Adiponectin as a predictor of mortality and readmission in patients with community-acquired pneumonia: a prospective cohort study.

Background: Adiponectin is secreted by adipocytes and is inversely associated with obesity. Given the association between low body mass index (BMI) and higher mortality risk after community-acquired pneumonia (CAP), we hypothesized that high adiponectin levels are associated with a higher risk of adverse clinical outcomes in patients with CAP. Methods: In a prospective cohort study of 502 patients hospitalized with CAP, adiponectin was measured in serum at admission. The associations between adiponectin and clinical outcomes were estimated with logistic regression analyses adjusted for age, sex, and measures of obesity (BMI, waist circumference or body fat percentage). Results: Adiponectin was associated with higher 90-day mortality for each 1 µg/mL increase [OR 1.02, 95% CI (1.00, 1.04), p = 0.048] independent of age and sex. Likewise, adiponectin was associated with a higher risk of 90-day readmission for each 1 µg/mL increase [OR 1.02, 95% CI (1.01, 1.04), p = 0.007] independent of age and sex. The association between adiponectin and 90-day mortality disappeared, while the association with 90-day readmission remained after adjusting for adiposity. Conclusion: Adiponectin was positively associated with mortality and readmission. The association with mortality depended on low body fat, whereas the association with readmission risk was independent of obesity.

Effect of Exercise Training on Prognosis in Community-Acquired Pneumonia: A Randomised Controlled Trial.

OBJECTIVE: To investigate the effect of standard care (SoC) combined with supervised in-bed cycling (Bed-Cycle) or booklet exercises (Book-Exe) versus SoC in community-acquired pneumonia (CAP). METHODS: In this randomised controlled trial, 186 patients with CAP were assigned to SoC (n = 62), Bed-Cycle (n = 61), or Book-Exe (n = 63). Primary outcome length of stay (LOS) was analysed with analysis of covariance. Secondary outcomes, 90-day readmission and 180-day mortality, were analysed with Cox proportional hazard regression and readmission days with negative-binominal regression. RESULTS: LOS was -2% (95% CI -24 to 25%) and -1% (95% CI -22 to 27%) for Bed-Cycle and Book-Exe, compared to SoC. 90-day readmission was 35.6% for SoC, 27.6% for Bed-Cycle, and 21.3% for Book-Exe. Adjusted hazard ratio (aHR) for 90-day readmission was 0.63 (95% CI 0.33-1.21) and 0.54 (95% CI 0.27-1.08) for Bed-Cycle and Book-Exe compared to SoC. aHR for 90-day readmission for combined exercise was 0.59 (95% CI 0.33-1.03) compared to SoC. aHR for 180-day mortality was 0.84 (95% CI 0.27-2.60) and 0.82 (95% CI 0.26-2.55) for Bed-Cycle and Book-Exe compared to SoC. Number of readmission days was 226 for SoC, 161 for Bed-Cycle, and 179 for Book-Exe. Incidence rate ratio for readmission days was 0.73 (95% CI 0.48-1.10) and 0.77 (95% CI 0.51-1.15) for Bed-Cycle and Book-Exe compared to SoC. CONCLUSION: Although supervised exercise training during admission with CAP did not reduce LOS or mortality, this trial suggests its potential to reduce readmission risk and number of readmission days.

Characterization of impaired beta and alpha cell function in response to an oral glucose challenge in cystic fibrosis: a cross-sectional study.

Aims: The purpose of the study was to further elucidate the pathophysiology of cystic fibrosis (CF)-related diabetes (CFRD) and potential drivers of hypoglycaemia. Hence, we aimed to describe and compare beta cell function (insulin and proinsulin) and alpha cell function (glucagon) in relation to glucose tolerance in adults with CF and to study whether hypoglycaemia following oral glucose challenge may represent an early sign of islet cell impairment. Methods: Adults with CF (≥18 years) were included in a cross-sectional study using an extended (-10, -1, 10, 20, 30, 45, 60, 90, 120, 150, and 180 min) or a standard (-1, 30, 60, and 120 min) oral glucose tolerance test (OGTT). Participants were classified according to glucose tolerance status and hypoglycaemia was defined as 3-hour glucose <3.9 mmol/L in those with normal glucose tolerance (NGT) and early glucose intolerance (EGI). Results: Among 93 participants, 67 underwent an extended OGTT. In addition to worsening in insulin secretion, the progression to CFRD was associated with signs of beta cell stress, as the fasting proinsulin-to-insulin ratio incrementally increased (p-value for trend=0.013). The maximum proinsulin level (pmol/L) was positively associated with the nadir glucagon, as nadir glucagon increased 6.2% (95% confidence interval: 1.4-11.3%) for each unit increase in proinsulin. Those with hypoglycaemia had higher 60-min glucose, 120-min C-peptide, and 180-min glucagon levels (27.8% [11.3-46.7%], 42.9% [5.9-92.85%], and 80.3% [14.9-182.9%], respectively) and unaltered proinsulin-to-insulin ratio compared to those without hypoglycaemia. Conclusions: The maximum proinsulin concentration was positively associated with nadir glucagon during the OGTT, suggesting that beta cell stress is associated with abnormal alpha cell function in adults with CF. In addition, hypoglycaemia seemed to be explained by a temporal mismatch between glucose and insulin levels rather than by an impaired glucagon response.

Impact of high-intensity interval training on cardiac structure and function after COVID-19: an investigator-blinded randomized controlled trial.

A large proportion of patients suffer from a persistent reduction in cardiorespiratory fitness after recovery from COVID-19, of which the effects on the heart may potentially be reversed through the effect of high-intensity interval training (HIIT). In the present study, we hypothesized that HIIT would increase left ventricular mass (LVM) and improve functional status and health-related quality of life (HRQoL) in individuals previously hospitalized for COVID-19. In this investigator-blinded, randomized controlled trial, 12 wk of supervised HIIT (4 × 4 min, three times a week) was compared with standard care (control) in individuals recently discharged from hospital due to COVID-19. LVM was assessed by cardiac magnetic resonance imaging (cMRI, primary outcome), whereas the pulmonary diffusing capacity (DLCOc, secondary outcome) was examined by the single-breath method. Functional status and HRQoL were assessed by Post-COVID-19 functional scale (PCFS) and King's brief interstitial lung disease (KBILD) questionnaire, respectively. A total of 28 participants were included (age 57 ± 10, 9 females; HIIT: 58 ± 11, 4 females; standard care: 57 ± 9, 5 females), LVM increased in the HIIT vs. standard care group with a between-group difference of 6.8 [mean, 95%CI: 0.8; 12.8] g; P = 0.029. There were no between-group differences in DLCOc or any other lung function metric, which gradually resolved in both groups. Descriptively, PCFS suggested fewer functional limitations in the HIIT group. KBILD improved similarly in the two groups. HIIT is an efficacious exercise intervention for increasing LVM in individuals previously hospitalized for COVID-19.NEW & NOTEWORTHY In this randomized clinical trial on individuals previously hospitalized for COVID-19, a 12 wk supervised high-intensity interval training (HIIT) scheme was found to increase left ventricular mass, whereas pulmonary diffusing capacity was unaffected. The findings indicate that HIIT is an efficacious exercise intervention for targeting the heart after COVID-19.

Effect of aerobic exercise training on the fat fraction of the liver in persons with chronic hepatitis B and hepatic steatosis: Trial protocol for a randomized controlled intervention trial- The FitLiver study.

BACKGROUND: The global prevalence of chronic hepatitis B is more than 300 million people, and in Denmark, 17,000 people are estimated to have chronic hepatitis B. Untreated, chronic hepatitis B can lead to the development of liver cirrhosis and liver cancer. There is no curable therapy. In persons with obesity and chronic hepatitis B infection, the development of hepatic steatosis imposes a double burden on the liver, leading to an increased risk of cirrhosis and liver cancer. In patients without chronic hepatitis B, exercise interventions have shown beneficial effects on hepatic steatosis through improvements in fat fraction of the liver, insulin resistance, fatty acid metabolism, and glucose metabolism, as well as activation of liver-induced regulatory protein secretion (hepatokines) after the exercise intervention. OBJECTIVE: To investigate in persons with chronic hepatitis B and hepatic steatosis: Primary: Whether exercise will decrease the fat fraction of the liver. Secondary: If exercise will affect hepatokine secretion and if it will improve lipid- and glucose metabolism, liver status, markers of inflammation, body composition, and blood pressure. METHODS: A randomized, controlled, clinical intervention trial consisting of 12 weeks of aerobic exercise training or no intervention. Thirty persons with chronic hepatitis B and hepatic steatosis will be randomized 1:1. Before and after the intervention, participants will undergo an MRI scan of the liver, blood sampling, oral glucose tolerance test, fibroscan, VO2max test, DXA scan, blood pressure measurements, and optional liver biopsy. Lastly, a hormone infusion test with somatostatin and glucagon to increase the glucagon/insulin ratio for stimulating secretion of circulating hepatokines will be performed. The training program includes three weekly training sessions of 40 min/session over 12 weeks. DISCUSSION: This trial, investigating high-intensity interval training in persons with chronic hepatitis B and hepatic steatosis, is the first exercise intervention trial performed on this group of patients. If exercise reduces hepatic steatosis and induces other beneficial effects of clinical markers in this group of patients, there might be an indication to recommend exercise as part of treatment. Furthermore, the investigation of the effect of exercise on hepatokine secretion will provide more knowledge on the effects of exercise on the liver. TRIAL REGISTRATION: Danish Capital Regions committee on health research ethics reference: H-21034236 (version 1.4 date: 19-07-2022) and ClinicalTrials.gov: NCT05265026.

Multidimensional individualized nutritional therapy for individuals with severe chronic obstructive pulmonary disease: study protocol for a registry-based randomized controlled trial.

BACKGROUND: Individuals with severe chronic obstructive pulmonary disease (COPD) are often at risk of undernutrition with low health-related quality of life (HRQoL). Undernutrition can worsen COPD and other comorbidities, be an independent predictor of morbidity and functional decline resulting in increased healthcare consumption and increased risk of death. Especially exacerbations and acute infections result in unintentional weight loss. The aim is to investigate the effect of an individualized nutritional intervention among individuals with severe COPD. METHODS: An open-label randomized controlled trial with two parallel groups. Participants are recruited from the pulmonary outpatient clinic at the Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital, North Zealand, Denmark, and randomly allocated to either the intervention (intervention + standard of care) or control group (standard of care). The intervention has a duration of 3 months and combines individual nutritional care with adherence support and practical tools. It contains 4 elements including an individual nutritional plan, regular contacts, adherence support, and weight diary. The primary outcome is a difference in HRQoL (EQ-5D-5L) between the intervention and control group 3 months after baseline. Difference in functional capacity (grip strength, 30-s stand chair test, and physical activity), disease-specific quality of life (COPD Assessment Test), anxiety and depression (Hospital Anxiety and Depression Scale), nutritional parameters (energy and protein intake), anthropometry (weight, body mass index, waist, hip, and upper arm circumference), body composition (total fat-free and fat mass and indices), and prognosis (exacerbations, oxygen therapy, hospital contacts, and mortality) 3 months after baseline will be included as secondary outcomes. Data will be collected through home visits at baseline and 1 and 3 months after baseline. DISCUSSION: Currently, nutritional care is a neglected area of outpatient care among individuals with severe COPD. If this patient-centered approach can demonstrate a positive impact on HRQoL, mortality, and hospital contacts, it should be recommended as part of end-of-life care for individuals with severe COPD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04873856 . Registered on May 3, 2021.

Pituitary-gonadal hormones associated with respiratory failure in men and women hospitalized with COVID-19: an observational cohort study.

Aim: To explore pituitary-gonadal hormone concentrations and assess their association with inflammation, severe respiratory failure, and mortality in hospitalized men and women with COVID-19, and compare these to hormone concentrations in hospitalized patients with bacterial community-acquired pneumonia (CAP) and influenza virus CAP and to concentrations in a reference group of healthy individuals. Methods: Serum concentrations of testosterone, estrone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and interleukin-6 (IL-6) were measured within 4 days of admission. Associations were assessed by logistic regression analysis in patients with COVID-19, and results were reported as odds ratio with 95% CI per two-fold reduction after adjustment for age, comorbidities, days to sample collection, and IL-6 concentrations. Results: In total, 278 patients with COVID-19, 21 with influenza virus CAP, and 76 with bacterial CAP were included. Testosterone concentrations were suppressed in men hospitalized with COVID-19, bacterial and influenza virus CAP, and moderately suppressed in women. Reductions in testosterone (OR: 3.43 (1.14-10.30), P = 0.028) and LH (OR: 2.51 (1.28-4.92), P = 0.008) were associated with higher odds of mehanical ventilation (MV) in men with COVID-19. In women with COVID-19, reductions in LH (OR: 3.34 (1.02-10-90), P = 0.046) and FSH (OR: 2.52 (1.01-6.27), P = 0.047) were associated with higher odds of MV. Conclusion: Low testosterone and LH concentrations were predictive of severe respiratory failure in men with COVID-19, whereas low concentrations of LH and FSH were predictive of severe respiratory failure in women with COVID-19.

Diabetes Status, c-Reactive Protein, and Insulin Resistance in Community-Acquired Pneumonia-A Prospective Cohort Study.

C-reactive protein (CRP) is commonly used to guide community-acquired pneumonia (CAP) treatment. A positive association between admission glucose and CRP levels has been observed in patients with CAP. The associations between prediabetes, unknown diabetes, acute-on-chronic hyperglycaemia, and CRP levels, and between admission CRP levels and insulin resistance (IR) in CAP, remain unexplored. This study investigated the associations firstly between chronic, acute, and acute-on-chronic hyperglycaemia and CRP levels, and secondly between admission CRP levels and IR in CAP. In a prospective cohort study of adults with CAP, the associations between chronic, acute, and acute-on-chronic hyperglycaemia (admission glucose minus HbA1c-derived average glucose) and CRP levels until admission day 3 were modelled with repeated-measures linear mixed models. IR was estimated with the homeostasis model assessment of IR (HOMA-IR). The association between admission CRP levels and HOMA-IR was modelled with linear regression. In 540 patients, no association between chronic, acute, or acute-on-chronic hyperglycaemia and CRP levels was found. In 266 patients, every 50 mg/L increase in admission CRP was associated with a 7% (95% CI 1-14%) higher HOMA-IR. In conclusion, our findings imply that hyperglycaemia does not influence CRP levels in patients with CAP, although admission CRP levels were positively associated with IR.

High mortality among patients with severe COVID-19 and Do Not Intubate orders.

INTRODUCTION: Moderate to severe respiratory distress among patients with COVID-19 is associated with a high mortality. This study evaluated ventilator support and mortality by Do Intubate (DI) or Do Not Intubate (DNI) orders. METHODS: This was a retrospective study of patients with COVID-19 and a supplemental oxygen requirement of ≥ 15 l/min. The patients were divided into two groups corresponding to the first and second wave of COVID-19 and were subsequently further divided according to DI and DNI orders and analysed regarding need of ventilator support and mortality. RESULTS: The study included 178 patients. The mortality was 24% for patients with DI orders (n = 115) and 81% for patients with DNI orders (n = 63) increasing to 98% (n = 46) for patients with DNI orders and very high flow oxygen requirements (≥ 30 l/min.). From the first to the second wave of COVID-19, the use of constant continuous positive airway pressure (cCPAP) increased from 71% to 91% (p less-than 0.001), whereas the use of mechanical ventilation decreased from 54% to 28% (odds ratio = 0.38 (95% confidence interval: 0.17-0.85)). CONCLUSION: The mortality was high for patients with DNI orders and respiratory distress with very high levels in supplemental oxygen in both the first and second wave of COVID-19 despite an increase in use of cCPAP and treatment with dexamethasone and remdesivir during the second wave. Hence, careful evaluation on transition to palliative care must be considered for these patients. FUNDING: none. TRIAL REGISTRATION: The study was approved by the Danish Patient Safety Authority (record no. 31-1521-309) and the Regional Data Protection Centre (record no. P-2020-492).

Association between Barthel Index, Grip Strength, and Physical Activity Level at Admission and Prognosis in Community-Acquired Pneumonia: A Prospective Cohort Study.

Background: Impaired functional status is a risk factor for hospitalization in patients with community-acquired pneumonia (CAP). The aim was to determine the influence of functional status and physical activity level on severe outcomes, including length of stay, admission to the intensive care unit (ICU), readmission, and mortality in patients with CAP. Methods: A prospective cohort study among patients hospitalized with CAP. Functional status was assessed with the Barthel index and grip strength, and physical activity level was assessed using the international physical activity questionnaire. Linear regression was used to assess the association with length of stay, and logistic regression was used to assess the risk of severe outcomes. Results: Among 355 patients admitted with CAP, 18% had a low Barthel index (<80), 45% had a low grip strength, and 75% had a low physical activity level. Low Barthel index was associated with increased risk of ICU admission (OR 3.6, 95% CI 1.2−10.9), longer length of stay (27.9%, 95% CI 2.3−59.7%), readmission within 30, 90, and 180 days (OR 2.1−2.4, p < 0.05), and mortality within 90 and 180 days (OR 4.2−5.0, p < 0.05). Low grip strength was associated with increased risk of 90 days readmission (OR 1.6, 95% CI 1.0−2.6, p < 0.05) and mortality within 30, 90, and 180 days (OR 2.6−3.2, p < 0.05). Low physical activity level was associated with increased risk of readmission within 90 and 180 days (OR 1.8−2.1, p < 0.05) and mortality within 30, 90, and 180 days (OR 3.3−5.5, p < 0.05). Conclusions: Impaired functional status and low physical activity level were associated with a longer length of stay and increased risk of ICU admission, readmission, and mortality in patients hospitalized with CAP. Routine assessment of functional status and physical activity level in clinical care could enable early identification of individuals with excess risk for a poor prognosis. Trial registration: ClinicalTrials.gov, NCT03795662.

Are Undernutrition and Obesity Associated with Post-Discharge Mortality and Re-Hospitalization after Hospitalization with Community-Acquired Pneumonia?

Undernutrition is associated with increased mortality after hospitalization with community-acquired pneumonia (CAP), whereas obesity is associated with decreased mortality in most studies. We aimed to determine whether undernutrition and obesity are associated with increased risk of re-hospitalization and post-discharge mortality after hospitalization. This study was nested within the Surviving Pneumonia cohort, which is a prospective cohort of adults hospitalized with CAP. Patients were categorized as undernourished, well-nourished, overweight, or obese. Undernutrition was based on diagnostic criteria by the European Society for Clinical Nutrition and Metabolism. Risk of mortality was investigated using multivariate logistic regression and re-hospitalization with competing risk Cox regression where death was the competing event. Compared to well-nourished patients, undernourished patients had a higher risk of 90-day (OR 3.0, 95% CI 1.0; 21.4) mortality, but a similar 30-day and 180-day mortality risk. Obese patients had a similar re-hospitalization and mortality risk as well-nourished patients. In conclusion, among patients with CAP, undernutrition was associated with increased risk of mortality. Undernourished patients are high-risk patients, and our results indicate that in-hospital screening of undernutrition should be implemented to identify patients at mortality risk. Studies are required to investigate whether nutritional therapy after hospitalization with CAP would improve survival.

Human visceral and subcutaneous adipose stem and progenitor cells retain depot-specific adipogenic properties during obesity.

Abdominal obesity associates with cardiometabolic disease and an accumulation of lipids in the visceral adipose depot, whereas lipid accumulation in the subcutaneous depot is more benign. We aimed to further investigate whether the adipogenic properties where cell-intrinsic, or dependent on a depot-specific or obesity-produced microenvironment. We obtained visceral and subcutaneous biopsies from non-obese women (n = 14) or women living with morbid obesity (n = 14) and isolated adipose stem and progenitor cells (ASPCs) from the stromal vascular fraction of non-obese (n = 13) and obese (n = 13). Following in vitro differentiation into mature adipocytes, we observed a contrasting pattern with a lower gene expression of adipogenic markers and a higher gene expression of immunogenic markers in the visceral compared to the subcutaneous adipocytes. We identified the immunogenic factor BST2 as a marker for visceral ASPCs. The effect of obesity and insulin resistance on adipogenic and immunogenic markers in the in vitro differentiated cells was minor. In contrast, differentiation with exogenous Tumor necrosis factor resulted in increased immunogenic signatures, including increased expression of BST2, and decreased adipogenic signatures in cells from both depots. Our data, from 26 women, underscore the intrinsic differences between human visceral and subcutaneous adipose stem and progenitor cells, suggest that dysregulation of adipocytes in obesity mainly occurs at a post-progenitor stage, and highlight an inflammatory microenvironment as a major constraint of human adipogenesis.

Long-term health after Severe Acute Malnutrition in children and adults- the role of the Pancreas (SAMPA): Protocol.

Background: Prenatal growth retardation may increase the risk of later chronic non-communicable diseases (NCDs), including diabetes; however, long-term effects of wasting malnutrition in childhood or adulthood are less studied. Pancreatic exocrine and endocrine functions, both critical for nutrition and NCD aetiology, may not fully recover following malnutrition. However, the evidence and mechanistic information is piecemeal. We hypothesise that wasting malnutrition at any age has long-term detrimental effects on endocrine and exocrine pancreatic structure and function. Methods: The SAMPA international research programme will assess pancreatic structure and function in 3700 participants from ongoing observational nutrition cohorts, two adolescent and four adult, in Zambia, Tanzania, Philippines, and India. Pancreas size, structure, and calcification will be assessed by ultrasound and computed tomography (CT) scan; exocrine function by faecal elastase and serum lipase; and endocrine function by haemoglobin A1c (HbA1c) and blood glucose, insulin and C-peptide concentrations during an oral glucose tolerance test (OGTT). In-depth hormonal analyses of incretins, glucagon, proinsulin and trypsinogen during OGTT and intravenous glucose tolerance tests will be done in subsets of adult participants. Pancreatic size and function outcomes will be compared between people with and without prior wasting malnutrition. Analyses will investigate effect modification by sex, current age, time since malnutrition, current body mass index and dietary patterns. Mathematical modelling of OGTT data will be used to estimate the relative contribution to glucose dysregulation of decreased insulin production, changes in insulin clearance and increased insulin resistance. Proinsulin/insulin ratio will be analysed in archived samples from the Tanzanian cohort using a nested case-control design to investigate whether abnormal values precede diabetes. Conclusions: SAMPA, a large-scale multi-centre research programme using data from people with or without prior wasting malnutrition to assess several aspects of pancreatic phenotype, will provide coherent evidence for future policies and programmes for malnutrition and diabetes.

Physical Inactivity and Sedentarism during and after Admission with Community-Acquired Pneumonia and the Risk of Readmission and Mortality: A Prospective Cohort Study.

BACKGROUND: Bed rest with limited physical activity is common during admission. The aim was to determine the association between daily step count and physical activity levels during and after admission with community-acquired pneumonia (CAP) and the risk of readmission and mortality. METHODS: A prospective cohort study of 166 patients admitted with CAP. Step count and physical activity were assessed with accelerometers during and after admission and were categorised as sedentary, light, or moderate-vigorous physical activity. Linear regression was used to assess the association between step count and length of stay. Logistic regression was used to assess the association between step count, physical activity level, and risk of readmission and mortality. RESULTS: Patients admitted with CAP were sedentary, light physically active, and moderate-to-vigorous physically active 96.4%, 2.6%, and 0.9% of their time, respectively, with 1356 steps/d. For every 500-step increase in daily step count on day 1, the length of stay was reduced by 6.6%. For every 500-step increase in daily step count during admission, in-hospital and 30-day mortality was reduced. Increased light and moderate-to-vigorous physical activity during admission were associated with reduced risk of in-hospital and 30-day mortality. After discharge, patients increased their daily step count to 2654 steps/d and spent more time performing light and moderate-to-vigorous physical activity. For every 500-step increase in daily step count after discharge, the risk of readmission was reduced. Higher moderate-to-vigorous physical activity after discharge was associated with a reduced risk of readmission. CONCLUSIONS: Increased physical activity during admission was associated with a reduced length of stay and risk of mortality, whereas increased physical activity after discharge was associated with a reduced risk of readmission in patients with CAP. Interventions focusing on increasing physical activity levels should be prioritised to improve the prognosis of patients admitted with CAP.

The association of physical activity and cardiorespiratory fitness with ß-cell dysfunction, insulin resistance, and diabetes among adults in north-western Tanzania: A cross-sectional study.

Introduction: Research on the associations of physical activity and cardiorespiratory fitness with ß-cell dysfunction and insulin resistance among adults in Sub-Saharan Africa (SSA) is limited. We assessed the association of physical activity and cardiorespiratory fitness with ß-cell function, insulin resistance and diabetes among people living with HIV (PLWH) ART-naïve and HIV-uninfected Tanzanian adults. Method: In a cross-sectional study, we collected data on socio-demography, anthropometry, fat mass and fat free mass and C-reactive protein. Data on glucose and insulin collected during an oral glucose tolerance test were used to assess ß-cell dysfunction (defined as insulinogenic index <0.71 (mU/L)/(mmol/L), HOMA-ß index <38.3 (mU/L)/(mmol/L), and overall insulin release index <33.3 (mU/L)/(mmol/L)), oral disposition index <0.16 (mU/L)/(mg/dL)(mU/L)-1, insulin resistance (HOMA-IR index >1.9 (mU/L)/(mmol/L) and Matsuda index <7.2 (mU/L)/(mmol/L), prediabetes and diabetes which were the dependent variables. Physical activity energy expenditure (PAEE), sleeping heart rate (SHR), and maximum uptake of oxygen during exercise (VO2 max) were the independent variables and were assessed using a combined heart rate and accelerometer monitor. Logistic regressions were used to assess the associations. Results: Of 391 participants, 272 were PLWH and 119 HIV-uninfected. The mean age was 39 ( ± 10.5) years and 60% (n=235) were females. Compared to lower tertile, middle tertile of PAEE was associated with lower odds of abnormal insulinogenic index (OR=0.48, 95%CI: 0.27, 0.82). A 5 kj/kg/day increment of PAEE was associated with lower odds of abnormal HOMA-IR (OR=0.91, 95%CI: 0.84, 0.98), and reduced risk of pre-diabetes (RRR=0.98, 95%CI: 0.96, 0.99) and diabetes (RRR=0.92, 95%CI: 0.88, 0.96). An increment of 5 beats per min of SHR was associated with higher risk of diabetes (RRR=1.06, 95%CI: 1.01, 1.11). An increase of 5 mLO2/kg/min of VO2 max was associated with lower risk of pre-diabetes (RRR=0.91, 95%CI: 0.86, 0.97), but not diabetes. HIV status did not modify any of these associations (interaction, p>0.05). Conclusion: Among Tanzanian adults PLWH and HIV-uninfected individuals, low physical activity was associated with ß-cell dysfunction, insulin resistance and diabetes. Research is needed to assess if physical activity interventions can improve ß-cell function and insulin sensitivity to reduce risk of diabetes and delay progression of diabetes in SSA.

Exercise Training During Working Hours at a Hospital Department: A Pilot Study.

OBJECTIVES: This pilot study tested the use of an exercise offer to hospital employees during working hours and changes in work and health parameters. METHODS: Employees (n = 214) from a medical department on a Danish hospital were invited to 30 minutes' exercise training twice weekly for 12 weeks. Outcomes included health- and work-related parameters. RESULTS: Eighty employees (mean age, 44.4 [SD, 10.7] years; 81.3% women) completed the study. Intervention adherence was 36.3% (SD, 25.1%). Aerobic capacity increased from 34.6 (95% confidence interval [CI], 32.3 to 36.9) to 36.7 (95% CI, 34.1 to 39.4) mL O 2 /min per kilogram, P = 0.004. Blood pressure decreased from 120 (95% CI, 117 to 123)/79 (95% CI, 76 to 81) to 116 (95% CI, 112 to 120)/76 (95% CI, 74 to 79) mm Hg, P = 0.003. Waist circumference and musculoskeletal pain decreased. Well-being, social capital, and quality of life increased. CONCLUSIONS: Despite low training adherence, completers improved outcomes related to metabolic and self-rated health.

Blood Pressure and Body Composition During First Year of Antiretroviral Therapy in People With HIV Compared With HIV-Uninfected Community Controls.

BACKGROUND: Body composition changes may explain the rapid increase in blood pressure (BP) in people with HIV (PWH) during the first year of antiretroviral therapy. METHODS: We analyzed data from a cohort of PWH and HIV-uninfected adults from the same communities in Mwanza, Tanzania. Blood pressure (BP, mm Hg) and body composition data were collected at baseline and 12-month follow-up. We used multivariable linear regression to compare BP changes in PWH and HIV-uninfected adults, and the relationship between changes in body composition and changes in BP. RESULTS: BP data were available for 640 PWH and 299 HIV-uninfected adults. Sixty-four percent were women and the mean age was 38 years. In PWH, systolic BP (SBP) increased (114-118) whereas SBP decreased (125-123) in HIV-uninfected participants. Fat mass increased by 1.6 kg on average in PWH and was strongly associated with the change in BP (P < 0.001). The greater increase in SBP in PWH was partly explained by the lower baseline SBP but PWH still experienced a 2.2 (95% CI: 0.3-4.2) greater increase in SBP after adjustment. Weight gain partially mediated the relationship between HIV and SBP increase in PWH; a 1-kg increase in fat mass accounted for 0.8 (95% CI: 0.6-1.1) increase in SBP. CONCLUSIONS: Weight and fat mass increase rapidly in PWH during the first 12 months of antiretroviral therapy and contribute to a rapid increase in SBP. Interventions to prevent excessive increase in fat mass are needed for PWH.

Biomarkers for iron metabolism among patients hospitalized with community-acquired pneumonia caused by infection with SARS-CoV-2, bacteria, and influenza.

Ferritin, the central iron storage protein, has attracted attention as a biomarker of severe COVID-19. Few studies have investigated regulators of iron metabolism in the context of COVID-19. The aim was to evaluate biomarkers for iron metabolism in the acute phase response to community-acquired pneumonia (CAP) caused by SARS-CoV-2 compared with CAP caused by bacteria or influenza virus in hospitalized patients. A cross-sectional study of 164 patients from the Surviving Pneumonia Cohort recruited between January 8, 2019 and May 26, 2020. Blood samples were collected at admission and analyzed for levels of C-reactive protein (CRP), ferritin, soluble transferrin receptor, erythroferrone, and hepcidin. Median (IQR) hepcidin was higher in SARS-CoV-2 with 143.8 (100.7-180.7) ng/mL compared with bacterial and influenza infection with 78.8 (40.1-125.4) and 53.5 (25.2-125.8) ng/mL, respectively. The median ferritin level was more than 2-fold higher in patients with SARS-CoV-2 compared with the other etiologies (p < 0.001). Patients with SARS-CoV-2 had lower levels of erythroferrone and CRP compared with those infected with bacteria. Higher levels of hepcidin and lower levels of erythroferrone despite lower CRP levels among patients with SARS-CoV-2 compared with those infected with bacteria indicate alterations in iron metabolism in patients with SARS-CoV-2 infection.

Glucometabolic changes influence hospitalization and outcome in patients with COVID-19: An observational cohort study.

AIMS: The aim was to report the prevalence of diabetes status in patients hospitalized with COVID-19 and assess the association between the glucometabolic status at admission and 90-day mortality. METHODS: Consecutive patients hospitalized with COVID-19 were included in the study. All participants included had an HbA1c measurement 60 days prior to or within 7 days after admission. We studied the association between diabetes status, the glycemic gap (difference between admission and habitual status), admission plasma-glucose, and mortality using Cox proportional hazards regression. RESULTS: Of 674 patients included, 114 (17%) had normal glucose level, 287 (43%) had pre-diabetes, 74 (11%) had new-onset, and 199 (30%) had diagnosed diabetes. No association between diabetes status, plasma-glucose at admission, and mortality was found. Compared to the 2nd quartile (reference) of glycemic-gap, those with the highest glycemic gap had increased mortality (3rd (HR 2.38 [1.29-4.38], p = 0.005) and 4th quartile (HR 2.48 [1.37-4.52], p = 0.002). CONCLUSION: Abnormal glucose metabolism was highly prevalent among patients hospitalized with COVID-19. Diabetes status per se or admission plasma-glucose was not associated with a poorer outcome. However, a high glycemic gap was associated with increased risk of mortality, suggesting that, irrespective of diabetes status, glycemic stress serves as an important prognostic marker for mortality.

Association of sickle cell trait with ß-cell dysfunction and physical activity in adults living with and without HIV in Tanzania.

This study aimed to investigate sickle cell trait (SCT) associations with physical activity, markers of insulin secretion and resistance, and glucose among people living with HIV infection (PLWH), both antiretroviral therapy (ART) naive and experienced, and HIV-uninfected adults. This was a cross-sectional study conducted in Mwanza, Northwestern Tanzania. We used data of 668 participants attained from two sub-studies of CICADA study. Mean age was 40 (SD 11.5) years, 402 (61.7%) were females and 157 (24.1%) had SCT. PLWH were 422 (64.7%), of these, 80 (18.9%) were on ART. People with SCT had higher risk of having an isolated ß-cell dysfunction compared to those without SCT (RRR = 1.82, CI: 1.10, 3.01, p = 0.02). People with SCT but without HIV infection had lower average acceleration on the trunk longitudinal axis (ACCx) and higher level of self-reported physical activity. 30 min oral glucose tolerance test among PLWH on ART was higher in those with SCT compared to those without SCT. People with SCT are at higher risk of having ß-cell dysfunction and those with SCT on ART are at more risk of developing diabetes. Future studies to investigate the interaction between SCT and HIV/ART on risk of diabetes should be considered.