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Type 2 Diabetes

Michael Jay Katz, MD, PhD

Wild Iris Medical Education is an approved provider for paramedic and EMT continuing education in California by the California Emergency Medical Services Agency: EMS CE Provider #49-0057.
Wild Iris Medical Education is an approved provider (#0007) of continuing education by the Continuing Education Coordinating Board for Emergency Medical Services (CECBEMS).
This course is appropriate for EMTs and paramedics.

This course includes straightforward answers to basic questions about Type 2 Diabetes for nurses and other health professionals who advise patients over the telephone (see the last section of the course: Telephone Counseling).

Diabetes mellitus—or, simply, diabetes—is a chronic illness, in which the body is exposed to continual high levels of blood glucose, a condition known as hyperglycemia. Glucose is a simple sugar and an important source of energy, especially for the brain. Low levels of blood glucose (hypoglycemia) cause generalized weakness, and if the hypoglycemia is severe and lasts longer than 30 minutes or so, brain cells begin to die.

On the other hand, too much blood glucose is also a serious health problem. In the short term, very high blood glucose levels can lead to life-threatening dehydration and coma. Over the long term, hyperglycemia damages capillaries and larger blood vessels by thickening their walls and narrowing their inner diameters. This reduces the blood flow to many areas of the body and causes permanent tissue damage, notably to the retinas and the kidneys. Long-term high blood glucose levels also damage nerve endings.

Diabetes causes persistent hyperglycemia, and it is a major health problem. It is the sixth leading cause of death listed on U.S. death certificates, although it contributes to a great many more deaths. People with diabetes are 2 to 4 times more likely to die of heart disease or stroke. Diabetes is the leading cause of new cases of blindness in adults and is the leading cause of endstage renal disease. More than 60% of nontraumatic lower limb amputations are performed on people with diabetes.

Almost all forms of diabetes stem from problems in the body's production and use of insulin, the hormone that is responsible for keeping blood glucose levels in check. One cause of diabetes is the inability to produce enough insulin; for this problem, treatments range from oral medications that increase insulin secretion (ie, secretagogues, such as tolbutamide) to injections of insulin itself.

Another cause of diabetes is the inability of body tissues to respond sufficiently to normal amounts of insulin, or insulin resistance; here, the treatments include exercise, weight loss, and, when needed, oral medications (insulin sensitizers, such as Metformin, Glyburide) that increase tissue responsiveness to insulin.

Of the various forms of diabetes, the two most common are:

• Type 1 diabetes, which is characterized by destruction of the insulin-secreting cells (beta cells) of the pancreas.
• Type 2 diabetes, which is characterized by insulin resistance and progressively reduced secretion of insulin by beta cells.

About 90% of people with diabetes have the type 2 form. The typical patient with type 2 diabetes is an adult who has had the disease for many years before it worsened sufficiently to cause symptoms that brought it to a physician's attention.

People who do not have especially high levels of blood glucose, but who do have inefficient ("impaired") mechanisms for handling blood glucose have a condition called prediabetes. Prediabetes often evolves into type 2 diabetes, but concerted lifestyle changes—weight loss, regular physical exercise, and a controlled diet—can delay or even prevent prediabetes from become diabetes.

Currently, diabetes is incurable, and it takes daily work to prevent or delay further damage to the body. The most successful model for treating diabetes is a team effort. The patient is the daily healthcare manager, and a group of professionals—including physicians, nutritionists, and nurses—act as guides, advisors, monitors, and counselors.

HISTORY OF DIABETES

Type 2 diabetes is one of the two main forms of diabetes mellitus, a disease that has been a problem during all of recorded human history. Diabetes is a Greek word that means "to pass through." Diabetes was the name given to diseases in which a person continually drinks great quantities of fluid, which then pass through the body and are excreted as great quantities of urine. Diabetes is thus characterized by polydipsia (prodigious drinking) and polyuria (prodigious urinating).

Even in early times, two different diabetes diseases were distinguished: diabetes insipidus and diabetes mellitus. Diabetes insipidus ("flavorless" diabetes) produces dilute, watery urine. This disease is now known to be caused most often by the insufficient secretion of ADH (anti-diuretic hormone) by the pituitary. In contrast, diabetes mellitus ("sweet" diabetes) produces urine that is thicker than normal, that tastes sweet, and that leaves crystals of sugar when the water in the urine is evaporated. Diabetes insipidus is rare and, even before the physiologic bases of the diseases were understood, when someone spoke simply of "diabetes," they were usually referring to diabetes mellitus.

Before the 20th century, diabetes mellitus was usually fatal. Most often, diabetes occurred in obese people older than 50 years of age. The disease came on gradually, with increasing thirst and correspondingly voluminous urination. The patient's mouth and skin were always dry, and the breath often had a sweetish odor.

The disease progressed inexorably, bringing with it a host of problems. Eyesight failed from cataracts and nerve problems. Muscles weakened, skin infections and pneumonias were common, and people developed gangrene of the lower limbs. Diabetes led to digestive troubles, kidney disease, and heart failure. Death was usually from what was then called "diabetic coma" (now called diabetic ketoacidosis), which came on suddenly and was always fatal within a few days.

In the less common cases in which children, teenagers, or young adults developed diabetes, the disease worsened much more rapidly. There were no good treatments for diabetes, although a low-carbohydrate diet slowed the progression of the disease in some obese people who developed the disease late in life.

The Discovery of Insulin

By the early 1800s, pancreatic damage was recognized in autopsies of people who died of diabetes, and late in that century German scientists showed that removing the pancreas from a dog would cause diabetes in the animal. However, diabetes could be prevented in these dogs if a piece of pancreas was sewn under the dog's skin, and this suggested that the pancreas made a substance that prevented diabetes.

Attempts to extract this substance failed because the pancreas also makes a number of destructive enzymes, the presence of which in the extracts would destroy the key anti-diabetes substance. In the early 1920s, the Canadian surgeon Frederick Banting and his assistant Charles Best, a medical student, devised a way to rid the pancreas of most of its destructive enzymes. From the remaining pancreatic tissue they extracted a hormone that would decrease the amount of sugar in the bloodstream and in the urine of diabetic dogs. They named this anti-diabetes hormone insulin. Before the discovery and purification of insulin, diabetes was a fatal disease; after Banting and Best's work, diabetes became a chronic illness.

Identifying the Two Types of Diabetes

At the beginning of the 20th century, diabetes mellitus was considered one disease, although young people who developed the disease died much more quickly than people who first became ill in middle or old age. The new treatment with insulin, however, began to highlight a number of other differences. As early as the 1930s, clinicians found that people with diabetes could be divided into two classes according to the way they reacted to an injection of insulin.

People with insulin-sensitive diabetes (who tended to be young and prone to developing ketosis) easily disposed of an oral dose of glucose after receiving an injection of insulin. In contrast, people with insulin-insensitive diabetes (who were usually middle-aged and did not have ketotic episodes) did not significantly reduce their blood glucose levels after receiving the same amount of insulin.

Today, insulin-sensitive diabetes are usually categorized as type 1 diabetes. In type 1 diabetes, the pancreas produces little or no insulin because the beta cells in the islets of Langerhans of the pancreas are not functioning. Type 1 diabetes shows up most commonly in young people, although it can occur in any age group (Eisenbarth et al., 2003).

Insulin-insensitive diabetes, on the other hand, is generally categorized as type 2 diabetes. Type 2 diabetes usually shows up in older adults, although it can occur at any age. A distinguishing feature of type 2 diabetes is that, even when there is a normal amount of circulating insulin, body tissues do not take up glucose as readily as normal. This is called insulin resistance, a condition in which normal concentrations of insulin in the blood produce less than the normal effects in the body.

More than 90% of people with diabetes have the type 2 form, previously called insulin-insensitive diabetes, non-insulin-dependent diabetes, type II diabetes, or adult-onset diabetes. In type 2 diabetes, the pancreas produces enough insulin to prevent ketone formation but, because of insulin resistance, not enough to prevent hyperglycemia. Although there is a hereditary (ie, genetic) predisposition for the disease, type 2 diabetes does not appear to have a single cause. Aging, a sedentary lifestyle, or excess intra-abdominal fat can activate or enhance a person's predisposition to develop type 2 diabetes.

Type 2 diabetes worsens more quickly if it is not treated. Both hyperglycemia and higher than normal circulating insulin levels (hyperinsulinemia) increases the existing insulin resistance. Hyperglycemia also injures the beta cells (the insulin-manufacturing cells) in the pancreas, and this makes it increasingly difficult for the pancreas to lower high levels of blood glucose. As these processes continue and interact with each other, the patient has more frequent and higher episodes of hyperglycemia, which, over time, damage the eyes, kidneys, nerves, and blood vessels (Masharani & German, 2004; Masharani, 2007).

INCIDENCE OF DIABETES

Approximately 180 million people in the world have type 2 diabetes. Undiagnosed type 2 diabetes is thought to be common; it is estimated that half of the cases remain undiagnosed (Buse et al., 2003). In the United States, more than 6% of the population has diabetes, and 9 out of 10 of those have type 2 diabetes.

Diabetes is more common in older people.

Total prevalence of diabetes by age group in the United States (National Diabetes Fact Sheet, 2007).

In the United States, diabetes is more common among non-whites.

Prevalence of diabetes by race/ethnicity in the United States (National Diabetes Fact Sheet, 2007)

Not only is diabetes common but it is also costly. In the United States, the life expectancy of people with diabetes is 10 years less than people without the disease, and people with diabetes are 3 times more likely to be hospitalized than people without the disease. Diabetes is the leading cause of blindness and of amputations not due to injury. Almost half the new cases of endstage renal disease are the result of diabetes. All told, more than 15% of American healthcare dollars are spent treating diabetes and its complications (DeWitt & Hirsch, 2003).

NORMAL GLUCOSE METABOLISM

Diabetes is a disease that unbalances the metabolism of carbohydrates. Normally, one of the central sources of metabolic energy is the simple sugar glucose, which is carried throughout the body in the bloodstream and which is stored mainly in the liver and muscles. Glucose is the source of quick energy, and we always need a certain minimum amount of glucose in the bloodstream. On the other hand, excess blood glucose can damage tissues. Insulin is the hormone that keeps blood glucose levels from getting too high, but diabetes disrupts the body's ability to use insulin effectively.

What Is Glucose?

Carbohydrates come in all sizes. Large carbohydrates such as polysaccharides (eg, starch) are chains of individual sugar molecules. The smallest carbohydrates are monosaccharides, individual sugar molecules. Glucose, which is a small water-soluble molecule, is a monosaccharide (Nussey & Whitehead, 2001).

Glucose is central to a number of chemical reactions in the cells, and it is the most important of the carbohydrates for most mammals. In addition to being used for energy, glucose molecules are the building blocks of certain structural molecules, glycoproteins and proteoglycans, and of the informational molecules, ribo- and deoxyribo-nucleic acids (Bender & Mayes, 2006).

Glucose is an essential molecule, but most tissues of the body can survive when there are low levels of blood glucose. The brain, however, is quite sensitive to low blood glucose, and it suffers irreversible damage if hypoglycemia lasts more than about half an hour (Ropper & Brown, 2005). The dependence of the brain on continuous supplies of glucose makes it crucial that the body maintain sufficient blood glucose levels at all times.

What Is Glycogen?

Much of the glucose in our bodies comes directly from the carbohydrates in our food. In a typical American diet, 60% of our carbohydrates is eaten in the form of starches, 30% in the form of sucrose, and 10% in the form of lactose. In the gastrointestinal tract, enzymes break these carbohydrates into monosaccharides (glucose, galactose, fructose), which are the only forms we can absorb. All carbohydrate absorption takes place in the small intestine.

Excess blood glucose is stored in the liver and in muscles as long chains (polysaccharides) called glycogens. After a meal, insulin in the bloodstream lowers the amount of circulating glucose by encouraging its storage in the form of glycogen molecules. Between meals, liver glycogen is broken down to maintain sufficient glucose in the bloodstream, and the production of glucose from glycogen is encouraged by another pancreatic enzyme, glucagon. In this way, two pancreatic hormones, insulin and glucagon, balance the amount of glucose in the bloodstream: insulin lowers the level of plasma glucose by encouraging liver cells to take up glucose and store it in the form of glycogen, while glucagon raises the level of plasma glucose by encouraging the liver to break down stored glycogen and release the resulting glucose molecules (Bender & Mayes, 2006).

The Role of Insulin

The healthy fasting level of blood sugar is less than 126 mg of glucose per 100 ml of plasma (126 mg/dl). Higher levels cause tissue damage. Normally, the body uses the kidneys to reduce the excesses of most chemicals in the blood. Unfortunately, the kidneys only begin excreting glucose in the urine when the plasma concentration is above 180 mg/dl, and the kidneys only excrete significant amounts when the plasma glucose levels are above 275 mg/dl (Bonnardeaux & Bichet, 2004). Therefore, by themselves, the kidneys cannot keep blood sugar levels low enough to prevent diabetes.

Blood sugar levels are kept low by the liver and muscle cells, which can absorb large amounts of glucose from the circulation. Insulin is the main signal that tells the liver and the muscles when to remove glucose from the blood.

Insulin is a protein molecule made in beta cells that are clustered in islets within the pancreas. During the production of insulin, a piece of the precursor molecule is cut off. This extra piece is called C-peptide. C-peptide is an unnecessary protein, and it is released into the bloodstream along with insulin. By measuring the amount of C-peptide in the blood, it is possible to calculate how much insulin has been produced by the pancreas (Davis, 2005).

Glucose is the main stimulus for insulin secretion, but the pancreas also releases insulin in response to elevated blood levels of amino acids or when signaled by the parasympathetic (vagal) nervous system. The opposite response—slowing or stopping insulin secretion—is caused by signals from the sympathetic nervous system. The sympathetic nervous system (the fight-or-flight system) is activated in stressful situations when higher blood glucose levels would be useful, such as in hypoglycemia, exercise, hypothermia, and trauma.

After they have been secreted from the pancreas, insulin molecules remain outside cells, and they work by interacting with specific receptors on a cell's membrane. Once activated, the receptor molecules speed up glucose transport into the cell. The insulin receptors also set off a cascade of intracellular events that regulate oxidation of glucose and lipids, storage and release of glucose, transport and metabolism of amino acids, protein synthesis, cell growth, cell differentiation, and even cell death (Buse et al., 2003; Davis, 2005).

Normal Insulin Secretion

When a person has not eaten in many hours, the pancreas secretes about 2 units (40 x 10-3 mg) of insulin per hour. After a meal, the person's blood insulin level rises quickly, and in an hour it reaches a peak about 5 times the fasting level. During a typical 24-hour period, the pancreas secretes 18 to 32 units (0.7–1.3 mg).

Circulating insulin is taken up and deactivated by the liver, the kidney, and the muscles. On average, an insulin molecule stays in the bloodstream for less than 10 minutes (Buse et al., 2003; Davis, 2005).

CAUSES OF TYPE 2 DIABETES

Type 2 diabetes results from the interaction of at least two different disorders. One is insulin resistance, a disorder arising in most of the tissues that respond to insulin. Another disorder arises only in the pancreatic beta cells, which do not secrete insulin efficiently in people with type 2 diabetes. Some of the problems associated with type 2 diabetes, such as obesity and hypertension, worsen insulin resistance and beta cell dysfunction.

Insulin Resistance and Its Causes

Insulin resistance is one of the two key disorders underlying type 2 diabetes. Insulin resistance is a molecular problem in which most tissues do not respond normally to insulin in the bloodstream, whether the insulin has been secreted by the pancreas or has been administered therapeutically.

All people with type 2 diabetes have insulin resistance. Insulin resistance exists in a person years before the diabetes is diagnosed, and the presence of insulin resistance in an asymptomatic person predicts the high probability of developing type 2 diabetes. Although diabetes is often thought of as a disease of the pancreas, insulin resistance is a problem in the cells throughout the body that respond to insulin. Usually, it is a problem in the molecular mechanisms by which cells recognize the insulin molecule and then produce the intracellular effects of this recognition.

There are many separate molecular sites that can be the source of insulin resistance. Insulin receptors (which are in the membranes of responding cells) are complex structures made of a number of separate subunits. The malfunctioning or mutation of any of these subunits can make them work inefficiently or make them insensitive to insulin, leading to insulin resistance. Insulin resistance can also be caused by the malfunctioning of any of the components of the intracellular cascade that connects the insulin receptors in the cell membrane to the glucose-processing machinery inside the cell (Buse et al., 2003).

GENETIC PREDISPOSITION

As with many pathologic processes, insulin resistance develops most readily in people with a genetic predisposition for it. In predisposed people, certain genes produce poorly functioning insulin receptor subunits or other molecules in the intracellular chain leading from the receptor to the actual glucose utilization machinery.

EXCESS VISCERAL FAT

Intra-abdominal fat is strongly associated with insulin resistance—more so than is extra-abdominal (subcutaneous) fat. Intra-abdominal fat is visceral fat, and an overabundance of visceral fat cells both causes and worsens insulin resistance. How does excess visceral fat cause insulin resistance?

The sympathetic nervous system signals fat cells to break down and release their stored fat. Insulin gives the opposite message; insulin tells fat cells to slow or stop the release of fat. Visceral fat cells are more responsive than other fat cells to the neural signals, but visceral fat cells are less responsive to insulin. In other words, visceral fat cells are easy to turn on and difficult to turn off. Thus, having too many visceral fat cells leads to too much free fatty acid in the bloodstream.

All the energy-balancing systems interact. When the level of free fatty acids in the bloodstream gets too high, the liver releases more glucose into the blood and less glucose is taken up by the liver and muscles, even when there is sufficient insulin available. At this point, therefore, the high level of free fatty acids has caused hyperglycemia.

Now the pancreas is activated. Hyperglycemia stimulates the pancreas to release more insulin. And in this way, the excess free fatty acids have indirectly triggered, at least temporarily, higher than normal levels of circulating insulin, ie, hyperinsulinemia.

If it had been subcutaneous fat cells that were releasing the excess fatty acids, the newly released insulin would turn off the tap by slowing or stopping the fatty acid release. Visceral fat cells, however, are less sensitive to insulin signals, and the feedback circuit is not very effective when visceral fat cells are the culprits. When visceral fat is the source of excess free fatty acids, the natural balancing mechanisms do not work well, and the hyperinsulinemia persists. This persistent hyperinsulinemia is a direct cause of insulin resistance (Rasouli et al., 2007).

This sequence of events showed in Box 3 can be express as the formula:

Fatty acids → Hyperglycemia → Hyperinsulinemia → Insulin resistance

and can be triggered by anything that causes high blood levels of free fatty acids, glucose, or insulin. Conditions that lead to insulin resistance through this mechanism include high levels of glucocorticoids (eg, Cushing disease or long-term treatment with prednisone), nonalcoholic fatty liver disease, and treatment with protease inhibitors (eg, for HIV) (Buse et al., 2003; Bechmann et al., 2005; Eckel et al., 2005).

OBESITY

Together, both genes and life experiences cause obesity. The tendency to be obese is heritable; thus genes are usually one cause of obesity. In rare cases, a single gene can cause obesity; in most cases, however, obese people have more than one contributory gene.

In addition to an inherited metabolic tendency to be overweight, eating patterns developed over time are key causes of excess weight gain. Aspects of a person's eating patterns are learned, but other parts are inborn and probably genetic. Normally, a number of proteins, hormones, and neural signals communicate with the hunger and satiety centers in the brain. These biochemical cues are triggered by fullness of the stomach, the presence of food in the small intestine, and the levels of fat and glucose in the blood. In many obese people, the food signals do not work properly, and these people's brains do not recognize when they have eaten a sufficient meal. This "satiety blindness" leads to overeating and weight gain.

The nongenetic contributions to a person's obesity can start in the womb. For example, a fetus who is undernourished in the first two trimesters of pregnancy will have a higher than normal chance of becoming an obese adult. In addition, psychological factors can contribute to obesity. Depression, especially when part of bipolar disorder, can lead to excess eating and weight gain. Emotional, physical, and sexual abuse can also lead to obesity. Finally, many medications can cause weight gain as a side effect.

Because obesity puts a person at risk for type 2 diabetes, all the causes of obesity, from genes to life experiences to medications, can contribute to a person's tendency to develop type 2 diabetes (Bechmann et al., 2005).

Abnormal Insulin Secretion

In addition to insulin resistance, people with type 2 diabetes have another key disorder. The beta cells in their pancreases do not secrete insulin normally. Together, insulin resistance and poorly functioning beta cells lead to the continual hyperglycemia that characterizes type 2 diabetes.

Insulin resistance means that a higher than normal amount of insulin in the bloodstream is needed to keep the plasma glucose levels low (<126 mg/dl). To maintain healthy blood glucose levels, the pancreatic beta cells in a person with insulin resistance are forced to secrete more than the normal amount of insulin. Therefore, people with insulin resistance generally have hyperinsulinemia (excess insulin in the bloodstream).

People with type 2 diabetes have insulin resistance; therefore, they often have hyperinsulinemia. But even when they have hyperinsulinemia the blood insulin levels are not high enough to prevent hyperglycemia. In other words, even when secreting high levels of insulin, their pancreas does not keep up with the demand. Part of the problem is that people with type 2 diabetes have fewer beta cells than normal. In addition, the existing beta cells in type 2 diabetics do not secrete insulin as quickly and in as large amounts as normal.

Even before type 2 diabetes develops, beta cell problems can be detected in glucose tolerance tests, which give abnormal test results in prediabetic individuals. As with insulin resistance, beta cell dysfunction precedes the development of overt hyperglycemia by many years (Buse et al., 2003).

In another parallel with insulin resistance, treating type 2 diabetes can improve the functioning of the beta cells, but it cannot bring beta cell functioning up to normal. At present, both insulin resistance and beta cell dysfunction can be improved but not cured (Nussey & Whitehead, 2001).

Metabolic Syndrome

Metabolic syndrome is the name for a particular group of health problems that are frequently found together. (It is also called dysmetabolic syndrome, insulin resistance syndrome, obesity dyslipidemia syndrome, or syndrome X.) Core problems of metabolic syndrome are obesity and insulin resistance; three additional problems are high blood pressure, high blood levels of triglycerides, and low blood levels of high-density lipoprotein cholesterol (HDLs). It is not clear whether metabolic syndrome causes type 2 diabetes, but it has been shown that having the syndrome quintuples a person's chances of developing type 2 diabetes (Eckel et al., 2005; Wassink et al., 2007).

Genetic Causes

The direct causes for type 2 diabetes include insulin resistance and abnormal insulin secretion by beta cells. The development of type 2 diabetes from these two underlying problems is hastened by the other disorders found in metabolic syndrome. Some aspects of all these predisposing problems are inherited, and in this way, the propensity for developing type 2 diabetes is inherited.

The specific genetic causes are not known in detail for most variants of type 2 diabetes, but most cases appear to be polygenic, that is, they involve more than one inherited problem (Buse et al., 2003; Davis, 2005).

INDIVIDUAL GENE PROBLEMS

Type 2 diabetes comes in many variants. A few uncommon variants result from single genetic mutations. These monogenic forms usually show up in young people, who then develop the disease no matter what their lifestyle. More than seventy variants of monogenic diabetes have been identified that are caused by different mutations of the insulin receptor—a problem that then leads to insulin resistance. Monogenic diabetes has also been caused by a mutation of the insulin molecule itself. Individual mutations in six different genes have been shown to cause alterations in the beta cells that can also lead to monogenic type 2 diabetes; these particular mutations cause a syndrome called maturity-onset diabetes of the young (MODY).

INTERACTIVE GENE PROBLEMS

The most common variants of type 2 diabetes, however, are polygenic. Polygenic type 2 diabetes usually occurs in older people, and it develops from a complex mix of genetic predispositions and outside factors. Some of the involved genes have been identified, but most are not yet known.

DIAGNOSIS

The health problems of diabetes come directly from hyperglycemia, and the medical diagnosis of the disease is not based on its cause but rather on evidence of persistent high plasma glucose levels, regardless of the cause. Diabetes is diagnosed in the presence of any of these hyperglycemic conditions:

• A fasting plasma glucose level of 126 mg/dl or higher on two separate days
  OR
• A 2-hour plasma glucose level of 200 mg/dl or higher in an oral glucose tolerance test (OGTT) on two separate days
  OR
• A random plasma glucose level of 200 mg/dl or higher and classical symptoms of diabetes (polyuria, polydipsia, weakness, or unexplained weight loss) (Buse et al., 2003)

Examination

The lab work necessary to diagnose diabetes should be included in, or followed by, a complete examination of the patient. The goal of the initial workup is to survey the health of the patient from head to toe. For a person who has or is suspected of having diabetes, there are four specific objectives:

• Attempt to classify the diabetes by cause (type 1, type 2, or other).
• Determine the stage of the diabetes in terms of the level and frequency of hyperglycemia.
• Identify any complications of diabetes that have already developed.
• Identify any other existing problems (eg, hypertension, dyslipidemia) that pose greater health risks in the presence of diabetes (ADA, 2007a)

MEDICAL HISTORY

Here are some aspects of the standard medical history that are especially important in a person with type 2 diabetes.

Present Health

Find out whether patients have increased urination (ask how many times a night they get up to go to the bathroom) or increased thirst. Are they frequently tired? Have they been feeling weak? Have they lost or gained weight? Are they unusually hungry? Do they have blurred vision? Do they have dry skin? Do people tell them their breath smells fruity?

Ask about signs and symptoms of peripheral vascular disease and neuropathies. Do their feet always seem cold? Do they turn white or blue? Do their feet feel numb, uncomfortable, or tingly? Do they have these problems in the hands? Are they sometimes surprised by sores on the feet that went unnoticed? Do they get pain or weakness in the legs when walking? Do they tumble?

If patients have already been diagnosed with diabetes, find out at what age they learned of the diagnosis and what the signs and symptoms were at the time. Get records of past blood chemistries (fasting plasma glucose levels, A1C values, and fasting lipid levels) and of past blood pressure readings. Also get details of acute episodes of hyper- or hypoglycemia. Finally, chart a history of the way the diabetes has been managed up to the present.

Medications

What medications does the person take? Many drugs can cause increased plasma glucose levels, even in people without diabetes. Specifically, ask patients whether they take or have taken glucocorticoids (eg, prednisone), anti-epileptics (eg, phenytoin), antihypertensives (eg, calcium channel blockers, diuretics, diazoxide, clonidine), antipsychotic drugs (eg, clozapine, olanzapine), antiretroviral drugs (eg, the protease inhibitors used to treat HIV infections), asthma drugs (beta 2 adrenergic agonists, epinephrine/adrenalin), pentamidine (long-term use), or H2-receptor blockers (eg, cimetidine).

Earlier History

Have patients ever been diagnosed with diabetes or prediabetes? Have they ever been told they had high blood sugar or sugar in the urine? Do they have high blood pressure, glaucoma, or high cholesterol? Have they had retinal, kidney, nerve, foot, artery, or heart problems? Do they get frequent infections? Do skin sores heal slowly or not at all? Have they had gangrene or amputations?

For a woman in her reproductive years, has she been having sporadic (or no) menstrual periods? Does she get itchy vaginitis or frequent candida (yeast) infections? Has she delivered a baby who weighed more than 9 lbs (4.1 kg)? Did she have gestational diabetes, polyhydramnios (excess amniotic fluid), or pre-eclampsia? Has she had an unexplained miscarriage?

For a man, has he had difficulty having erections?

Family History

For the family history, ask specifically whether the patient has any close relatives who have (or had) diabetes? What type of diabetes was it? How early did it show up? Did the person need to take insulin? Was the person overweight? If the person is not alive, what was the cause of death? Does the patient have relatives who are overweight? Do heart or artery problems run in the family? Have any close relatives had strokes?

Social History

As a basis for planning the patient's proper diet, write down the typical daily diet. Ask: "What do you eat for breakfast? … lunch? … supper? Do you have snacks between breakfast and lunch? … lunch and supper? … supper and bedtime? What do you drink during the day?" (Buse et al., 2003). Ask how much exercise patients get each week. Ask whether they smoke or have ever smoked. Find out what they know about diabetes and diabetes self-care.

Review of Systems

One common complication after many years of hyperglycemia is nerve damage, or autonomic neuropathy. A thorough review of systems can help to identify damage to the autonomic nervous system. Be sure to ask whether the patient has been having any of these problems:

• Cardiovascular: high heart rate at rest, dizziness or fainting when the patient stands suddenly, difficulty exercising
• Gastrointestinal: difficulty swallowing, bloating, nausea, constipation, diarrhea, leaking of feces
• Genitourinary: impotence, reduced vaginal lubrication, inability to empty the bladder, recurrent urinary tract infections
• Skin: reduced sweating of hands or feet

Physical Examination

The physical exam should include a thorough search for signs of diabetic complications and for other problems, such as abdominal obesity or hypertension, that compound the risks posed by diabetes.

OBESITY

The most commonly used measure of obesity is the body mass index (BMI). This is measured using the formula

BMI = weight in kilograms / height in meters²
or
BMI = weight in pounds x 703 / height in inches²

The BMI has been shown to be a good indirect indication of the percentage of body fat, and it is the most commonly used measure of total body fat.

When weight is measured in kilograms and height in meters, the BMI obesity definitions for adults are as follows.

OBESITY DEFINITIONS: BMI (kg/m2)

Normal		18.5–24.9
Overweight		25.0–29.9
Obese	Class 1	30.0–34.9
	Class 2	35.0–39.9
	Class 3 (extreme obesity)	>40.0

As a broad generalization, the excess fat on people with type 2 diabetes tends to be central (in the face, neck, chest, and abdomen) rather than in the arms or legs. When there is excess of fat inside the abdomen, the person has a round, "apple" shape. This form of obesity is associated with metabolic syndrome. A diabetic person with intra-abdominal obesity has a high risk of developing atherosclerotic cardiovascular disease.

Intra-abdominal fat is visceral fat, which is the more dangerous type of fat. Studies have shown that simply measuring a person's waist circumference gives a good indication of the amount of visceral fat. To get a standard waist circumference, measure around the smallest (minimal) circumference anywhere in the waist region (below the ribs and above the top margins of the hip bones). A waist circumference of >37 in (94 cm) in men and >31.5 in (80 cm) in women is considered a warning sign, and a circumference of >40 in (102 cm) in men and >35 in (88 cm) in women puts a person in a high-risk category for developing cardiovascular disease.

VITAL SIGNS

Record the patient's resting blood pressure. In a person with diabetes, resting blood pressures (repeated on separate days) of >130/85 mm Hg are a warning sign of future problems. In addition, measure orthostatic blood pressure (ie, just after the person has stood up). Diabetic autonomic neuropathy can slow a person's vasoconstrictive responses, and suddenly standing may produce notable hypotension. Autonomic neuropathy can also produce resting tachycardia, which you will pick up when checking the patient's heart rate.

SKIN

Autonomic neuropathy can cause reduced sweating, which makes the skin (especially on hands and feet) dry and itchy. Diabetes also makes a person prone to infections and makes skin sores heal slowly. Look for ulcers and skin erosions, especially in places on the peripheral extremities that are bumped frequently, such as the pretibial regions and the feet. In patients using insulin, check the skin areas that are used as injection sites.

EYES

People with diabetes get retinopathies, cataracts, and glaucoma. Examine the optic fundi for retinal hemorrhages, which appear as small round red spots, for "cotton wool" patches, which are gray or white areas with fluffy borders, and for "hard" exudates, which are small whitish spots with sharp edges. Diabetic autonomic neuropathy can produce miotic pupils with sluggish light reflexes.

MOUTH

Dental diseases are more common in people with diabetes, so examine the patient's teeth and gums. Ketosis gives a fruity, acetone-like odor to a person's breath.

CARDIOVASCULAR SYSTEM

Macrovascular problems lead to poor peripheral circulation. Quantifying the strength of all the peripheral pulses provides a baseline for monitoring the patient's circulation. Be sure to record both the ankle and feet pulses. Note whether the feet are cool and pale, and check the capillary refill under the nails of the toes.

EXTREMITIES

In diabetes, the feet and ankles can suffer from reduced micro- and macrovascular circulation, poor healing, and peripheral neuropathy. Study the skin on the feet for erosions, ulcers, and infections. Check for toenail problems. Examine the ankle and foot joints for deformities and injuries.

NERVOUS SYSTEM

Diabetic neuropathies show up only after many years of hyperglycemia. Peripheral sensory and motor neuropathies injure the longest nerves first and show up in the feet before the hands. Over the years, peripheral neuropathies slowly move proximally. Sensory problems include paresthesias, numbness, and pain; motor problems include reduced deep tendon reflexes and muscle weakness.

Test the patient's toes, ankles, and fingers bilaterally for proprioception, vibration, and monofilament sensation (using a standardized diabetes monofilament). Try to quantify any deficits so that you can objectively follow the progression or appearance of problems. (See Nerve Problems in the section on Chronic Complications below for more details.)

Laboratory Tests

An initial diabetes examination screens for abnormalities and also establishes baseline values that you will use to evaluate the treatment program and to follow the progress of the disease objectively.

BLOOD GLUCOSE TESTS

Fasting Plasma Glucose (FPG)

Among the various measurements of the body's ability to produce and use glucose, the blood level of glucose after an 8-hour fast is the standard. After 8 or more hours without eating, the body should maintain plasma glucose levels in the range of 90 to 100 mg/dl.

In the United States, measurements of the concentration of molecules in the blood are traditionally given in terms of milligrams per deciliters, or mg/dl. Standard chemistry prefers millimoles per liter, mmol/l. Plasma glucose levels—the key laboratory values in evaluating diabetes—are sometimes given in each of the units. This graph shows how the concentration of plasma glucose translates from mg/dl to mmol/l.

People whose fasting blood level of glucose are frequently 100 to 125 mg/dl are not able to use glucose optimally and are said to have prediabetes; they are said to have impaired fasting glucose (IFG). When a person's fasting blood glucose levels are frequently ≥126 mg/dl, the continual hyperglycemia threatens his health, and he is said to have diabetes.

Fasting plasma glucose (FPG) is the preferred diagnostic test for diabetes, except in pregnant women. Formally, diabetes is diagnosed when a person's FPG is ≥126 mg/dl on at least two different days.. It is important to confirm high FPG values on a second day, because the FPG varies from day to day (ADA, 2007a).

CATEGORIES OF GLUCOSE METABOLISM

Glucose metabolism is categorized by level of fasting plasma glucose.
Fasting Plasma Glucose Levels
Normal	≤100 mg/dl
Prediabetes	100–125 mg/dl
Diabetes	≥126 mg/dl

Oral Glucose Tolerance Test (OGTT)

A more complicated test, the oral glucose tolerance test, can also be used to diagnose diabetes. In an OGTT, the patient drinks a sugar-water solution (75 g glucose in 300 ml water), and the plasma glucose level is measured after 2 hours. For values, see table above. Again, high plasma glucose levels must be confirmed by a test on a second day. For an OGTT, constraints include:

• Test must be given after an overnight fast
• Patient must have been receiving at least 150–200 g of carbohydrates daily for the 3 days preceding the test
• Patient must not have an acute illness
• Patient must not be taking medications that affect glucose tolerance, such as diuretics, contraceptive pills, glucocorticoids, niacin, or phenytoin

Currently, fasting plasma glucose (FPG) measurements are the preferred test for diagnosing diabetes. Oral glucose tolerance tests are used mainly for research studies and to resolve borderline results from FPG tests (Buse et al., 2003).

A1C Test

The A1C test is also called the A1c, hemoglobin A1c, HbA1c, glycohemoglobin, glycated hemoglobin, and glycosylated hemoglobin test. This test is used to monitor a patient's blood glucose levels during treatment—it is not used to diagnosis diabetes (ADA, 2007a).

The A1C test measures the percent of hemoglobin to which glucose molecules have become attached—ie, the percent of glycosylated hemoglobin. As a person's plasma glucose level rises, more hemoglobin molecules become glycosylated. Red blood cells (and their hemoglobin) are replaced after about 4 months, and the amount of glycosylated hemoglobin at any one time reflects the average plasma glucose level over the last 2 to 3 months.

Be aware that the exact level of "normal" for an A1C test varies somewhat from laboratory to laboratory. Another caveat is that the A1C test can be inaccurate when the patient has genetic mutations of the hemoglobin, conditions that change the amount of red blood cells in the circulation (eg, bleeding, hemolysis, anemia), renal failure, or alcoholism. The following graph shows the average plasma glucose levels that are indicated by various A1C values.

The overall average blood glucose level for the past 2 to 3 months as indicated by various A1C values.

A 1% change in an A1C value reflects a change of about 30 mg/dl in average plasma glucose. Normal levels of plasma glucose produce an A1C value of about 5%. As the A1C value increases, so does the likelihood of complications. The American Diabetes Association recommends that people with diabetes aim for A1C levels <7%, although this goal can be hard to achieve for many people with diabetes (ADA, 2007a).

A1C values are averages, and A1C values will lower (and therefore appear to be improved) if there are significant periods of excessively low plasma glucose levels (ie, hypoglycemia). Also, the A1C values will not reflect short swings in plasma glucose levels, as happen with brittle diabetes. To recognize hypoglycemic periods or short-term shifts in plasma glucose levels, patients should monitor their glucose levels regularly. The true level of glycemic control can be seen best through a combination of A1C tests and daily blood glucose readings (Buse et al., 2003; ADA, 2007a).

BLOOD LIPID TESTS

Dyslipidemia (ie, an unhealthy level of blood lipids) increases a person's risk of developing a variety of health problems, most notably atherosclerotic cardiovascular disease. Type 2 diabetes is characteristically accompanied by dyslipidemia. This dyslipidemia, which is a component of metabolic syndrome and is associated with obesity, includes:

• Elevated blood levels of triglycerides
• Reduced blood levels of high-density lipoproteins (HDL)
• The LDL particles are smaller and denser than usual and contain more than the usual amounts of free cholesterol. This means the cholesterol in type 2 diabetes is more easily added to atherosclerotic plaque.

FASTING PLASMA LIPID LEVELS

Triglycerides	normal	<150 mg/dl
	borderline high	150–199 mg/dl
	high	≥200 mg/dl
HDL cholesterol	low	<40 mg/dl
	high	≥60 mg/dl
LDL cholesterol	optimal	<100 mg/dl
	borderline high	130–159 mg/dl
	high	≥160 /mg/dl

The dyslipidemia of type 2 diabetes is not always improved by simply reducing the patient's hyperglycemia: dyslipidemia may need direct treatment (Masharani & German, 2004; Masharani, 2007).

LIVER ENZYMES

Record a baseline set of values for liver functioning. Most of the medications used to lower blood glucose levels are deactivated in the liver. If the liver is not functioning properly or if it later develops problems, the dosages or types of medications may need to be adjusted.

URINE TESTS

At one time, diabetes treatment was monitored by measuring the amount of glucose in the urine. Finger-stick blood glucose measurements are more sensitive and more accurate, and they have replaced urine tests for monitoring daily plasma glucose levels.

Glucose Levels

In the kidneys, glucose that is initially filtered from the blood is almost fully reabsorbed before the urine is excreted. This reabsorption is very efficient, even when there is an excess of blood glucose up to levels of about 180 mg/dl. (Reabsorption is not absolute—normal urine does contain a small amount of glucose.)

Beyond 180 mg/dl, however, the kidney cannot reabsorb all the glucose that it filters. Therefore, at mild levels of hyperglycemia, some glucose begins to spill into the urine. Above a blood glucose level of about 275 mg/dl, all the excess glucose is spilled into the urine (Bonnardeaux & Bichet, 2004).

By the time measurable sugar appears in the urine, hyperglycemia is already at an unhealthy level. Nonetheless, urine testing is an easy and quick warning of mild hyperglycemia, and urine tests are sometimes used for screening. Commercial plastic or paper strips (eg, Clinistix, Diastix, Miltistix, Uristix) can be dipped in fresh urine and will change color in different concentrations of sugar (Silkensen & Kasiske, 2004).

Ketone Levels

Ketones are released into the blood when fatty acids are being used for energy instead of glucose. When significant amounts of ketones are found in the urine of a person with diabetes, his hyperglycemia is usually >300 mg/dl. Patients on insulin therapy who have not taken sufficient insulin have measurable ketones in the urine.

Albumin Levels

Protein (albumin) leaking into the urine of a person with diabetes usually indicates kidney damage. Significant kidney damage is preceded by a period during which only a small amount of albumin is found in the urine, an amount less than that detectable by regular reagent strips (eg, Albustix). This early microalbuminuria can be qualitatively recognized using specialized reagent strips (Micral-Test) or tablets (Micro-Bumintest) (Silkensen & Kasiske, 2004).

RENAL FUNCTION TESTS

Diabetes is the leading cause of endstage renal disease. Therefore, it is important to monitor indicators of kidney function. A periodic record should be kept of serum creatinine and blood urea nitrogen (BUN) levels, and a glomerular filtration rate (GFR) should be calculated with each blood test. The GFR can be estimated using a formula that requires the serum creatinine level and the age, weight, and sex of the patient (Oh, 2006).

Newly Discovered Hyperglycemia

People who do not know that they have diabetes may come to an office, clinic, or emergency room with hyperglycemia. Sometimes their hyperglycemia is discovered incidentally and with no other clues. On the other hand, these patients may have symptoms of diabetes, such as polydipsia, polyuria, weakness, fatigue, blurred vision, headache, dizziness, or dehydration. At times, such patients already have diabetic complications, for example, coronary artery disease, peripheral vascular problems, nonhealing wounds, or recurrent skin or genitourinary tract infections.

If patients not known to have diabetes present with mild hyperglycemia (<300 mg/dl), with no serious dehydration, and with no other significant disorders, they should be scheduled for a full diabetes evaluation. If they present with hyperglycemia of >200 mg/dl and classic symptoms of diabetes, they can be diagnosed as having diabetes and should be scheduled for a full diabetes evaluation. If they present with moderate to severe hyperglycemia (>400 mg/dl), they should be evaluated immediately and given insulin and fluids if necessary.

Moderate to severe hyperglycemia in a person not previously known to have diabetes is usually triggered by another recent problem, so in these cases, look for infections or acute cardiac or kidney problems.

TREATMENT

Ideally, patients with diabetes should be treated by a team of healthcare providers. The primary physician does not have the time to help each patient manage everyday care. The many necessary interactions with a patient, especially at the beginning of therapy, should be divided among a team of specialists—nurses, dietitians, physical therapists, and psychological counselors. Medical complications should be referred to specialty physicians, such as ophthalmologists, cardiologists, renal specialists, podiatrists, and psychiatrists.

Pregnant women pose special challenges for diabetes care and therefore need special caretakers. During pregnancy, weight-loss programs should be terminated, oral hypoglycemic medications are contraindicated, and insulin therapy should be intensified. Congenital malformations are more common in diabetic pregnancies when the diabetes is not well-controlled, and infants are often of larger than normal birthweight.

These and other potential complications make it important for diabetic women of reproductive age to understand the risks of a pregnancy, and their diabetes care teams should include nurse-midwives or obstetricians specializing in diabetes.

The primary physician, with help from the patient and the treatment team, formulates an initial plan from the various treatment options. The arsenal of treatment options ranges from lifestyle changes to medications.

Lifestyle Changes

The primary lifestyle changes used to treat type 2 diabetes are weight loss, increased physical activity, smoking cessation, and planned meals (see Recommended Diabetic Diet, below). The most effective ways to reduce the insulin resistance that underlies type 2 diabetes are weight loss and exercise.

Changing a lifestyle requires guidance and willpower. Losing weight takes encouragement, monitoring, and practical advice—even for people who are only mildly overweight. Moving from a sedentary pattern to a program of physical activity is also extremely challenging for newly diagnosed diabetes patients.

Time works against lifestyle changes. Lost weight is notorious for reappearing: people who diet on their own tend to regain the lost weight in less than a year. Organized dieting programs such as Weight Watchers, TOPS (Take Off Pounds Sensibly), and Overeaters Anonymous can help mildly overweight patients to maintain lower weights. For patients who are moderately or severely overweight, however, professional behavioral therapy may be necessary.

Lifestyle changes and medications work least often in severely obese patients. For these patients, bariatric surgery is an option. Surgery is considered if the patient has tried monitored dieting, exercise regimens, and medications.

Typically, surgery is only recommended for extremely obese patients, ie, patients with a body mass index (BMI) ≥40 kg/m² (extreme obesity). Less overweight patients—those with a BMI of 35.0–39.9 kg/m²—are considered for surgery when they have sleep apnea, type 2 diabetes, or components of metabolic syndrome.

The best hospitals for bariatric surgery are those that do a significant number of the surgeries and that use a team (physician, psychologist, and dietician) to treat patients. Even in the best of circumstance, however, slimming down to a person's ideal weight is not a realistic goal. With optimal treatment, bariatric patients are likely to lose 50% to 60% of their excess weight.

Smoking worsens insulin resistance and speeds up the appearance of diabetic complications. Explain the medical consequences to any patient who smokes, and strongly recommend that the patient stop smoking. It is difficult for smokers to quit on their own, so help them get into a program that includes support, counseling, and the availability of anti-smoking medications.

WEIGHT LOSS

Even a modest weight loss makes a difference for an overweight or obese person, and losing 5% to 7% of the original weight and keeping the weight off is a realistic goal. The best weight loss results come from structured programs that include individualized counseling, meals with reduced calories and fats, regular physical activity, and frequent contacts with a professional advisor.

To lose weight, a person must eat fewer calories each day. The American Diabetes Association (ADA, 2007c) recommends that, even for weight loss, a daily diet should be balanced and moderate. Neither very low carbohydrate (ie, <130 g/day) nor very high protein (ie, >35% of total daily calories) diets are recommended in weight loss programs for a person with diabetes. Instead, low-fat, low-calorie diets are preferred.

RECOMMENDED BALANCE OF FOOD TYPES

carbohydrates	45% to 65% of total daily calories
fats	20% to 35% of total daily calories
proteins	15% to 20% of total daily calories
Total daily calories are determined by the individual's specific weight loss goals.
Source: ADA, 2007c.

Well-controlled research studies have confirmed the common experience that it is difficult to lose even modest amounts of weight and then to keep the weight off. One successful program uses reduced-calorie, low-fat diets designed to meet the limits shown below.

DAILY CALORIES/FAT FOR WEIGHT-LOSS DIETS

Initial weight	Total daily calories	Total daily fat
120–174 lb	1200	33 g
175–219 lb	1500	42 g
220–249 lb	1800	50 g
>250 lb	2000	55 g
Source: ADA, 2007c.

For overweight or obese patients with type 2 diabetes, dietary fat should be watched carefully. Reducing the overall calories in a person's diet will improve the lipid profile. Reducing the amount of fat improves the lipid profile even further. It is important to remove foods that are high in saturated fats, such as:

• Fatty meats, eg, bacon and sausage
• Chicken or turkey when they are eaten with the skin
• Egg yolks
• Butter
• Lard and shortening
• Hydrogenated and partially hydrogenated vegetable oils
• Coconut oil, palm oil, and cocoa butter
• Cream, half-and-half, and ice cream
• Cookies, cakes, muffins, and pastries

Fat-rich foods should be replaced with foods that have high water and fiber content, eg, fruits, vegetables, legumes, and low-fat soups.

It is best to tailor the foods of any diet program to the dieter, and it is ideal to have a nutritionist or dietician as part of the diabetes care team. In addition to food planning, these professionals can suggest patterns of eating that help in weight loss. For example, scheduling regular eating times helps a person to control eating. For people with type 2 diabetes, spacing meals roughly every 4 hours during the day is optimal (Buse et al., 2003).

Increased Physical Activity

Exercise not only contributes to losing weight but also to maintaining weight loss; nonetheless, exercise alone rarely leads to significant weight loss and a reduced-calorie diet is usually necessary. A regular exercise program has independent metabolic effects that reduce insulin resistance in people with type 2 diabetes. It also helps lower blood triglycerides, raise blood HDLs, and reduce hypertension. Exercise immediately reduces blood glucose levels, and regular exercise reduces a person's average level of hyperglycemia (ie, it lowers A1C values).

Regular exercise may be the single most important lifestyle change for people with type 2 diabetes (Buse et al., 2003). Both moderate aerobic and moderate resistance exercises are recommended for most people with type 2 diabetes. The goal is at least 150 minutes of exercise per week, distributed over 3 to 4 days.

AEROBIC EXERCISE

For most people with type 2 diabetes, the recommendation is to schedule a minimum of 2.5 hours of moderately intensive aerobic exercise a week. The exercise sessions should be spread over at least three days, without skipping more than two days in a row. Ideally, the person should exercise a full 30 minutes at a time, because a 30-minute session is about twice as beneficial as one lasting 20 minutes.

Aerobic exercises include walking, dancing, bicycling, jogging, swimming, water aerobics, and many sports. "Moderate intensity" means that the exercise brings a person's heart rate up to between 1/2 and 3/4 of his maximum rate—the rate at which a person is still able to carry on a conversation (ADA, 2007a).

RESISTANCE EXERCISE

Patients should try to add resistance exercises to their weekly schedule. Resistance exercises use muscular strength to push or pull a weight; these exercises include push-ups, pull-ups, weight lifting, and exercises on weight machines. The recommendation is to have resistance exercise sessions three days a week, and with three sets of 8 to 10 weight repetitions per session. It is suggested that people use a resistance weight that they can push (or pull) for only 8 to 10 repetitions without stopping to rest.

EXERCISE SCHEDULES

For exercise to have a substantial role in treating diabetes, the activities must be regular and long-term. Therefore, they must fit realistically into the patient's life. Exercise schedules must be practical, so it is important that the patient be involved in setting up the exercise regimen. An exercise specialist or physical therapist should sit down with each patient and to help create a manageable exercise plan. The professional should meet with patients regularly to monitor and advise them.

Many patients with type 2 diabetes live sedentary lives. For them, the exercise schedule should begin gradually, with short regular walks or brief exercise sessions. Over time, the length and the intensity of the exercise sessions should be increased. Trainers should present each increase as an accomplishment, as a goal met, not as the addition of a further burden.

EXERCISE RESTRICTIONS

The physician in a diabetes team should screen each patient for health problems that must be accommodated in the exercise program. Very few problems preclude adding more physical activity to the daily life of a person with diabetes, but certain problems put special constraints on those activities.

Insulin or Insulin Secretagogues

An exercise session uses up circulating glucose. If a patient takes insulin or insulin secretagogues, their effect may suddenly be too much for the lowered level of plasma glucose during exercise. In this case, the person becomes hypoglycemic. The general solution is for people who take insulin or insulin secretagogues to eat additional carbohydrates before exercising. See the section below on Insulin Therapy for a discussion of hypoglycemia.

Cardiovascular Disease

Before a sedentary person with diabetes and cardiovascular risks starts a new exercise program, it is usually best to administer a stress test. (This is not always needed for young, otherwise healthy people with diabetes.) If the test shows cardiovascular problems, it is still possible to create a gradually increasing exercise plan, with the patient warned not to overexert and to watch for chest, jaw, or arm tightness or pain and for palpitations or shortness of breath.

Hypertension

The general rule is to bring a person's blood pressure into a healthy range before initiating an exercise program.

Retinopathy

Proliferative diabetic retinopathy or severe nonproliferative retinopathy puts a patient at risk for vitreous hemorrhages or retinal detachment. There is controversy over whether vigorous exercise can cause these problems, so consult a retinal ophthalmologist before advising exercise programs for people with diabetic retinopathy.

Peripheral Neuropathy

A person who lacks the ability to fully sense injury to the feet, ankles, and legs can damage skin and joints without realizing it. Therefore, diabetic patients with peripheral neuropathy should limit themselves to low-impact exercises, such as swimming, bicycling, and arm exercises.

Autonomic Neuropathy

Damage to the autonomic nervous system can cause reduced or inappropriate responses to exercise. Diabetic patients who have autonomic neuropathy should be given a thorough cardiac examination before beginning a new exercise program.

Medications

ANTI-OBESITY DRUGS

Lifestyle changes and counseling are the first steps in treating obesity. When these steps do not lead to sufficient weight loss, medications can be tried. One drug used for obesity is the appetite suppressant sibutramine (Meridia), which works in the brain to make a person feel full earlier in a meal. Other central nervous system medications that have been used for obesity are fluoxetine (Prozac), diethylpropion (Tenuate), and bupropion (Wellbutrin, Zyban).

The anti-obesity drug orlistat (Xenical) works quite differently. Orlistat is a malabsorption agent that inhibits intestinal lipase and reduces the intestine's absorption of fat; thus Orlistat is helpful only for meals containing fat. A frequent side effect of this drug and its recent OTC variant (Alli) is sudden bouts of diarrhea. Patients should be made aware of this when the medication is prescribed.

Weight that has been lost with the aid of medications is typically regained when the medication is stopped. For this reason, drug therapy works best when it is used as part of a treatment plan that includes lifestyle changes and counseling.

ORAL HYPOGLYCEMICS

For most people with type 2, medications are part of their treatment programs. Oral hypoglycemics are the most commonly used medications, but many people with type 2 diabetes need insulin. Typically, treatment for a person with type 2 diabetes starts with a trial of lifestyle interventions. If these are not sufficient to improve the patient's metabolic problems, then oral hypoglycemic medications are tried, usually beginning with Metformin.

Oral medications for treating type 2 diabetes fall roughly into five classes. The two most commonly prescribed classes are insulin secretagogues (drugs that increase insulin secretion) and insulin sensitizers (drugs that decrease insulin resistance).

The three lesser-used classes are alpha-glucosidase inhibitors (drugs that slow glucose absorption in the intestines), incretin-related drugs, and glucagon suppressors. All the oral anti-diabetic medications should be used cautiously or not at all in people with significant liver or kidney problems (Masharani & German, 2004; Davis, 2005; Masharani, 2007).

Insulin Secretagogues

Sulfonylureas stimulate beta cells to release insulin. Sulfonylureas cannot be used for type 1 diabetes because the beta cells are not functioning; on the other hand, sulfonylureas are the most-prescribed drugs for the treatment of type 2 diabetes. Sulfonylureas are secretagogues, and their main adverse effect is hypoglycemia, especially in older adults.

The sulfonylureas are divided into two groups. The first-generation drugs are:

• Acetohexamide (Dymelor): rarely used.
• Chlorpropamide (Diabinese): rarely used.
• Tolbutamide (Orinase): typically taken before each meal and at bedtime, acts over 6–10 hours
• Tolazamide (Tolinase): typically taken twice a day, acts over 20 hours with maximum effect in 4–14 hours

The second-generation sulfonylureas, which are more potent releasers of insulin, are:

• Glimepiride (Amaryl): typically taken once daily, acts over 24 hours
• Glipizide (Glucotrol, Glucotrol XL): typically taken once daily, acts over 24 hours
• Glyburide (DiaBeta, Glynase PresTab, Micronase): typically taken once daily, acts over 16–24 hours

Meglitinides are another class of insulin secretagogues:

• Nateglinide (Starlix): typically taken before each meal, acts quickly and briefly, blood levels peak within 1 hour, acts over a short period (<4 hours)
• Repaglinide (Prandin): typically taken before each meal, acts quickly and briefly, blood levels peak within 1 hour, acts over a short period (<4 hours)

Insulin Sensitizers

Metformin, a biguanide, is the classic insulin sensitizer. It counteracts insulin resistance by reducing the amount of glucose released by the liver and, to a lesser extent, by improving the ability of muscle cells to extract glucose from the circulation. Technically, metformin is anti-hyperglycemic, not hypoglycemic. It does not cause insulin to be released from the pancreas, and therefore, it rarely causes hypoglycemia, even in large doses:

• Metformin (Glucophage, Glucophage XR)—typically taken with meals, acts over 24 hours

The second class of insulin sensitizers is the thiazolidinediones:

• Pioglitazone (Actos): typically taken once daily with breakfast, acts over 24 hours. Patients with heart failure should not take pioglitazone.
• Rosiglitazone (Avandia): typically taken once daily with breakfast, acts over 24 hours.

Rosiglitazone has recently (May 2007) been associated with an increased risk of serious heart problems. Therefore, a diabetes specialist and/or a cardiologist should be involved if this drug is used (FDA, 2007; Nissen & Wolski, 2007).

Alpha-Glucosidase Inhibitors

Alpha-glucosidase inhibitors are glucose absorption retardants that slow the digestion and absorption of glucose; this lowers the hyperglycemic peak that occurs after a meal. These drugs work locally (in the intestine) and temporarily:

• Acarbose (Precose): typically taken three times daily, with the beginning of each meal
• Miglitol (Glyset): typically taken three times daily, with the beginning of each meal

Incretin-Related Drugs

The incretins are gastrointestinal hormones that have a number of hypoglycemic effects including the stimulation of insulin secretion. One of the incretin-related drugs, exenatide, mimics incretin actions; the other incretin-related drug, sitagliptin, prolongs incretin actions:

• Exenatide (Byetta)—administered by injection twice daily, 1 hour before breakfast and dinner
• Sitagliptin (Januvia)—oral medication taken once daily

Glucagon Suppressors

Amylin is a natural hormone that suppresses the secretion of glucagon, delays the emptying of the stomach, and decreases appetite. Pramlintide is a synthetic analogue of amylin:

• Pramlintide (Symlin): administered by injection three times daily, just before each major meal

INSULINS

Over the years, the ability of pancreatic beta cells to secrete insulin continues to decrease in people with type 2 diabetes. When the pancreas can only secrete 20% to 30% of the normal amount of insulin, a person begins to need insulin therapy.

Typically, type 2 diabetes is diagnosed when a person has already lost about half of his normal insulin-producing ability, and the majority of people with type 2 diabetes begin to need insulin less than 10 years after their diagnosis (DeWitt & Hirsch, 2003).

The ability of beta cells to secrete insulin declines progressively in most patients with type 2 diabetes. Type 2 diabetes is typically diagnosed approximately 12 years into the disease, when the person has already lost about 50% of the normal insulin secretory ability (adapted from DeWitt & Hirsch, 2003).

Currently, insulin therapy is recommended when the combination of lifestyle changes and oral medications cannot reduce the A1C index below 8% (DeWitt & Hirsch, 2003). The idea of taking insulin injections can scare patients, but by reducing the levels and durations of their hyperglycemic episodes, patients can delay or prevent the otherwise inevitable debilitating complications of the disease. When insulin injections are incorporated into the treatment of poorly controlled diabetes, patients feel better and they report that their quality of life has improved (DeWitt & Hirsch, 2003).

Types of Therapeutic Insulin

Three things distinguish the available forms of insulin: how fast they act, when they peak, and how long they act.

Three insulin analogues plus inhaled insulin are rapid-acting (in 5–15 min), reach their peak of action in 1 hour, and act for only a short time (<5 hours):

• Insulin aspart (NovoLog)
• Insulin lispro (Humalog)
• Insulin glulisine (Apidra)
• Insulin human inhalation powder (Exubera)

When injected, regular insulin (short-acting, natural-acting) begins acting in 30–60 minutes, reaches its peak of action in 2–3 hours, and acts for 5–8 hours:

• Regular insulin

The intermediate-acting insulins begin acting in 2–4 hours, reach a peak of action in 4–10 hours, and act for 10–16 hours:

• NPH insulin
• Lente insulin

The effects of long-acting insulins can last for up to a day:

• Ultralente insulin is called "long acting," but its effects are not dramatically different from NPH or Lente
• Insulin glargine (Lantus) is a long-acting insulin analogue. It reaches a steady state in 2–3 hours, it does not have a peak of activity, and it acts steadily for 20–24 hours.
• Insulin detemir (Levemir) is a long-acting insulin analogue. It reaches a steady state in 3–8 hours, it does not have a peak of activity, and it acts steadily for 6–24 hours.

To match the daily changes in blood glucose levels (ie, high after meals and low during the night), an insulin-dependent patient must mix a variety of insulins. Mixed injections have a rapid onset, give two peaks, and last for 10–16 hours. For convenience, insulins are available in a few dual-acting, pre-mixed formulations:

• 70/30 NPH/regular
• 50/50 NPH/regular
• 75/25 lispro (NPH-like)/lispro (Humalog Mix 75/25)
• 70/30 aspart (NPH-like)/aspart (NovoLog Mix 70/30)

Herbs, An Unrecognized Threat

It has been estimated that almost half of the adults who have diabetes try alternative therapies: acupuncture, Ayurveda, biofeedback, chelation, chiropractic care, energy healing, herbs, homeopathy, hypnosis, massage, naturopathy, Reiki therapy, relaxation, unusual diets, or yoga (Garrow & Egede, 2006). Herbs and dietary supplements can be a problem for people with diabetes who are taking insulin or insulin secretagogues (such as sulfonylureas), because some herbs and supplements lower glucose levels. When used along with prescribed medications, the following compounds have the potential to cause unexpected bouts of hypoglycemia:

• Concentrated soluble fiber (beta-glucan) from barley
• Bitter melon (Momordica charantia) or balsam pear, the active ingredient is also called MAP30
• Gymnema or Asclepidacea extracts
• CoQ10 (Sierpina, 2003; Natural Standard, 2007)

At each visit with your patient, ask whether they are trying any herbs or supplements to help treat their diabetes.

ADDRESSING HYPOGLYCEMIA

The most serious risk of insulin therapy is hypoglycemia. Hypoglycemia can cause unconsciousness, and if not corrected by the addition of glucose to the bloodstream, can eventually be fatal. A very low blood glucose level (<10 mg/dl) begins causing irreversible brain damage in as short as 30 minutes.

As a rule, hypoglycemia is less a risk for people with type 2 diabetes than for those with type 1, but it still occurs. All diabetes patients should learn to recognize the feelings caused by hypoglycemia. Initially, patients should test their plasma glucose levels in different situations to compare their subjective sensations with the actual glucose levels. They should also occasionally check blood glucose levels in the middle of the night to make sure they are not getting too hypoglycemic while sleeping.

For people on insulin therapy, missing a meal or exercising vigorously are the most common causes of hypoglycemia. Diabetic patients who take anti-sympathetic drugs, such as beta-blockers, should be warned that these medications blunt the symptoms of hypoglycemia, making a potentially life-threatening situation less obvious. Patients need to recognize the following:

• Weakness
• Shakiness
• Dizziness
• Faintness
• Feeling warm
• Hunger
• Headache
• Irritability
• Confusion
• Pale skin

Sugar is the treatment for hypoglycemia. Patients should be told to take 15 g of glucose (1/2 cup of fruit juice, 5 small pieces of hard candy, or 3 standard glucose tablets) if they feel hypoglycemic. If the symptoms persist for more than 10 to15 minutes, they should repeat the 15-g dose of sugar. If both doses do not improve the symptoms, the patient should report to a physician, clinic, or hospital.

All patients who take critical medications, such as insulin or insulin secretagogues, should carry medical identification, such as a Medic-Alert tag. Patients on insulin therapy also need to be given specific instructions about how to handle hypoglycemic episodes. These patients should always have with them tablets of sugar or hard candy. At home, they should have an emergency glucagon kit, and family and friends should be taught how and when to give an intramuscular injection of glucagon (Masharani & German, 2004; Masharani, 2007).

Recommended Diabetic Diet

For all types of diabetes, a fundamental part of treatment is controlling the composition and quantity of meals. People with type 2 diabetes who take fixed doses of insulin or insulin secretagogues must strictly schedule their meals and their medications to avoid periods of hypo- and hyperglycemia; for these people, as with people who have type 1 diabetes, counting carbohydrates and using exchange lists are important parts of their daily eating plan (Buse et al., 2003; ADA, 2007c).

Most people with type 2 diabetes do not take fixed doses of insulin. For these people, the top priority of a proper diet is striking a balance that minimizes hyperglycemia, encourages weight loss (when needed), reduces dyslipidemia, and lowers blood pressure. These goals can be accomplished when the person's meals have reduced calories, low saturated and trans fat, low cholesterol, and low amounts of sodium, with an appropriate overall mix of carbohydrates, fats, and proteins. Detailed carbohydrate counting of each meal is not necessary.

There is no exact mix of nutrients that comprises the optimal diet for people with type 2 diabetes. The recommended balance for all healthy adults is also the best guide for people with diabetes; however, when building a diet with this overall mix of macronutrients, there are some special recommendations for people with type 2 diabetes.

CARBOHYDRATES

A person with diabetes should aim for approximately 130 gm of carbohydrates each day. Although diets high in carbohydrates can cause hyperglycemia, low-carbohydrate diets (ie, <130 gm/day) are not recommended, because foods containing carbohydrates are important sources of energy, fiber, vitamins, and minerals. Fruits, vegetables, whole grains, legumes, and low-fat milk are all recommended. Foods with whole grains have been shown to reduce insulin sensitivity.

There is no need to avoid using sucrose as a sweetener (in moderation), and naturally occurring fructose is also not harmful. The standard reduced-calorie sweeteners—such as mannitol, sorbitol, and xylitol—are safe for people with diabetes and have about one-half  the calories of equivalent amounts of sugar. Likewise, artificial (non-nutritive) sweeteners—such as acesulfame potassium, sucralose, and aspartame—are safe for people with diabetes, in moderation (ADA, 2007a).

Glycemic Index

The glycemic index is a standard way to compare the effects of different foods on the blood glucose level after a meal. Foods with lower glycemic index cause less of a spike in blood glucose after they are eaten. Low glycemic-index foods include oats, barley, bulgur, beans, lentils, legumes, pasta, pumpernickel (coarse rye) bread, apples, oranges, milk, yogurt, and ice cream. Theoretically, these foods should make blood glucose control easier for people with diabetes; in reality, studies show that diets with low–glycemic-index foods make glycemic control only slightly easier than diets with high–glycemic-index foods.

Carbohydrate Counting

Limiting carbohydrates in the diet is a key part of controlling hyperglycemia. When regular doses of insulin or insulin secretagogues are needed to cope with the glucose load after meals, it is important to match the dose to the amount of carbohydrates that are eaten at each meal. Patients can estimate the carbohydrates in their meals by summing the approximate grams in each serving. The labels of most foods help patients to make these estimates.

Another way to keep track of carbohydrates is through a standardized set of foods and portions in the form of exchange lists. A single carbohydrate serving is considered to have 15 grams of carbohydrates, and a person with diabetes should have 8.5 to 9 servings of carbohydrates each day, divided among 4 meals. On an exchange list, specific foods are listed in terms of portions equivalent to one carbohydrate serving, so a person can choose preferred foods to fill out the daily allotment. See table below for carbohydrate equivalents.

PORTIONS EQUAL TO ONE CARBOHYDRATE SERVING

Starches	1 slice of bread
	1/3 cup of cooked pasta
	3/4 cup of dry cereal
	4–6 crackers
Fruits	1 small piece of fruit
	1/2 cup of fruit juice
Milk	1 cup nonfat (skim) milk
	1/2 cup of yogurt
Desserts	2 small cookies
	1/2 cup of ice cream

Exchange lists are co-published by The American Dietetic Association and the American Diabetes Association. Nutritionists, dieticians, and diabetes educators have these lists, and the websites of the two Associations (http://www.diabetes.org, http://www.eatright.org) tell how to get copies of "Exchange Lists for Meal Planning." The best way for a patient to learn how to estimate the carbohydrate content of his meals is through individualized training sessions with diabetes nutrition instructors (ADA, 2007c).

FATS

Dietary fats contribute to the total calories consumed, but the amount of fat in a meal has only a small affect on the level of blood glucose after the meal. The more important consideration for people with type 2 diabetes is their risk for developing coronary heart disease. Dietary fats play a major role in the formation of atherosclerotic plaque. To reduce the likelihood of atherosclerotic cardiovascular disease, a person—especially, a person with type 2 diabetes—should limit the saturated fatty acids, trans fatty acids, and cholesterol in meals.

Fats should make up 20% to 35% of a person's total daily calories. Saturated fats should be limited to less than 7% of total daily calories, trans fats minimized, and cholesterol limited to less than 200 mg per day. Most of the daily fat intake should be monounsaturated or polyunsaturated (a "Mediterranean" diet).

Two or more servings of fish per week (but not commercially fried fish filets) are recommended for their long polyunsaturated fatty acids. Other healthy fats are found in many seeds and nuts, olives, olive oil, and canola oil.

Plant sterols and stanols (types of natural vegetable fats) can lower blood cholesterol levels and are good substitutes for other fats. To increase the sterols and stanols in the diet, patients can replace other types of fat with commercial margarine spreads (eg, Benecol, Take Control) or dietary supplement capsules (eg, Benecol Softgels, Cholest-Off, Cholesterol Success Plus).

PROTEIN

As with fats, proteins in a meal do not significantly raise after-meal glucose levels. Proteins (actually, the amino acids derived from the proteins) do increase insulin secretion, and in this way, eating protein with carbohydrates helps a person with type 2 diabetes to reduce the spike of blood glucose after a meal. For the same reason, however, proteins are not good snacks for preventing the hypoglycemia of vigorous exercise or hypoglycemic episodes in the middle of the night.

In a healthy diet, proteins should contribute about 15% to 20% of a day's total calories. The best sources of protein for a person with type 2 diabetes are poultry, veal, fish, eggs, milk, cheese, and soy products.

FIBER

Some plant carbohydrates, such as cellulose, gums, and pectins, cannot be broken down and digested by humans. These are called dietary fiber. Insoluble dietary fiber, such as cellulose (eg, bran), speeds the movement of food through the digestive tract.

Soluble dietary fiber, such as gums and pectins (eg, oatmeal) slows the rate of absorption of digestible nutrients. A high quantity of soluble fiber in a patient's diet can reduce blood cholesterol and can modestly reduce hyperglycemia and insulin resistance.

The recommendation for the general public is 14 grams of fiber for every 1000 calories in a person's everyday diet. For people with diabetes, the recommendation is higher—a total of 50 grams of fiber per day, regardless of the total daily calories. Plants contain dietary fiber. Legumes, cereals with ≥5 gm fiber/serving, fruits, vegetables, and whole-grain products are recommended.

MICRONUTRIENTS

Micronutrients are the additional substances that people need to ingest in small amounts. As with the general population, people with diabetes need sufficient vitamins and minerals in their diets to meet the body's daily needs. Poorly controlled diabetes or weight loss diets can cause nutritional deficiencies, and the minimum daily vitamin and mineral needs may require the patient to take daily supplements. Other people with diabetes who may need supplements are older adults, pregnant women, lactating women, and strict vegetarians.

No scientific evidence currently exists that any vitamins or antioxidants have special beneficial effects for people with diabetes who do not have vitamin deficiencies. Although not absolutely necessary, some clinicians recommend that patients with type 2 diabetes take a daily supplement of 0.4–1.0 mg folic acid, 0.4 mg vitamin B12, and 10 mg pyroxidine (Buse et al., 2003).

Similarly, no mineral supplements have clear beneficial effects for diabetes beyond their role in general health. Deficiencies in chromium, potassium, magnesium, and zinc can worsen insulin resistance. Potassium and magnesium deficiencies are easily identified in tests of blood chemistry.

Chromium and zinc deficiencies are harder to measure. Chromium picolinate supplements have been used in an attempt to reduce insulin resistance, but the FDA has concluded that there is insufficient scientific evidence to recommend these supplements to all people with diabetes (Center for Food Safety and Applied Nutrition, 2005).

BEVERAGES

Caloric beverages tend to be sugary, so they should be replaced by artificially sweetened drinks. Most fruit juices contain more sugar than people realize, and juices should not be drunk by people with diabetes merely to quench their thirst.

Drinking a moderate amount of alcohol can reduce the risk of developing type 2 diabetes, coronary heart disease, and stroke. Drinking higher amounts of alcohol brings a host of health problems, including an increased risk for developing diabetes. Those people with diabetes who choose to drink should drink only moderately.

Mixed drinks can contain significant amounts of carbohydrates, so people with diabetes should pay attention to the content of their drinks. It is also best for people with diabetes to drink alcohol with food—especially at night, to avoid a later episode of hypoglycemia.

Moderate drinking means two drinks per day for men and one drink per day for women. Heavy drinking means three or more drinks per day for men and two or more drinks per day for women.

Alcohol should not be drunk by pregnant women or by people with liver disease, pancreatitis, advanced neuropathy, or very high levels of blood triglycerides.

INDIVIDUALIZED NUTRITION PLANS

The American Diabetes Association and The American Dietetic Association make available many detailed recommendations about healthy eating for people with diabetes. Frequently, however, it is necessary for diabetes educators to translate the recommendations into terms that are practical and understandable for individual patients. For this task, a diabetes treatment team needs trained dietitians or nutritionists.

Creating a Treatment Plan

PROBLEM LIST

Diabetic patients are more likely than most nondiabetic patients to present with a variety of other problems. Therefore, the team of health professionals taking responsibility for the care of a person with diabetes must keep a careful watch on the health of the whole person.

Treatment of a person with type 2 diabetes begins with a thorough medical history and examination. From this, the physician generates a list of problems along with their degrees of severity. The following would be typical.

The physician then chooses a plan from the available treatment options, making sure that the included treatments address all the major problems on the list. For diabetic hyperglycemia, the physician begins by choosing from lifestyle changes, proper diet, and medications. For diabetic complications, such as retinopathy, albumin in the urine, or nonhealing foot wounds, referrals are made to the appropriate specialists or specialty clinics. For women of reproductive age, diabetic family planning specialists are recommended.

For all patients with diabetes, the physician schedules a session of individualized diabetes education, because diabetes management requires the knowledgeable participation of patients in their own care. Finally, the plan includes a schedule of regular visits for monitoring the patient's progress.

The treatment for type 2 diabetes must be realistic. The initial plan is only a prototype, and it must be tailored to the specific patient. Diabetes is a chronic illness, and, except for people living in long-term care facilities, the day-to-day management of the disease is in the hands of the patient and family.

The most successful approach is for the physician to present the prototype to the patient and work together to craft it into a plan that the patient can realistically carry out. The other team members—nutritionists, physical therapists, nurses—should help to design the details of the diet, exercise, and medication schedules so that they fit most comfortably into the life of the particular patient. Team members have the shared responsibility for explaining the plan's rationale, so the patient can believe in it and be willing to make the effort necessary to carry it out.

MAIN TREATMENT GOAL

Much detail is available on specific treatment guidelines. A good up-to-date source is the information provided by the American Association of Clinical Endocrinologists (AACE, 2007). Central to all treatment plans for people with type 2 diabetes is the same glycemic goal: patients should aim for an A1C <7% (AACE, 2007; ADA 2007a). In other words, people with diabetes should try to keep their average blood glucose levels below 170 mg/dl. This has been shown to be a realistic goal and a goal that will improve the health of a wide variety of people with type 2 diabetes.

A1C levels are checked at each visit to monitor the patient's progress. The A1C level is only an average value. To ensure that it has not been artificially lowered by periods of hypoglycemia, it is important to have the patient record blood glucose readings at key times each day (eg, first thing in the morning and 2 hours after meals) and then bring the records to each office visit.

THERAPEUTIC PROGRESSION

Although the treatment plan for a patient with type 2 diabetes must be tailored to the individual, the usual progression begins with lifestyle interventions. Next, oral hypoglycemics are added. Finally, the treatment is changed to insulin therapy.

Step 1: Lifestyle Changes

Weight loss, increased physical activity, and improved diet can all reduce hyperglycemia in a person with type 2 diabetes. These lifestyle changes will also improve many of the health problems that often accompany type 2 diabetes, notably, obesity, hypertension, and dyslipidemia.

Each of these lifestyle changes requires a long-term, steady effort. They are all hard changes to sustain, and the best successes come when they are carried out in supervised programs. Therefore, the first step for a patient with type 2 diabetes is to schedule or to enroll in a regular exercise program and to get help planning appropriate meals. Overweight or obese patients should also enroll in a weight-loss program.

Initially, lifestyle changes are given a 3- to 6-month trial. If they succeed in producing A1C values <7%, the lifestyle changes are continued and the patient is seen (and A1C levels are measured) every 3 to 6 months.

If the 3- to 6-month trial does not lead to an A1C value <7%, the patient should continue the lifestyle changes and add step 2.

Step 2: Oral Hypoglycemics

At some point, the treatment for type 2 diabetes usually includes medications. In the United States, about 85% of the people being treated for diabetes take anti-diabetes drugs. People with type 1 diabetes need regular doses of insulin. Some people with type 2 diabetes also need insulin, but most people with type 2 diabetes are being treated with a mix of weight loss, proper diet, exercise, and oral medications.

Treatment with insulin and oral medications for people with diabetes (U.S., 1999–2001) (National Diabetes Fact Sheet, 2007).

When lifestyle changes become insufficient to keep A1C values low, it is time to add an oral hypoglycemic. There is currently insufficient scientific data to dictate a first choice. Metformin is usually recommended, however, because it is generic (and so is least expensive), it has proved to be effective when added to lifestyle changes, it can be paired with most other hypoglycemics if needed, and it rarely if ever causes hypoglycemia (Buse et al., 2003; ADA, 2007a). Metformin should not be given to people who are being treated for congestive heart failure.

The addition of metformin is given a 3- to 6-month trial. If this succeeds in producing A1C values <7%, the regimen is continued, and the patient is seen (and A1C levels are measured) every 3 to 6 months.

If the 3- to 6-month trial does not lead to an A1C value <7%, the patient should continue the lifestyle changes and add step 3 (Buse et al., 2003).

Step 3: Additional Medications

The next step in treating type 2 diabetes is more individualized. In general, another type of oral hypoglycemic is added to the metformin treatment and the lifestyle changes. When choosing the additional drug, it is useful to have records of first-thing-in-the-morning blood glucose levels. If these levels are low (most of them <130 mg/dl) and if A1C is >7%, it is likely that there is a significant hyperglycemic peak after meals. Therefore, the best choices for the second anti-diabetes medication are usually drugs that lower after-meal glucose peaks, such as:

• An alpha-glucosidase inhibitor, which slows the absorption of glucose from the intestine
• A glinide (nateglinide or repaglinide), which lowers postprandial glucose levels
• A short-acting insulin, which lowers postprandial glucose levels

In contrast, if morning blood glucose levels are high (most of them >200 mg/dl), it is usually necessary to directly increase insulin levels. This means adding sulfonylureas, glinides, or insulin injections. Experience and detailed information about the individual patient are needed for this decision (Buse et al., 2003).

Step 4: Insulin Therapy

When the combination of lifestyle changes and hypoglycemics cannot reduce A1C values below about 8%, it is time to consider insulin therapy. Insulin therapy often begins with a two-drug regimen: metformin plus a daily bedtime injection of insulin glargine. Patients prefer simple treatment regimens, but over time, most patients require a more complex schedule of insulin injections (DeWitt & Hirsch, 2003). Mooradian and colleagues (2006) present an excellent discussion on the way to begin insulin therapy in patients with type 2 diabetes.

Educating for Self-Management

In addition to the treatment steps, the overall program for a person with diabetes should include a patient education program. It is the patients who must carry out the treatment. They will be the frontline member of the treatment team, and they must understand and believe in their particular plan. Specifically, the patient must understand:

• The basics of how diabetes affects the body
• How to make decisions about what and when to eat
• Why a regular exercise program is important
• How to match medications to eating and exercising schedules
• How to take care of the feet
• How to monitor blood glucose levels
• What to do when contracting another illness (eg, the flu)
• Symptoms of hypoglycemia, the situations most likely to cause it, and how to treat it
• How to delay or prevent major complications of diabetes
• How diabetes affects the reproductive life
• What community agencies, such as the local American Diabetes Association chapter, are available for help and information

Patient education should be an entire program of its own, with trained counselors who meet with the patient regularly and who are available for questions between visits (Buse et al., 2003; Joslin Diabetes Center, 2006; ADA, 2007a). To help set up diabetes education programs, The American Association of Diabetes Educators (telephone: 800-TEAM-UP4) provides the names of local diabetes educators and contact information for education programs throughout the country.

HOME MONITORING BLOOD GLUCOSE

A key part of the education program is teaching patients how to check their blood glucose levels. Patients should measure their blood glucose levels for two reasons:

• It provides a detailed record so medical advisors can recommend adjustments to meals, exercise, or medications.
• It gives the patient immediate feedback on how daily routines are affecting blood sugar levels.

All diabetic patients should check their blood glucose levels at a variety of times. This makes the abstract numbers (eg, mg/dl) more real to the patient. It also builds a detailed record of the daily variation of glucose levels, which is especially useful while the initial treatment plan is being adjusted. Moreover, if patients watch their blood glucose levels over an extended period of time, they will learn to recognize the feeling of hypoglycemia and help to distinguish it from other uncomfortable sensations.

The frequency with which a patient checks the glucose level is an individual decision. Patients beginning insulin therapy are usually asked to monitor their blood glucose 4 times a day until an optimal regimen of meals, exercise, and injections is established. After they have established a stable pattern, patients can reduce the number of blood tests to 2 or 3 times a day. When their life pattern changes, when they get symptoms of hypoglycemia, or when they develop another illness, patients are advised to test more frequently.

Patients with type 2 diabetes who do not take insulin usually settle into a schedule of checking blood glucose levels once a day. Typically, they are asked to vary the test times so that within each week they check levels:

• First thing in the morning
• Before lunch
• Before dinner
• 1 to 2 hours after each meal
• Before going to sleep

Occasionally, they should set an alarm and check their blood glucose level in the middle of the night. In addition, they should measure their blood glucose level when they get symptoms of hypoglycemia and when they develop another illness.

In all cases, patients should be given a target range of glucose values and told to report by telephone or email to a member of their diabetes team when a home test value falls out of the range. Patients are also instructed to bring a log of all the interim blood glucose values to each office visit.

HANDHELD GLUCOSE MONITORS

Glucose monitors are pocket-sized, handheld electronic devices. Most home monitors measure the glucose concentration in a drop of whole capillary blood from a finger prick. Clinical laboratories, however, measure the glucose concentration in plasma (blood without the cells) from venous blood. Glucose is about 15% more concentrated in plasma than in whole blood. The newer home monitors make this correction, so the home numbers can be compared directly to the published standards. On the other hand, some older home monitors give the whole-blood glucose levels; therefore, patients should read the information on the box of test strips for their monitor to see if they are getting plasma glucose levels or whole-blood glucose levels.

Old or new, home monitors must be calibrated occasionally to ensure the reliability of their readings. One method for checking the accuracy of patients' monitors is to ask them to bring their monitor each time blood is being drawn for a laboratory test. The patient takes a reading using the monitor within 1 to 2 minutes of when the lab technician draws a blood sample. In this way, the monitor can be compared directly with the clinical test results.

Home testing supplies come with a variety of features, and they are changing and improving continually. Each January, the American Diabetes Association publishes an updated guide to basic products (blood and urine testing equipment, oral hypoglycemics, insulins, insulin delivery devices, and hypoglycemic treatments) used by people with diabetes. The most recent guide can be read online at http://www.diabetes.org/diabetes-forecast/back-issues.jsp.

LONG-TERM MANAGEMENT

After an initial 6 to 12 months of trying out and modifying a program of therapy, the skeleton of a long-term program takes shape. Patients should have a schedule of regular visits with the physician and with other members of the diabetes care team. At each visit, the team reviews A1C values and daily blood glucose records, screens for the development and/or progression of diabetic complications, and offer advice and help with problems in daily healthcare routines. When lab values or the clinical picture suggest the treatment routine needs to be changed, the patient should meet with healthcare workers more frequently until health is again stabilized.

Blood Glucose Goals

Two sets of data should be used to follow a patient's glycemic control: A1C values and daily blood glucose records.

The A1C values show the average level of hyperglycemia in the preceding 2 to 3 months. (See earlier graph to translate A1C values into average plasma glucose levels.) The target for adults with diabetes is an A1C of less than 7%, or about 170 mg/dl. Although the ideal would be an A1C of less than 6% (about 135 mg/dl), it is difficult for most people with diabetes to get these low A1C values without having significant periods of hypoglycemia.

In addition to following A1C values, the patient's daily glucose levels are examined. The American Diabetes Association suggests aiming for a majority of pre-meal glucose values to be in the range of 90 to 130 mg/dl and the majority of glucose values 1 to 2 hours after a meal to be <180 mg/dl (ADA, 2007a).

Patients whose blood glucose values are close to the targets should be re-examined every 6 months. Patients whose blood glucose values are out of the target ranges or whose medications have changed are re-examined every 3 months.

Other Long-term Goals

People with type 2 diabetes are at risk for developing cardiovascular disease, therefore blood pressure and lipid profiles are monitored. Target goals are:

• Blood pressure <130/80 mm hg
• Fasting plasma LDL-cholesterol <100 mg/dl
• Fasting plasma HDL-cholesterol >40 mg/dl
• Fasting plasma triglycerides <150 mg/dl

The liver is the major site of the degradation of most anti-diabetes drugs, including insulin. Liver dysfunction can lead to abnormally high or prolonged levels of these drugs in the blood, thus liver function should be monitored by checking liver enzymes periodically.

Kidney damage is a classic complication of diabetes. Among the values to be monitored are serum creatinine levels and urine albumin levels. Estimates of glomerular filtration rates (GFR) should be calculated from the creatinine values.

At each visit, the patient's feet should be examined for skin or joint damage, and his ability to sense stimuli in his feet should be assessed.

People with diabetes should have regular eye exams, checking for glaucoma, cataracts, and retinal damage.

RELATED ILLNESSES AND TISSUE DAMAGE

People with diabetes face two kinds of ongoing health threats. On the one hand, they sometimes develop acute complications, the two most common of which are diabetic ketoacidosis and hyperglycemic hyperosmolar state. (Another possible emergency—hypoglycemia—is discussed in the section on Insulin Therapy, above.) On the other hand, diabetes continually injures tissues microscopically, and as these microscopic injuries accumulate, they lead to observable problems such as heart disease or kidney failure.

Acute Complicat