Think Like a Pancreas

by Gary Scheiner

  Cut to the chase: Those who are extremely obese but otherwise healthy can certainly benefit from the insulin-sensitizing effects of TZDs. The possibility of developing heart complications from TZD use has discouraged many people. And the fact remains that you can gain the same benefits TZDs offer simply by exercising and losing weight.

  4. Digestion blockers (mostly for type 2s, rarely for type 1s)

  Before being absorbed into the bloodstream, carbohydrates must be broken down into simple sugar molecules by enzymes in the small intestine. One of the enzymes involved in breaking down carbohydrates is called alpha glucosidase. By inhibiting this enzyme, carbohydrates are not broken down as efficiently and glucose absorption is delayed. When taken with meals, alpha-glucosidase inhibitors (acarbose and miglitol) tend to improve after-meal blood sugar control. However, because of the way they work, up to 75 percent of users experience abdominal pain, diarrhea, and gas.

  Cut to the chase: Acarbose and miglitol may provide some help for those who experience blood sugar spikes after carbohydrate-rich meals. And because they don’t cause hypoglycemia and may diminish between-meal appetite, they could aid those trying to lose weight. However, the side effects are more than most people are willing to endure.

  5. Pancreas helper (mostly for type 2s, rarely for type 1s)

  The newest of the diabetes medications, DPP-4 inhibitors (sitagliptin, saxagliptin), work by blocking an enzyme that breaks down a substance called GLP-1 (glucagon-like peptide 1). By increasing the amount of GLP-1 in circulation, DPP-4 inhibitors

  •make it easier for the pancreas to release its stored-up insulin when blood sugar is elevated,

  •decrease glucagon secretion from the pancreas,

  •promote the growth and duplication of cells in the pancreas that produce insulin,

  •slow the movement of food from the stomach into the intestines, and

  •decrease appetite.

  Sitagliptin and saxagliptin can be used in combination with other diabetes medications, but those with poor kidney function must use them very carefully. Although they have been proven effective for improving blood sugar levels without causing hypoglycemia, they have not been shown to reduce weight.

  Cut to the chase: DPP-4 inhibitors offer multiple ways to improve glucose control with minimal side effects. They are the only oral diabetes medications that promote the growth and function of insulin-producing cells in the pancreas—a key to overcoming insulin resistance and managing blood sugar in type 2 diabetes.

  Injectable Treatments for Diabetes

  Until just five years ago the only injectable treatment for diabetes was insulin. Now we have three other injectables, with more on the way. Why the sudden upswing? As scientists learn more about how the human body actually regulates blood sugar levels, new and innovative treatments are unfolding before our very eyes.

  1. Exenatide and liraglutide (mostly for type 2s, rarely for type 1s)

  As mentioned earlier in our discussion of DPP-4 inhibitors, GLP-1 is a very important molecule in blood sugar regulation. Whenever we eat food that contains carbohydrates (sugar or starch), some of the sugar comes in contact with the inner lining of the small intestine. When this happens, cells of the intestine secrete special chemical messengers. One of these chemical messengers, glucagon-like peptide-1, or GLP-1 for short, helps the pancreas to release a rapid burst of insulin, decreases other hormones that raise blood sugar levels, slows digestion, and decreases appetite. Unlike insulin taken by injection or certain oral medications, GLP-1 does not promote low blood sugar or weight gain. Insulin secretion increases only when blood sugars are high and decreases as blood sugars approach normal.

  Unlike DPP-IV inhibitors, which increase the amount of GLP-1 indirectly, exenatide and liraglutide, for all practical purposes, are GLP-1, except that they last much longer in the body than naturally occurring GLP-1. Currently, liraglutide (brand name Victoza) is a once-daily injectable, and exenatide (brand name Byetta) is taken twice daily, both via prefilled pens. Plans are under way to develop a form of exenatide that needs to be taken only once a week.

  Pens for injecting Victoza and Byetta

  Because they require a functioning pancreas to work correctly, exenatide and liraglutide are intended mainly for people with type 2 diabetes. However, new research has shown that type 1s can benefit as well. Varying degrees of nausea are common during the first few weeks of usage, but this usually subsides over time. Those with gastrointestinal problems or kidney disease are usually not good candidates for either medication.

  Cut to the chase: Despite having to be taken by injection and the short-term nausea that many users experience, exenatide and liraglutide have the potential to offset many of the factors that contribute to elevated blood sugar in type 2 diabetes. No other diabetes medication matches their ability to facilitate weight loss.

  2. Pramlintide (for type 1s and type 2s who take mealtime insulin)

  As mentioned previously, amylin is a hormone that the beta cells of the pancreas normally secretes along with insulin. People with type 1 diabetes secrete no amylin. Those with type 2 usually secrete insufficient amounts.

  Pens for injecting Symlin

  Classified as an “incretin” hormone because it affects the production of other hormones, amylin acts on the central nervous system to

  •slow the emptying of the stomach’s contents into the small intestine, where it is then absorbed into the bloodstream;

  •blunt the secretion of glucagon by the pancreas (ironically, people with type 1 diabetes secrete extra glucagon right after meals); and

  •decrease appetite.

  By slowing digestion, reducing food intake, and minimizing glucagon production at mealtimes, amylin minimizes the blood glucose rise that occurs after meals. Postprandial spikes, as these are called, can influence one’s energy level, intellect, emotions, and physical abilities. There is also growing evidence that spikes can raise the HbA1c and contribute to the development of long-term complications.

  Pramlintide (brand name Symlin), the medication equivalent of the amylin hormone, is taken by injection via prefilled pen in fixed doses before meals. Due to its acidity, in its current form pramlintide cannot be mixed with insulin, and its effects only last a few hours. R&D specialists are working to develop a form of pramlintide that can be premixed with insulin, so someday the extra injections may not be necessary.

  Besides aiding with postmeal blood sugar control, pramlintide can also be a valuable weight-loss tool. Users of pramlintide lose an average of six and a half pounds (three kilograms) over the first six months of use, mainly by consuming smaller portions at meals and snacking less often.

  Pramlintide is intended for people who take insulin at mealtimes. Although not yet approved by the FDA for use by children, several studies have shown that pramlintide is safe and effective when adolescents use it in a supervised manner.

  The most common side effect of pramlintide is nausea, typically twenty to forty minutes after injection. This usually dissipates entirely after a few weeks as the body becomes re-accustomed to having the amylin hormone present. Use of pramlintide has also been associated with an increased risk of hypoglycemia. Because digestion of carbohydrates is delayed when pramlintide is taken, insulin doses may need to be reduced and/or delayed as well.

  Cut to the chase: Use of pramlintide certainly adds work and complexity to diabetes care, and the early side effects can be a detriment. However, postprandial (after-meal) glucose control continues to be a major challenge for most people who take mealtime insulin, and pramlintide has the potential to resolve this issue. And given that many people with type 1 and type 2 diabetes have difficulty controlling their appetite, adding pramlintide to one’s treatment has obvious benefits in terms of lifestyle and weight control.

  Factor 3: Food

  Whoever said that there is no such thing as a free lunch really knew what they were talking about. Almost everything we eat or drink can cause blood sugar levels to rise.
/>   The three major nutrients found in food are protein, fat, and carbohydrate. Protein’s effect on blood sugar is minimal. One exception is when very little carbohydrate is consumed. Without dietary carbohydrate to provide glucose for meeting the body’s energy needs, the liver begins to convert some dietary protein to glucose. For example, if you wake up to a breakfast of nothing but eggs and sausage, you may see a noticeable glucose rise a few hours later even though there was virtually no carbohydrate in the meal. However, when carbohydrate is present in a meal or snack, protein has little to no effect on the blood sugar.

  Likewise, dietary fat’s impact on blood sugar is usually of little significance. However, consumption of large amounts of fat can cause two distinct effects. First, it may slow the digestion of the carbohydrates that were consumed along with the fat, resulting in a slower, more gradual postmeal glucose rise. Second, large amounts of dietary fat, particularly saturated fat, can produce their own delayed rise in the blood sugar level several hours later. Here’s how:

  Step 1. You eat a high-fat meal or snack (this is the fun part).

  Step 2. In a few hours the fat begins to digest; this continues for several more hours.

  Step 3. The level of triglycerides in the bloodstream rises.

  Step 4. High triglycerides in the bloodstream cause the liver to become resistant to insulin.

  Step 5. When the liver is not responding well to insulin, it secretes more glucose than usual into the bloodstream.

  Step 6. The blood glucose rises steadily as the liver’s glucose output goes up.

  For example, when having a heavy dinner at a restaurant, the carbohydrates may take a few hours to kick in due to fat slowing the digestion. Then, after you’ve gone to sleep the blood sugar may rise again through the night as the liver begins secreting more glucose than usual. But once again, these occurrences are reserved for situations when large quantities of fat are consumed. Small amounts of fat usually have no noticeable effect on the blood sugar.

  Large amounts of fat in a meal or snack may slow the digestion of carbohydrate and produce a secondary blood sugar rise after the carbohydrates have finished exerting their effects.

  Carbohydrates are the nutrients that have the major effect on blood sugar levels. Carbohydrates (or carbs, for short) include simple sugars like glucose, sucrose (table sugar), fructose (fruit sugar), and lactose (milk sugar) as well as complex carbohydrates, better known as starches. Think of simple sugars as individual railroad cars, and starch as a whole bunch of cars linked together to make a train. Most starches are composed of many glucose molecules linked together.

  Now here’s the statement that has most people running to call their aunt who claims to know everything about everything. From the standpoint of blood sugar control, whether the carbohydrates you eat are in the form of sugars or starches doesn’t matter. Both will raise the blood sugar by the same amount. A cup of rice containing forty-five grams of complex carbohydrate (starch) will raise the blood sugar just as much as a can of regular (nondiet) soda that contains forty-five grams of simple carbohydrate (sugar). And both will do it pretty fast.

  You see, when you eat something that contains starch, the individual sugar molecules become unhooked from each other. This process takes place quickly, beginning the moment food comes in contact with saliva in the mouth. The individual sugar molecules start reaching the bloodstream within minutes—as soon as they pass through the stomach and reach the small intestine.

  Table 3-4. Simple vs. complex carbohydrates

  Foods rich in sugar

  (simple carbohydrates) Foods rich in starch

  (complex carbohydrates)

  fruit potatoes

  fruit juice rice

  raisins/dried fruit noodles/pasta

  regular soda cereal

  sports drinks oatmeal

  candy bread

  chocolate crackers

  cookies and cakes bagels

  pies and pastries pizza

  muffins tortillas

  milk pancakes

  ice cream waffles

  yogurt beans

  sport drinks peas

  table sugar corn

  honey pretzels

  syrup chips

  jelly popcorn

  beer matzah

  Also be aware that some “sugar-free” products can raise blood sugar. Having spent my first three years after college working in advertising, I can tell you that marketing people will do just about anything to get you to buy their products—even if that means bending the truth a little. “Sugar-free” can be put on a food label if the food does not contain sucrose (table sugar). However, a sugar-free food can contain complex carbohydrates, fructose (fruit sugar), and a variety of “sugar substitutes” such as sorbitol, xylitol, mannitol, lactitol, isomalt, and maltodextrin—all of which raise the blood sugar, albeit more slowly and to a lesser degree than ordinary carbohydrates do.

  There are only a few artificial sweeteners that have no significant effect on blood sugar levels. These include saccharin, acesulfame K, sucralose, and aspartame. But once again, be careful. Products that contain these artificial sweeteners may also contain sugar substitutes or other carbohydrates that will raise your blood sugar level. The bottom line is that you should always read the label and make getting good at counting the grams of carbohydrate in your meals and snacks a priority.

  We’ll talk more about carb counting in the next chapter.

  Factor 4: Physical Activity

  Physical activity is a potent tool for lowering blood sugar. It does this by burning large amounts of glucose and improving the way insulin works, a process known as “insulin sensitization.”

  Think again about our door-and-lock analogy. Insulin is the key that opens up your cells, allowing sugar to ramble inside and get burned for energy. When you’ve been lying around like a sloth, your muscle cells aren’t burning a lot of energy, so they only have a few doors available to open.

  Now imagine that you temporarily lose your senses and decide to do your own gardening and landscaping work instead of paying a professional to do it. You. Yourself. With no real outdoor skills whatsoever (okay, I’m speaking from experience). All of a sudden, your muscle cells need lots more energy. As you begin accidentally mowing over the flowers that your wife painstakingly planted in the spring, the few doors that exist on your muscle cells don’t allow the sugar to get in fast enough. The solution, as you might have guessed, is for your body’s cells to make more doors and “grease the hinges.” And that’s just what happens.

  Suddenly, those insulin keys find that opening the doors and shuttling sugar out of the bloodstream and into your cells is much easier, which gives you the energy to clean up the huge mess you created in the yard.

  Unfortunately, nothing lasts forever. The extra doors your body’s cells built are only temporary. After being sedentary for a day or more, the doors get taken down and you return to the way things were before your activity level increased. In fact, extended periods of inactivity can reduce your sensitivity to insulin, resulting in a state of insulin resistance. This, as you may have guessed, is a major characteristic of type 2 diabetes, but it can happen to people with type 1 as well.

  As for burning glucose, the body burns almost exclusively sugar during the early phases of any form of exercise, and it continues to burn sugar throughout. Depending on your size and the nature of your physical activity, you might burn upward of 100 grams of glucose per hour! Below, in Table 3-5, is a general estimate of the amount of sugar utilized when you exercise:

  Table 3-5. Glucose burned per sixty minutes of physical activity

  But what’s that? You’ve heard that blood sugar can go up during exercise? True, it can. But the physical activity is not what causes it. Physical activity always burns sugar and improves insulin sensitivity; maybe something else is going on at the same time, something we call a “stress response.” This can take place during competitive activities, very high-intensity/short-duration exercises, judged
performances, and sports that involve quick bursts of movement. To learn more about the stress response, see Factor 5 below.

  Factor 5: Stress Hormones

  Last weekend I decided to stay up late and watch a scary movie. It had something to do with super-gross vampires who get their jollies by eating the flesh of unsuspecting hotel guests. Anyway, after the final gutwrenching, heart-pumping scene, I decided to check my blood sugar. And I’ll be darned—it had risen about 200 mg/dl (11 mmol/l) during the movie. With blood that sweet, I felt like the grand prize for any vampires that might happen to be lurking in my neighborhood.

  Earlier, I mentioned that the liver serves as a storehouse for glucose, keeping it in a concentrated form called glycogen. The liver breaks down small amounts of glycogen all the time, releasing glucose into the bloodstream to nourish the brain, nerves, heart, and other alwaysactive organs.

  The liver’s release of glucose depends largely on the presence of certain hormones. Of all the hormones in the body, only insulin causes the liver to take sugar out of the bloodstream and store it in the form of glycogen. All the other hormones—including stress hormones, sex hormones, growth hormones, and glucagon—cause the liver to secrete glucose back into the bloodstream (see Figure 3-1 below).

  Cortisol and growth hormone are produced in a twenty-four-hour cycle and are responsible for the blood sugar rise that we sometimes see during the night or in the early morning. The other stress hormones, particularly epinephrine (adrenaline), are produced when our body needs a rapid influx of sugar for energy purposes. The glucose rise I experienced during the scary movie was no doubt the work of stress hormones.