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Look AHEAD: Intensive lifestyle intervention less effective in those with higher HbA1c

Research is needed to help develop interventions that are effective for those with higher HbA1c.

In the Look AHEAD (Action for Health in Diabetes) randomised controlled trial, an intensive lifestyle intervention, aimed at achieving at least 7% weight loss by means of calorie restriction and increased moderate-intensity physical activity, has previously been shown to have no significant effect on cardiovascular disease (CVD) mortality and morbidity compared with standard diabetes education in people with type 2 diabetes. However, the effects differed according to previous CVD history. The aim of the present post hoc analysis was to assess whether effects of the intervention differed according to baseline HbA1c.

A total of 5145 participants were randomised to either the intensive intervention or standard care. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalisation for angina.

As would be expected, in the study cohort as a whole, the risk of the primary outcome was higher with increasing HbA1c quintile, ranging from 11.2% in quintile 1 (Q1) to 20.2% in Q5, over a median follow-up of 9.6 years. Randomisation to the intensive intervention was associated with a lower risk of CVD in HbA1c Q1 (hazard ratio [HR] 0.68) and Q2 (HR 0.80), but with a higher risk in Q5 (HR 1.27); the intervention had a neutral effect in Q3 and Q4. Modelling showed that the intervention was protective against CVD at a baseline HbA1c below 6.8%, neutral at 6.8–8.7% and associated with increased risk above 8.6%. Similar outcomes were observed with different CVD composite outcomes.

Notably, in Q5, the intensive intervention arm had a lower risk of all-cause death, cardiovascular death and heart failure, while the risk of myocardial infarction, angina and stroke was higher. It is possible that, as randomisation was not blinded, clinicians were more likely to monitor for these less severe CVD events earlier in the lifestyle group. Also notable was the fact that fewer than half of the participants in the intervention group were able to achieve the target 7% weight loss; however, those who did achieve the target had the lowest risk of CVD, even among individuals in the highest HbA1c quintile at baseline.

As this was a post hoc analysis, the results can only be exploratory. Furthermore, the study’s inclusion criteria mean that it represents a cohort with a higher burden of obesity and hypertension, but more favourable lipid and glucose profiles, than the broader population with type 2 diabetes in the US. Despite these limitations, the authors conclude that the effect of this intensive lifestyle intervention differed according to baseline HbA1c, and that research is needed to help develop interventions that are effective for those with higher HbA1c.

Click here to read the study in full.

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