|Diabetes is a strong risk factor for ocular, neural, renal, cardiovascular and other consequences and its prevalence is rising steeply throughout the world, especially in developing countries. Research during the last decade has also clearly shown that the link between glucose and cardiovascular risk extends below glucose levels that are in the diabetes range. For example, a) a large 6 year epidemiologic study of > 10,000 men and women (and only 243 with diabetes) reported that a 1% rise in HbA1c above 5% predicted a 2030% rise in the risk of incident CVD (1); and b) a meta-analysis of prospective epidemiologic studies that recorded fasting glucose levels in more than 200,000 people reported that a 1 mmol/L higher fasting level above 4.9 mmol/L predicted a 23% higher risk of ischemic heart disease (2). Thus, the link between glucose or HbA1c and cardiovascular events is similar to the relationship between blood pressure or lipid levels and cardiovascular events: there is no clear “safe” threshold (3).
Several large, relatively short-term trials have reported that lifestyle interventions and a variety of drugs can reduce new diabetes in people with dysglycaemia. Most of the tested therapies have also promoted regression to normoglycaemia and improved cardiovascular risk factors, and an analysis of data from the STOP-NIDDM study supported the hypothesis that acarbose may also prevent cardiovascular events in people with impaired glucose tolerance (4). Despite this finding, whether or not glucose lowering reduces cardiovascular events in people with impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) continues to be studied and remains unknown.
Rosiglitazone is a thiazolidinedione that clearly lowers glucose levels, increases insulin sensitivity and reduces lipolysis. There is an emerging body of evidence suggesting that this drug may also prevent type 2 diabetes, preserve b-cell function and reduce atherosclerosis and risk factors for atherosclerosis. Ramipril is an angiotensin-converting enzyme (ACE) inhibitor that prevents cardiovascular events in high-risk people, including those with diabetes. Data from the HOPE study strongly suggested that it may also prevent new diabetes. Since that time, several cardiovascular trials using either ACE-inhibitors or angiotensin-2 receptor blockers have supported the hypothesis that type 2 diabetes can be prevented by inhibition of the reninangiotensinaldosterone system.
The DREAM study (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) is a large, international, multicentre trial which prospectively tested the hypothesis that either rosiglitazone and/or ramipril may reduce type 2 diabetes in 5,269 individuals with IFG or IGT with no history of cardiovascular disease (5).The main results of the DREAM trial are that treatment with Rosiglitazone 8 mg a day decreased new onset of diabetes in this population by 60% and treatment increased the likelihood or reversion to normal glucose tolerance by 70-80%. 7 people needed to be treated for 3 years to prevent one case of diabetes.
- Khaw KT,Wareham N, Bingham S, Luben R,Welch A,Day N. Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk. Ann Intern Med 141(6):413-20, 2004
- Lawes CM, Parag V, Bennett DA, Suh I, Lam TH,Whitlock G et al. Blood glucose and risk of cardiovascular disease in the Asia Pacific region.Diabetes Care 27(12):2836-42, 2004.
- Gerstein HC, Pogue J,Mann JF, Lonn E,Dagenais GR,McQueen M et al.The relationship between dysglycaemia and cardiovascular and renal risk in diabetic and non-diabetic participants in the HOPE study: a prospective epidemiological analysis.Diabetologia 48(9):1749-55, 2005.
- Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA 23;290(4):486-94, 2003.
- Gerstein HC,Yusuf S, Holman R, Bosch J, Pogue J; The DREAM Trial Investigators. Rationale, design and recruitment characteristics of a large, simple international trial of diabetes prevention: the DREAM trial. Diabetologia 47(9):1519-27, 2004.
- Dream Trial Investigators. Effect of Rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomized controlled trial (DREAM Trial). Lancet Sept 2006