Should We Treat Impaired Glucose Tolerance and Impaired Fasting Glycemia?
Authors: Holman Rury 
Published: April 2004

Type 2 diabetes is a major problem because of its high and increasing prevalence worldwide and its association with increased morbidity and mortality, especially cardiovascular disease, which results in high costs to the individual and to society. The number of people worldwide with diabetes is predicted to exceed 300 million by the year 2025, more than all of the people living currently in North America. Despite major efforts to improve the management of diabetes it remains in the twenty‐first century the leading cause of blindness, end‐stage renal disease, and lower extremity amputations in industrialized nations. The vast majority of those with diabetes (>90%) have type 2 diabetes (T2DM), who confers a two to four times greater risk of heart disease and stroke than in the general population, with a concomitant reduction in life expectancy of 5–10 years. As T2DM may remain undetected for many years, with more than half of those diagnosed presenting with clinically detectable complications, it is evident that preventing or at least delaying the onset of T2DM could be of major benefit.

Impaired glucose tolerance (IGT) and impaired fasting glycemia (IFG) are defined dysglycemic states that are known risk categories for the future development of diabetes and for cardiovascular disease (CVD). Both are associated frequently with hypertension, dyslipidemia, and other features of the metabolic syndrome. As up to 50% of individuals found to have IGT are likely to develop T2DM within 10 years, the possibility of identifying them at an earlier stage and offering intervention strategies designed to reduce T2DM and CVD risk is an attractive one. While it may not be practicable to screen the entire population for dysglycemia, targeted assessment of people thought to be at high risk of T2DM, e.g. because of their age, obesity, ethnicity, family history of diabetes, is feasible and could be incorporated as part of routine care in the community.

The Finnish Diabetes Prevention Study (DPS) and US Diabetes Prevention Program (DPP) have both demonstrated that intensive lifestyle management, aimed at reducing weight and increasing exercise, can successfully delay the onset of T2DM in individuals who have IGT; relative risk was reduced by 58% in each study. Over the long term, however, lifestyle changes alone may be insufficient and alternative therapies such as pharmacological interventions are likely to be required. The DPP showed that metformin therapy could delay the onset of T2DM, with a relative risk reduction of 31%, although this approach was less successful in older and in less overweight subjects. Similarly, the STOP‐NIDDM study demonstrated that acarbose administration could delay the onset of T2DM, with a relative risk reduction of 25% in subjects with IGT. Initial results for the thiazolidinedione troglitazone in the DPP and TRIPOD (Troglitazone In the Prevention of Diabetes) studies have also shown that progression to diabetes may be delayed in those with IGT or previous gestational diabetes respectively.

The dramatically increasing prevalence of diabetes suggests that novel strategies to reduce the risks of developing both T2DM and CVD are necessary if the predicted medical and economic burdens of these conditions are to be minimized. The potential to reduce new cardiovascular events or progression to diabetes, with a postprandial glucose regulator and/or an angiotensin II receptor blocker, is being investigated in 9523 IGT subjects by the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. In addition, the possibility that progression to diabetes can be reduced by a thiazolidinedione and/or an ACE (angiotensin‐converting enzyme) inhibitor is being investigated in over 5269 subjects with IGT by the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial.

Testing for dysglycemia should be undertaken routinely in subjects thought to be at increased risk of developing T2DM. Those found to have IGT or IFG should be given lifestyle advice and reviewed on a regular basis. Where lifestyle advice alone is insufficient, pharmacological therapy should be considered with prevention targeted at those at highest risk of developing T2DM and CVD. In addition to metformin and acarbose, the efficacy of different pharmacological agents, alone or in combination, in preventing diabetes needs to be established. The results of the NAVIGATOR and DREAM studies are awaited.