Impaired Fasting Glucose and Impaired Glucose Tolerance: Implications for Care

David M. Nathan, MD; Mayer B. Davidson, MD; Ralph A. DeFronzo, MD; Robert J. Heine, MD, PHD, FRCP; Robert R. Henry, MD; Richard Pratley, MD; Bernard Zinman, MD

Disclosures

Diabetes Care. 2007;30(3):753-759. 

In This Article

Introduction

Type 2 diabetes is now epidemic. In the U.S., there has been a 61% increase in incidence between 1990 and 2001.[1] There are currently 1.5 million new cases per year, and the prevalence in 2005 was almost 21 million.[2] The epidemic has affected developed and developing countries alike, and the worldwide prevalence of diabetes is projected to increase dramatically by 2025.[3] The increase in type 2 diabetes is related to lifestyle changes that have resulted in overweight, obesity, and decreased physical activity levels. These environmental changes, superimposed on genetic predisposition, increase insulin resistance, which, in concert with progressive ß-cell failure, results in rising glycemia in the nondiabetic range. In addition to the risk for diabetes, insulin resistance and impaired insulin secretion are accompanied by a host of major cardiovascular disease (CVD) risk factors including hypertension and dyslipidemia. Further reduction in insulin secretion over time results in increasing glycemia and the development of diabetes, which in turn is associated with the development of microvascular and cardiovascular complications.

The transition from the early metabolic abnormalities that precede diabetes, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), to diabetes may take many years; however, current estimates indicate that most individuals (perhaps up to 70%) with these pre-diabetic states eventually develop diabetes.[4–10] During the pre-diabetic state, the risk of a CVD event is modestly increased.[11­22] With the development of diabetes, however, there is a large increase in risk for CVD, as well as for long-term complications affecting the eyes, kidneys, and nervous system. The complications of diabetes, which are the cause of major morbidity and mortality, are related to its duration, chronic level of glycemia, and other risk factors.

Although clinical trials have demonstrated the effectiveness of intensive glycemic and blood pressure control to reduce the long-term complications of diabetes, the public health burden of the disease remains enormous. The magnitude of the epidemic, coupled with complex treatment requirements that are difficult and costly to implement, make the prevention of diabetes a critical public health goal. Between 1997 and 2006, eight major clinical trials examined whether lifestyle or pharmacologic interventions would prevent or delay the development of diabetes in populations at high risk by virtue of having IFG and/or IGT.[4,5,23–28] The study populations often had other recognized risk factors for diabetes including obesity, a prior history of gestational diabetes, or a positive family history of diabetes. All of these trials demonstrated reductions in the development of diabetes of 25­60% over the period of follow-up. The largest reductions (∼60%) were accomplished with lifestyle interventions aimed at weight loss and increasing physical activity and with thiazolidinediones.[4,5,24,25,27] Lesser degrees of reduction (25­30%) have been achieved with other drugs.[5,23,24,28]

The availability of interventions that have been shown to decrease the development of diabetes has stimulated consideration whether such interventions should be recommended and implemented, in whom, and under what circumstances. To address these issues, the American Diabetes Association convened a consensus development conference on 16­18 October 2006 focusing on the pre-diabetic states of IFG and IGT. Following the presentations of invited speakers and in-depth discussions, a seven-member panel of experts in diabetes, endocrinology, and metabolism developed this consensus position based on the questions below. The expert members were also asked to note where additional information or studies would be necessary to answer these questions.

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