Body-size phenotypes and cardiometabolic risk in Rheumatoid Arthritis

Objectives: Obesity is a significant contributor to metabolic complications. However, such complications are not uniform in people with similar body-size. The existence of normal-weight individuals with and obese individuals without metabolic complications has been described in the general population and is important in the context of cardiovascular disease (CVD). This has not been investigated in rheumatoid arthritis (RA), a condition associated with increased cardiometabolic risk. This study aims to identify the prevalence and predictors of body-size phenotypes in RA and investigate their associations with CVD risk. Methods: Body mass index (BMI: kg/m2), body fat (BF) and fat free mass (FFM), RA characteristics and CVD risk factors were assessed in 363 (262 females) volunteers with RA. Abnormal cardiometabolic status was defined as the presence of >1 of the following: hypertension, increased triglycerides or increased Low or reduced High Density Lipoprotein, high glucose, insulin resistance. Results: Among normal-weight, overweight, and obese participants 25%, 45.8%, 57.1% respectively were metabolically abnormal. Old age (B= 1.032, err=0.011; p= 0.005), waist circumference (B= 1.057, err= 0.011; p= 0.000), and smoking cessation (B= 1.425, err= 0.169; p=0.036) were significant predictors for metabolic abnormality. Conclusions: A significant number of RA patients present with different body-size and metabolic phenotypes. BMI alone is not a sufficient indicator of cardiometabolic risk in RA; this may have significant implications in their CVD risk evaluation. Body fat distribution seems to be a significant contributor to such abnormalities. Further research is needed, focusing on the metabolic properties of specific adipose depots of RA patient

Obesity in chronic inflammation using rheumatoid arthritis as a model: definition, significance, and effects of physical activity & lifestyle

A thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of PhilosophyBackground: Inflammation is the natural reaction of the body to an antigen. In some conditions, this reaction continues even after the elimination of the antigen, entering a chronic stage; it targets normal cells of the body and causes extensive damage. Rheumatoid arthritis (RA) is such a condition. It associates with significant metabolic alterations that lead to changes in body composition and especially body fat (BF) increases. In the general population, increased body fat (i.e. obesity) associates with a number of health disorders such as systemic low grade inflammation and a significantly increased risk for cardiovascular disease (CVD). Both effects of obesity could have detrimental effects in RA. Increased inflammation could worsen disease activity while obesity could further increase the already high CVD risk in RA. However, obesity in RA has attracted minimal scientific attention. Aims: The present project aimed to: 1) assess whether the existing measures of adiposity are able to identify the changes in body composition of RA patients, 2) if necessary develop RA-specific measures of adiposity, 3) investigate the association of obesity with disease characteristics and CVD profile of the patients, 4) and identify factors that might affect body weight and composition in these patients. Methods: A total of 1167 volunteers were assessed. Of them 43 suffered from osteoarthritis and 82 were healthy controls. These, together with 516 RA patients were used in the first study. Their body mass index (BMI), BF, and disease characteristics were assessed. In the second, third, fourth and fifth studies a separate set of 400 RA patients was assessed. In addition to the above assessments, their cardiovascular profile and more detailed disease characteristics were obtained. For the final study, 126 RA patients were assessed for all the above and also data on their physical activity levels and their diet were collected. Results: Assessments of adiposity for the general population are not valid for RA patients. Thus, we proposed RA-specific measures of adiposity. These are able to better identify RA patients with increased BF. We were also able to find associations between obesity and disease activity. Both underweight and obese RA patients had more active disease compared to normal-weight patients. Obese patients had significantly worse CVD profile compared to normal-weight. The newly devised measures of adiposity were able to identify those at increased risk. However, not all obese individuals were unhealthy and not all normal-weight healthy. Among our patients we were able to identify subtypes of obesity with distinct phenotypic characteristics that warrant special attention. Finally, we were able to identify factors that influence body weight and composition. Cigarette smoking protected against obesity while its cessation associated with increased adiposity. Physical activity was also found to be protective against obesity while diet or inflammation of the disease failed to produce any significant results. Conclusions: Obesity is a significant threat to the health of RA patients. The measures of adiposity developed herein should be used to identify obese RA patients. Physical activity seems like the sole mode for effective weight management in this population. Health and exercise professionals should actively encourage their patients to exercise as much as they can. This study has created more questions than it answered; further research in the association of obesity and inflammation, as well as in ways to treat it, is essential

Obesity in chronic inflammation using rheumatoid arthritis as a model : definition, significance, and effects of physical activity & lifestyle

Background: Inflammation is the natural reaction of the body to an antigen. In some conditions, this reaction continues even after the elimination of the antigen, entering a chronic stage; it targets normal cells of the body and causes extensive damage. Rheumatoid arthritis (RA) is such a condition. It associates with significant metabolic alterations that lead to changes in body composition and especially body fat (BF) increases. In the general population, increased body fat (i.e. obesity) associates with a number of health disorders such as systemic low grade inflammation and a significantly increased risk for cardiovascular disease (CVD). Both effects of obesity could have detrimental effects in RA. Increased inflammation could worsen disease activity while obesity could further increase the already high CVD risk in RA. However, obesity in RA has attracted minimal scientific attention. Aims: The present project aimed to: 1) assess whether the existing measures of adiposity are able to identify the changes in body composition of RA patients, 2) if necessary develop RA-specific measures of adiposity, 3) investigate the association of obesity with disease characteristics and CVD profile of the patients, 4) and identify factors that might affect body weight and composition in these patients. Methods: A total of 1167 volunteers were assessed. Of them 43 suffered from osteoarthritis and 82 were healthy controls. These, together with 516 RA patients were used in the first study. Their body mass index (BMI), BF, and disease characteristics were assessed. In the second, third, fourth and fifth studies a separate set of 400 RA patients was assessed. In addition to the above assessments, their cardiovascular profile and more detailed disease characteristics were obtained. For the final study, 126 RA patients were assessed for all the above and also data on their physical activity levels and their diet were collected. Results: Assessments of adiposity for the general population are not valid for RA patients. Thus, we proposed RA-specific measures of adiposity. These are able to better identify RA patients with increased BF. We were also able to find associations between obesity and disease activity. Both underweight and obese RA patients had more active disease compared to normal-weight patients. Obese patients had significantly worse CVD profile compared to normal-weight. The newly devised measures of adiposity were able to identify those at increased risk. However, not all obese individuals were unhealthy and not all normal-weight healthy. Among our patients we were able to identify subtypes of obesity with distinct phenotypic characteristics that warrant special attention. Finally, we were able to identify factors that influence body weight and composition. Cigarette smoking protected against obesity while its cessation associated with increased adiposity. Physical activity was also found to be protective against obesity while diet or inflammation of the disease failed to produce any significant results. Conclusions: Obesity is a significant threat to the health of RA patients. The measures of adiposity developed herein should be used to identify obese RA patients. Physical activity seems like the sole mode for effective weight management in this population. Health and exercise professionals should actively encourage their patients to exercise as much as they can. This study has created more questions than it answered; further research in the association of obesity and inflammation, as well as in ways to treat it, is essential.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Cardiorespiratory fitness levels and their association with cardiovascular profile in patients with rheumatoid arthritis: a cross-sectional study.

OBJECTIVE: The aim of this study was to investigate the association of different physical fitness levels [assessed by the maximal oxygen uptake (VO2max) test] with cardiovascular disease (CVD) risk factors in patients with RA. METHODS: A total of 150 RA patients were assessed for cardiorespiratory fitness with a VO2max test and, based on this, were split in three groups using the 33rd (18.1 ml/kg/min) and 66th (22.4 ml/kg/min) centiles. Classical and novel CVD risk factors [blood pressure, body fat, insulin resistance, cholesterol, triglycerides, high-density lipoprotein (HDL), physical activity, CRP, fibrinogen and white cell count], 10-year CVD risk, disease activity (DAS28) and severity (HAQ) were assessed in all cases. RESULTS: Mean VO2max for all RA patients was 20.9 (s.d. 5.7) ml/kg/min. The 10-year CVD risk (P = 0.003), systolic blood pressure (P = 0.039), HDL (P = 0.017), insulin resistance and body fat (both at P < 0.001), CRP (P = 0.005), white blood cell count (P = 0.015) and fibrinogen (P < 0.001) were significantly different between the VO2max tertiles favouring the group with the higher VO2max levels. In multivariate analyses of variance, VO2max was significantly associated with body fat (P < 0.001), HDL (P = 0.007), insulin resistance (P < 0.003) and 10-year CVD risk (P < 0.001), even after adjustment for DAS28, HAQ and physical activity. CONCLUSION: VO2max levels are alarmingly low in RA patients. Higher levels of VO2max are associated with a better cardiovascular profile in this population. Future studies need to focus on developing effective behavioural interventions to improve cardiorespiratory fitness in RA

Internal training exposure:development and construct validation of an individualised method using heart rate variability

PURPOSE: The aim was to develop and validate an individualised internal training exposure method by deriving weighting factors for each heart rate (HR) from detrended fluctuation analysis of heart rate variability (DFA-α1) during a graded exercise test.METHODS: Thirty-seven participants (17 females; 32.72 ± 9.26 years; maximal oxygen uptake, VO2max = 48.32 ± 7.95 mL kg-1 min-1) completed a step- and a ramp incremental test to measure blood lactate (BLa), DFA-α1, and cardiorespiratory fitness (CRF) variables, i.e. speed at lactate, ventilatory thresholds (LTs/VTs), and VO2max. Exponential fitting of the fractional elevation of HR (ΔHR) with BLa (individualised training impulse; iTRIMP) or DFA-α1 (αTRIMP) generated individualised coefficients for both methods. The TRIMP weightings were interpolated values of BLa or DFA-α1 derived at each ΔHR through coefficients to represent individualised physiological intensity. Principal component regression evaluated the relationship between combined CRF variables and the TRIMP coefficients or weightings.RESULTS: Large inter-individual variation was observed at the same physiological thresholds (ΔHR at LT1/VT1 = 0.51-0.83 and LT2/VT2 = 0.63-0.96), underscoring the need for TRIMP methods to weight ΔHR and account for different exposure at similar intensity. CRF had a moderate relationship with coefficients for iTRIMP and αTRIMP methods (R2average = 0.52-0.67), but a moderate to strong relationship with their weightings at a fixed ΔHR (R2average = 0.67-0.78).CONCLUSION: αTRIMP is a valid and practically accessible method for quantifying internal training exposure using ECG-based HR monitors, which individualises physiological intensity through DFA-α1-derived weightings among individuals of varied fitness exercising at same percentages of HR.</p

Exercise intensity measurement using fractal analysis of heart rate variability: Reliability, agreement and influence of sex and cardiorespiratory fitness

The study aimed to establish the test-retest reliability of detrended fluctuation analysis of heart rate variability (DFA-α1) based exercise intensity thresholds, assess its agreement with ventilatory- and lactate-derived thresholds and the moderating effect of sex and cardiorespiratory fitness (CRF) on the agreement. Intensity thresholds for thirty-seven participants (17 females) based on blood lactate (LT 1/LT 2), gas-exchange (VT 1/VT 2) and DFA-α1 (αTh 1/αTh 2) were assessed. Heart rate (HR) at αTh 1 and αTh 2 showed good test-retest reliability (coefficient of variation [CV] &lt; 6%), and moderate to high agreement with LTs ( r  = 0.40 - 0.57) and VTs ( r  = 0.61 - 0.66) respectively. Mixed effects models indicated bias magnitude depended on CRF, with DFA-α1 overestimating thresholds versus VTs for lower fitness levels (speed at VT 1 &lt;8.5 km⋅hr -1), while underestimating for higher fitness levels (speed at VT 2 &gt;15 km⋅hr -1; VO 2max &gt;55 mL·kg -1·min -1). Controlling for CRF, sex significantly affected bias magnitude only at first threshold, with males having higher mean bias (+2.41 bpm) than females (-1.26 bpm). DFA-α1 thresholds are practical and reliable intensity measures, however it is unclear if they accurately represent LTs/VTs from the observed limits of agreement and unexplained variance. To optimise DFA-α1 threshold estimation across different populations, bias should be corrected based on sex and CRF. </p

Vascular Structure and Functional Responses to Consecutive High-Fat Feeding between Insulin Treatment Regimens in Adults with Type 1 Diabetes and Matched Controls.

Background Impaired vascular health is prevalent in type 1 diabetes (T1D); however, it remains unknown whether di!erent insulin treatment regimens mediate indices of vascular structure or function. Methods Sixteen individuals with T1D receiving either multiple daily injection therapy (MDI; n=8; age: 32±13years; BMI:26.0±5.9kg.m2; HbA1c:53.7±11.2mmol/mol [7.1±3.2%]) or continuous subcutaneous insulin infusion (CSII; n=8; age:35±18years; BMI:26.3±4.6kg.m2; HbA1c: 58.6±9.7mmol/mol [7.5±3.0%]) and ten matched controls (CON; age:31±13years; BMI: 24.3±2.9kg.m2) consumed two high fat (HF) meals at 4-hour intervals. Carotid artery intima-media thickness (CIMT) and flow mediated dilation (FMD) was assessed at baseline, with further FMD assessment at 3-hrs following the ingestion of each meal using high resolution B-mode ultrasound. Bolus insulin dose was standardised using the carbohydrate-counting method. Results CIMT was significantly higher in individuals with T1D compared to controls (p=0.039); treatment stratification within T1D revealed MDI mediated this e!ect (MDI vs. CON: p=0.049; CSII vs. CON: p=0.112). FMD remained unchanged following the first meal (p=0.204) but was significantly impaired following the second meal (p=<0.001); post- hoc analysis revealed MDI mediated this e!ect of impaired FMD after the second meal (MDI vs. CON: p=0.048; CSII vs. CON: p=0.416). Conclusions Our findings indicate that patients treated with MDI therapy have higher CIMT (a structural marker of subclinical atherosclerosis) compared to controls but not CSII therapy. FMD was impaired following a second HF meal irrespective of a diabetes status. Considering the pre-existing heightened cardiovascular disease risk in T1D therapeutic strategies to reduce postprandial risk warrants further research

ACSM pre-participation health screening guidelines: a UK university cohort perspective.

PURPOSE: Pre-participation health screening is recommended to detect individuals susceptible to serious adverse cardiovascular complications during exercise. Although expert opinion and best available scientific evidence have informed recent modifications, there remains limited experimental data to support or refute current practice. We therefore aimed to quantify the impact of change to the ACSM pre-participation health screening guidelines on risk classification and referral for medical clearance in a large cohort of undergraduate university students. METHODS: Participants attended the laboratory on a single occasion to undergo pre-participation health screening. Information concerning health status was obtained via self-report questionnaire and objective physiological assessment with all data recorded electronically and evaluated against ACSM screening guidelines (9 and 10 Edition). RESULTS: Five-hundred and fifty-three students completed the study. The 9th Edition screening guidance resulted in eighty-two (15%) subjects classified as high-risk, almost one quarter (24%) classified as moderate-risk, and almost two-thirds (61%) classified as low-risk. In comparison, the updated 10 Edition screening guidance resulted in a significant reduction in those previously classified as either high-risk (5%) or moderate risk (2%), respectively. The majority of subjects (93%) were therefore cleared to begin a structured exercise programme. Taken together, approximately one-third (32%) fewer medical referrals were required when applying the updated 10 Edition guidance (χ (4) = 247.7, P<0.001). CONCLUSION: The updated ACSM 10 Edition pre-participation screening guidance reduces medical referrals by approximately one-third. These findings are in keeping with previous reports and thus serve to consolidate and justify recent modification - particularly when applied to young adult or adolescent populations. The findings and arguments presented should be used to refine and inform future guidance

The Effect of High-Fat Diet on Intramyocellular Lipid Content in Healthy Adults: A Systematic Review, Meta-Analysis, and Meta-Regression

\ua9 2024 The AuthorsFatty acids are stored within the muscle as intramyocellular lipids (IMCL). Some, but not all, studies indicate that following a high-fat diet (HFD), IMCL may accumulate and affect insulin sensitivity. This systematic review and meta-analysis aimed to quantify the effects of an HFD on IMCL. It also explored the potential modifying effects of HFD fat content and duration, IMCL measurement technique, physical activity status, and the associations of IMCL with insulin sensitivity. Five databases were systematically searched for studies that examined the effect of ≥3 d of HFD (&gt;35% daily energy intake from fat) on IMCL content in healthy individuals. Meta-regressions were used to investigate associations of the HFD total fat content, duration, physical activity status, IMCL measurement technique, and insulin sensitivity with IMCL responses. Changes in IMCL content and insulin sensitivity (assessed by hyperinsulinemic-euglycemic clamp) are presented as standardized mean difference (SMD) using a random effects model with 95% confidence intervals (95% CIs). Nineteen studies were included in the systematic review and 16 in the meta-analysis. IMCL content increased following HFD (SMD = 0.63; 95% CI: 0.31, 0.94, P = 0.001). IMCL accumulation was not influenced by total fat content (P = 0.832) or duration (P = 0.844) of HFD, physical activity status (P = 0.192), or by the IMCL measurement technique (P &gt; 0.05). Insulin sensitivity decreased following HFD (SMD = –0.34; 95% CI: –0.52, –0.16; P = 0.003), but this was not related to the increase in IMCL content following HFD (P = 0.233). Consumption of an HFD (&gt;35% daily energy intake from fat) for ≥3 d significantly increases IMCL content in healthy individuals regardless of HFD total fat content and duration of physical activity status. All IMCL measurement techniques detected the increased IMCL content following HFD. The dissociation between changes in IMCL and insulin sensitivity suggests that other factors may drive HFD-induced impairments in insulin sensitivity in healthy individuals. This trial was registered at PROSPERO as CRD42021257984