Jean Louis Chiasson

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Research Group on Diabetes and Metabolic Regulation, Research Center, Centre hospitalier de l'Université de Montréal and Department of Medicine, Université de Montréal, Montreal, Que., Canada


The increasing prevalence of diabetes is reaching epidemic proportion worldwide. Because of the associated morbidity and mortality, it is exerting major pressure on the healthcare system. With a better understanding of the pathophysiology of type-2 diabetes, the concept of primary prevention has emerged. A number of studies have confirmed that intensive lifestyle modification was very effective in the prevention of diabetes in the impaired glucose tolerance (IGT) population. However, maintaining long-term lifestyle modification is a major challenge. It is, therefore, important to have other strategies, either pharmacological or surgical, that can be used as an adjunct or alternative to lifestyle modification. The Chinese study showed that metformin and acarbose could reduce the risk of diabetes by 65 and 83%, respectively, in IGT subjects. The efficacy of metformin was confirmed by the Diabetes Prevention Program (31% risk reduction) and that of acarbose by the STOP-NIDDM trial (36% risk reduction) in a similar high-risk population. The TRIPOD study showed that troglitazone could reduce the risk of diabetes by 55% in Hispanic women with a history of gestational diabetes. And more recently, the XENDOS study showed that orlistat could reduced the risk of diabetes by 37% in obese subjects when used as an adjunct to an intensive lifestyle program. Three studies have suggested that bariatric surgery in morbidly obese subjects could reduce the risk of diabetes to near zero. Furthermore, a number of studies have examined the effect of a renin angiotensin aldosterone system inhibitor, as well as statin and hormone replacement therapy on the prevention of type-2 diabetes in high-risk subjects as secondary outcomes and have suggested that they could be of potential benefit. The accumulating evidence is now overwhelming. Yes, diabetes can be prevented or delayed in high-risk populations. With this new information, we need to design new strategies to screen high-risk populations and to implement the new treatments that have proven effective in the prevention of type-2 diabetes.

Copyright © 2006 Nestec Ltd., Vevey/S. Karger AG, Basel

We are facing a worldwide explosion in the prevalence of type-2 diabetes mellitus [1]. Because it is associated with high morbidity and excess mortality imposing a major burden on healthcare cost [2-4], it is definitely one of the major challenges of the 21st century.

Though it is generally accepted that type-2 diabetes develops in genetically susceptible individuals, it is also recognized that it is usually precipitated by environmental factors such as sedentary lifestyle and obesity [5, 6]. These factors contribute to the development of insulin resistance and, in those subjects with limited p-cell mass capacity, probably genetically determined, to the development of glucose intolerance, initially impaired glucose tolerance (IGT), and eventually type-2 diabetes [7]. This understanding of the pathophysiology of glucose intolerance served as the rationale for the concept of the prevention of type-2 diabetes. This concept has now been confirmed by a number of prospective trials that have shown that both non-pharmacological and pharmacological treatments as well as bariatric surgery in a high-risk population with IGT could prevent, or at least delay, the progression to diabetes.

The evidence for pharmacological and surgical intervention as a means to prevent or delay the progression of IGT to type-2 diabetes is reviewed here.

Pharmacological Interventions for the Prevention of Diabetes as Primary Endpoint

Insulin resistance overstresses the p cells and, in genetically susceptible individuals, results in a reduction in their capacity to secrete insulin. This combination of impaired insulin action and secretion will favor the development of IGT, a prediabetic state characterized by postprandial hyper-glycemia. This moderate postprandial hyperglycemia is sufficient to induce glucose toxicity and further contribute to the progression of IGT to diabetes. Therefore, it was hypothesized that any pharmacological intervention that would decrease insulin resistance and/or the stress on the p cells could potentially prevent or delay the progression of IGT to type-2 diabetes. Overall, 5 randomized controlled trials have examined the effect of drug interventions on the prevention of diabetes in IGT subjects as a primary outcome (table 1).

The Chinese study published in 2001 examined the effect of acarbose and metformin on the incidence of type-2 diabetes in 321 subjects with IGT over a 3-year period [8]. Both acarbose and metformin were effective in reducing the risk of diabetes by 83% (p = 0.0001) and 65% (p = 0.0002), respectively, compared to an incidence of 11.6% in the control group (table 1). The efficacy of both drugs in preventing type-2 diabetes was very impressive.

Table 1. Pharmacological interventions for the prevention of type-2 diabetes as a primary outcome


Number of subjects


Duration of study years

Incidence of diabetes in control group %/year

Risk reduction


The Chinese

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