Introduction

Metabolic syndrome, a combination of risk factors including high fat mass, hypertension, insulin resistance and dyslipidemia, is more common in patients with osteoarthritis (OA), compared to those without OA, and plays a role in its etiology and progression.^1,2 Low-grade chronic inflammation is seen as a key component of metabolic syndrome and is associated with OA.^2-4 Furthermore, hepatocellular and intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) accumulation are associated with insulin resistance, while hepatocellular lipid (HCL) accumulation is also correlated with other components of the metabolic syndrome and inflammation.^5-7 Inflammation and insulin resistance may help explain the relationship between metabolic syndrome and OA and could be targeted to reduce progression of OA. Studies show lifestyle interventions, such as hypocaloric and whole-food plant-based diets (WFPD), mindfulness, and/or exercise interventions, can reduce inflammation and symptoms in patients with OA.^8-11 Also, a WFPD has been shown to reduce both HCL and IMCL levels.¹² Yet, no studies have investigated the synergistic effects of a multidisciplinary lifestyle intervention in OA patients and its effect on HCL, IMCL, and EMCL levels.

Methods

Adults with knee and/or hip OA and metabolic syndrome were randomized into a 16-week multidisciplinary lifestyle program, “Plants for Joints” group (PFJ), or a control group (CG).¹³ The PFJ group received personal diet and exercise counseling followed by 10 group meetings with 6-12 participants consisting of theoretical and practical training on a WFPD, exercise, and stress management. The CG received usual care; medication was unchanged in both groups. In a subgroup of 32 participants (n=17 PFJ, n=15 CG) a MR spectroscopy (MRS) study was performed on a 3T scanner (Philips Healthcare, Best, The Netherlands) using a posterior coil located in the table and an anterior torso-coil covering the abdominal region and the upper leg. MRS acquisitions and secondary outcomes were acquired at baseline and after 16 weeks.

MRS data were acquired in accordance with a previous study.^14,15 Briefly, data were acquired using a multi-echo stimulated-echo acquisition mode (STEAM). Five spectra were acquired with echo times of 10, 15, 20, 25, and 30ms and a repetition time of 3500ms. For HCL, a single voxel (20×20×20mm3) was positioned in the right hepatic lobe, avoiding major blood vessels, bile ducts and liver margins (Figure 1). For IMCL and EMCL, a single voxel (15×25×25 mm3) was placed in the right rectus femoris halfway between the knee joint and groin. HCL was determined using the proton density fat fraction (PDFF) calculated from spectral data fitted in jMRUI version 4.0 and Matlab R2021a (Mathworks, Natick, MA, USA).^16,17 IMCL and EMCL spectra, acquired at an echo time of 11ms, were manually phased using jMRUI and referenced to the creatine-methyl resonance at 3 ppm. AMARES was used to estimate lipid signal amplitudes to calculate the total muscle fat, IMCL, and EMCL. Outcomes are expressed as percentage of the sum of unsuppressed water and total fat peaks.

Secondary outcomes included total body fat mass (FM) via DEXA, blood serum measurements (HbA1c, C-reactive protein (CRP), fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides), blood pressure, and anthropometric measurements (waist circumference, weight, and height).

A linear regression analysis was performed to compare MRS and secondary outcomes between the PFJ group and CG after 16 weeks (controlled for baseline values, sex, age and BMI). Differences between groups at baseline, as well as within groups between baseline and end, were analyzed respectively with a two-sample or one-sample t-test when normally distributed or a Wilcoxon-Rank test when skewed. Results were reported as mean (SD) or median [Q3 – Q1] depending on data distribution. A p-value of <0.05 was considered significant.

Results

Participants were 62.8 (6.7) years old (84.4% female) (Table 1). Two from each group dropped out before the second MRI and several spectra were excluded or missing from baseline or end (PFJ group: liver n=1 and muscle n=8; CG: liver n=2; muscle n=3). The groups were similar at baseline and within the CG there was no change (Table 1). After 16 weeks the PFJ group had lower HCL (p <0.001) and FM (p <0.001) levels compared to the CG (Figures 2A-B and 3A-B). There was no difference in muscle fat distribution between groups at end-intervention (Figures 2C-F). Both HbA1c and CRP were lower in the PFJ group compared to the CG (Figures 2G-H and 3C-D). Specific metabolic syndrome components (fasting blood glucose and waist circumference) and total and LDL-cholesterol improved after the intervention (Table 1).

Discussion

The WFPD lifestyle intervention reduced HCL and FM and improved metabolic and inflammatory markers in patients with OA compared to usual care. There were no observable changes in muscle fat distribution within or between groups, however the low number of quantifiable spectra for muscle fat may have impaired our ability to detect changes. The reduction in HCL levels is larger than results shown after an exclusive WFPD intervention.¹² Furthermore, the simultaneous reductions of HCL, FM, HbA1c, and CRP in this study supports the previously described associations between body and liver fat, insulin resistance, and inflammation.^5,6

Conclusion

A 16-week WFPD multidisciplinary lifestyle program resulted in a reduction of total body FM and HCL and improved metabolic and inflammatory markers in patients with metabolic syndrome-associated OA.

Acknowledgements

Research was funded by ZonMW (The Netherlands Organization for Health Research and Development) grant number 555003210.

References

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