Type 2 diabetes has multiple risk factors and, at the current state of knowledge, is regarded as a heterogeneous disorder. Given these facts, interventions can be targeted at the multiple risk factors, either in the entire population or in high-risk subjects, perhaps using both approaches. Tuomilehto and colleagues have succinctly summarized these approaches6. Given the widespread and increasing prevalence of obesity in the USA and other countries274,275, a population-based strategy to reduce obesity is likely to lead to widespread benefits for diabetes and related disorders.
The evidence to date, however, does not suggest that obesity prevention or reduction is effective on a large scale. Community- and population-based approaches have been tried in limited numbers of studies with, at best, small impacts on obesity. This is an area that needs further work, especially given the strong environmental components working to reduce physical activity and increase energy intake in Western societies276.
The studies of obesity prevention in children must be confirmed and expanded. Public policy must be addressed and changes made in order to increase activity, maintain weight for adults at near normal levels, and induce weight loss for overweight and obese people277. Such strategies echo the recommendations of Joslin over 80 years ago1, mentioned at the beginning of this chapter.
A high-risk strategy involves identification of persons with levels of pre-diabetic risk factors that place them at high risk to develop diabetes in the near future6. This is the approach that was taken in all of the larger clinical trials recently completed. These studies have identified persons with IFG or postchallenge glucose levels characteristic of IGT, obesity, family history of diabetes, history of gestational diabetes, etc., for lifestyle or pharmacological intervention. These approaches have now been shown to work for lifestyle change, which has been replicated in three studies55,69,72 and in very different populations. Results for metformin have been significant in only one large trial72, and were consistent but non-significant in one smaller study212. Further details are required to more fully understand the recent acarbose results223, but a second trial is underway (DAISI) and should soon provide information.
With efficacy of lifestyle changes established, it remains to be determined what the most efficient, cost-effective strategies are to identify and intervene in such high-risk subjects. In addition, longer-term follow-up is needed to determine the duration of the effects of lifestyle change, before beginning to understand the impacts on chronic complications and mortality. Pharmacological treatment approaches in high-risk subjects who are otherwise well must be carefully considered from a side-effect and cost standpoint, as well as for their efficacy. High-risk approaches must complement a wider public health approach aimed at general reduction of obesity and physical inactivity, since it is not possible to medically treat all subjects at the relatively late stages of diabetes development when IGT and declining beta-cell function are already evident278,279.
A number of questions in the high-risk strategy remain unanswered. While it is now known that diabetes incidence can be reduced among persons with IFG or IGT, it is not clear whether there are additional subsets of high-risk subjects among those with IFG or IGT who can be identified. Such people might include those with low insulin response, or higher levels of obesity, who may respond to specific subinterventions as suggested by the TRIPOD study220. The evidence available suggests that weight loss is important if glucose levels are to be lowered. However, physical activity improves insulin action, even in the absence of weight loss. The effect of these different components of risk over the longer term remains largely unknown. Will it be useful to identify high-risk patterns of genes in individuals to target for intervention? The current epidemic of obesity and increasing diabetes rates has occurred over too short a time to implicate changes in the genetic structure of populations, but with evolving technology it might be cost-effective to identify genetically high risk subjects for intervention in the near future. Such issues remain unknown at present. Genetic screening of people currently involved in prevention trials may prove useful, once specific genes can be targeted. This may allow the identification of subjects who responded to the intervention due to their combination of genes and environmental changes.
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