Resistance exercise but not aerobic exercise lowers remnant-like lipoprotein particle cholesterol in type 2 diabetes: A randomized controlled trial☆
Introduction
Higher levels of physical fitness are associated with reduced all-cause mortality, primarily due to reduced rates of cardiovascular disease and cancer [1]. In diabetes, where risk of death from coronary artery disease (CAD) is 2 to 4 times that of the general population [2], high aerobic fitness is associated with a 45–70% reduction in overall mortality [3], [4]. We also know that in men, muscular strength adds to the survival advantage of aerobic fitness [5] although the mechanism is unknown.
There is a mismatch between the magnitude of survival benefit seen with exercise and the magnitude of change in cardiovascular risk indices. Improvements in traditional cardioprotective indices such as glycemia, blood pressure and concentrations of low density lipoprotein cholesterol (LDL-C), triglycerides and high-density lipoprotein cholesterol (HDL-C) have been reported, but they are often minor [6]. One explanation is that these classic cardiovascular disease risk factors do not always reflect sub-clinical etiology accurately, and that risk assessment limited to these markers fails to identify a significant proportion of patients at risk for coronary artery disease [7]. Emerging evidence suggests a role for the measurement of remnant-like lipoprotein particle cholesterol (RLP-C) concentration, identifying cholesterol associated with very low density lipoprotein (VLDL) and chylomicron remnants, in coronary artery risk assessment [8], [9], [10].
Despite the well characterized health benefits of exercise, there remains some controversy surrounding the optimal exercise modality, duration, frequency and/or intensity for cardioprotection. Although many reports, including a recent meta-analysis [6] and a large Italian study [11], have examined the effects of both aerobic and resistance exercise on the lipoprotein profile, none has examined the effect of exercise modality on remnant lipoproteins specifically.
Recently, the Diabetes Aerobic and Resistance Exercise (DARE) trial investigated the effect of aerobic and resistance exercise training, alone or in combination, on levels of HbA1c and several other coronary artery risk factors in patients with type 2 diabetes (T2D) [12]. The DARE trial was the largest exercise trial (n = 251) of its kind and revealed that aerobic and resistance exercise each improved glycemic control, reflected in HbA1c, but their combination reduced HbA1c at least twice as much as either type of exercise alone. The objective of this current study, was to assess the effects of aerobic and resistance exercise alone and in combination, on levels of RLP-C in the DARE trial participants. We hypothesized that in DARE participants, RLP-C would decrease to a greater extent in Aerobic and in Resistance training groups than in Control. Further, we hypothesized that the decrease in RLP-C would be greater in Combined than either Aerobic or Resistance groups.
Section snippets
Study design
The design of the DARE trial, including details of the exercise intervention programs, is described in detail elsewhere [12]. Briefly, the DARE study was a single-center, randomized, controlled trial with a parallel group design. After a 4-week run-in period to assess compliance, previously inactive people with T2D were randomized to one of 4 groups: aerobic training group (“Aerobic”), resistance exercise group (“Resistance”), combined aerobic training and resistance exercise group
Results
The participants in all groups were similar in age, sex, duration of diabetes and medication use (see Table 1). Details of screening, enrollment, adherence to the intervention protocol and follow-up assessments have been published previously [12]. Participants had dietary counseling with the aim of maintaining baseline weight. However all groups had similar slight decreases in overall caloric intake over time. No significant inter-group differences in macronutrient composition were observed.
Discussion
Cholesterol in remnant-like lipoprotein particles (RLP-C) correlates with coronary artery disease and is an independent risk factor for this in the presence of normal total cholesterol levels [23]. The main finding in this study is that resistance exercise lowers RLP-C in subjects with T2D. Our study does not support a beneficial contribution of aerobic exercise in T2D on RLP-C. To the best of our knowledge, this is the first time a sustained beneficial effect of resistance exercise on remnant
Conclusion
This report has provided evidence of the effects of exercise training on RLP-C in subjects with T2D. In particular resistance exercise but not aerobic exercise induced substantial reduction in concentration of RLP-C which was not reflected in triglyceride levels.
Acknowledgements
The measurements of remnant-like particle cholesterol and apolipoprotein B-48 for the present paper were supported by internal funds (TCO and SP). SP is supported by a New Investigator Award from the Heart and Stroke Foundation of Canada. The main DARE trial was supported by grants from the Canadian Institutes of Health Research (Grant #MCT-44155) and the Canadian Diabetes Association (The Lillian Hollefriend Grant). Dr. Sigal was supported by a New Investigator Award from the Canadian
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Trial registration: ClinicalTrials.gov study ID NCT00195884, http://www.clinicaltrials.gov.