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- May 12, 2008 |
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"Can We Prevent Progression to Type 2 Diabetes? Recent Evidence"Prof. Hertzel Gerstein (biography)
English - 2006-12-04 - 38 minutes
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Summary :
Type 2 diabetes accounts for 90% of all diabetes and currently affects at least 5% of adults worldwide and is rapidly rising in prevalence. Affected people are at high risk of serious eye, kidney, nerve and vascular diseases which can lead to premature mortality. Large clinical trials have reported that lifestyle interventions (i.e. activity and weight loss), and the drugs metformin, acarbose and orlistat can reduce the incidence of diabetes. Whether or not preventing diabetes also prevents the chronic consequences of diabetes remains unknown. However, one report has suggested that acarbose may reduce the risk of cardiovascular disease in people with IGT. Clearly, interventions that prevent both diabetes and its sequelae are the most attractive.
Ramipril is an angiotensin-converting enzyme inhibitor (ACE-I) that is now proven to prevent cardiovascular events in high-risk people, including those with diabetes. Data from the HOPE study strongly suggested that it also prevents 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 renin–angiotensin–aldosterone system.
Thiazolidinediones (glitazones) are a class of agents that bind to peroxisome proliferator-activated gamma receptors in fat cells, and to a lesser extent in liver and muscle. Rosiglitazone and pioglitazone are currently used to treat diabetes. They enhance hepatic and peripheral insulin sensitivity, lower glucose levels in dysglycaemic individuals, increase hepatic insulin clearance, reduce hepatic fat and inflammatory cytokines, increase adiponectin and promote preadipocyte differentiation into adipocytes. They may also prevent damage to beta cells and preserve insulin secretion. Two clinical trials with troglitazone (no longer clinically available) also suggested that they reduce the incidence of diabetes, and the recent PROactive trial using pioglitazone suggests they may reduce cardiovascular events.
The DREAM trial was a large, international, multicentre trial testing whether ramipril and/or rosiglitazone prevents type 2 diabetes. A total of 5,269 people aged 30 years or older (mean age 55 years; 59% women, mean weight 85 kg) with impaired fasting glucose alone (14%), impaired glucose tolerance alone (57.5%) or both abnormalities (28.5%) were recruited in 191 clinical centres located in 21 countries. They were randomly allocated to ramipril 15 mg/day or placebo and/or rosiglitazone 8 mg/day or placebo, and followed for a median of 3 years. The primary outcome was the development of either diabetes or death.
Ramipril and rosiglitazone had independent effects on the study outcomes and were reported separately (1;2). Ramipril was associated with a nonsignificant 9% reduction in the primary outcome. However, it significantly increased regression to normoglycaemia. Rosiglitazone significantly reduced diabetes by 60% and increased regression to normoglycaemia; 0.5% of participants on rosiglitazone, compared to 0.1% on placebo, developed nonfatal heart failure during the 3 year trial.
Both ramipril and rosiglitazone, therefore, have favourable, different effects on glucose levels and related abnormalities. The modest metabolic effects of ramipril may contribute to the clinical benefits of ACE-I on prevention of cardiovascular events that have been proven in other trials. The 60% reduction in diabetes with rosiglitazone may lead to a reduction in serious cardiovascular, eye, kidney, neurologic and other consequences of diabetes.
Learning objectives :
After viewing this presentation the participant will be able to discuss:
- What is disease prevention?
- Why prevent type 2 diabetes?
- Evidence for reduced diabetes risk with ACE inhibitors
- The DREAM trial: modest improvement of glycemic status in people with IFG/IGT with ramipril, and reduced diabetes risk with rosiglitazone
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