Combination of exercise and GLP-1 receptor agonist treatment reduces severity of metabolic syndrome, abdominal obesity, and inflammation: a randomized controlled trial | Cardiovascular Diabetology
research population
At inclusion, before the hypocaloric diet, the study population consisted of 215 participants (63% female), aged 42 ± 12 years, with a mean BMI of 37.0 ± 2.9. See Table 1 and baseline characteristics in Additional File 1: Table S1. Smoking and alcohol consumption at inclusion are shown in Additional file 1: Table S2.
The observed mean MetS-Z contains 0.57, between 3road and 4day The quartiles of the reference population, indicating a significant cardiometabolic risk in the study population. Figure 1 of this study shows the MetS-Z quartiles and their associated risks. At inclusion, the mean MetS-Z for female participants was at 3road Interquartiles of the MetS-Z score, while the mean for men is on the boundary of 3road and 4day quartile. The distribution of scores was similar between the groups. Between the three visits, the pattern of MetS-Z change was broadly similar in males and females (see Additional file 1: Figures S2 and S3 for MetS-Z in females and males, respectively). At inclusion, 62% of participants had hypertension and 45% had prediabetes.
MetS-Z observed before and after the hypocaloric diet and at week 52 in the randomized group. Individual per-protocol participants (black dots) were randomized to observe MetS-Z at three visits before (week -8), after (week 0) and at the end of the trial 52 weeks), presented as a boxplot. Top of box indicates upper quartile; bottom of box is lower quartile; mean observed white diamond; median black horizontal line; whiskers ± 1.5 times interquartile range or highest or lowest observed value .Boxplot overlay of MetS-Z quartiles associated with future diabetes risk [12] and coronary heart disease [13] Compared to the first quartile and adjusted for individual MetS factors. For diabetes, unadjusted risks are also shown in brackets. MetS-Z Metabolic syndrome severity z-score. T2DM type 2 diabetes, coronary heart disease coronary heart disease
A total of 166 participants (85%) completed the study by taking the final assessment at week 52. Consequently, 15% of participants were lost to follow-up (placebo: 9, exercise: 8, liraglutide: 8, combination: 4), Additional file 1: Figure S1. Overall, the pattern of loss to follow-up was uniform, with the most common reason for loss to follow-up being personal life circumstances (eg, work-related changes). The per-protocol population included 130 participants (placebo = 39; exercise = 26, liraglutide = 36; combination = 29).
Changes in body weight and percent body fat have been previously published [24]Overall, the results of the trial showed that participants lost 13.1 kg (~12%) of body weight after the hypocaloric diet, see Table 1. After a year, the placebo group gained weight. Both the exercise group and the liraglutide group decreased total fat percentage while maintaining body weight. Combination group decreased body weight and fat percentage (Table 2) [24].
In the Results section below, we present the results for participants who completed the trial according to the prescribed interventions (Table 2 and Additional file 1: Table S3 and Figure 2). For the intention-to-treat analysis (including all randomized participants), see Additional file 1: Table S4.
Changes during hypocaloric diet and from randomization to week 52. Per-protocol analysis of mixed models estimated change in metabolic syndrome severity z-score (A), the prevalence of metabolic syndrome (Second), robot fat percentage (C), and high-sensitivity C-reactive protein (Man) during hypocaloric diet (shaded area; weeks -8 to 0) and treatment (weeks 0 to 52). Variation is the estimated mean difference ± standard error from the mean. Changes in high-sensitivity C-reactive protein are expressed as percentages by the ratio of back-transformed log data and are shown with 95% confidence intervals. The between-group change is the estimated mean difference with a 95% confidence interval and p-value. Results were adjusted for age group (
Variations in Metabolic Syndrome
During the hypocaloric diet, MetS-Z decreased from 0.52 to 0.06, P < 0.001 (Table 1 and Figure 2A).This reduction shifts the mean Mets-Z of all groups from the top 3road and bottom 4day The quartiles of the reference population indicating a higher risk of diabetes and CHD are on average close to the limit of 2nd and 3road quartiles, which indicate a lower risk of diabetes and coronary heart disease following a low-calorie diet (Figure 1). Table 1 shows diet-induced mean changes in individual MetS factors, which together translate into a mean reduction in the prevalence of MetS from 55% to 29% after a hypocaloric diet (Fig. 2B). In addition, the participants' prevalence of hypertension was halved (from 62 percent to 33 percent), and their prevalence of prediabetes was reduced by two-thirds (from 45 percent to 15 percent). Insulin resistance measured by HOMA-IR was 3.9 ± 2.4 before the hypocaloric diet and decreased by 56% to 1.7 ± 1.0 after the diet (Table 1).
After one year of hypocaloric diet, there was no change in MetS-Z in the placebo and exercise groups (Table 2). Compared with placebo, MetS-Z decreased by 0.37 in the liraglutide group, P < 0.001, and 0.48 in the combination treatment group, P < 0.001 (Fig. 2A).Notably, the mean MetS-Z in the liraglutide and combination groups shifted from higher risk 3 toroad to lower risk 2nd quartiles, indicating a reduction in risk on top of the reduction in risk with a low-calorie diet (Figure 1). Participants with metabolic syndrome at week 52 had a similar prevalence in the active-treatment group and a higher prevalence in the placebo group (Fig. 2B). The prevalence among participants with hypertension or prediabetes was generally lower in the active treatment group and significantly lower in the liraglutide treatment group.
Adjustment for blood pressure or lipid-lowering medications, smoking, and alcohol consumption at inclusion did not affect the results of the analysis (Additional file 1: Table S5).
The reduction in insulin resistance observed during hypocaloric exercise was maintained in the sustained-exercise group, whereas insulin resistance increased in the placebo and liraglutide groups after one year (Table 2).
changes in fat distribution
Android fat percentage decreased from 44.3% ± 4.7 before the low-calorie diet to 2.9% after the diet, P < 0.001 to 41.4% ± 6.0 (Table 1). See Additional File 1: Table S6 for absolute masses. At inclusion, men had a lower percentage robotic fat than females (41.3 vs. 46.0%, respectively), and men had a greater reduction in robotic fat percentage than women during the hypocaloric diet (-4.6 vs. -2.0%, respectively) .
After one year, there was no change in fat percentage in androids and females in the placebo group; however, fat mass increased in both androids and females (Table 2 and Additional File 1: Table S7). In general, the active treatment group seemed to lose relatively more humanoid fat than female fat. Compared with the placebo group, the exercise group reduced the percentage of robotic fat by 2.6%, P = 0.022, and the liraglutide group reduced the percentage of robotic fat by 2.8%, P = 0.006, Fig. 2C. Consequently, participants in the exercise group and the liraglutide group reduced their robotic fat percentages by about 6 percent throughout the trial period. The combined treatment group reduced robot fat percentage by 6.1 percentage points compared with the placebo group, P < 0.001, approximately double that of exercise or liraglutide alone. Furthermore, in men, android fat percentage was significantly reduced only in the combined treatment group, whereas in women, android percentage was reduced in all active treatment groups (Table 2).
Changes in high-sensitivity C-reactive protein
The median concentration of the inflammatory marker hsCRP was 3.8 mg/L before the low-calorie diet, and decreased by 32% to 2.4 mg/L after the diet, P < 0.001, Table 1.
After one year, hsCRP concentrations did not change in the placebo and exercise groups (Table 2 and Fig. 2D). In the liraglutide group, hsCRP was reduced by 36%; however, this reduction was not different from the placebo group. Compared with the placebo group, hsCRP was reduced by 43% in the combined treatment group, P = 0.030. In the intention-to-treat analysis, hsCRP was reduced by 35% in the combination treatment group, but this change was not different from that in the placebo group (Additional file 1: Table S4).
insist on intervention
In the per-protocol population, the exercise group performed 156 ± 54 minutes per week at an intensity of 78 ± 4% of maximum heart rate, while the combination group performed 144 ± 67 minutes per week at an intensity of 78 ± 5% of maximum heart rate. Study drug in all groups The average dose is at least 2.6 mg/day.Details on exercise and study drug adherence in the intention-to-treat population have been published previously [24].
Safety
Gastrointestinal adverse events (eg, one or more episodes of nausea, diarrhea, or vomiting within a year) were more common in the group receiving liraglutide (placebo: 45%, exercise: 65%, liraglutide group: 86%, combined drug group) group: 71%). Serious adverse events occurred in 4%, 8%, 12%, and 8% of the placebo, exercise, liraglutide, and combination groups, respectively.All safety findings previously reported [24].
