Issue 119 Item 9 Lifestyle Change Is Best Bet for Diabetes Prevention

For preventing diabetes in people at risk, lifestyle intervention “wins hands down” over medications. That, according to Dr. Robert S. Sherwin said at the annual scientific sessions of the American Diabetes Association.

Still, glucose-lowering drugs may play an important secondary preventive role in some individuals with “prediabetes,” said Dr. Sherwin, the C.N.H. Long Professor of Medicine at Yale University, New Haven.

Earlier this year, a panel convened by the ADA and the National Institutes of Health issued new recommendations for physicians to begin screening overweight people aged 45 years and older for impaired glucose tolerance (IGT; 2-hour blood glucose level 140-199 mg/dL on the 75-g oral glucose tolerance test) or for impaired fasting glucose (IFG; 110-125 mg/dL).

The panel advised weight loss and increased activity, but eschewed routine use of drugs until more data are available (Diabetes Care 25[4]:742-49, 2002).

Dr. Sherwin, who chaired the panel, offered this advice on “prediabetes” care:

First, prescribe lifestyle intervention plus daily aspirin therapy, along with a statin or an ACE inhibitor if appropriate.

If lifestyle intervention fails to reduce glucose levels after 3 months, try again.

If levels remain high after another 3 months, consider adding a glucose-lowering agent in selected patients.

It’s not yet clear whether early use of glucose-lowering drugs will ultimately reduce the risk of macrovascular complications. “The key is not just glucose, but whether any of the agents used to lower glucose can also affect cardiovascular disease progression,” he noted.

The new focus on diabetes prevention was triggered by the results of the landmark Diabetes Prevention Program (DPP). (See story below) That trial clearly showed that the onset of diabetes can be prevented or delayed with intensive diet and exercise and, to a lesser degree, metformin.

At least two other large trials have shown the benefits of lifestyle intervention. In the Da Qing (China) IGT and Diabetes Study of 110,660 subjects with IGT, interventions including diet alone, exercise alone, or diet plus exercise reduced the incidence of type 2 diabetes by 31%-46% over 6 years (Diabetes Care 20[4]:537-44, 1997). And in a Finnish study of 872 IGT subjects, intensive lifestyle intervention produced a 58% reduction in the risk of type 2 diabetes over an average of 3.2 years—exactly the same benefit seen in the DPP (N. Engl. J. Med. 344[18]:1343-50, 2001).

“No matter where you look all over the world, lifestyle intervention works,” said Dr. Sherwin, president of the American Diabetes Association in 2000-2001.

Of course, lifestyle modification isn’t easy. Even with the intensive efforts used in the DPP, only half of the highly motivated study subjects met their weight reduction goals. Also, some weight regain and increase in glucose levels occurred after year 1 in both the DPP and the Finnish studies.

It may be tempting to turn to medications as an easier option, but their use in prevention, rather than treatment, changes the risk-benefit assessment. The potential for side effects looms large, since patients will presumably need to take the drugs for years, if not for life, he noted.

It may be possible to prevent diabetes with drugs other than the glucose reducers. Post-hoc analyses of two studies designed to look at other outcomes found that pravastatin reduced the development of diabetes by 30% compared with placebo in the 5,974 participants in the Scotland Coronary Prevention Study. And ramipril reduced the risk by 34% in the 9,541-patient Heart Outcomes Prevention Evaluation.

If those results are confirmed by studies designed specifically to assess diabetes prevention, these drugs might have an impact similar to that of glucose-lowering drugs, while also delivering cardiovascular benefits, Dr. Sherwin said.

“Patients who are developing type 2 diabetes are in the process of developing macrovascular complications even before they develop bona fide diabetes. It’s clear that we need to intervene with the agents that we know can reduce cardiovascular risk,” he said.