Stop prediabetes to prevent Type 2, urge experts

By Roxanne Nelson, a writer based in Washington

The incidence of Type 2 diabetes mellitus (DM) has tripled over the past 30 years and continues to rise. It has become the nation's most costly health problem, according to the American Diabetes Association (ADA). In 1997, adding together medical costs, disability, work hours lost, and premature death, diabetes ran up a tab of $98 billion.

In an effort to control Type 2 DM, which appears to be reaching epidemic proportions both in the United States and abroad, a new emphasis has been placed on halting the disease while still in its formative stages. "Prediabetes is a hot topic now," said Keith Campbell, R.Ph., associate dean and professor of pharmacy practice at Washington State University College of Pharmacy. "It's a new name for medical terminology that most of the general public previously didn't understand."

Traditionally, the term prediabetes was defined as a period during which glucose tolerance is normal, but there is an increased risk of developing diabetes at some future date. Under this definition, examples of increased risk might include a family history, a positive antibody test for diabetes, or prior diagnosis of gestational diabetes. In March 2002, a joint press release issued from the Department of Health & Human Services and ADA announced that the association had redefined pre- diabetes as the period when an individual's blood glucose levels are higher than normal but have not yet reached the point of a diabetes diagnosis. Medically, this condition is known as impaired glucose tolerance or impaired fasting glucose. Research indicates that left unchecked, most individuals with this condition will develop Type 2 DM within 10 years.

A person is generally considered to have prediabetes if his or her fasting plasma glucose is between 110 and 125 mg/dl or an oral glucose tolerance falls between 140 and 199 mg/dl. According to HHS secretary Tommy Thompson, nearly 16 million Americans may be prediabetic. That is in addition to the estimated 17 million who already have full-fledged diabetes.

The prevalence of both impaired glucose tolerance and Type 2 diabetes increases with age and affects 42% of persons between the ages of 65 and 74. Minority groups such as Hispanics, African-Americans, and Native Americans are also at a higher risk. As both the number of minorities and older adults increases in the country, the overall prevalence of prediabetes is expected to continue rising over the next decade.

Campbell believes that the public will now have a better understanding of what prediabetes is. "Saying that you have impaired glucose tolerance doesn't mean much to the average person," he pointed out. "Prediabetes pretty much gives an image that people are at a high risk. That name conjures up images that someone who has certain characteristics will eventually end up with Type 2 diabetes."

Syndrome X

Type 2 DM develops over a period of years, usually along with several metabolic abnormalities that are also risk factors for cardiovascular disease. "Many people have genes that enable them to become obese and with the kind of obesity that puts them at risk for diabetes, hypertension, heart disease, and polycystic ovarian syndrome—or Syndrome X, as these symptoms are called," said Francine Kaufman, M.D., a pediatric endocrinologist at Children's Hospital in Los Angeles and president-elect of ADA.

Syndrome X, also known as metabolic syndrome, is a term coined by Stanford University endocrinologist Gerald Reaven that identifies a cluster of risk factors that put individuals at a significantly increased risk of Type 2 DM and cardiovascular illness. The four major risk factors are central obesity (waist circumference > 102 cm for men and > 88 cm for women), impaired fasting glucose, dyslipidemia (HDL cholesterol < 45 mg/dl for women and < 35 mg/dl for men, or triglycerides > 150 mg/dl), and hypertension.

'Diabesity' in all age groups

Historically, Type 2 DM was almost universally a disease of older adults and rarely found below middle age. The Centers for Disease Control & Prevention, however, reports that between 1990 and 1998, overall prevalence of diabetes increased by about one-third in the 43 states surveyed, crossing all demographics, including age. The rate of Type 2 DM increased 76% in individuals between the ages of 30 to 39 years.

Numerous studies have targeted excess body fat as a major risk factor for Type 2 DM. The prevalence of obesity—defined as body mass index (BMI) 30 kg/m²—rose from 12% in 1991 to 18% in 1998. By the year 2000, 20% of the U.S. population met the criteria for obesity. The well-acknowledged link between obesity and diabetes has led researchers to describe the condition as diabesity.

"The diabesity concept goes hand-in-hand with prediabetes," said Campbell, "Meaning that, as they get older and gain weight, they gain diabetes." But adults are not the only ones who are gaining weight. Childhood obesity has doubled over the past three decades. In 1970, approximately 5% of the six- to 17-year-old population met the criteria for clinical obesity, with that number jumping to 11% by 1998. And by 2000, 22% of children and adolescents were considered to be overweight.

"The rise of childhood, adolescent, and adult obesity is, in large part, due to the interplay of genetics and the environment," said Kaufman. "With an environment replete with food—and fat-laden, calorie-laden food—and in an environment where there is little push for physical activity, these genes express themselves and people become obese."

The growing increase of childhood obesity has correlated with another phenomenon—a steady rise in the number of children and adolescents who are diagnosed with Type 2 DM. Once a rarity during childhood, pediatricians are seeing patients with fasting plasma glucose and/or oral glucose tolerance levels that are indicative of prediabetes. In some cases, they already have full-blown Type 2 DM.

Preventing disease

Diabetes is the final stage of a long process that begins with impaired glucose levels. Prediabetes is the beginning, but many experts believe that Type 2 DM is not the final, inevitable outcome. Changes in lifestyle and diet as well as pharmaceutical agents are being studied to see whether they can prevent disease progression, or, at the very least, delay its onset.

STOP NIDDM, the first international study in persons with impaired glucose tolerance that investigated primary prevention of diabetes by pharmacological intervention, evaluated acarbose (Precose, Bayer) versus placebo. Currently approved for the treatment of Type 2 DM, acarbose is an oral alpha glucosidase inhibitor. Since it inhibits the enzyme necessary for carbohydrate breakdown in the gastrointestinal tract, thus causing a slower and lower rise of blood sugar, researchers believed it might be effective for patients with prediabetes.

The study population consisted of 1,429 men and women with impaired glucose tolerance, who were randomized to receive either acarbose or placebo. After 3.3 years, results showed that acarbose significantly reduced the development of diabetes. "The risk of developing Type 2 diabetes was reduced by 25% in patients who had received the study drug," commented study author Robert Josse, M.D., a professor in the department of nutritional sciences at St. Michael's Hospital Health Centre in Toronto, Canada. "And it reduced the risk of cardiovascular disease, including hypertension."

The risk was further reduced to 36% in patients receiving acarbose whose impaired glucose tolerance was confirmed by a second two-hour glucose load. "However, following a diet and exercise program has been shown to have the greatest effect on reducing the development of diabetes," said Josse. "That is where the greatest changes are demonstrated."

The Diabetes Prevention Trial showed that lifestyle intervention was more effective than pharmaceutical agents. This multicenter national trial randomized 3,234 participants to receive either metformin (Glucophage, Bristol-Myers Squibb), another oral agent currently approved for treating Type 2 DM, or participate in a diet and exercise regimen. Goals were to lose 7% of body weight and maintain the loss, have a daily intake of less than 25% fat, engage in 150 minutes of exercise a week, and stick to a daily caloric intake of 1,200-1,800 kcal/day. A third study arm received a placebo.

Results showed that 7.8% of the participants using metformin went on to develop diabetes (11% of placebo users) versus 4.8% who followed the lifestyle intervention. Overall reduction of Type 2 DM was 58% in the lifestyle group versus 31% in those using metformin. The researchers found lifestyle intervention to be beneficial regardless of sex, BMI, ethnicity, or age, and concluded that lifestyle was more effective than metformin.

Screening

A panel of experts, convened by ADA and HHS, recommended that overweight individuals 45 years and older be screened for prediabetes during a normal doctor's office visit. Physicians should also consider screening younger adults and children 10 years and older if they are significantly overweight and have one or more risk factors, including having a family history of diabetes, being among a minority deemed at high risk, or having high blood pressure or elevated triglyceride levels.

Prescription drugs were not recommended as a first line of treatment for prediabetes, but the panel did suggest that these agents could be beneficial to some people. Pharmacists can play a major role in this, according to Campbell. "I'm a strong believer that pharmacists are in the right place at the right time to make a difference in the lives of people with chronic diseases. Pharmacists can help identify people at risk, for either having diabetes or being on a pathway to getting the disease," he said.

There are numerous certification programs in disease state management for pharmacists, and community pharmacists, especially, are in an ideal position to identify people at risk, added Campbell. "And I think if the pharmacist communicates correctly, people will be delighted. People may be more apt to listen to their pharmacists than their doctors, because surveys have shown that pharmacists are the most trusted members in health care, ahead of doctors."

 

Roxanne Nelson. Stop prediabetes to prevent Type 2, urge experts. Drug Topics 2002;24:23s.