Resistance exercise but not aerobic exercise lowers remnant-like lipoprotein particle cholesterol in type 2 diabetes: A randomized controlled trial

Abstract

The comparative effects of aerobic and resistance exercise on triglyceride-rich lipoproteins including remnant lipoproteins are controversial. This study examined exercise effect on remnant-like lipoprotein particle cholesterol (RLP-C) in type 2 diabetes. Participants were randomized to control (Control), aerobic (Aerobic), resistance (Resistance), or both (Combined) exercise groups. Baseline and 6-month fasting RLP-C and apolipoprotein B48 concentrations were measured. Data analysis was on an intention-to-treat basis.

At 6 months, RLP-C was lower in all groups; ΔRLP-C mg/dl, (95% confidence interval), Control −3.91, (−6.21 to −1.6), p = 0.001; Aerobic −3.89, (−6.41 to −1.36), p = 0.003, Resistance −7.52, (−9.89 to −5.15), p = 0.0001, Combined −7.50, (−9.87 to −5.13), p = 0.0001. Total triglycerides were significantly lower in Resistance and Combined groups only; −17.7 mg/dl (−32.8 to −2.7), p = 0.02 and −27.5 (−42.5 to −11.5), p = 0.001, respectively. Inter-group comparisons showed no difference in RLP-C change between Aerobic and Control and a significant difference in RLP-C change only where groups incorporating resistance exercise were compared with those without. There was no significant difference in RLP-C change between Resistance and Combined. Inter-group comparisons of total triglycerides change were significant only between Combined and Control. Changes in apolipoprotein B48 were not significant in inter-group comparisons.

In conclusion, our data indicate that resistance exercise training, not aerobic, lowers RLP-C in type 2 diabetes. This effect was not revealed by changes in total triglycerides and apolipoprotein B48. The discordance between changes in RLP-C and apolipoprotein B48 in response to resistance exercise may indicate (a) a decrease in VLDL remnant and not chylomicron remnant particle number and/or (b) a depletion of cholesterol in chylomicron and/or VLDL remnants.

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.