Prevention of diabetes and cardiovascular disease among prediabetic individuals: lifestyle versus drug interventions

Prediabetes refers to impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), the stage preceding the development of clinical diabetes. IGT is defined as 2-h post-load glucose 140mg/dl (7.8mmol/l) and <200mg/dl (11.1mmol/l); IFG as fasting plasma glucose 110mg/dl (6.1mmol/l) and <126mg/dl (7.0mmol/l). More recently, HbA1c of 5.7–6.4% was added as another criterion for defining prediabetes. According to the Third National Health and Nutrition Examination Survey, 1988–1994, the prevalence of IFG in the US population 20 years of age was 6.9% and that of IGT in those 40–74 years of age was 15.8%. No matter how it is defined, prediabetes is associated with a substantially elevated risk of cardiovascular disease (CVD). This finding provides support for the ‘ticking clock’ hypothesis, which postulates that ‘the clock for coronary heart disease starts ticking before the onset of clinical diabetes.’ The evidence is also compatible with the ‘common soil’ hypothesis, which posits that diabetes and cardiovascular disease share common pathophysiological and environmental antecedents, i.e., ‘they spring from a common soil.’ In the Nurses’ Health Study cohort, participants who converted from prediabetes to type 2 diabetes during follow-up had a more atherogenic risk profile (e.g., higher BMI values and greater prevalence of hypertension and hypercholesterolemia) and increased incidence of CVD than those who did not convert. However, individuals with preexisting diabetes at baseline had the most adverse CVD risk profiles and the highest incidence of CVD during follow-up. Therefore, prediabetes, diabetes, and cardiovascular disease constitute a continuum of cardiometabolic risk. As a consequence, early management of prediabetes through lifestyle interventions or pharmacological means is not only critical to reduce the progression from prediabetes to diabetes, but also to decrease the long-term risk of CVD. In this issue of European Journal of Cardiovascular Prevention and Rehabilitation, Hopper et al. reported a meta-analysis of prospective, randomized controlled trials (RCTs) that evaluated the effects of lifestyle intervention or pharmacological treatment on diabetes prevention among individuals with IGT and/or IFG. Ten RCTs with 23,152 patients were included in the metaanalysis. The average duration of the trials was 3.75 years. Overall, the interventions reduced the risk of diabetes by 17% (95%CI 14–20%), with lifestyle interventions more effective than drug-based ones (RR1⁄4 0.52, 0.46–0.58 vs 0.70, 0.58–0.85, p< 0.05). No significant benefit in either total or cardiovascular mortality was observed for either intervention. This meta-analysis confirms earlier data showing the superiority of lifestyle interventions over drug-based treatment for diabetes prevention among prediabetic individuals. In the Diabetes Prevention Program (DPP), the lifestyle intervention group experienced a 58% decrease in the risk of diabetes over a 3-year period compared to controls. This effect was considerably greater than that in the metformin group (31%). Findings were similar for incidence of the metabolic syndrome, with the lifestyle group experiencing 41% risk reduction, and the metformin group 17% risk reduction, compared with placebo. The strong relationship between diabetes and CVD outcomes suggests that interventions that are effective in preventing diabetes would also reduce risk of CVD. However, this meta-analysis found no benefits of lifestyle or pharmacological interventions on total or CVD death. Lack of power is a major limitation of this metaanalysis as the vast majority of trials were not designed to examine CVD outcomes. Of the 10 RCTs combined, there were only 274 CVD deaths in the intervention groups and 85 in the control groups. Some trials had no CVD deaths in either group. Besides relatively small