Shock to the System
- Mark Schapiro
- Posted March 11, 2013
I'm told it was the beginning of a lovely New England day, that morning some years ago when I woke up in a hospital bed. There was an odd, terrifying sensation of not really being there; the sinking realization that I was, truly, there. The news, wafting in from some far-off doctor, was that I had experienced a seizure and broken both shoulders. I recall thinking foggily that this explanation fit with the location of the jagged pain, as if a javelin had been thrown at my chest.
The real cause of this extraordinary circumstance was diabetes, a disease in which blood sugar levels run abnormally high. In the 24 years since I developed diabetes at age 19, I had taken daily injections of insulin to keep my blood sugar levels steady and maintain a normal metabolism. But when I had the seizure, it seems, a hectic lifestyle had caught up with me, throwing off this chemically imposed equilibrium.
Two days before the accident, I had flown in from Paris, my home at the time, to attend the wedding of a close friend on Fishers Island, off the coast of Connecticut. Despite my jet-lagged state, I plunged into the celebration, drinking, dancing, and even jogging on an empty stomach -- activities that can significantly lower blood sugar. Then early Sunday morning as I slept, my blood sugar plummeted, causing a violent convulsion that ripped one shoulder out of its socket and sent me tumbling out of bed to smash the other on the floor. The time bomb that ticks inside every insulin-dependent diabetic had gone off.
A friend found me and called the emergency medical service. Within minutes, a team arrived and rushed me in a speedboat to a hospital on the mainland. Later, a doctor provided the news that if had spent another hour in that unconscious state I might have been permanently brain-damaged. It was all pretty sobering.
Confined to a hospital bed for two weeks, my arms bound in slings, I had plenty of time to reflect on the forces that had brought me there. And during the subsequent months of recuperation and the year of physical therapy to regain the use of my shoulders, it was impossible not to consider how to avoid such a state in the future. It certainly seemed imperative to discover what I perhaps did not want to know: what this disease is all about and how to wrestle with its destructive potential -- a power that can land a diabetic in bed with broken bones, or lead to far more serious complications, even death.
A clever foe
I have what is known as type 1 diabetes, a genetically linked disease that usually arises in the first 20 years of life. The doctor's diagnosis hit like a hurricane during the summer after freshman year in college. An aunt who had served in the medical corps during World War II first recognized the symptoms: lethargy, dehydration, and excessive urination. She also was aware of the genetic legacy of my grandfather's diabetes.
If I didn't have the disease, I could be fascinated by its complexity, as are many of the physicians who study it. "Heart disease is a one-organ disease," says Donald Simonson, an associate professor at Harvard Medical School and former head of clinical research at the Joslin Diabetes Center in Boston. "But diabetes affects everything -- biochemistry, physiology -- everything."
People with type 1 diabetes are unable to manufacture insulin, a hormone that regulates the metabolism of glucose, the essential fuel for every living cell. This condition is distinguished from type 2 diabetes, in which insulin production is impaired but the body can still eke out enough of hormone to sustain life.
Under normal circumstances, insulin functions like an internal messenger. The body's supply of glucose (sugar) for energy comes from the breakdown of food we eat, as well as a separate manufacturing process in the liver. When this sugar reaches sufficient levels in the bloodstream, two things happen: First, certain cells in the pancreas, known as beta cells, produce and release insulin into the bloodstream. Then the insulin signals the cells to absorb sugar from the blood and be converted to energy; at the same time, it sends messages to the liver to stop making extra glucose.
Type 1 diabetes blocks this signaling process by destroying the beta cells and, thus, insulin production. Without insulin, the glucose from food stays in the bloodstream, unable to enter the cells and give the body energy - meaning that your body will starve even as you're eating. Meanwhile, the liver continues to pump out glucose because it doesn't receive a clear signal to stop. Both actions contribute to high levels of sugar in the blood.
"The glucose can't get into the cells to give the body energy," says Simonson. "It is an extremely wasteful state."
Since the body needs glucose to live, this wasteful state has serious consequences. In the absence of insulin, glucose-starved cells break down fat and muscle in a desperate attempt for fuel. The body becomes dehydrated as the kidneys work overtime to flush out excess sugar from the blood. And fat metabolism releases toxins called ketones, which can poison the system and lead to coma and death.
Before the discovery of a usable injectable form of insulin in the 1920's, people with type 1 diabetes died from the disease, either through starvation or a poisonous buildup of ketones known as ketoacidosis. Since that time, type 1 diabetics have been able to restrain this metabolic turmoil by injecting themselves regularly with insulin. But this life-giving substance demands its side of the bargain. If you don't have diabetes, the insulin your body makes is automatically timed and adjusted to the amount of food you've eaten. But diabetics must calculate how much food to eat -- and when -- with each insulin dose, or blood sugar will drop too low, producing a state known as hypoglycemia.
Spend enough time with a diabetic and you'll no doubt see him or her get edgy -- a sign that glucose levels are falling. Eating usually solves the problem. "I have to feed the machine," I find myself quipping to friends when I feel shaky. But if sugar continues to decrease, the brain is denied fuel, which can lead to loss of consciousness -- the scenario that unfolded that morning in New England.
Despite insulin's ability to prevent immediate damage, the drug can't always prevent long-term complications. Within about 15 to 30 years, most people with diabetes develop a weakening of the small blood vessels in the eyes and kidneys. This degenerative process makes diabetes a leading cause of blindness and puts an estimated one third of diabetics at risk for developing kidney disease. Diabetes can also damage the large blood vessels, doubling the risk for heart attack and stroke and creating chronic circulatory problems. In addition, many people with diabetes develop some nerve degeneration, often marked by diminished sensitivity in their extremities. These complications are believed to result from excess glucose levels as well as other unidentified factors.
Over the last decade, scientists have made great strides in unraveling the causes of type 1 diabetes. The illness is now believed to be an autoimmune disease that results from a grand mistake in the body's defense system. Like precise heat-seeking missiles gone haywire, certain immune cells may mistakenly target for destruction the beta cells of the pancreas -- a process that can begin years before the disease actually appears. "We've had a change from the idea that you could suddenly develop diabetes," says George Eisenbarth, M.D., Ph.D, executive director of the Barbara Davis Center for Childhood Diabetes at the University of Colorado Health Sciences in Denver and the former head of Joslin's immunology section. "The disease is the end of a long process," he says. "If you developed diabetes at age 19, I could have picked up abnormalities in your immune system at around age 10." Researchers have even identified the cluster of genes -- in a genetic neighborhood known as the HLA region of chromosome 6 -- that are abnormal in people who have type 1 diabetes.
According to the American Diabetes Association (ADA), I am one of a million and a half Americans whose genetic roll of the dice produced that same HLA defect. There are close to 26 million people with type 2 diabetes, making the disease one of America's most widespread chronic afflictions and one of the biggest medical killers. A diverse group, we diabetics are a significant constituency, testifying to the equal-opportunity forces of fate.
Life with the needle
After my diagnosis, I began making regular visits to the college health center -- an antiseptic zone where I learned the basics of living with diabetes. The goal is to mimic as closely as possible a healthy person's normal daily fluctuations in blood sugar. This glucose control entails a daily balancing act: between food, which raises blood sugar, and insulin, which lowers it; and among protein, carbohydrates, and fats, which release glucose into the bloodstream at different rates.
Other factors must also be considered. Because alcohol can drastically lower blood sugar, the ADA advises people with diabetes to drink only in moderation and cautions people who do imbibe to make sure there are no contraindications with their medication by getting a doctor's approval first. Exercise is recommended, but it can mean adjusting the insulin doses since blood sugar can suddenly drop several hours after physical activity. For a diabetic, all these vagaries of daily life are shot through with meaning.
As the health center nurse taught me to check my urine for glucose and to give myself insulin injections, I felt like my world was imploding. While my housemates were consuming ice cream or pizza with abandon at 3 a.m., I anxiously measured food by the gram on a tiny scale, trying to adhere to the ADA's strict dietary regimen. (That was some years ago, and the ADA has since relaxed some of its guidelines, allowing those of us with diabetes an occasional sweet as long as we keep our blood sugar under control.) Ahead of me, I thought, was a life of being "different": no more travel, no more girlfriends, a life tied to a needle and to medicine. Developing diabetes didn't turn out to be the apocalypse I feared, but as my own physician, Brian Levy, M.D., then an endocrinologist at New York University Medical Center, observed, "It's sort of like having a nagging parent, and you can't cut the strings."
I was not exactly at ease with the idea of living with a biological chaperone forever. I recall the early days, when out of some vaguely placed shame, diabetes was one of my most closely held secrets. "For six months I thought I knew you," exclaimed one close friend after she learned I had the disease. "But I've had no idea about this major part of your life." Until then, I had almost believed that it was not part of me, that I had been occupied by some foreign presence that could be shoved aside at will. Over time, the secret began working its way through my tangle of emotions until I freely admitted my condition.
Still, it was hardly a serene acceptance. After college, I became a journalist, and soon gloried in the erratic hours, the pressures, the drinking. I began to push the limits. Traveling widely in the course of work, I rarely gave my body time to adjust to the time changes. I smoked almost a pack of cigarettes a day, disregarding studies showing that diabetic smokers face dramatically increased risks of heart disease and eye problems.
My daily insulin injections and avoidance of simple sugars were my only concessions to the disease; otherwise, I lived as if I didn't have it. Hypoglycemic reactions did scare me: I recall, once after a strenuous day of walking in the Peruvian Andes, growing progressively sweaty, irritable, and weak as my blood sugar plunged. In rudimentary Spanish, I tried desperately to explain to a hotel clerk why I needed orange juice -- pronto! But I made little effort to understand insulin's infernal demands. Ultimately it took those broken shoulders - and the threat of brain damage -- before the disease captured my attention.
How tight is right?
At the Connecticut hospital, I learned that I was years behind the times in managing my diabetes. I was still using urine samples to monitor my blood sugar, while the standards had changed to using a glucometer as a more accurate measure of control. "A mere prick of the finger," said the hospital's diabetes counselor, as she waved the device and proceeded to stab her finger without batting an eye. Later, I saw a specialist in New York who introduced me to the concept of tight control. "There's a general perception that excessive glucose is the primary culprit in complications," says Harry Shamoon, M.D., associate dean for clinical research at Albert Einstein College of Medicine in New York City. It's known that diabetics who develop complications often have a history of excessively high glucose levels.
Keeping a tight rein on glucose increases the risk of severe hypoglycemia (a condition involving impaired mental functioning or seizure), the state the led to my accident. But despite the increased risk of hypoglycemia, experts have proven that the best way to manage diabetes is though tight control.
Some doctors have also found a link between blood sugar levels and psychosocial factors such as a person's stress level. While it's clear that stress can raise blood sugar in type 2 diabetics, and that learning to relax can improve their glucose control, the role of stress in type 1 diabetics like myself is more complex. Some research has found that difficult life events raise blood sugar in people with type 1; in other studies, hard times seem to lower sugar levels.
Whatever the outcome of studies on stress and diabetes, I am certain that my own "psychosocial factors," like my presently healthy love life, contribute to my current level of control. And while moods can affect blood sugar, the reverse is also true. My own blood sugar levels have a direct correlation with my state of mind. At 80 to 115 (80 to 115 milligrams of glucose per deciliter of blood, which is within the normal range), I feel a pleasant sense of equilibrium, a sensibility that most people, I imagine, take for granted. With a blood sugar above 180 I feel sluggish or, sometimes, like crawling out of my skin.
The main trade-off for good glucose control has been giving up any illusions of being carefree. Carrying an insulin kit, a blood sugar testing device and assorted snacks, and sticking to a regular schedule of eating, I have forgotten what it was like not to consider all of these details. I still live at a somewhat erratic pace. But the insulin helps reshape my schedule -- a regimen that seems a small price to pay for reducing my risk of complications. Before the accident, I used to think nothing of downing a shot or two of vodka after work, or half a bottle of wine with dinner. Now I weigh these small pleasures against their impact on my blood sugar. In the course of my work, I often show up for interviews with a can of orange juice, cracking it open at the first shaky signs of hunger and explaining why. What surprises me at those moments is how "normal" most people consider my disease, which I have regarded as a most unlucky brush with fate.
Closing in on a cure
There's no doubt that the deck will be stacked for my future children. The numbers are clear: A diabetic father runs roughly an 8 percent risk of giving the disease to his children. A diabetic woman, on the other hand, has only a 4 percent chance of passing the disease along to her offspring.
Fortunately, children in the next generation who inherit the genes for diabetes may have a chance to prevent the development of the disease. Using tests that detect the presence of the beta cell antibodies, researchers can determine who will develop diabetes and have begun experimenting with ways to prevent the illness. In one such treatment, called beta cell resting, researchers have been able to prevent diabetes in some children (studied from several months to two years) by administering low doses of insulin before the disease develops. This therapy lowers the body's own insulin production, allowing beta cells to rest. While inactive, the cells are believed to undergo a chemical change that prevents them from becoming immune-cell targets. Researchers hope the treatment will free people from dietary restrictions and, more important, prevent long-term complications.
In another approach to disease prevention, prediabetics were given immunosuppressant drugs, commonly used to prevent tissue rejection in transplant patients. These drugs weaken the immune system, preventing beta cell destruction. The hitch is that the medications also subdue the healthy immune response, so patients are left vulnerable to a host of diseases. For that reason, researchers are experimenting with immunosuppressant drugs that may cause less damage to the immune system.
Scientists also are exploring treatments for those who already have the disease. Researchers are performing stem cell transplants that allow newly-diagnosed type 1 diabetics to stop using insulin after receiving treatment with their own stem cells. In another technique, scientists are implanting a healthy pancreas, which can fuel a diabetic's body without the need for insulin injections. Because all the patients who receive transplants face a lifetime of therapy with immunosuppressant drugs in order to prevent rejection, the surgery is generally reserved for patients who also require a kidney transplant and thus will be receiving this type of medication anyway.
An alternative to pancreas transplant may one day be able to safely eliminate type 1 diabetes and stave off its complications in all people with the disease. Scientists have actually cured diabetes in animals by implanting healthy islets of Langerhans, the tissue in the pancreas that contains the critical beta cells. These cells then begin pumping out insulin to normalize glucose levels.
The advantage of islet cells is that they can be treated before they're transplanted to prevent rejection. One Canadian project involved implanting a huge number of islet cells into humans, with very promising results, and several leading U.S. diabetes research centers are working on islet cell studies as well.
Coming to terms
A few years after my seizure, I got a closeup look at the havoc a diabetic's body wreaks on itself. In Eisenbarth's laboratory at the Joslin Center, I peered through a microscope at a slide of pink pancreatic tissue, watching as the killer immune cells clustered like black ink spots around the insulin-producing islets. In the face of these microscopic ciphers that can alter the course of a life, Eisenbarth is humble.
"Just a few amino acids out of billions in each cell can determine whether you get diabetes or not," he muses.
Later that day, Andrzej Krolewski, M.D., of the epidemiology and genetics section at Joslin, showed me an autoradiogram, a type of x-ray of human genes. The genes appeared on the paper like pieces of photocopied Scotch tape, each strip displaying an apparently random pattern of dark splotches. These images allow scientists to detect the defective genes that predispose someone to diabetes -- a distinctive imprint that Krolewski calls "the genetic music."
Seeing those chromosomes and the embattled pancreatic tissue was somehow, strangely, reassuring. Such indisputable physical evidence lifts a certain weight -- of denial and rebellion -- off my shoulders. Diabetes does seem after all to get down to genetic mathematics, to chance, to a roll of the dice. I've begun to settle with that idea. And if my body is to be at war with itself, then I will keep striving to maintain a ceasefire - a peace that has to be reaffirmed each day.
CDC: 26 million have diabetes, U.S. Centers for Disease Control and Prevention, news release, Jan. 27, 2011.
Mayo Clinic. Type 1 Diabetes. June 2009. http://www.mayoclinic.com/health/type-1-diabetes/DS00329
Aikens JE, et al. Daily stress variability, learned resourcefulness, regimen adherence, and metabolic control in type I diabetes mellitus: evaluation of a path model. J Consult Clin Psychol Feb;60(1):113-8.
Alcohol, Alcohol Everywhere. American Diabetes Association.
American Diabetes Association. Frequently Asked Questions. http://www.diabetes.org/nutrition-and-recipes/nutrition/faqs.jsp
Mayo Clinic. Diabetes: Is it inherited? August 2004. http://www.mayoclinic.com/health/diabetes/AN00534
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