Lifestyle and Drug Therapies Effectively Prevent Type 2 Diabetes

Type 2 diabetes affects approximately 8% of adults in the United States. An additional 10 million Americans are at high risk for the disease. This type of diabetes begins gradually, later in life. Most people with type 2 diabetes produce plenty of insulin, but their tissues resist the action of the hormone, so their blood sugar levels rise; some people develop the disease as their insulin production gradually slows down.

Although treatment may prevent some complications of type 2 diabetes, which can include atherosclerosis, vision impairment, and nerve damage, it cannot eliminate the condition altogether. As a result, prevention of type 2 diabetes remains preferable. In a recent study in the New England Journal of Medicine (NEJM), researchers from the Diabetes Prevention Program Research Group sought to determine whether lifestyle intervention or drug treatment could be used to prevent or delay the onset of type 2 diabetes.

The researchers gathered 3,234 subjects who they determined to be at high risk for diabetes based on elevated blood sugar levels. They assigned the subjects to one of three interventions: twice-daily treatment with 850 mg of metformin (a drug commonly used to lower blood sugar in people with type 2 diabetes), lifestyle intervention, or placebo. The goal of the lifestyle intervention was to achieve a weight reduction of at least 7% of initial body weight through a low-fat, low-calorie diet, and to complete at least 150 minutes of moderate-intensity physical activity per week. As measured by the researchers, the lifestyle intervention group achieved much greater weight loss and increased their physical activity level more than the metformin or placebo groups.

After almost 3 years of follow-up, the scientists found that the incidence of type 2 diabetes was 58% lower in the lifestyle intervention group and 31% lower in the metformin group than in the placebo group. In addition, the incidence of type 2 diabetes was 39% lower in the lifestyle intervention group than in the metformin group.

The NEJM study showed that lifestyle intervention and treatment with metformin effectively prevents type 2 diabetes in people at high risk for the condition, regardless of race, ethnicity, gender, or age. The combination of increased physical activity, dietary changes, and weight loss produces particularly effective results.

June 2002 Update

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New Diabetes Guidelines from the ADA

In the January 2002 supplemental issue of Diabetes Care, the American Diabetes Association (ADA) released a compilation of all its position statements on diabetes care, including three new ones. It includes the first update of the ADA's nutrition guidelines since 1994.

One of the reports, Evidence-Based Nutrition Principles for the Treatment and Prevention of Diabetes, outlines changes as to how diabetics should approach carbohydrate intake, giving them more dietary freedom. Previously, diabetics were advised to avoid eating simple sugars and fast-acting carbohydrates like table sugar because these were believed to be more rapidly absorbed than complex starches found in such foods as potatoes, thus aggravating hyperglycemia. But there is little scientific evidence to support this theory. In fact, the simple sugar sucrose is no worse for a diabetic than starch, so the ADA now recommends simply using the carbohydrate terms sugar, starch, and fiber instead.

The new guidelines also advise that it's more important for people with diabetes to monitor and adjust their insulin requirements according to the total amount of carbohydrates in food rather than the source or type. They therefore dismiss the practical value of the glycemic index, which calculates how quickly the carbohydrate content of a person's overall diet raises blood sugar levels. Nevertheless, some carbohydrate sources are healthier than others, so the ADA recommends diabetics get their carbohydrates from whole grains, fruits, and vegetables because they are also rich in fiber, vitamins, and minerals.

Diets rich in carbohydrates and low in fats used to be recommended for all patients with diabetes but this has changed since the discovery that diets rich in monounsaturated fatty acids lead to improvements in HDL ("good") cholesterol levels, triglyceride levels, and overall diabetes control.

The use of fructose as an added sweetener is not recommended, but natural fructose in fruits and other sweeteners like saccharin and aspartame appear to be safe. The guidelines address many other important nutrition issues, but specifically they recommend that diabetics get 60%–70% of their caloric intake from carbohydrates and monounstaturated fats, 15%–20% from protein, and less than 10% from saturated fats. Overall, these new options afford diabetics more choices in their diets-choices that will provide a diet more people can adhere to.

Another of the reports, Treatment of Hypertension in Adults with Diabetes, addresses hypertension, which occurs in up to 60% of diabetics and substantially increases the risk of vascular problems, such as coronary heart disease and other serious complications. The most recent evidence supports the use of aggressive hypertension treatment to avoid these complications. The ADA recommends people with diabetes aim for a blood pressure (BP) of less than 130/80 mm Hg. If a diabetic's BP is 130–139/80–89, the report suggests adopting behavioral changes such as reducing salt intake, losing weight, and becoming more physically active. However, if his or her BP is greater than 140/90, drug treatment should be started. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), diuretics, and beta blockers are recommended as first-line treatments. In many cases, patients will need three or more drugs to control their BP.

The third report, Standards of Medical Care for Patients with Diabetes Mellitus, is a comprehensive guide intended to provide an overview of the components of diabetes care, treatment goals, and tools to evaluate the quality of care. It also goes over strategies for successful guideline implementation. For instance, successful programs give patients access to nurses for case management services, diabetes educators, and group visits.

For the complete reports, go to http://care.diabetesjournals.org/content/vol25/suppl_1/.
April 2002 Update

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Angiotensin-II-receptor Antagonists for Diabetic Nephropathy

Anyone with type 2 diabetes knows about the host of complications that can result if blood sugar is not kept under tight control. One complication is diabetic nephropathy, or kidney damage. When functioning normally, our kidneys keep proteins and other beneficial substances in the blood and filter out waste products, which the body excretes as urine. Diabetes can interfere with this process. As a result, waste products remain in the blood and protein is excreted into the urine (proteinuria).

Angiotensin-converting-enzyme (ACE) inhibitors have been shown to slow the progression of renal, or kidney, disease in patients with type 1 diabetes. ACE inhibitors are widely given to patients with type 2 diabetes for the same purpose, even though there's less evidence they are effective. A set of studies published in the September 20, 2001 New England Journal of Medicine examined the effects of a different class of drugs, called angiotensin-II-receptor antagonists on nephropathy caused by type 2 diabetes.

The first study involved 1,715 patients with type 2 diabetes, above-normal blood pressure, urinary protein excretion of at least 900 mg per day, and serum creatinine levels (a marker of kidney damage) between 1-3 mg/dL. Each day, the patients took either 300 mg of the angiotensin-II-receptor antagonist irbesartan, 10 mg of the calcium-channel blocker amlodipine, or a placebo. After an average of 2.6 years, significantly fewer patients receiving irbesartan experienced a doubling of serum creatinine, end-stage renal disease, or death than patients taking either amlodipine or placebo (33% vs. 41% vs. 39%).

In another study, which involved a similar patient group, investigators studied the effects of the angiotensin II-receptor antagonist losartan versus the effects of a placebo. At the end of 3.4 years, patients taking losartan had a 25% risk reduction in the incidence of serum creatinine doubling and a 28% risk reduction of end-stage renal disease compared to patients taking a placebo. However, losartan did not have any effect on the rate of death.

An editorial accompanying the NEJM articles suggests that although angiotensin-II-receptor antagonists performed well in these trials, they are still far from effective in all patients. In addition, this study did not compare the performance of angiotension-II-receptor antagonists to that of the widely used ACE inhibitors.
October 2001 Update

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Diet and Exercise Dramatically Delay Type 2 Diabetes

Americans at high risk for type 2 diabetes can sharply lower their chances of getting the disease with diet and exercise, according to the results of a major clinical trial. The same study also found the oral diabetes drug metformin (Glucophage) reduces diabetes risk, though less dramatically.

The findings came from the Diabetes Prevention Program (DPP), a major clinical trial comparing diet and exercise to metformin in 3,234 people with impaired glucose tolerance, a condition that often precedes diabetes. Smaller studies in China and Finland had previously shown diet and exercise can delay type 2 diabetes in at-risk people. But the DPP, conducted at 27 centers nationwide, is the first major trial to show diet and exercise can effectively delay diabetes in a diverse American population of overweight people with impaired glucose tolerance (IGT). IGT is a condition in which blood glucose levels are higher than normal but not yet diabetic.

Of the 3,234 participants enrolled in the DPP, 45 percent are from groups that suffer disproportionately from type 2 diabetes: African Americans, Hispanic Americans, Asian Americans and Pacific Islanders, and American Indians. The trial also recruited others known to be at higher risk for type 2 diabetes, including people age 60 and older, women with a history of gestational diabetes, and people with a first-degree relative with type 2 diabetes.

Participants ranged from age 25 to 85, with an average age of 51. All had impaired glucose tolerance as measured by an oral glucose tolerance test, and all were overweight, with an average body mass index (BMI) of 34. They were randomly assigned to one of the following groups: intensive lifestyle changes with the aim of reducing weight by 7 percent through a low-fat diet and exercising for 150 minutes a week; treatment with the drug metformin (850 mg twice a day), approved in 1995 to treat type 2 diabetes; and a standard group taking placebo pills in place of metformin.The latter two groups also received information on diet and exercise.

During an average follow up of about 3 years, about 29 percent of the group receiving standard treatment developed diabetes. In contrast, 14 percent of the diet and exercise, and 22 percent of the metformin arms developed diabetes. Volunteers in the diet and exercise arm achieved the study goal, on average a 7 percent — or 15-pound — weight loss, in the first year and generally sustained a 5 percent total loss for the study's duration. Participants in the lifestyle intervention arm received training in diet, exercise (most chose walking), and behavior modification skills.

In all, participants in the random intensive lifestyle intervention reduced their risk of type 2 diabetes by 58 percent, and those who received metformin reduced their risk of getting type 2 diabetes by 31 percent.
September 2001 Update

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FDA Approves First Automatic and Non-Invasive Blood Glucose Monitor

People with diabetes who regularly monitor their blood glucose levels are less likely to develop the disease’s complications such as heart disease, blindness and kidney disease. Unfortunately, traditional blood glucose monitoring is time-consuming and requires sticking the finger for blood. So many diabetics test themselves less frequently than recommended.

A new bloodless glucose-monitoring device recently approved by the FDA could make monitoring easier. Made by Cygnus Inc., GlucoWatch Biographer is a prescription wristwatch-like device with sensors on its underside that monitor glucose levels. By a process called reverse iontophoresis, it applies a very low electric current to extract glucose samples from the skin’s interstitial fluid every 20 min for 12 hours, even during sleep. The device, which must be first calibrated using a finger-prick reading, stores the readings and sounds an alarm if the glucose reaches a pre-selected level.

The FDA approved the device on the basis of clinical trials done on both type I and type II adult diabetics. No research has been conducted on children. The studies compared GlucoWatch readings with traditional finger-prick blood glucose tests and found measurements were fairly consistent. However, up to 25% of the time, the results differed by more than 30% and sometimes GlucoWatch gave completely erroneous readings. The device was less effective at detecting very low glucose levels than very high levels. Also, it was not accurate if the patient’s arm was too sweaty and perspiration is common with hypoglycemia, or low blood sugar. GlucoWatch caused skin irritation in up to 50% of users.

GlucoWatch should not be used as a replacement for finger-prick blood tests. Any treatment decisions and all alarm values should be confirmed with blood glucose tests. But as the first automatic and non-invasive device, GlucoWatch may help patients better manage their diabetes.
June 2001 Update

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National Cholesterol Education Program Releases New Guidelines for Treating and Preventing High Cholesterol

On May 15, 2001, the National Cholesterol Education Program (NCEP) — coordinated by the National Heart, Lung, and Blood Institute (NHLBI) — released the first major revision of its recommendations for detecting and lowering high cholesterol in adults since 1993.

One of the fundamental features of the new guidelines is the accurate assessment of heart disease risk using a new "global risk assessment tool" that combines multiple risk factors into a measure of a person's absolute risk of developing coronary heart disease within the next 10 years. According to the guidelines, patients who have a risk of 20% or higher should receive aggressive therapy to control cholesterol levels. In addition to aggressive treatment of high LDL cholesterol, as laid out in the 1993 report, the revised guidelines also recommend a more assertive treatment approach for diabetes, low HDL levels, and high triglyceride levels.

Specific changes include:

• Treating high cholesterol more aggressively for those with diabetes, even if they do not have heart disease.
• A full lipid profile (which measures total cholesterol, LDL, HDL, and triglycerides) as the first test for high cholesterol (rather than simply testing total cholesterol and HDL and performing a full lipid profile only if total cholesterol is high).
• A new level at which low HDL becomes a major risk factor for heart disease. The 1993 guidelines defined a low HDL as less than 35 mg/dL; now it is less than 40 mg/dL.
• More aggressive treatment of high triglyceride levels.
• Advising against the hormone replacement therapy (HRT) as an alternative to cholesterol-lowering drugs for post-menopausal women.

Another key change in the guidelines is intensified lifestyle recommendations regarding nutrition, exercise, and weight control to treat high cholesterol. The updated diet advises that less than 7% of daily calories come from saturated fat and limits dietary cholesterol to less than 200 mg per day. It also allows up to 35% of daily calories from total fat, provided most come from unsaturated or monounsaturated fat, which doesn't raise cholesterol levels. Additionally, the guidelines strongly underscore the need for weight control and physical activity, both of which improve various heart disease risk factors.

The revised recommendations also emphasize careful attention to the metabolic syndrome, a particular cluster of cardiovascular risk factors that is becoming increasingly common in the United States. Characteristics of metabolic syndrome include too much abdominal fat, high blood pressure, high blood sugar, elevated triglycerides, and low HDL.

For more information, see the "Live Healthier, Live Longer" Web site by going to the NHLBI home page at www.nhlbi.nih.gov and clicking on ATP III Cholesterol Guidelines under Highlights.

May 2001 Update

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Treating Nerve Pain Caused by Diabetes

One of the unpleasant complications of diabetes is pain in the arms and legs due to nerve damage (diabetic neuropathy). As many as 45% of people with diabetes go on to develop this problem, which can make both getting through the day and sleeping through the night difficult. Probably the best way to limit this complication is through good control of blood sugar, although some medications may help a little. There are a number of medications — ones typically used to treat depression or control seizures — which can offer some relief. However, many people cannot tolerate these drugs at a dose sufficient to control pain.

A study published last year in the Journal of the American Medical Association points to gabapentin (an anti-seizure drug) as a possibly effective and well-tolerated option for this condition. One-hundred-sixty-five patients participated in this research. Study investigators randomly assigned these individuals to receive either gabapentin or a placebo. When researchers studied the pain diaries of these patients, they found that patients taking gabapentin enjoyed significantly greater symptom relief and improvement in sleep when compared to patients taking the placebo.

In this study, gabapentin proved to be as effective as tricyclic antidepressants in reducing symptoms of diabetic neuropathy. It also worked faster with relatively minor and potentially avoidable adverse side effects such as drowsiness and lightheadedness. For more information on diabetic neuropathy, see page 837 in the Family Health Guide.

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The Importance of Controlling Diabetes in Preventing Heart Disease

Cardiovascular disease is the number one killer of adults in the United States. In early November 1999, diabetes joined the ranks of high cholesterol and high blood pressure as one of the key, official, modifiable risk factors for cardiovascular disease.

Diabetes has long been recognized as an important contributor to many types of cardiovascular disease. Individuals with this condition are three times as likely to die of a stroke or to develop heart failure when compared with people who do not have diabetes. People with diabetes are also more prone to atherosclerosis, the leading cause of heart attacks. Part of the reason diabetes is such a heavy hitter is that it often comes along with other significant risk factors. For example, people with diabetes often also have other conditions that add to heart disease risk, for example, high LDL (low-density lipoprotein, or "bad") cholesterol, low levels of HDL (high-density lipoprotein, or "good") cholesterol, high blood pressure, high triglycerides, and insulin resistance.

Major health organizations, including the National Heart, Lung, and Blood Institute and the American Heart Association, are particularly concerned because the incidence of Type 2 diabetes is on the rise. Why? Because Americans are becoming more overweight, less active, and older. While it is true that some of the predisposing factors for diabetes cannot be controlled, such as genetics and advancing age, individuals can take steps to reduce their chances of developing this illness (and its complications). To prevent developing type 2 diabetes, people need to exercise regularly and maintain a healthy weight. Regular checks of blood pressure, cholesterol, and glucose are also important.

If you do have diabetes, remember there is no such thing as a mild form of this disease. Work with your doctor to implement lifestyle changes that can help control this condition. And if lifestyle changes don't help enough, don't shy away from the medications your doctor may recommend. Taking control of diabetes can translate into myriad health benefits. For more information on risk factors for heart disease, including diabetes, see page 654 in the Family Health Guide.

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High Blood Pressure Drugs and Diabetes Risk

Past studies have suggested that two types of drugs used to treat high blood pressure also promote the development of type 2 diabetes. These results led doctors to think twice about prescribing thiazide diuretics and beta blockers to their patients at high risk for diabetes. But a new, extensive study shows thiazide diuretics do not appear to increase the risk of diabetes, while beta blockers may contribute. The data also suggest that perhaps the risk of developing type 2 diabetes is associated with high blood pressure itself, and not the medications used to treat it.

Thiazide diuretics and beta blockers are the first line of treatment for most people with high blood pressure. Both therapies reduce the risk for strokes and heart attacks and have been shown to help people with high blood pressure live longer. Thiazide diuretics such as hydrochlorothiazide and chlorthalidone decrease blood pressure by reducing the volume of fluid in the body. Beta blockers such as propanolol and atenolol decrease blood pressure by blocking the nervous system’s response to stress and thereby relaxing the heart muscle. Earlier studies suggested that both drug classes might affect glucose tolerance and lead to diabetes, but a more recent study suggests something different.

To determine the relationship between the use of antihypertensive medications and the risk of developing diabetes, researchers in the U.S. followed 12,550 nondiabetic adults. They evaluated 3,804 hypertensive and 8,746 nonhypertensive patients for signs of diabetes three and six years later. Results showed that adults with high blood pressure (treated or untreated) were 2.5 times more likely to develop diabetes than were adults without hypertension. The scientists also analyzed the results by medication. The risk of developing diabetes was 28% greater for patients taking beta blockers than for patients taking no medication, regardless of hypertension. Patients taking other drugs to treat their hypertension were not at an increased risk.

The researchers pointed out that their study was limited by the lack of information regarding the dosage and duration of treatment with antihypertensive drugs. In addition to this, their results may have been affected by the perceived risk of diabetes and its influence on what drugs doctors prescribe. But the study was an improvement on past studies that were smaller and influenced by confounding factors.

In light of the results, doctors can now easily identify a group of patients at high risk for developing diabetes — those who take beta blockers — and perhaps help them develop a prevention program. In addition, physicians should be reassured about prescribing thiazide diuretics. The study investigators noted that despite the apparent increase in risk for diabetes associated with beta blockers, these drugs do have proven benefits for people with heart disease, and that a careful weighing of the potential risks against known benefits is important.

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Ramipril for Diabetics with Heart Disease

The incidence of heart disease in the general population has been dropping. This is good news of course, but for individuals with diabetes, the statistics are not so promising. In fact, men with type 2 diabetes have experienced only a modest decline in heart disease rates, while women with diabetes have actually experienced an increase.

Heart disease accounts for 70% of deaths in people with diabetes. So, the outcome of a recent study, which demonstrated that the angiotensin-converting enzyme (ACE) inhibitor, ramipril, significantly lowered the incidence of heart disease, stroke, and death in people with diabetes who had a history of heart disease and hypertension, should be welcome news.

The Heart Outcomes Prevention Evaluation (HOPE) study included people with and without diabetes. More than one-third of the participants had diabetes. Of the participants with diabetes, the average age was a little over 65 years old, and one-third were women. All had a history of heart disease and half had a history of high blood pressure as well. All study volunteers were randomly assigned to either ramipril or a placebo. While ramipril did not lower the blood pressure of participants much — as it was originally intended to do — it did lower their risk for heart attack by 22%, their risk for heart disease by 37%, and their risk for stroke by 33%. Other studies conducted to evaluate the effects of ACE inhibitors on blood pressure in people with diabetes have had similar outcomes.
October 2000 Update

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Screening Children for Type 2 Diabetes

As obesity in the United States reaches epidemic proportions, the number of children diagnosed with type 2 diabetes has been increasing dramatically. Until recently, type 1, or juvenile-onset, diabetes was the most common form of the disease in this age group, so many children with type 2 diabetes have been either undiagnosed or misdiagnosed as having type 1 diabetes. Research suggests that a child age 10 (or younger if puberty begins before age 10) should be screened every two years for type 2 diabetes if he or she is 120% or more of his or her ideal weight and has one or more of the following risk factors:

• a family history of type 2 diabetes in first- or second-degree relatives (that is, in a sibling, parent, grandparent, cousin, blood aunt or uncle)
• is American Indian, African-American, Hispanic, Asian, South Pacific Islander
• has signs of insulin resistance (for example, excess sugar in the urine) or conditions associated with insulin resistance (for example, dark, velvety patches on the skin or high blood pressure)

Because a decrease in physical activity and an increase in the intake of calories and fat are major causes of obesity, personal preventive measure can be taken against the onset of type 2 diabetes in children. When a child's blood glucose levels are still normal, or even if they are elevated but not enough for a diagnosis of diabetes to be made, taking action can have long-term benefits in all children at high risk for type 2 diabetes. Overweight or obese children with any of the bulleted risk factors mentioned above should be strongly encouraged to maintain a healthy diet (high in fruits and vegetables and low in fat) and to exercise at least 30 minutes per day.
October 2000 Update

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