Concurrent Joint Hypermobility Syndrome and Spondyloarthropathy: A New Spondyloarthropathy Subgroup With a Less Severe Disease Phenotype?

BACKGROUND: The coexistence of joint hypermobility syndrome (JHS) and spondyloarthropathy (SpA) presents a challenging clinical conundrum due to the contradictory clinical signs that may be present. Classic features such as restricted spinal movement or early morning back stiffness may not be present. Timely diagnosis and appropriate management of these patients are difficult as they tend to have lower scores on validated objective measures. METHODS: We performed a medical records review study to identify patients with both JHS and SpA who had presented to the Leicester Spondyloarthropathy clinic. Patients were diagnosed with axial SpA if they met the Assessment of SpondyloArthritis international Society classification criteria. Their imaging was reviewed by a consultant musculoskeletal radiologist. RESULTS: Four cases were identified from the patient database (female; average age, 37.5 years). All patients presented with lower back pain or sacroiliac joint pain but preserved spinal movement with a negative Schober's test. Two had a history of symptoms for more than 10 years. All had a Beighton score of greater than 6. Three of the patients were HLA positive, and 3 had a positive family history. All patients thus far have had their symptoms adequately controlled on nonsteroidal anti-inflammatory drugs and physiotherapy. CONCLUSIONS: The coexistence of JHS and SpA is rare but important to recognize. These patients are difficult to diagnose as they may present late because of preserved spinal movements. It is unclear whether the preserved flexibility masks the true extent of disease or whether clinically they represent a less severe disease phenotype.

Non-viral liver disease burden in HIV-monoinfected individuals: a longitudinal observational retrospective cohort study.

Recent advances in antiviral therapy have improved outcomes in HIV-positive individuals co-infected with hepatitis B and C virus (HBV/HCV). Our aim was to assess prevalence and predictors of chronic liver disease (CLD) due to the metabolic syndrome (MS), alcohol and antiretrovirals (ARVs) use in HIV-monoinfected individuals. This was a retrospective cohort study (2005-2012). HIV-positive patients with negative HBV/HCV serology and at least two elevated alanine aminotransferase (ALT) levels six months apart were included. Data are presented as mean ± SD or percentage. Despite negative viral serology, 27% (1047/3872) of HIV-positive individuals had persistently elevated ALT. Only 243 (23.2%) were investigated (by imaging in the majority, only 58 undergoing liver biopsy/transient elastography). CLD was identified in 66.2%, this being clinically significant in one in four individuals. Potential CLD risk factors were alcohol (44.2%), hepatotoxic ARVs (74.1%) and MS risk factors (68%) with 68.7% having >1 risk factor. On multivariate logistic regression analysis serum triglyceride (OR 1.482, 95% CI 1.053-2.086, p = .024) was the only independent predictor of CLD. Overall, 4.3% were referred to Hepatology services. In conclusion, less than 6% of HIV-monoinfected individuals with persistently elevated ALT undergo objective assessment of hepatic fibrosis. Despite non-stringent criteria, some degree of non-viral CLD is identified in approximately two-thirds of those investigated, risk factors being synonymous with those for the MS. This increasing yet under-recognised non-viral CLD burden warrants timely recognition to prevent long-term morbidity and mortality.

Bed-rest and exercise remobilization: Concurrent adaptations in muscle glucose and protein metabolism.

BACKGROUND: Bed-rest (BR) of only a few days duration reduces muscle protein synthesis and induces skeletal muscle atrophy and insulin resistance, but the scale and juxtaposition of these events have not been investigated concurrently in the same individuals. Moreover, the impact of short-term exercise-supplemented remobilization (ESR) on muscle volume, protein turnover and leg glucose uptake (LGU) in humans is unknown. METHODS: Ten healthy males (24 ± 1 years, body mass index 22.7 ± 0.6 kg/m2) underwent 3 days of BR, followed immediately by 3 days of ESR consisting of 5 × 30 maximal voluntary single-leg isokinetic knee extensions at 90°/s each day. An isoenergetic diet was maintained throughout the study (30% fat, 15% protein and 55% carbohydrate). Resting LGU was calculated from arterialized-venous versus venous difference across the leg and leg blood flow during the steady-state of a 3-h hyperinsulinaemic-euglycaemic clamp (60 mU/m2/min) measured before BR, after BR and after remobilization. Glycogen content was measured in vastus lateralis muscle biopsy samples obtained before and after each clamp. Leg muscle volume (LMV) was measured using magnetic resonance imaging before BR, after BR and after remobilization. Cumulative myofibrillar protein fractional synthetic rate (FSR) and whole-body muscle protein breakdown (MPB) were measured over the course of BR and remobilization using deuterium oxide and 3-methylhistidine stable isotope tracers that were administered orally. RESULTS: Compared with before BR, there was a 45% decline in insulin-stimulated LGU (P < 0.05) after BR, which was paralleled by a reduction in insulin-stimulated leg blood flow (P < 0.01) and removal of insulin-stimulated muscle glycogen storage. These events were accompanied by a 43% reduction in myofibrillar protein FSR (P < 0.05) and a 2.5% decrease in LMV (P < 0.01) during BR, along with a 30% decline in whole-body MPB after 2 days of BR (P < 0.05). Myofibrillar protein FSR and LMV were restored by 3 days of ESR (P < 0.01 and P < 0.01, respectively) but not by ambulation alone. However, insulin-stimulated LGU and muscle glycogen storage were not restored by ESR. CONCLUSIONS: Three days of BR caused concurrent reductions in LMV, myofibrillar protein FSR, myofibrillar protein breakdown and insulin-stimulated LGU, leg blood flow and muscle glycogen storage in healthy, young volunteers. Resistance ESR restored LMV and myofibrillar protein FSR, but LGU and muscle glycogen storage remained depressed, highlighting divergences in muscle fuel and protein metabolism. Furthermore, ambulation alone did not restore LMV and myofibrillar protein FSR in the non-exercised contralateral limb, emphasizing the importance of exercise rehabilitation following even short-term BR.

The impact of physical inactivity on glucose homeostasis when diet is adjusted to maintain energy balance in healthy, young males.

BACKGROUND & AIMS: It is unclear if dietary adjustments to maintain energy balance during reduced physical activity can offset inactivity-induced reductions in insulin sensitivity and glucose disposal to produce normal daily glucose concentrations and meal responses. Therefore, the aim of the present study was to examine the impact of long-term physical inactivity (60 days of bed rest) on daily glycemia when in energy balance. METHODS: Interstitial glucose concentrations were measured using Continuous Glucose Monitoring Systems (CGMS) for 5 days before and towards the end of bed rest in 20 healthy, young males (Age: 34 ± 8 years; BMI: 23.5 ± 1.8 kg/m2). Energy intake was reduced during bed rest to match energy expenditure, but the types of foods and timing of meals was maintained. Fasting venous glucose and insulin concentrations were determined, as well as the change in whole-body glucose disposal using a hyperinsulinemic-euglycemic clamp (HIEC). RESULTS: Following long-term bed rest, fasting plasma insulin concentration increased 40% (p = 0.004) and glucose disposal during the HIEC decreased 24% (p < 0.001). Interstitial daily glucose total area under the curve (tAUC) from pre-to post-bed rest increased on average by 6% (p = 0.041), despite a 20 and 25% reduction in total caloric and carbohydrate intake, respectively. The nocturnal period (00:00-06:00) showed the greatest change to glycemia with glucose tAUC for this period increasing by 9% (p = 0.005). CGMS measures of daily glycemic variability (SD, J-Index, M-value and MAG) were not changed during bed rest. CONCLUSIONS: Reduced physical activity (bed rest) increases glycemia even when daily energy intake is reduced to maintain energy balance. However, the disturbance to daily glucose homeostasis was much more modest than the reduced capacity to dispose of glucose, and glycemic variability was not negatively affected by bed rest, likely due to positive mitigating effects from the contemporaneous reduction in dietary energy and carbohydrate intake. CLINICAL TRIALS RECORD: NCT03594799 (registered July 20, 2018) (https://clinicaltrials.gov/ct2/show/NCT03594799).

Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization.

BACKGROUND: Bed rest (BR) reduces whole-body insulin-stimulated glucose disposal (GD) and alters muscle fuel metabolism, but little is known about metabolic adaptation from acute to chronic BR nor the mechanisms involved, particularly when volunteers are maintained in energy balance. METHODS: Healthy males (n = 10, 24.0 ± 1.3 years), maintained in energy balance, underwent 3-day BR (acute BR). A second cohort matched for sex and body mass index (n = 20, 34.2 ± 1.8 years) underwent 56-day BR (chronic BR). A hyperinsulinaemic euglycaemic clamp (60 mU/m2 /min) was performed to determine rates of whole-body insulin-stimulated GD before and after BR (normalized to lean body mass). Indirect calorimetry was performed before and during steady state of each clamp to calculate rates of whole-body fuel oxidation. Muscle biopsies were taken to determine muscle glycogen, metabolite and intramyocellular lipid (IMCL) contents, and the expression of 191 mRNA targets before and after BR. Two-way repeated measures analysis of variance was used to detect differences in endpoint measures. RESULTS: Acute BR reduced insulin-mediated GD (Pre 11.5 ± 0.7 vs. Post 9.3 ± 0.6 mg/kg/min, P < 0.001), which was unchanged in magnitude following chronic BR (Pre 10.2 ± 0.4 vs. Post 7.9 ± 0.3 mg/kg/min, P < 0.05). This reduction in GD was paralleled by the elimination of the 35% increase in insulin-stimulated muscle glycogen storage following both acute and chronic BR. Acute BR had no impact on insulin-stimulated carbohydrate (CHO; Pre 3.69 ± 0.39 vs. Post 4.34 ± 0.22 mg/kg/min) and lipid (Pre 1.13 ± 0.14 vs. Post 0.59 ± 0.11 mg/kg/min) oxidation, but chronic BR reduced CHO oxidation (Pre 3.34 ± 0.18 vs. Post 2.72 ± 0.13 mg/kg/min, P < 0.05) and blunted the magnitude of insulin-mediated inhibition of lipid oxidation (Pre 0.60 ± 0.07 vs. Post 0.85 ± 0.06 mg/kg/min, P < 0.05). Neither acute nor chronic BR increased muscle IMCL content. Plentiful mRNA abundance changes were detected following acute BR, which waned following chronic BR and reflected changes in fuel oxidation and muscle glycogen storage at this time point. CONCLUSIONS: Acute BR suppressed insulin-stimulated GD and storage, but the extent of this suppression increased no further in chronic BR. However, insulin-mediated inhibition of fat oxidation after chronic BR was less than acute BR and was accompanied by blunted CHO oxidation. The juxtaposition of these responses shows that the regulation of GD and storage can be dissociated from substrate oxidation. Additionally, the shift in substrate oxidation after chronic BR was not explained by IMCL accumulation but reflected by muscle mRNA and pyruvate dehydrogenase kinase 4 protein abundance changes, pointing to lack of muscle contraction per se as the primary signal for muscle adaptation.

Physical inactivity and health inequality during coronavirus: a novel opportunity or total lockdown?

Government-restricted movement during the coronavirus pandemic in various countries around the world has led to rapid and fundamental changes in our health behaviour. As well as being at a higher risk of contracting and being hospitalised with COVID-19, the elderly, those with chronic disease and lower socioeconomic groups are also disproportionately affected by restriction of movement, further widening the physical activity health inequality. In this viewpoint we discuss the physiological sequelae of physical inactivity, and the additional burden of ageing and inflammation. We provide recommendations for public health promotion and interventions to try to mitigate the detrimental effects of physical inactivity and rebalance the health inequality.