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Reducing Inflammation with Diet & Exercise

Inflammation plays a major role in diabetes-associated cardiovascular disease (CVD). However, there is uncertainty whether diet and physical activity interventions can be successfully integrated into healthcare settings and reduce markers of inflammation and risk of CVD in patients with type 2 diabetes (T2D). This study, funded by the British Heart Foundation, examined the systemic markers of inflammation in a 12-month, real-world, multicenter, randomized, controlled trial that investigated the effect of diet, diet plus physical activity, and usual care in 593 individuals from Southwest England, with newly diagnosed T2D. During the first six months, serum C-reactive protein (CRP) improved by 21 percent (36 to 1.4) and 22 percent (38 to 3.1)in diet and diet plus physical activity arms versus usual care. There were also improvements in adiponectin and soluble intercellular adhesion molecule-1 (sICAM-1).

Mature couple riding bicyclesThough medication-adjusted CRP was improved between 6 and 12 months for usual care, both interventions were more successful in reducing the relative risk of a high-risk CRP level of >3 mg/L (risk ratios of 0.72 [0.55 to 0.95] for diet versus usual care and 0.67 [0.50 to 0.90] for diet plus activity versus usual care). Furthermore, sICAM-1 (a marker of vascular risk), remained substantially lower than usual care in both intervention arms at 12 months. Motivational, unsupervised diet and/or diet plus physical activity interventions given soon after diagnosis in real world healthcare settings improve markers of inflammation and cardiovascular risk in patients with T2D, even after accounting for the effect of adjustments to medication to try and control blood pressure, glycated hemoglobin, and lipids.

Systemic markers of low-grade inflammation represent an important adjunct to the capture of conventional cardiovascular risk factors. Of the measures that are readily available, high-sensitivity serum concentration of CRP is the most widely used and appears to have consistent predictive value in various populations and groups. Individuals with a CRP level of greater than 3 mg/L are considered at high risk of cardiovascular disease. People with type 2 diabetes tend to have higher markers of inflammation, and circulating CRP concentrations increase continuously across the spectrum of fasting glucose concentrations beginning at the lowest quartile of normal fasting glucose. In patients with type 2 diabetes, CRP is an independent risk factor for cardiovascular events, risk of death, atherosclerotic progression, and development of peripheral vascular disease.

Increased physical activity and dietary advice implemented by healthcare professionals is recommended by international consensus in the management of T2D. The effect of diet and/or physical activity on inflammation-associated cardiovascular risk in patients with T2D has been poorly characterized. Of the studies that exist, most represent small efficacy trials involving only a handful of patients and with the investment of significant resources to support lifestyle changes (eg, supervision of exercise). These small studies confirm that intensive interventions designed to reduce weight and/or increase participation in supervised exercise can lead to profound beneficial effects on inflammatory markers in people with T2D.
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Study Procedures

  • The usual-care arm was designed to serve as a control group and consisted of standard dietary and exercise advice after randomization, with reviews by a study doctor and nurse at baseline as well as at six and 12 months.
  • The intensive diet intervention arm aimed to enable patients to lose five percent to 10 percent of their initial body weight. The diet was not prescriptive; goals were negotiated individually with each participant. Participants saw a dietitian at three, six, nine, and 12 months, and this contact was supplemented by dietary advice and goal setting by nine 30-minute appointments with study nurses—approximately one every six weeks over the course of the study.
  • Patients in the intensive diet and physical activity group received the same dietary intervention as the intensive diet group, but were also asked to undertake at least 30 minutes of brisk walking on at least five days per week over and above their existing physical activity.
  • Each subject was given a pedometer (Digi-Walker CW200; Yamax, Yamasa Tokei Keiki Co., Ltd., Tokyo, Japan) and a folder containing motivating literature and pages for recording daily physical activity (pedometer readings). Activity targets were gradually increased over five weeks and maintained for the remainder of the study.
  • Activity was discussed during the same nurse appointments in order to keep the total contact time the same as in the intensive diet intervention group.

Inflammatory Markers and Results

The study measured C-Reactive Protein as well as IL-6, adiponectin, and soluble intercellular adhesion molecule-1 (sICAM-1). Of 1,634 patients who were screened by telephone, 593 were enrolled into Early ACTivity In Diabetes (ACTID) and the characteristics of each group were similar at baseline (See Table 1 in full study). Changes in HbA1c as well as measures of insulin resistance (HOMA-IR) and weight were greater in both intervention arms, compared to usual care, with no substantial difference between interventions. The activity group increased their mean daily step count from 6,399 (3,056) to 7,680 (2,818) and 7,621 (2,778) at six and 12 months, respectively. Approximately 90 percent of potential blood samples were available for assessment of CRP, IL-6, adiponectin, and sICAM-1.

The results show that motivational unsupervised diet and diet plus physical activity interventions, integrated into healthcare settings and with relatively modest resource implications, generate beneficial changes in various inflammatory markers in early T2D. Notably, even after adjustments to medication were made to try and achieve predefined clinical targets, both interventions were better than usual care for patients with a higher risk of CVD (ie, with a CRP >3 mg/L) and for measures of vascular risk (sICAM-1). There was no substantially greater benefit from adding physical activity advice to dietary advice.

At six months, there was a similar mean reduction in CRP in both interventions versus usual care of 21 percent to 22 percent. By 12 months, the effect on mean CRP level was substantially attenuated, but the analysis of dichotomous high-risk CRP revealed a substantial reduction in the risk of a high-risk CRP value (>3 mg/L), with mean relative risk (RR) reductions of 28% percent for diet and 33 percent for diet plus physical activity and numbers needed to treat for benefit of 10 and eight participants, respectively.

This article is excerpted from an article in JAMA,Journal of the American Heart Association , Effect of Diet or Diet Plus Physical Activity Versus Usual Care on Inflammatory Markers in Patients with Newly Diagnosed Type 2 Diabetes: The Early ACTivity In Diabetes (ACTID) Randomized, Controlled Trial.and was originally posted on Today’s Practitioner.

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