Читать книгу The Diabetes Code - Dr. Jason Fung - Страница 11

THE WHOLE BODY EFFECT

DIABETES, UNLIKE VIRTUALLY every other known disease, has the unique and malignant potential to devastate our entire body. Practically no organ system remains unaffected by diabetes. These complications are generally classified as either microvascular (small blood vessels) or macrovascular (large blood vessels).

Certain organs, such as the eyes, kidneys, and nerves, are mostly supplied by small blood vessels. Damage to these small blood vessels results in the visual problems, chronic kidney disease, and nerve damage typically seen in patients with long-standing diabetes. Collectively, these are called microvascular diseases.

Other organs, such as the heart, brain, and legs, are perfused by large blood vessels. Damage to larger blood vessels results in narrowing called atherosclerotic plaque. When this plaque ruptures, it triggers the inflammation and blood clots that cause heart attacks, strokes, and gangrene of the legs. Together, these are known as macrovascular diseases.

How diabetes causes this damage to blood vessels will be discussed throughout this book. It was widely considered to be simply a consequence of high blood glucose, but the truth, as we’ll see, is far different. Beyond the vascular diseases are many other complications, including skin conditions, fatty liver disease, infections, polycystic ovarian syndrome, Alzheimer’s disease, and cancer. However, let’s begin with the problems associated with small blood vessels.

MICROVASCULAR COMPLICATIONS

Retinopathy

DIABETES IS THE leading cause of blindness in the United States.¹ Eye disease—characteristically retinal damage (retinopathy)—is one of the most frequent complications of diabetes. The retina is the light-sensitive nerve layer at the back of the eye that sends its “picture” to the brain. Diabetes weakens the small, retinal blood vessels, which causes blood and other fluids to leak out. During routine physical eye examinations, this leakage can be visualized with a standard ophthalmoscope.

In response to this damage, new retinal blood vessels form, but they are fragile and easily broken. The result is more bleeding and the eventual formation of scar tissue. In severe cases, this scar tissue can lift the retina and pull it away from its normal position, ultimately leading to blindness. Laser treatment can prevent retinopathy by sealing or destroying the leaky new blood vessels.

Approximately 10,000 new cases of blindness in the United States are caused by diabetic retinopathy each year.² Whether retinopathy develops depends on how long a person has had diabetes as well as how severe the disease is.³ In type 1 diabetes, most patients develop some degree of retinopathy within twenty years. In type 2 diabetes, retinopathy may actually develop up to seven years before the diabetes itself is diagnosed.

Nephropathy

THE MAIN JOB of the kidneys is to clean the blood. When they fail, toxins build up in the body, which leads to loss of appetite, weight loss, and persistent nausea and vomiting. If the disease goes untreated, it eventually leads to coma and death. In the United States, more than 100,000 patients are diagnosed with chronic kidney disease annually, costing $32 billion in 2005. The burden is not only financially enormous, but emotionally devastating.

Diabetic kidney disease (nephropathy) is the leading cause of end stage renal disease (ESRD) in the United States, accounting for 44 percent of all new cases in 2005.⁴ Patients whose kidneys have lost over 90 percent of their intrinsic function require dialysis to artificially remove the accumulated toxins in the blood. This procedure involves removing the patient’s “dirty” blood, running it through the dialysis machine to clean out its impurities, and then returning the clean blood to the body. To stay alive, patients require four hours of dialysis, three times per week, indefinitely, unless they receive a transplant.

Figure 3.1. Adjusted prevalence rates of end stage renal disease⁵

Diabetic kidney disease often takes fifteen to twenty-five years to develop, but, like retinopathy, it may occasionally be diagnosed before type 2 diabetes, itself. Approximately 2 percent of type 2 diabetic patients develop kidney disease each year. Ten years after diagnosis, 25 percent of patients will have evidence of kidney disease.⁶ Once established, diabetic nephropathy tends to progress, leading to more and more kidney impairment until eventually the patient requires dialysis or transplantation.

Neuropathy

DIABETIC NERVE DAMAGE (neuropathy) affects approximately 60–70 percent of patients with diabetes.⁷ Once again, the longer the duration and severity of diabetes, the greater the risk of neuropathy.⁸

There are many different types of diabetic nerve damage. Commonly, diabetic neuropathy affects the peripheral nerves, first in the feet, and then progressively in the hands and arms as well, in a characteristic stocking-and-glove distribution. Damage to different types of nerves will result in different symptoms, including

•tingling,

•numbness,

•burning, and

•pain.

The incessant pain of severe diabetic neuropathy is debilitating, and the symptoms are commonly worse at night. Even powerful painkillers such as narcotic medications are often ineffective. Instead of pain, patients may sometimes experience complete numbness. Careful physical examination reveals decreased sensations of touch, vibration, and temperature, and a loss of reflexes in the affected parts of the body.

While a loss of sensation may seem innocuous, it is anything but. Pain protects us against damaging trauma. When we stub our toes, or lie in the wrong position, pain lets us know that we should quickly adjust ourselves in order to prevent further tissue damage. If we are unable to feel pain, we may continue to experience repeated episodes of trauma. Over years, the damage becomes progressive and sometimes deformative. A typical example is the foot. Significant nerve damage can lead to the complete destruction of the joint—a condition called Charcot foot—and may progress to the point where patients are unable to walk, and may even require amputation.

Another nerve disorder affecting the large muscle groups is called diabetic amyotrophy, which is characterized by severe pain and muscle weakness, particularly in the thighs.⁹

The autonomic nervous system controls our automatic body functions, such as breathing, digestion, sweating, and heart rate. Damage to these nerves may cause nausea, vomiting, constipation, diarrhea, bladder dysfunction, erectile dysfunction, and orthostatic hypotension (a sudden, severe drop of blood pressure on standing up). If the nerves to the heart are affected, the risk of silent heart attacks and death increases.¹⁰

No current treatment reverses diabetic nerve damage. Drugs may help the symptoms of the disease but do not change its natural history. Ultimately, it can only be prevented.

MACROVASCULAR COMPLICATIONS

Atherosclerosis (hardening of the arteries)

ATHEROSCLEROSIS IS A disease of the arteries whereby plaques of fatty material are deposited within the inner walls of the blood vessel, causing narrowing and hardening. This condition causes heart attacks, strokes, and peripheral vascular disease, which are collectively known as cardiovascular diseases. Diabetes greatly increases the risk of developing atherosclerosis.

Atherosclerosis is popularly but incorrectly imagined as cholesterol slowly clogging the arteries, much as sludge might build up in a pipe. In actuality, it results from injury to the artery, although the exact cause of the injury is unknown. There are many contributing factors, including but not limited to age, genetics, smoking, diabetes, stress, high blood pressure, and lack of physical activity. Any breach of the artery’s walls can initiate an inflammatory cascade. Cholesterol (a waxy, fat-like substance found in all cells of the body) infiltrates the damaged area and narrows the blood vessel. The smooth muscle that supports the tissue of the blood vessel proliferates, and collagen, a structural protein found abundantly in the body, also accumulates in response to this injury. Again, the result is a further narrowing of the blood vessel. Rather than a single episode that can be simply repaired, this response occurs in reaction to chronic injuries to the vessel wall.

The end result is the development of plaque, known as the atheroma, which is a pocket of cholesterol, smooth muscle cells, and inflammatory cells inside the blood vessel wall. This progressively limits the flow of blood to affected organs. If this atheroma ruptures, a blood clot forms. The sudden blockage of the artery by the clot prevents normal blood circulation and starves the downstream cells of oxygen, causing cell death and cardiovascular disease.

Heart disease

HEART ATTACKS, KNOWN medically as myocardial infarctions, are the most well-recognized and feared complication of diabetes. They are caused by atherosclerosis of the blood vessels supplying the heart. The sudden blockage of these arteries starves the heart of oxygen, resulting in the death of part of the heart muscle.

The Framingham studies of the 1970s established a strong association between heart disease and diabetes.¹¹ Diabetes increases the risk of cardiovascular disease two- to fourfold, and these complications develop at a younger age compared to nondiabetics. Sixty-eight percent of diabetics aged sixty-five or older will die of heart disease, and a further 16 percent will die of stroke.¹² Reducing the risk of macrovascular disease is therefore of primary importance. The extent of death and disability resulting from cardiovascular diseases is many times greater than that resulting from microvascular diseases.

Over the past three decades, there have been significant improvements in the treatment of heart disease, but gains for diabetic patients have lagged far behind. While the overall death rate for nondiabetic men has decreased by 36.4 percent, it has only decreased 13.1 percent for diabetic men.¹³

Stroke

A STROKE IS caused by atherosclerosis of the large blood vessels supplying the brain. A sudden disruption of the normal blood flow starves the brain of oxygen and a portion of the brain may die. Symptoms vary depending upon which part of the brain is affected, but the devastating impact of stroke cannot be underestimated. In the United States, it is the third leading cause of death and the biggest contributor to disability.

Diabetes is a strong independent risk factor in stroke, meaning that, on its own, diabetes increases a person’s risk of having a stroke by as much as 150–400 percent.¹⁴ Approximately a quarter of all new strokes occur in diabetic patients.¹⁵ Every year of diabetes increases the risk of stroke by 3 percent,¹⁶ and the prognosis is also far worse.

Peripheral vascular disease

PERIPHERAL VASCULAR DISEASE (PVD) is caused by atherosclerosis of the large blood vessels supplying the legs. The disruption of normal blood flow starves the legs of oxygen-carrying hemoglobin. The most common symptom of PVD is pain or cramping that appears with walking and is relieved by rest. As the blood vessels narrow and circulation worsens, pain may also appear at rest and especially at night. PVD significantly reduces mobility, which can lead to long-term disability.

Skin with a poor blood supply is more likely to be damaged and takes longer to heal. In diabetics, minor cuts or injuries to the feet may become non-healing foot ulcers. In severe cases, these areas where the skin has broken down, revealing underlying tissue, can progress to gangrene. At this point, blood supply has been greatly reduced or completely lost, the tissue dies, and amputation of the affected limb—a treatment of last resort—often becomes necessary to treat chronic infections and relieve pain.

Diabetes, along with smoking, is the strongest risk factor for PVD. Approximately 27 percent of diabetic patients with PVD will progressively worsen over a five-year period, and 4 percent of them will need an amputation.¹⁷ Patients with gangrene and those requiring amputation may never walk again, which can result in a cycle of disability. A loss of function of the limbs leads to less physical activity, which in turn leads to progressive deconditioning of the muscles. Weaker muscles lead to less physical activity, and the cycle repeats.

OTHER COMPLICATIONS

Alzheimer’s disease

ALZHEIMER’S DISEASE IS a chronic, progressive, neurodegenerative disease that causes memory loss, personality changes, and cognitive problems. It is the most common form of dementia, and the sixth leading cause of death in the United States.¹⁸ Alzheimer’s disease may reflect the inability to use glucose normally, perhaps a type of selective insulin resistance in the brain. The links between Alzheimer’s disease and diabetes have grown so strong that many researchers have suggested Alzheimer’s disease can be called type 3 diabetes.¹⁹ These arguments go far beyond the scope of this book, however.

Cancer

TYPE 2 DIABETES increases the risk of most common cancers, including breast, stomach, colorectal, kidney, and endometrial cancers. This may be related to some of the medications used to treat diabetes and will be further discussed in chapter 10. The survival rate of cancer patients with pre-existing diabetes is far worse than for nondiabetics.²⁰

Fatty liver disease

NON-ALCOHOLIC FATTY liver disease (NAFLD) is defined as the storage and accumulation of excess fat in the form of triglycerides exceeding 5 percent of the total weight of the liver. This condition can be detected using an ultrasound to examine the abdomen. When this excess fat causes damage to the liver tissue, which can be revealed through standard blood tests, it is called non-alcoholic steatohepatitis (NASH). Current estimates suggest that NAFLD affects 30 percent and NASH 5 percent of the U.S. population; both are important causes of liver cirrhosis (irreversible scarring of the liver).²¹

NAFLD is virtually non-existent in recent-onset type 1 diabetes. By contrast, the incidence in type 2 diabetes is estimated at upwards of 75 percent. The central role of fatty liver is more fully explained in chapter 7.

Infections

DIABETICS ARE MORE prone to all types of infections, which are caused by foreign organisms invading and multiplying in the body. Not only are they more susceptible to many types of bacterial and fungal infections than nondiabetics, the effects also tend to be more serious. For example, diabetics have a four- to fivefold higher risk of developing a serious kidney infection.²² All types of fungal infections, including thrush, vaginal yeast infections, fungal infections of the nails, and athlete’s foot, are more common in diabetic patients.

Among the most serious infections for diabetics are those involving the feet. Despite adequate blood glucose control, 15 percent of all diabetic patients will develop non-healing foot wounds during their lifetime. Infections in these wounds often involve multiple microorganisms, making broad-spectrum antibiotic treatment necessary. However, the decreased blood circulation associated with PVD (see above) contributes to the poor wound healing. As a result, diabetics have a fifteen-fold increased risk of lower-limb amputation, and account for over 50 percent of the amputations done in the United States, excluding accidents. It is estimated that each of these cases of infected diabetic foot ulcers costs upwards of $25,000 to treat.²³

There are many contributing factors to the higher rates of infection. High blood glucose may impair the immune system. As well, poor blood circulation decreases the ability of infection-fighting white blood cells to reach all parts of the body.

Skin and nail conditions

NUMEROUS SKIN AND nail conditions are linked to diabetes. Generally, they are more of an aesthetic concern than a medical one; however, they often indicate the underlying serious condition of diabetes, which requires medical management.

Acanthosis nigricans is a gray-black, velvety thickening of the skin, particularly around the neck and in body folds, caused by high insulin levels. Diabetic dermopathy, also called shin spots, are often found on the lower extremities as dark, finely scaled lesions. Skin tags are soft protrusions of skin often found on the eyelids, neck, and armpits. Over 25 percent of patients with skin tags have diabetes.²⁴

Nail problems are also common in diabetic patients, particularly fungal infections. The nails may become yellowy-brown, thicken, and separate from the nail bed (onycholysis).

Erectile dysfunction

COMUNITY-BASED POPULATION studies of males aged 39–70 years found that the prevalence of impotence ranges between 10 and 50 percent. Diabetes is a key risk factor, increasing the risk of erectile dysfunction more than threefold and afflicting patients at a younger age than usual. Poor blood circulation in diabetics is the likely reason for this increased risk. The risk of erectile dysfunction also increases with age and severity of insulin resistance, with an estimated 50–60 percent of diabetic men above the age of 50 having this problem.²⁵

Polycystic ovarian syndrome

AN IMBALANCE OF the hormones can cause some women to develop cysts (benign masses) on the ovaries. This condition, called polycystic ovarian syndrome (PCOS), is characterized by irregular menstrual cycles, evidence of excessive testosterone, and the presence of cysts (usually detected by ultrasound). PCOS patients share many of the same characteristics as type 2 diabetics, including obesity, high blood pressure, high cholesterol, and insulin resistance. PCOS is caused by elevated insulin resistance²⁶ and increases the risk of developing type 2 diabetes three-to fivefold in young women.

TREAT THE CAUSE, NOT THE SYMPTOMS

WHEREAS MOST DISEASES are limited to a single organ system, diabetes affects every organ in multiple ways. As a result, it is the leading cause of blindness. It is the leading cause of kidney failure. It is the leading cause of heart disease. It is the leading cause of stroke. It is the leading cause of amputations. It is the leading cause of dementia. It is the leading cause of infertility. It is the leading cause of nerve damage.

But the perplexing question is why these problems are getting worse, not better, even centuries after the disease was first described. As our understanding of diabetes increases, we expect that complications should decrease. But they don’t. If the situation is getting worse, then the only logical explanation is that our understanding and treatment of type 2 diabetes is fundamentally flawed.

We focus obsessively on lowering blood glucose. But high blood glucose is only the symptom, not the cause. The root cause of the hyperglycemia in type 2 diabetes is high insulin resistance. Until we address that root cause, insulin resistance, the epidemic of type 2 diabetes and all of its associated complications will continue to get worse.

We need to start again. What causes type 2 diabetes? What causes insulin resistance and how can we reverse it? Obviously, obesity plays a large role. We must begin with the aetiology of obesity.

SIMON

When he came to the Intensive Dietary Management (IDM) program, Simon, 66, weighed 267 pounds, with a waist circumference of 135 cm and a BMI of 43. He had been diagnosed with type 2 diabetes eight years earlier and was taking the medications sitagliptin, metformin, and glicizide to control his blood glucose. In addition, he had a history of high blood pressure and part of one kidney had been removed because of cancer.

We counseled him on a low-carbohydrate, healthy-fat diet and suggested that he start fasting for 24 hours, three times per week. Within six months, he was down to a single medication, canagliflozin, which he continued taking for a period of time to help with weight loss. After another year, we discontinued this medication as Simon’s weight and blood glucose had significantly improved. He has not needed any medications since.

At his last checkup, Simon’s hemoglobin A1C was 5.9%, which is considered nondiabetic, and he had maintained a 45-pound weight loss for two years and counting. Today, he is ecstatic about the change in his overall health. He has gone from wearing a size 46 pant to a 40, and the type 2 diabetes, which he believed was a lifelong disease, has completely reversed. Simon continues to follow a low-carbohydrate diet and fasts once or twice per week for 24 hours.

BRIDGET

When we first met Bridget, 62, she had a ten-year history of type 2 diabetes, chronic kidney disease, and high blood pressure. She was severely insulin resistant, requiring a total of 210 units of insulin every day to keep her blood glucose under control. She weighed 325 pounds, with a waist size of 147 cm and a BMI of 54.1.

Determined to get off insulin, she started with a seven-day fast but felt so well and so empowered that she continued for another two weeks. By the end of the 21 days, she had not only stopped all her insulin but required no diabetic medications at all. To maintain her weight loss, she switched from fasting continuously to fasting for 24 to 36 hours every other day, and she resumed taking dapagliflozin to help control her weight. During this time her A1C was 6.8%, which was actually better than when she was taking insulin.

Before starting the IDM program, Bridget had very low energy levels and could barely make it into my office on her own two legs. Once she started to fast, her energy levels improved significantly and she was easily able to walk around. Her dress size dropped from size 30 to 22. Bridget has been off insulin for three years now and has maintained a total weight loss of 63 pounds over that time. Her blood pressure has normalized and she has stopped taking medication.