thirst. These symptoms subside soon after treatment with injected insulin begins. After a few weeks of insulin therapy, many patients experience a dramatic reduction of insulin requirements, almost as if the diabetes were reversing. Blood sugars may become nearly normal, even with discontinuation of insulin injections. This benign “honeymoon period” may last weeks, months, or even as long as a year. If the medical treatment is conventional, the honeymoon period eventually terminates and the well-known roller coaster of blood sugar swings ensues.
Why doesn’t the honeymoon period last forever? My experience with patients indicates that it can, with proper treatment. But there are several likely reasons why it does not with conventional treatment. At this writing, however, they still remain speculative.
The normal human pancreas contains many more insulin-producing beta cells than are necessary for maintaining normal blood sugars. For blood sugar to increase abnormally, at least 80 percent of the beta cells must have been destroyed. In early type 1 diabetes, many of the remaining 20 percent have been weakened by glucose toxicity from constant high blood sugars and by beta cell overwork. These beta cells can recover if they are given a rest with the help of injected insulin. Even if they recover, however, they still must work at least five times as hard to match the job of a normal pancreas working at 100 percent capacity. Eventually, with conventional treatment, this overwork helps cause them to burn out.
It is now believed that high blood glucose levels are toxic to beta cells. Even a brief blood sugar increase after a high-carbohydrate meal may take a small toll. Over time, the cumulative effect may wipe them out completely.
The autoimmune attack upon beta cells, the presumed cause of type 1 diabetes, is focused upon several proteins. One is insulin, and another is GADA, present on the special vesicles—or bubbles—that are formed at the outer membrane of the beta cell. These vesicles contain insulin granules. Normally, they burst at the surface of the cell, releasing insulin granules into the bloodstream. The more vesicles created when more insulin is manufactured, the greater the autoimmune attack upon the beta cell. If less insulin is released, less GADA is exposed to attack.
Based upon my experience with the fair number of type 1 diabetics I’ve treated from the time of diagnosis, I’m convinced that the honeymoon period can be prolonged indefinitely. The trick is to assist the pancreas and keep it as quiescent as possible. With the meticulous use of small doses of injected insulin and with the essential use of a very low carbohydrate diet, the remaining capacity of the pancreas, I believe, can be preserved.
Low serum free testosterone levels can cause insulin resistance in men, and elevated levels can cause insulin resistance in women. Since the situation for women is discussed in Appendix E, “Polycystic Ovarian Syndrome,” here we will cover only low testosterone in men.
The clues that remind me to test men for low free serum testosterone are:
Excessive breast tissue
Abdominal obesity without overeating
A need to inject large doses of insulin (typically more than 65 units per day) in order to normalize blood sugar
These three clues need not all appear—any one of them is good reason to perform a blood test.
When serum free testosterone is below the lower fifth of the normal range, I prescribe self-injection of testosterone cipionate (200 mg/ml) once or twice per week. We then periodically retest on a day midway between two injections and repeat testing until the level is in the middle of the normal range. I usually start with injections of 0.2 ml in a “tuberculin” syringe or 20 units in a long-needle insulin syringe.
I don’t prescribe testosterone gel or skin patches because most men find them to be irritating or difficult to remember to use. They would rather inject once or twice weekly.
With testosterone use, I usually see about a one-third drop in insulin requirement and more rapid weight loss.
Another kind of stress to which your body can become subject—and which can muddy and in some instances wreak havoc on your best efforts to control blood sugars—is infection. I have saved this category of stress for last not because it is the least important, but because, when present, it can be the most important.
A kidney infection, for example, can triple insulin requirements overnight. When blood sugar rises unexpectedly after weeks of normal values, it is wise to suspect infection. I have noted that my own blood sugars rise 24 hours before the onset of a sore throat or cold. Everyone in my family takes Sambucus lozenges (made from an extract of the black elderberry tree) at the first sign of a cold, and I highly recommend it. You can purchase them by mail order from Rosedale Pharmacy, (888) 796-3348; from www.rx4betterhealth.com; or at most health food stores.
Quite often, dental infections won’t be obvious, but high blood sugars cause dental infections, and in the typical vicious circle of diabetes, these infections can cause very high blood sugars. You cannot easily control blood sugars under these circumstances. I have seldom met a long-standing diabetic over age forty (with a history of uncontrolled blood sugars) who had all his teeth.
Frequent dental infections can be a sign of diabetes for those who have not already been diagnosed. I have had many patients who have undergone multiple root canals or gum treatments prior to the diagnosis of diabetes.
If your insulin* “isn’t working”—that is, your normal dose isn’t acting as you think it should be—and you have determined that your insulin isn’t contaminated (for example, by reusing syringes) or expired, the first place to look is in your mouth.
First, look at your gums to see if there’s any sign of infection—e.g., redness, swelling, tenderness to pressure. Put some water with crushed ice in your mouth for 30 seconds. If a tooth hurts, you should suspect an infection.
Get an emergency appointment with your dentist immediately. He can determine if you have a superficial infection, and can X-ray where your teeth are sensitive, but he should refer you to an endodontist (a dentist who deals with root canals and the jawbone) or a periodontist (who treats infected gums). This kind of infection is extremely common in diabetics and should be addressed as rapidly as possible in order to allow you to bring your blood sugars under control. We will discuss this subject further in Chapter 21.
As you know by now, type 2 diabetes involves two metabolic defects—insulin resistance and inadequate insulin production to overcome this resistance. Although insulin resistance can occur at many sites along the pathways involved in glucose metabolism, there appears to be a common factor causing defects at a variety of sites—inflammation. Inflammation results from the response of the immune system to intrusions such as infection. When a wound becomes infected, the pain, swelling, redness, warmth, and production of pus or fluids are all part of the immune response that aims to destroy the intruding organisms. Other causes of inflammation that can generate insulin resistance include mesenteric fat that covers the intestines (abdominal obesity), autoimmune disorders such as systemic lupus erythematosus, juvenile rheumatoid arthritis, and celiac disease. It is likely that even unlucky genetic inheritance can cause other, unknown inflammatory disorders.
I’ve had several diabetic patients who also had lupus. Their lupus often became more severe in warm weather and at night. These were the times when their blood sugars would also dramatically increase.
Sometimes, but certainly not always, markers of inflammation will show up when testing the blood. Such tests include serum beta2 microglobulin, C-reactive protein, ferritin, complement C3, erythrocyte sedimentation rate, tumor necrosis factor alpha, and serum fibrinogen activity. When one or more of these tests are positive, further workup by an immunologist may be warranted.
I have seen reports of many studies where anti-inflammatory antioxidants have supposedly been successfully used to reduce insulin resistance, but I have never observed this firsthand. I do not object to experimentation, but I also do not expect dramatic results. Some of the treatments discussed include green tea and green tea extract, R-alpha lipoic acid (R-ALA), and sources of omega-3 fatty acids such as fish oil, flaxseed, and perilla oil.
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