Prevention of type 2 diabetes

The rise of type 2 diabetes in the 20th century has taken place in parallel with the rise of obesity, and lifestyle factors including excess calorie intake relative to energy expenditure are largely responsible. Primary prevention of type 2 diabetes could be achieved at a population level by lifestyle interventions which lead to healthier eating and increased physical exercise. Secondary prevention targets individuals with borderline elevations of blood glucose or other markers of risk. Randomized controlled trials have shown that both lifestyle and pharmacological agents can be of benefit in preventing or slowing progression to overt diabetes. Many other benefits are associated with a healthier lifestyle, including reduced cardiovascular risk and avoidance of obesity-related complications such as cancer. Diabetes prevention can therefore form a useful component of a wider health improvement strategy.

Introduction

The twentieth century saw a dramatic rise in the incidence of type 2 diabetes, and a Rising incidence of type 1 diabetes. Both forms of diabetes appear to have been rare in the 19th century, and their subsequent increase in genetically stable populations must therefore be due to non-genetic factors.

This view is supported by the observation that an increasing incidence of type 2 diabetes first began in industrialized and more affluent countries and spread subsequently to other parts of the world as these adopted a "western" lifestyle - so-called "coca-colonization".

Type 2 diabetes is strongly associated with obesity, itself associated with ready access to food and a more indolent lifestyle. Conversely, periods of famine have repeatedly been shown to reduce the incidence of diabetes. Apollinaire Bouchardat is wrongly said to have noticed an improvement in his diabetic patients during the siege of Paris (1870-1), but civilian populations exposed to famine during both world wars have repeatedly been observed to show a reduced morbidity and/or mortality from diabetes.

One basic question in diabetes prevention relates to what you are trying to achieve. Is avoidance of hyperglycaemia, obesity, the metabolic syndrome or cardiovascular risk the major objective? There is considerable overlap between these goals, but there are also important differences in emphasis. For example, "isolated" obesity or hyperglycaemia may be considered relatively harmless conditions when present in isolation from other components of the metabolic syndrome, whereas the greatest reduction in morbidity and mortality is to be expected from intervention in those with multiple risk factors.

Since lifestyle can be modified, most cases of type 2 diabetes are in theory preventable. Diet and exercise form the mainstay of such strategies, but a number of pharmacological interventions have also been proposed and tested. This experimental work goes hand in hand with investigations which set out to understand the pathways and mechanisms by which diabetes develops.

Strategies of Prevention

A prevention strategy can be implemented at three mains levels:

Primary Prevention aims to prevent a condition which does not as yet exist (e.g. moving from normoglycaemia to abnormal glucose levels), and is therefore targeted to the whole population. Mayor Bloomberg's (unsuccessful) attempt to limit the size of soft drinks containers on sale in New York in the attempt to tackle obesity is one example. Avoidance of obesity is the major target of primary prevention, and increased exercise or restricted calorie intake thus form the mainstay of primary prevention of diabetes.

Secondary Prevention is based on the earliest possible identification of the disease for early evidence-based intervention. In diabetes, this identification is based on evidence of disordered glucose metabolism, which may be assessed by the oral glucose tolerance test or measurement of fasting glucose or HbA1c. Secondary prevention is typically offered via a two-step process in which population screening is followed by intervention in those with dysglycaemia.

Tertiary Prevention is offered to those who already have the condition in its early stages when it is potentially reversible. This is most effectively achieved by weight loss, whether achieved by diet, drugs or bariatric surgery. Such interventions have shown that obesity-related diabetes is potentially reversible, even after many years of hyperglycaemia.

This section of Diapedia will focus on primary and secondary prevention of type 2 diabetes, but the success of some types of tertiary prevention provides proof of principle that hyperglycaemia can be reversible even when all might seem lost.

Rationale for the Prevention of type 2 diabetes

It would clearly be desirable for people to avoid the personal burden of diabetes, which includes adherence to a demanding health regimen, cost, psychological consequences and increased morbidity and mortality.

These individual costs are also reflected at a societal level. The health costs of diabetes are immense, and steadily rising, and numerous analysis suggest that the the increased "up front" costs of screening and early intervention to prevent diabetes will be highly cost-effective in the longer term. As described above, the benefits of such intervention go well beyond prevention of hyperglycaemia, and should be measured in terms of reductions of obesity, cardiovascular disease and other associated morbidity and social costs.

Feasibility of diabetes prevention.

Diabetes may be a highly undesirable condition, but certain standard considerations must be satisfied before practical measures for secondary prevention can be implemented. Thus, the natural history of the condition should be known, and should include a useful preclinical window of opportunity for intervention. Next, there should be well validated screening measures with good predictive yield. Finally, effective interventions must be available.

Type 2 diabetes has a long and well-characterized preclinical prodrome. Screening measures are also well-established, but (despite considerable overlap) there are important qualitative differences between the populations identified by the glucose tolerance test (IGT), raised fasting glucose (IFG) and sub-threshold elevation of HbA1c.

The predictive value of screening and the benefits of intervention cannot therefore be assumed to apply equally to individuals identified by each of these three measures. This is of particular importance because most intervention trials have used the glucose tolerance test as their endpoint.

Last, but not least, there is ample evidence that effective interventions are available for lowering blood glucose levels and delaying the onset of overt diabetes. This having been said, long-term outcome measures of benefit are generally lacking in type 2 diabetes. Thus, it has yet to be shown beyond doubt that delaying the onset of diabetes will be cost-effective in terms of reducing the burden of diabetic complications, cardivascular end-points and so forth. Furthermore, the potential benefits of diabetes prevention are unequally distributed: for example, the benefits will be high in young people with co-existing cardiovascular risk factors, but low in otherwise healthy older people.

Types of Study

As always, randomized controlled trials (RCTs) are the most effective test of an intervention. This is because (1) randomization to control and intervention arms avoids selection bias, (2) the non-specific effects of participation in a study (Hawthorne Effect) are neutralized by equal attention to control and intervention groups.

RCTs also have important limitations. The participants are volunteers, and thus more highly motivated than unselected members of the population. The entry criteria are stricter: for example, a second OGTT is typically performed to confirm IGT in RCTs, whereas the test is so poorly reproducible that a substantial minority of participants will be misclassified by a single test. Finally, the degree of attention and input from the clinical team will be much greater than in normal clinical practice.

Summary

Prevention of diabetes is greatly preferable to life-long treatment, and diabetes meets the criteria for a condition which justifies screening and intervention. This having been said, many obstacles to effective screening and intervention for type 2 diabetes have emerged, and the benefits have to date been more apparent in theory than in practice.

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