Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19.

OBJECTIVE: Diabetes mellitus (DM) is a major risk factor for severe coronavirus disease 2019 (COVID-19) for reasons that are unclear. RESEARCH DESIGN AND METHODS: We leveraged the International Study of Inflammation in COVID-19 (ISIC), a multicenter observational study of 2,044 patients hospitalized with COVID-19, to characterize the impact of DM on in-hospital outcomes and assess the contribution of inflammation and hyperglycemia to the risk attributed to DM. We measured biomarkers of inflammation collected at hospital admission and collected glucose levels and insulin data throughout hospitalization. The primary outcome was the composite of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy. RESULTS: Among participants (mean age 60 years, 58.2% males), those with DM (n = 686, 33.5%) had a significantly higher cumulative incidence of the primary outcome (37.8% vs. 28.6%) and higher levels of inflammatory biomarkers than those without DM. Among biomarkers, DM was only associated with higher soluble urokinase plasminogen activator receptor (suPAR) levels in multivariable analysis. Adjusting for suPAR levels abrogated the association between DM and the primary outcome (adjusted odds ratio 1.23 [95% CI 0.78, 1.37]). In mediation analysis, we estimated the proportion of the effect of DM on the primary outcome mediated by suPAR at 84.2%. Hyperglycemia and higher insulin doses were independent predictors of the primary outcome, with effect sizes unaffected by adjusting for suPAR levels. CONCLUSIONS: Our findings suggest that the association between DM and outcomes in COVID-19 is largely mediated by hyperinflammation as assessed by suPAR levels, while the impact of hyperglycemia is independent of inflammation.

Effect of standing posture during whole body vibration training on muscle morphology and function in older adults: a randomised controlled trial.

BACKGROUND: Whole body vibration (WBV) is a novel modality of exercise shown to improve musculoskeletal function. This study aims to examine the effects of standing posture during low magnitude WBV training on muscle function and muscle morphology in older adults. METHODS: Nineteen men and women (50-80 years) were recruited to a three month randomised controlled trial and allocated to one of three groups: WBV with flexed knees (FK), WBV with locked knees (LK), or sham WBV with flexed knees (CON). Exposure was intermittent (1 min WBV:1 min rest) for 20 min, three times per week for 13 weeks. Measurements were taken at baseline and at three months. Primary outcomes included upper and lower body muscle function (strength, power and velocity). Secondary outcomes were muscle morphology, balance, habitual and maximal gait velocity, stair climb power, and chair stand performance. RESULTS: Sixteen subjects completed the study. Relative (%) upper body contraction velocity improved significantly after WBV with FK compared to LK (FK 16.0%, LK -7.6%, CON 4.7, p = 0.01). Relative upper body strength (LK 15.1%, p = 0.02; FK 12.1%, p = 0.04; CON 4.7%) increased significantly following WBV compared to control. Absolute (p = 0.05) and relative (p = 0.03) lower leg strength significantly improved with both standing postures (LK 14.4%; FK 10.7%; CON 1.3%). Only the LK group differed significantly from CON in relative leg strength gains (p = 0.02). Potentially clinically meaningful but statistically non-significant improvements in lower leg muscle cross-sectional area (LK 3.7 cm², FK 2.4 cm², CON 2.2 cm² p = 0.13) were observed after WBV with LK compared to the other groups. No significant effects of WBV on any functional performance tests were observed. CONCLUSIONS: Our results suggest that WBV may improve muscle strength and contraction velocity in some muscle groups in older adults. However, hypothesised differential adaptation to standing posture (FK > LK) was observed only for upper body contraction velocity, making recommendations regarding this prescriptive element inconclusive. The efficacy, mechanism of action and long term feasibility of WBV for musculoskeletal health in older adults warrants continued investigation in robustly designed, sufficiently powered future studies. TRIAL REGISTRATION: ACTRN12609000353291.

The effect of whole body vibration exposure on muscle or bone morphology and function in older adults: a systematic review of the literature.

CONTEXT AND OBJECTIVE: The aim of this study was to examine the effect of whole body vibration (WBV), a novel exercise modality, on muscle or bone morphology and function in older adults. METHODS: A literature search of published randomised controlled trials (RCTs) was conducted using multiple databases and hand searching for study designs reporting the effects of WBV in older adults on any outcomes related to muscle function, or muscle or bone morphology. Concomitant exercise was only included if the control group performed the same exercise as the active WBV group, but without vibration. RESULTS: Six RCTs met the inclusion criteria of this review, three reporting measures of muscle only, two assessing bone measures only and one detailing measures of both bone and muscle. Study design varied greatly across the six trials and only six of 35 musculoskeletal outcomes analysed were statistically significant. All statistically significant improvements were of muscle function. CONCLUSIONS: The published literature to date provides only weak support for the efficacy of WBV exposure for muscle function, muscle morphology, or bone architecture in older adults. Irregularities in study design and WBV protocols across the literature and poor quality trials contribute to this inconsistency, revealing the need for more uniformity in future trials. Future research should be more robust in design, include larger cohorts, longer interventions and standardisation of protocols. They should also investigate the optimal dose-response relationships and variation in vibration characteristics, to determine the true efficacy, clinical relevance, and underlying mechanisms of muscle and bone adaptations.