9.5: Maintaining Blood-Glucose

The body constantly uses glucose. The brain continuously needs a lot of ATP energy, but—unlike other organs—can’t use fatty acids as fuel. Glucose is the only fuel that the brain can use under normal circumstances. The blood transports the needed glucose to the brain.

How do we keep enough glucose in the blood if we don’t consume any carbohydrates and our glycogen stores are used up, as during starvation or while on a low-carbohydrate diet? The answer is that glucose can be made from some amino acids (Figure 9.4).* Glucose can be made from pyruvate, but not from acetate (Figure 9.4). Since fatty acids are broken down only to acetate, glucose can’t be made from fatty acids.

Figure 9.4: Glucose and Ketone Production in Starvation and Carbohydrate-free Diets

^{*Some amino acids (those made into pyruvate) can be made into glucose, whereas others (those made into acetate) cannot. Vitamin B₆ is a part of a coenzyme used in reactions that convert amino acids to pyruvate or acetate. In the trucks-carrying-lumber analogy, the lumber is aminos (NH₂).}

Low-Carb Diets/Starvation

Carbohydrate makes up the bulk of most diets throughout the world, and is the usual source of glucose. When a person isn’t consuming carbohydrate for whatever reason, glycogen—our storage form of glucose—is soon gone, giving the body no choice but to use amino acids from protein to make the needed glucose. Throughout history, the usual reason why people aren’t consuming carbohydrate is that there’s no food—they’re starving.

During starvation, the body first breaks down the proteins least essential for survival (e.g., some proteins in liver and skeletal muscle) and, as a last resort, starts breaking down proteins in the heart muscle, etc. Obviously, starvation would be rapidly fatal if the body had to incessantly break down its protein to provide the brain with glucose.

At the start of starvation, anyway, most people have stores of body fat. If the brain could in some way use fatty acids as fuel, it would slow the breakdown of body protein and lengthen survival. The body does, in fact, make an alternate fuel from fatty acids, using the scarcity of glucose as a signal of starvation.

When glucose is scarce, aerobic metabolism is sluggish, and acetate accumulates, like cars jamming up behind a stalled car. This unusual accumulation of acetate causes them to combine to form ketones (Figure 9.4). The brain uses the ketones as fuel in increasing amounts during starvation, lessening its need for glucose and slowing the breakdown of body protein. Of course, once the body’s fat stores are used up, body protein is used unremittingly as fuel, and death is imminent.

Low-carb diets show up regularly in the steady stream of popular weight-loss diets. They’re popular because they promote fast weight loss—lots of water is lost. Glycogen is depleted, and protein is broken down to provide amino acids for glucose production. Glycogen and protein hold about 3 times their weight in water, whereas fat doesn’t hold any (Chap. 5). When the dieter goes back to a normal diet, the body rapidly restores the lost glycogen, protein, water—and weight, much to the dieter’s dismay.

Dieters also like low-carb diets because the ketones cause a loss of appetite,* and some of the ketones are lost in urine and breath. Ketones have caloric value, and this “easy loss of calories” is touted in popular books promoting these diets. But this loss usually amounts to less than 60 calories a day.

Keep in mind that ketone production is basically an emergency response to starvation, in which case the benefit far outweighs risk. A risk of ketone production is that ketones are acidic, and excessive amounts can cause a condition called ketosis or acidosis. This lowers the pH of blood and tissue fluid, which can be life-threatening (Chap. 3). About 50 grams (200 calories worth) of carbohydrate a day prevents ketosis.

^{*This is a blessing for the starving—it eases the pain of hunger in a famine. But sometimes the ketones cause nausea.}

Blood-Glucose

Glucose in the blood (blood-glucose) is kept within a normal range by the action of two hormones made in the pancreas: insulin and glucagon. After ingesting carbohydrate, blood-glucose rises, and insulin is secreted in response. Insulin lowers blood-glucose by promoting the entry of glucose into cells and the production of glycogen. When one hasn’t eaten for a few hours, blood-glucose falls, and glucagon is secreted in response. Glucagon triggers the breakdown of liver glycogen to glucose, which is then released into the blood.

Although glycogen is stored in both liver and muscle, liver glycogen is used to maintain blood-glucose levels, whereas muscle glycogen is used locally to provide glucose to fuel muscle activity

Diabetes

Diabetes is characterized by an abnormally high blood-glucose that “spills over” into the urine (glucose isn’t normally in urine). Glucose brings water with it, so lots of water is also lost through the urine. Often, the first sign of diabetes is increased urination and thirst.

About 15% of adults in the U.S. has diabetes. One of the most severe effects is damage to blood vessels. Since blood vessels deliver blood throughout the body, the consequences depend on which vessels are affected and how severely. Diabetics have a much higher risk of stroke, and heart, eye, and kidney diseases. Sometimes, a foot or toe has to be amputated when tissue there dies from poor circulation, infection, gangrene, etc.

How fast diabetes progresses varies. Some diabetics develop severe symptoms fast, whereas others have only mild and non-progressing disease. In the U.S., diabetes is the leading cause of blindness, kidney failure, and amputations in the lower leg.

Type 1 and type 2 diabetes are the most common kinds.* In type 1 diabetes, there’s a shortage or complete lack of insulin due to destruction of the pancreatic cells that make insulin. It’s an autoimmune disease, in which the body mistakenly sees a normal part of the body (in this case, the pancreatic cells that make insulin) as foreign, and destroys it.

Type 1 diabetes isn’t related to obesity. It occurs most commonly among children and young adults. Effective treatment came with the discovery of insulin and its use as a drug.† Before then, type-1 diabetes was quite rapidly fatal. Progress is being made in prevention, by early screening for the autoantibodies, and treatment to prevent or delay destruction of the insulin-making cells.

Glucose can’t enter cells without insulin. Without insulin, the cells lack glucose, in spite of large amounts in the blood. The cells make ketones in response to this lack of glucose. In severe, untreated, insulin-dependent diabetes, this persistent ketone production can lead to fatal acidosis (high acidity of blood and tissue fluids).

About 90-95% of diabetics have type 2 diabetes. Most are overweight. But not all overweight people develop this disease, since a genetic susceptibility is involved. The diabetes usually occurs after age 40, and is characterized by a resistance to insulin action. This means that the cells can’t adequately take in glucose from the blood, despite plenty of insulin.

Asians, especially South Asians, have a higher risk of type-2 diabetes at a similar body weight as Caucasians. One reason seems to be that Asians have more abdominal fat at a given body weight.

A cornerstone in prevention and treatment is a healthy diet and regular exercise to prevent obesity, or if already overweight, to lose weight or not gain any more. Regular exercise, not only helps maintain a healthy weight, but increases a cell’s responsiveness to insulin. There are also various drugs that help. Treatment focuses on maintaining normal blood pressure and normal blood levels of glucose and fat.

As expected, type 2 diabetes is common in the U.S., where obesity is common. Obesity brings out a genetic susceptibility to diabetes, just as alcohol consumption can bring out a genetic susceptibility to alcoholism, or a high-salt diet can bring out a genetic tendency to salt-sensitive high blood pressure. Interaction of environment and genetics is a common theme in disease.

This “expression of certain genes” applies to many other situations as well, e.g., people who are genetically endowed with Olympic-caliber endurance (muscles of mostly red fibers, etc.) may not know it because their endurance has never been put to test. Likewise, inherently superior musical ability, computer skills, etc., may go unrealized.

^{*There’s also gestational diabetes, which occurs in about 3-5% of pregnancies, and is usually controlled by diet. It usually goes away after delivery, but the woman has a higher risk of developing type 2 diabetes later.
†For this 1921 discovery, Frederick Banting and John MacLeod won a 1923 Nobel Prize. In 1922, 14-year-old Leonard Thompson became the first diabetic to be treated with insulin injections.}

Hypoglycemia (Low Blood Sugar)

The problem of too much or too little is a familiar theme. Hypoglycemia is a condition of abnormally low blood glucose—hypo(low) glyc(glucose) emia(in the blood)—combined with symptoms that are relieved by sugar. Symptoms range from mild (e.g., dizziness, nervousness, hunger) to severe (e.g., convulsions, coma).

Although severe hypoglycemia can result from excess insulin made by a pancreatic tumor, the most common cause is excess insulin taken by a diabetic. An insulin overdose can lower blood glucose to the point of fainting or coma (the brain is dependent on glucose from the blood).

A diabetic can also lose consciousness from a lack of insulin. If a diabetic feels dizzy or weak and the cause isn’t known, sugar (e.g., fruit juice, candy) will help if the problem is low blood-glucose. If the cause is a lack of insulin, the blood sugar will already be high, and a bit more won’t make much difference.

For those who don’t have diabetes, the most common cause of hypoglycemia is a burst of insulin in response to ingesting a lot of carbohydrate on an empty stomach (reactive hypoglycemia). The symptoms are fairly mild and occur 2 to 4 hours after eating.*

The advice is to ingest smaller “doses” of carbohydrate (an apple rather than a candy bar) in more frequent and well-­spaced intervals (regularly spaced meals and snacks vs, skipping breakfast and then grabbing a sweet-roll in late morning). All cases of hypoglycemia should be checked by a physician, to rule out more serious causes.

Many people decide on their own that they have hypoglycemia when they actually don’t. This is because symptoms are vague, and a diagnosis of “hypoglycemia” is promoted by some misguided health-practitioners and some best-selling diet-and-health books. A common and effective tactic in selling is to create a “non-disease” and then sell its cure in the form of books, nostrums, etc. Many who do this are truly sincere. But sincerity doesn’t make up for a lack of supporting scientific evidence.

^{*More severe reactive hypoglycemia sometimes occurs in athletes during an athletic event, from a combination of carbohydrate-loading just before an event and the rapid use of glucose during the event.}