(How) can we prevent type 2 diabetes?

Type 2 diabetes is a progressive disease. It develops over years as a result of declining pancreatic β-cell compensation for chronic and often worsening insulin resistance. Preventing type 2 diabetes requires modification of the underlying disease biology to slow, stop, or reverse the decline in β-cell compensation. Data from six randomized trials reveal several interventions that reduce the number of high-risk people who develop diabetes during relatively short periods of treatment. Interventions that reduce body fat or that mitigate the effect of excess fat to cause insulin resistance provide the greatest risk reduction and the best evidence for real disease modification. At least two studies indicate that disease modification is possible soon after glucose levels enter the diabetes range. These findings, combined with the fact that falling β-cell compensation leads to rising glycemia, provide a rationale for an intervention strategy that begins with lifestyle modification and progresses to pharmacological therapy aimed at reducing insulin resistance if lifestyle approaches fail to prevent glucose from rising to the diabetes range. Our knowledge base in this field is still quite rudimentary, and we have no information about truly long-term (i.e., for decades) prevention of type 2 diabetes. Even for the short to intermediate term, additional work is needed to determine optimal application of the general strategy described above, to examine combination approaches to prevention, and to test new interventions as they become available. Such work should focus on disease modification, not just cases of diabetes, as a major outcome. © 2007 by the American Diabetes Association.