The consequences of uncontrolled diabetes are severe: blindness, kidney failure, increased risk of heart disease, and painful peripheral nerve damage. Today, most practitioners focus treatment on strict blood sugar control. While diabetes is characterized by excess blood glucose (the form of sugar used by cells as energy), this simplified approach can actually hasten the progression of the most common form of diabetes and does nothing to address the damage it causes.
A new approach to diabetes recognition and treatment is needed because the conventional wisdom has failed us. America is in the midst of a diabetes epidemic. Over the past 20 years, the number of adults diagnosed with diabetes has more than doubled, and children are being diagnosed with diabetes in alarming numbers. Diabetes has rapidly emerged as a leading culprit in the epidemic of heart disease that is sweeping the country, and it is a leading cause of amputation and blindness among adults.
It is crucial that diabetics (and those predisposed to diabetes) understand the ways in which blood glucose causes damage and take active steps to interrupt these processes. The most notorious process is glycation, the same process that causes food to brown in an oven. Glycation (defined as sugar molecules reacting with proteins to produce nonfunctional structures in the body) is a key feature of diabetes-related complications because it compromises proteins throughout the body and is linked to nerve damage, heart attack, and blindness.
Oxidative stress is also central to the damage caused by diabetes. Diabetics suffer from high levels of free radicals that damage arteries throughout the body, from the eyes to the heart. Once again, it is important that diabetics understand their need for antioxidant therapy to help reduce oxidative stress and lower the risk of diabetic complications.
There are two types of diabetes: type 1 and type 2. Underlying either form of diabetes is a disorder of insulin production, use, or both. Insulin is a hormone responsible for transporting glucose into cells. When there is excess glucose in the blood, insulin is secreted from the pancreas and signals the liver and muscles to store glucose as glycogen. Insulin also stimulates adipose tissue to store glucose as fat for long-term energy reserves. Insulin receptors are found in all cells throughout the body. In a healthy person, blood glucose levels are extremely stable (Kumar V et al 2005). Normal fasting glucose levels range between 70 and 100 mg/dL.
Type 1 diabetes. Type 1 diabetes, formerly known as insulin-dependent diabetes, is an autoimmune condition that occurs when the body attacks and destroys the cells (called beta cells) that make insulin. Type 1 diabetes accounts for about 5 to 10 percent of cases. Because type 1 diabetics can no longer make insulin, insulin replacement therapy is essential.
Type 2 diabetes. Type 2 diabetes, formerly known as non-insulin-dependent diabetes, occurs when the body is no longer able to use insulin effectively and gradually becomes resistant to its effects. It is a slowly progressing disease that goes through identifiable stages. In the early stages of diabetes, both insulin and glucose levels are elevated (conditions called hyperinsulinemia and hyperglycemia, respectively). In the later stages, insulin levels are reduced, and blood glucose levels are very elevated. Although few people are aware of this crucial distinction, therapy for type 2 diabetes should be tailored to the stage of the disease.
Risk factors for type 2 diabetes include aging, obesity, family history, physical inactivity, ethnicity, and impaired glucose metabolism. Type 2 diabetes is also a prominent risk of metabolic syndrome, a constellation of conditions that includes insulin resistance along with hypertension, lipid disorders, and overweight. For details, see the chapter titled Metabolic Syndrome.
Glycation and oxidative stress are central to the damage caused by diabetes. Unfortunately, neither of them figures into conventional treatment for diabetes, which is generally concerned only with blood sugar control.
Glycation occurs when glucose reacts with protein, resulting in sugar-damaged proteins called advanced glycation end products (AGEs) (Kohn RR et al 1984; Monnier VM et al 1984). One well-known AGE among diabetics is glycated hemoglobin (HbA1c). HbA1c is created when glucose molecules bind to hemoglobin in the blood. Measuring HbA1c in the blood can help determine the overall exposure of hemoglobin to glucose, which yields a picture of long-term blood glucose levels.
Glycated proteins cause damage to cells in numerous ways, including impairing cellular function, which induces the production of inflammatory cytokines (Wright E Jr. et al 2006) and free radicals (Forbes JM et al 2003; Schmidt AM et al 2000). In animal studies, inhibiting glycation protects against damage to the kidney, nerves, and eyes (Forbes JM et al 2003; Sakurai S et al 2003). In a large human trial, therapies that resulted in each 1 percent reduction in HbA1c correlated with a 21 percent reduction in risk for any complication of diabetes, a 21 percent reduction in deaths related to diabetes, a 14 percent reduction in heart attack, and a 37 percent reduction in microvascular complications (Stratton IM et al 2000).
High levels of blood glucose and glycation also produce free radicals that further damage cellular proteins (Vincent AM et al 2005) and reduce nitric oxide levels. Nitric oxide is a potent vasodilator that helps keep arteries relaxed and wide open. Oxidative stress in diabetes is also linked to endothelial dysfunction, the process that characterizes atherosclerotic heart disease. According to studies, diabetes encourages white blood cells to stick to the endothelium, or the thin layer of cells that line the inside of arteries. These white blood cells cause the local release of pro-inflammatory chemicals that damage the endothelium, accelerating atherosclerosis (Lum H et al 2001). Diabetes is closely associated with severe coronary heart disease and increased risk of heart attack.
Common symptoms of diabetes include increased thirst and urination, unusual weight changes, irritability, fatigue, and blurry vision. Clinical abnormalities include hyperglycemia and glucose in the urine. The breath might smell sweet because of ketones in the blood (ketosis), which are naturally sweet smelling. Dark outgrowths of skin (skin tags) may also appear.
The most common clinical tests used to diagnose diabetes are measures of blood glucose. The common fasting glucose test measures the amount of glucose in the blood after fasting. Prediabetes is diagnosed if the fasting blood glucose level is between 100 and 125 mg/dL. Diabetes is diagnosed if the fasting blood glucose level rises to 126 mg/dL or above.
The glucose tolerance test is used to measure insulin response to high glucose levels. During this test, patients are given glucose, and the rise in blood glucose levels is measured. Prediabetes is diagnosed if the glucose level rises to between 140 and 199 mg/dL. Diabetes is diagnosed if blood glucose levels rise to 200 mg/dL or higher.
The HbA1c test is also helpful in diagnosing less severe cases of diabetes. From this test clinicians can estimate the average blood glucose level during the preceding two to four months. Normally 4 to 6 percent of hemoglobin is glycosylated, which corresponds to average blood glucose between 60 and 120 mg/dL. Mild hyperglycemia increases HbA1c to 8 to 10 percent (or 180 to 240 mg/dL), while severe hyperglycemia increases HbA1c values up to 20 percent. For diabetics, a healthy HbA1c level is less than 7 percent, which corresponds to an average blood glucose level of 150 mg/dL or less.
Before discussing therapy for type 2 diabetes, it is important to understand the logic behind conventional therapy—and to understand why this logic is flawed. Type 2 diabetics are routinely told they need to boost their levels of insulin, which will help drive blood glucose into their cells and lower their blood glucose levels. Unfortunately, this assumption defies common sense.
In the early stages of type 2 diabetes, insulin levels are already elevated (hyperinsulinemia). This is because the problem isn’t with insulin production; rather, the underlying defect in type 2 diabetes is a metabolic defect of insulin utilization. The delicate insulin receptors on cell membranes are less responsive to the insulin than are the insulin receptors of people without type 2 diabetes, which means that less glucose is absorbed from the blood stream than would be normally, and glucose levels slowly rise.
This elevation in glucose upsets the body’s natural balance, prompting the pancreas to discharge copious amounts of insulin to normalize glucose levels. This short-term, biological fix successfully drives glucose into cells, thereby lowering blood glucose levels, but it also hastens the disease’s progress. Eventually, the fragile insulin receptors become less sensitive (insulin resistant), which means that the pancreas must secrete even more insulin to keep clearing the blood of glucose. In later stages of the disease, the pancreas becomes “burned out” and can no longer produce adequate insulin. Insulin levels drop far below normal, allowing blood glucose to rise even higher and inflict greater damage.
Unfortunately, many early-stage diabetics are prescribed drugs (such as sulfonylureas) that are designed to boost insulin levels. Considering that insulin levels are already high, this strategy is counterproductive and may actually serve to hasten the disease by further exhausting the insulin receptors on cell membranes. Also, insulin itself is a powerful hormone that, in high levels, can inflict damage. Evidence suggests that high levels of insulin may suppress growth hormone synthesis and release among obese and overweight people (who are prone to hyperinsulinemia) (Luque RM et al 2006). There is also evidence that increased levels of insulin contribute to the proliferation of colorectal cells, which suggests that high levels of insulin may be a factor in the development of colorectal cancer (Tran TT et al 2006).
There are acute differences between the early stages of diabetes and the advanced stages. Thus, it doesn’t make sense to treat all people with type 2 diabetes the same. In the early stages of the disease, people suffer from both hyperglycemia and hyperinsulinemia. Rather than take drugs that further increase the level of insulin in the blood, people with type 2 diabetes would do better to pursue therapies that increase the sensitivity of insulin receptors on the cell membranes.
One of the best defenses against mild to moderate type 2 diabetes and hyperinsulinemia is improved diet and exercise. Although the disease has a genetic component, many studies have shown that diet and exercise can prevent it (Diabetes Prevention Program Research Group 2002; Diabetes Prevention Program Research Group 2003; Muniyappa R et al 2003; Diabetes Prevention Program Research Group 2000). One study also showed that while some medications delay the development of diabetes, diet and exercise work better. Just 30 minutes a day of moderate physical activity, coupled with a 5 to 10 percent reduction in body weight, produces a 58 percent reduction in the incidence of diabetes among people at risk (Sheard NF 2003). The American Diabetes Association recommends a diet high in fiber and unrefined carbohydrates and low in saturated fat (Sheard NF et al 2004). Foods with a low glycemic index are especially recommended because they blunt the insulin response. For more information on glycemic index, see the chapter titled Obesity.
The high-carbohydrate, high-plant-fiber (HCF) diet popularized by James Anderson, MD, has substantial support and validation in the scientific literature as the diet of choice in the treatment of diabetes (Anderson JW et al 2004; Hodge AM et al 2004). The HCF diet is high in cereal grains, legumes, and root vegetables and restricts simple sugar and fat intake. The caloric intake consists of 50 to 55 percent complex carbohydrates, 12 to 16 percent protein, and less than 30 percent fat, mostly unsaturated. The total fiber content is between 25 and 50 g daily. The HCF diet produces many positive metabolic effects, including the following: lowered postmeal hyperglycemia and delayed hypoglycemia; increased tissue sensitivity to insulin; reduced low-density lipoprotein (LDL) cholesterol and triglyceride levels and increased high-density lipoprotein (HDL) cholesterol levels; and progressive weight loss.
A healthy diet for diabetics is also rich in potassium. Potassium improves insulin sensitivity, responsiveness, and secretion. A high potassium intake also reduces the risk of heart disease, atherosclerosis, and cancer. Insulin administration induces potassium loss (Khaw KT et al 1984; Norbiato G et al 1984).
People who are obese have a far greater tendency to develop type 2 diabetes than those who are relatively slim. Therefore, weight loss accompanied by increase in exercise and a healthy diet is effective for diabetes prevention and treatment (Mensink M et al 2003; Sato Y 2000; Sato Y et al 2003).
In addition to diet and exercise, the prescription drug Metformin has been proven to increase insulin sensitivity in people with mild to moderate hyperglycemia. Metformin is now the most commonly prescribed oral antidiabetic drug in the world. It works by increasing insulin sensitivity in the liver (Joshi SR 2005). It also has a number of other beneficial effects, including weight loss, reduced cholesterol-triglyceride levels, and improved endothelial function.
Metformin is tolerated better than many other antidiabetic prescription drugs, but people with congestive heart failure or kidney or liver disease are not candidates for metformin therapy. Neither are people who use alcohol to excess. A benchmark assessment of kidney function, followed by an annual renal evaluation, is essential. Vitamin B12 levels should also be checked regularly because chronic use of metformin could cause a deficiency in both folic acid and vitamin B12, resulting in neurological impairment and disruption in homocysteine clearance. Also, metformin should not be used for two days before or after having an x-ray procedure with an injectable contrast agent because of the rare risk of lactic acidosis.
Metformin is effective on its own, but it may also be prescribed in combination with another class of insulin sensitizers called thiazolidinediones (TZDs; e.g., pioglitazone, or Actos®, and rosiglitazone, or Avandia®). TZDs increase insulin sensitivity and stimulate release of insulin from beta cells in the pancreas. TZD treatment also improves blood pressure and relieves vascular and lipid defects (Meriden T 2004). However, TZDs have potentially serious side effects, including liver toxicity, which requires regular monitoring of liver function (Isley WL 2003; Marcy TR et al 2004).
In addition to these two prescription drugs, many nutrients have been shown to increase insulin sensitivity, protect vulnerable cell membranes, and reduce the damaging effects of elevated glucose (see “Nutritional Supplementation for Diabetics,” below). Ideally, a combination of improved diet, exercise, supplementation, and insulin-sensitizing prescription drugs can reverse mild to moderate hyperglycemia before stronger drugs are needed and permanent damage is done.
Some people, however, will not have the benefit of this knowledge before their type 2 diabetes advances to a more dangerous stage. In severe hyperglycemia, the pancreas becomes burned out after producing high levels of insulin for a long time. Insulin levels drop as a result of decreased production, and blood glucose levels are allowed to rise to very high, toxic levels. Although diet and exercise, along with supplementation, are still strongly recommended, a number of prescription drugs might also be necessary.
Sulfonylurea drugs stimulate pancreatic secretion of insulin. Unfortunately, they are often prescribed as first-line treatment for mild to moderate type 2 diabetics, even when their use is inappropriate. By increasing levels of insulin, which are already raised, sulfonylurea drugs actually hasten the progression of early type 2 diabetes by exhausting insulin receptors faster, which causes the pancreas to burn out more quickly. Sulfonylurea drugs should really be considered a “last resort” for people with severe hyperglycemia.
Insulin replacement therapy is also a last resort for type 2 diabetics. While insulin therapy is universal—and essential—among type 1 diabetics, it is reserved for only severe, refractory (nonresponsive to treatment) type 2 diabetics. Proper dosing and monitoring of blood glucose are essential as too much insulin causes low blood sugar and coma, and too little insulin creates hyperglycemia. A new delivery system for insulin was recently approved by the US Food and Drug Administration. This new system allows for inhaled insulin.
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