Diet and activity interventions can improve inflammatory markers in early type 2 diabetes

Thompson D, Walhin JP, Batterham AM, et al.
J Am Heart Assoc. 2014 May 8;3(3):e000828. doi: 10.1161/JAHA.114.000828

Background

High-sensitivity serum concentration of C-reactive protein (CRP is the most widely used systemic marker of low-grade inflammation, and appears to have consistent predictive value for cardiovascular (CV) risk [1]. People with type 2 diabetes (T2D) show increasing circulating CRP levels with increasing fasting glucose concentrations [2]. In T2D patients, CRP is an independent risk factor for CV events [3,4], risk of death [5], atherosclerotic progression [6] and development of peripheral disease [7].
Small studies suggest that intensive interventions focussing on weight reduction and increasing supervised exercise activity can lead to beneficial effects on inflammatory markers in people with T2D. But because supervised physical activity cannot be provided in most healthcare settings, the clinical relevance of these findings are unclear.
Early ACTivity In Diabetes (ACTID) was designed to evaluate the effect of physical activity over and above that of dietary intervention on inflammation in patients with T2D, while controlling for overall contact time with patients. The physical activity component in ACTID was unsupervised. 593 patients were randomised in a 2:5:5 ratio to usual care, an intensive diet intervention or the intensive diet intervention plus activity.

Main results

• Small but clinically meaningful benefits of both interventions as compared with usual care were seen after 6 months, with regard to CRP, IL-6, soluble intercellular adhesion molecule-1 (sICAM) and adiponectin. The effects for CRP and adiponectin were attenuated at 12 months, but this was mainly due to an improved profile in the usual care-arm. Improvements in sICAM-1 and IL-6 were similar at 12 and 6 months.
• CRP levels were considered as a dichotomised variable, thus high vs. low-to-moderate CRP, with a cut-off point of CRP>3 mg/L. After 6 months, the risk difference for having a high-risk CRP level was -3.6 (95%CI: -12.2 to 5.1) % for diet vs. usual care, -10.7 (95%CI: -19.6 to -1.7)% for diet+activity vs. usual care , and -7.1 (95%CI: -14.4 to 0.2)% for diet+activity vs. diet.
  After 12 months, the risk differences were -10.7 (95%CI: -20.0 to -1.4)% for diet vs. usual care, -12.6 (95%CI: -22.2 to -3.0)% for diet+activity vs. usual care and -1.9 (95%CI: -9.5 to 5.6)% for diet+activity vs. diet.
• At 6 months, tendencies for the effect of the diet+activity intervention to be moderated by sex, baseline CRP level and statin use were observed. At 12 months, the effect of this intervention tended to be modified by sex and statin use, and was significantly modified by CRP baseline level.
• Change in body mass mediated approximately 40% of the total effect on CRP and more than half of the effect on adiponectin, in both interventions.
  

Conclusion

These results show that motivational unsupervised diet and diet plus physical activity interventions, integrated into healthcare can generate beneficial changes in several inflammatory markers in early T2D. The interventions had relatively modest resource implications. Both interventions reduced the proportion of patients with a high-risk CRP level. Even after medication was adjusted to attempt achievement of clinical targets, both interventions were better than usual care for patients with higher CV risk (CRP>3 mg/L) and for measures of vascular risk (sICAM-1). Adding physical activity advice to dietary advice did not yield a substantially higher benefit. Weight loss appears central to changes in circulating markers of inflammation.  

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References

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