| 1. |
- Carroll, Harriet A., et al.
(författare)
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Effect of acute hypohydration on glycemic regulation in healthy adults : A randomized crossover trial
- 2019
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Ingår i: Journal of Applied Physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 126:2, s. 422-430
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Tidskriftsartikel (refereegranskat)abstract
- he aim of this study was to investigate the acute effect of hydration status on glycemic regulation in healthy adults and explore underlying mechanisms. In this randomized crossover trial, 16 healthy adults (8 men, 8 women) underwent an oral glucose tolerance test (OGTT) when hypohydrated and rehydrated after 4 days of pretrial standardization. One day before OGTT, participants were dehydrated for 1 h in a heat tent with subsequent fluid restriction (HYPO) or replacement (RE). The following day, an OGTT was performed with metabolic rate measurements and pre- and post-OGTT muscle biopsies. Peripheral quantitative computer tomography thigh scans were taken before and after intervention to infer changes in cell volume. HYPO (but not RE) induced 1.9% (SD 1.2) body mass loss, 2.9% (SD 2.7) cell volume reduction, and increased urinary hydration markers, serum osmolality, and plasma copeptin concentration (all P 0.007). Fasted serum glucose [HYPO 5.10 mmol/l (SD 0.42), RE 5.02 mmol/l (SD 0.40); P 0.327] and insulin [HYPO 27.1 pmol/l (SD 9.7), RE 27.6 pmol/l (SD 9.2); P 0.809] concentrations were similar between HYPO and RE. Hydration status did not alter the serum glucose (P 0.627) or insulin (P 0.200) responses during the OGTT. Muscle water content was lower before OGTT after HYPO compared with RE [761 g/kg wet wt (SD 13) vs. 772 g/kg wet wt (SD 18) RE] but similar after OGTT [HYPO 779 g/kg wet wt (SD 15) vs. RE 780 g/kg wet wt (SD 20); time P 0.011; trial time P 0.055]. Resting energy expenditure was similar between hydration states (stable between 1.21 and 5.94 kJ·kg 1 ·day 1 ; trial P 0.904). Overall, despite acute mild hypohydration increasing plasma copeptin concentrations and decreasing fasted cell volume and muscle water, we found no effect on glycemic regulation.
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| 2. |
- Carroll, Harriet A., et al.
(författare)
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Hydration status affects thirst and salt preference but not energy intake or postprandial ghrelin in healthy adults : A randomised crossover trial
- 2019
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Ingår i: Physiology and Behavior. - : Elsevier BV. - 0031-9384. ; 212
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Tidskriftsartikel (refereegranskat)abstract
- Background: Few studies have investigated the effect of hydration status on appetite for food in healthy adults. Prior work suggests hydration status does not alter appetite or energy intake, with mixed findings regarding appetite hormone secretion. However, an extensive investigation into both the psychological and physiological appetitive responses to hydration status has never been conducted. Objective: To investigate the effect of hydration status on multiple facets of appetite. Design: After 3 days pre-trial standardization, a range of appetite tasks were conducted when hypohydrated (HYPO) and euhydrated (EUHY) in 16 healthy participants (8 men). Hydration status was manipulated via dehydration in a heat tent for 60 min and subsequent fluid restriction (HYPO) or replacement (EUHY). The next day, a food reward computer task was completed followed by an ad libitum pasta meal. Pre- and post-prandial visual analogue scales assessing hunger, fullness, and flavour desires (sweet, salty, savoury and fatty) were additionally completed. Blood samples were taken the previous day before the hydration interventions in a euhydrated state, and in the fasted and post-prandial state during HYPO and EUHY. Results: HYPO induced -1.9 ± 1.2% body mass change, compared to -0.2 ± 0.6%, with accompanying changes in markers of hypohydration which were not seen during EUHY. A higher desire for foods was associated with a higher water content but the association was weaker in EUHY compared to HYPO, (β= -0.33 mm/g of food water content, p < 0.001) in the food reward task. Visual analogue scales showed similar hunger and fullness between interventions, but during HYPO there was consistently higher thirst (average range in difference 27–32 mm across all time points) and lower fasted desire for salt (−23, 95% CI −10, −35 mm). Ad libitum energy intake (HYPO 1953 ± 742 kJ, EUHY 2027 ± 926 kJ; p = 0.542) and post-prandial ghrelin concentrations (HYPO 180 ± 65 pg mL−1, EUHY 188 ± 71 pg mL−1; p = 0.736) were similar by hydration status. Conclusions: An acute manipulation to hydration status altered desire for salt and foods of differing water contents, but did not influence energy intake at an ad libitum pasta meal. Further research should investigate whether these appetites would alter food choice.
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| 3. |
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| 4. |
- Gallo, Widet, et al.
(författare)
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miR-483-5p associates with obesity and insulin resistance and independently associates with new onset diabetes mellitus and cardiovascular disease
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Our aim was to identify serum microRNAs (miRNAs) in healthy humans which associate with future onset of both diabetes mellitus and cardiovascular disease. We performed global profiling of 753 mature human miRNAs in serum of 12 pilot subjects followed by measurement of 47 consistently expressed miRNAs in fasting serum of 553 healthy subjects from the baseline exam (1991–1994) of the population based Malmö Diet and Cancer Study Cardiovascular Cohort (MDC-CC), of whom 140 developed diabetes, and 169 cardiovascular diseases during follow-up. We used multivariate logistic regression to test individual miRNAs for association with incident diabetes and cardiovascular disease as compared to control subjects (n = 259). After Bonferroni correction and adjustment for age and sex, each SD increment of log-transformed miR-483-5p was significantly associated with both incident diabetes (OR = 1.48; 95% CI 1.18–1.84, P = 0.001) and cardiovascular disease (OR = 1.40; 95% CI 1.15, 1.72, P = 0.001). In cross sectional analysis, miR-483-5p was correlated with BMI (r = 0.162, P = 0.0001), fasting insulin (r = 0.156, P = 0.0002), HDL (r = -0.099, P = 0.02) and triglycerides (r = 0.11, P = 0.01). Adjustment for these metabolic risk factors, as well as traditional risk factors attenuated the miR-483-5p association with incident diabetes (OR = 1.28 95% CI 1.00–1.64, P = 0.049) whereas its association with incident cardiovascular disease Remained virtually unchanged (OR = 1.46 95% CI, 1.18–1.81, P = 0.0005). In conclusion, miR-483-5p associates with both diabetes and cardiovascular disease. The association with diabetes seems partly mediated by obesity and insulin resistance, whereas the association with incident cardiovascular disease is independent of these metabolic factors and traditional cardiovascular disease risk factors.
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| 5. |
- Gallo, Widet, et al.
(författare)
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Replication study reveals miR-483-5p as an important target in prevention of cardiometabolic disease
- 2021
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAlterations in levels of circulating micro-RNAs might reflect within organ signaling or subclinical tissue injury that is linked to risk of diabetes and cardiovascular risk. We previously found that serum levels of miR-483-5p is correlated with cardiometabolic risk factors and incidence of cardiometabolic disease in a case–control sample from the populations-based Malmö Diet and Cancer Study Cardiovascular Cohort (MDC-CC). We here aimed at replicating these findings and to test for association with carotid atherosclerosis.MethodsWe measured miR-483-5p in fasting serum of 1223 healthy subjects from the baseline examination of the population-based, prospective cohort study Malmö Offspring Study (MOS) and correlated miR-483-5p to cardiometabolic risk factors and to incidence of diabetes mellitus and coronary artery disease (CAD) during 3.7 (± 1.3) years of follow-up using logistic regression. In both MOS and MDC-CC we related mir-483-5p to carotid atherosclerosis measured with ultrasound.ResultsIn cross-sectional analysis miR-483-5p was correlated with BMI, waist circumference, HDL, and sex. After adjustment for age and sex, the association remained significant for all risk factors except for HDL. Logistic regression analysis showed significant associations between miR-483-5p and new-onset diabetes (OR = 1.94, 95% CI 1.06–3.56, p = 0.032) and cardiovascular disease (OR = 1.99, 95% CI 1.06–3.75, p = 0.033) during 3.7 (± 1.3) years of follow-up. Furthermore, miR-483-5p was significantly related with maximum intima-media thickness of the carotid bulb in MDC-CC (p = 0.001), but not in MOS, whereas it was associated with increasing number of plaques in MOS (p = 0.007).ConclusionmiR-483-5p is related to an unfavorable cardiometabolic risk factor profile and predicts diabetes and CAD, possibly through an effect on atherosclerosis. Our results encourage further studies of possible underlying mechanisms and means of modifying miR-483-5p as a possible interventional target in prevention of cardiometabolic disease.
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| 6. |
- Gezelius, Emelie, et al.
(författare)
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Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN)
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Cardiovascular disease is common in patients with small cell lung cancer, partly reflecting its high correlation with smoking. Cardiovascular comorbidities may limit patient tolerance to cytotoxic drugs, thereby influencing the choice and intensity of treatment and, ultimately, patient survival. In light of the challenges relating to assessing cardiovascular status clinically in newly diagnosed lung cancer, objective biomarkers of cardiovascular vulnerability are warranted. Here, we show that circulating levels of ST2, an established biomarker in heart failure, and adrenomedullin, a vasodilator peptide known to reflect several aspects of cardiovascular status, strongly correlate with survival in small cell lung cancer. Our data, which are based on a large, randomized trial cohort, suggest the potential use of cardiovascular biomarkers in guiding clinicians in making individualized treatment decisions. Cardiovascular comorbidity is common in small cell lung cancer (SCLC) and may significantly affect treatment tolerability and patient outcome. Still, there are no established biomarkers for objective and dynamic assessment as a tool for improved treatment decisions. We have investigated circulating levels of midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial-natriuretic peptide (MR-proANP), copeptin (surrogate for vasopressin) and suppression-of-tumorigenicity-2 (ST2), all known to correlate with various aspects of cardiovascular function, in a SCLC cohort (N = 252) from a randomized, controlled trial (RASTEN). For all measured biomarkers, protein levels were inversely associated with survival, particularly with ST2 and MR-proADM, where the top versus bottom quartile was associated with an adjusted hazard ratio of 2.40 (95% CI 1.44-3.98; p = 0.001) and 2.18 (95% CI 1.35-3.51; p = 0.001), respectively, in the entire cohort, and 3.43 (95% CI 1.73-6.79; p < 0.001) and 3.49 (95% CI 1.84-6.60; p < 0.001), respectively, in extensive disease patients. A high combined score of MR-proADM and ST2 was associated with a significantly reduced median OS of 7.0 months vs. 14.9 months for patients with a low combined score. We conclude that the cardiovascular biomarkers MR-proADM and ST2 strongly correlate with survival in SCLC, warranting prospective studies on the clinical utility of MR-proADM and ST2 for improved, individualized treatment decisions.
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| 7. |
- Hallengren, Erik, et al.
(författare)
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Genetic determinants of growth hormone and GH-related phenotypes
- 2017
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 18, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Higher fasting Growth Hormone (GH) has been associated with increased cardiovascular morbidity and mortality. Our objective was to find genetic determinants of fasting GH in order to facilitate future efforts of analyzing the association between fasting growth hormone and cardiovascular disease. A genome-wide association study (GWAS) was performed in a discovery cohort of 4134 persons (58% females; age 46-68 yrs), linking SNPs to fasting hs-GH. Fifteen SNPs were replicated in an independent cohort of 5262 persons (28.9% females; age 56-85 yrs). The best performing SNP was analyzed vs GH-related variables in a third independent cohort (n = 24,047; 61% females; age 44-73 yrs). A candidate gene approach searched for significant SNPs in the genes GH1 and GHR in the discovery cohort and was replicated as previously described.RESULTS: In the GWAS, the minor allele of rs7208736 was associated with lower GH in the discovery cohort (p = 5.15*10^-6) and the replication cohort (p = 0.005). The GH reducing allele was associated with lower BMI (P = 0.026) and waist (P = 0.021) in males only. In the candidate gene approach rs13153388 in the GHR-gene was associated with elevated GH-levels (P = 0.003) in the discovery cohort only and reduced height (P = 0.003).CONCLUSION: In the first GWAS ever for GH, we identify a novel locus on chromosome 17 associated with fasting GH levels, suggesting novel biological mechanisms behind GH secretion and GH-related traits. The candidate gene approach identified a genetic variant in the GHR, which was associated with an elevation of fasting hs-GH and lower height suggesting reduced GHR ligand sensitivity. Our findings need further replication.
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| 8. |
- Lindenberger, Marcus, et al.
(författare)
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Cardiovascular biomarkers and echocardiographic findings at rest and during graded hypovolemic stress in women with recurrent vasovagal syncope
- 2019
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Ingår i: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1045-3873 .- 1540-8167. ; 30:12, s. 2936-2943
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Vasovagal reflex is the most common type of syncope but its etiology is not fully elucidated. Venous return and cardiac output are key in hemodynamic control. The aim of the study was to assess cardiovascular biomarkers and echocardiographic measures at rest and during hypovolemia in women with and without a history of vasovagal syncope. Methods: Fourteen women (aged 18-30) suffering from recurrent vasovagal syncope and 15 age-matched healthy women were included. Graded lower body negative pressure (LBNP) was used to create central hypovolemic stress until signs of presyncope occurred. Echocardiography was applied at rest and throughout LBNP. Cardiovascular biomarkers: copeptin, mid-regional proadrenomedullin, mid-regional pro-ANP, C-terminal proendothelin-1, and plasma norepinephrine were measured both at rest and throughout graded hypovolemia to presyncope. Results: Women prone to vasovagal syncope presented with a narrower right ventricle (RV) (29 ± 1 vs 32 ± 1 mm, P <.05), smaller left atrium (36 ± 2 vs 47 ± 3 cm3, P <.01) and lower cardiac output at rest (3.1 ± 0.2 vs 3.7 ± 0.2 L/min, P <.05) and during graded hypovolemia (P <.05). Copeptin was elevated at rest (4.3 ± 0.8 vs 2.5 ± 0.2 pmol/L, P <.05) and increased more in women with vasovagal syncope during progression of LBNP (P <.01). At rest, lower C-terminal proendothelin-1 (35 ± 5 vs 46 ± 2 pmol/L, P <.05) and higher norepinephrine levels (1.1 ± 0.1 vs 0.8 ± 0.1 nmol/L, P <.01) were seen in women with vasovagal syncope. Conclusion: Women prone to vasovagal syncope demonstrate reduced cardiac preload, lower cardiac output, as well as increased release of vasopressin in rest and during hypovolemic challenge. The results emphasize the importance of venous return and cardiac output in the pathogenesis of vasovagal syncope.
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| 9. |
- Melander, Olle, et al.
(författare)
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Comparison of cardiovascular disease and cancer prevalence between Mediterranean and north European middle-aged populations (The Cilento on Ageing Outcomes Study and The Malmö Offspring Study)
- 2021
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Ingår i: Internal and Emergency Medicine. - : Springer Science and Business Media LLC. - 1828-0447 .- 1970-9366. ; 16:6, s. 1567-1572
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Tidskriftsartikel (refereegranskat)abstract
- Mediterranean diet protects from both cardiovascular disease (CVD) and cancer. In the 1960s, Ancel Keys defined the concept of Mediterranean diet in the South Italian region of Cilento and proposed it as a key factor for healthy ageing in the region. The aim of the current study was to compare the prevalence of CVD and cancer between a middle-aged population from Cilento and those of a Northern European population from Malmö, Sweden. We clinically characterized two middle-aged (50–67 years of age) population-based samples from Cilento (n = 809) and Malmö (n = 1025), Sweden, respectively. Logistic regression was used to calculate odds ratios (95% confidence interval) for disease prevalence in Malmö versus Cilento inhabitants adjusted for age and sex (model 1) and adjusted for all cardiometabolic risk factors (model 2). The prevalence of hypertension, current smoking, diabetes mellitus and levels of body mass index and triglycerides were lower, whereas HDL-cholesterol was higher in Malmö than in Cilento. LDL-cholesterol was higher and estimated glomerular filtration rate was lower in Malmö than in Cilento. The odds ratio for cardiovascular disease in Malmö versus Cilento inhabitants was 1.13 (0.69–1.87) (P = 0.62) in model 1, whereas it was significantly elevated in model 2 [2.03 (1.14–3.60) (P = 0.016)]. Moreover, the odds ratio for cancer in Malmö versus Cilento was 2.78 (1.81–4.27) (P < 0.001) in model 1 and 3.11 (1.97–4.92) (P < 0.001) in model 2. The higher odds of CVD and cancer in Malmö versus Cilento, when risk factors were accounted for, suggests the existence of unknown protective factors in Cilento.
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| 10. |
- Molvin, John, et al.
(författare)
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Cardiovascular biomarkers predict post-discharge re-hospitalization risk and mortality among Swedish heart failure patients
- 2019
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Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 6:5, s. 992-999
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim of this study was to assess the predictive role of biomarkers, associated with cardiovascular stress and its neuroendocrine response as well as renal function, in relation to mortality and risk of re-hospitalization among consecutive patients admitted because of heart failure (HF).METHODS AND RESULTS: A total of 286 patients (mean age, 75 years; 29% women) hospitalized for newly diagnosed or exacerbated HF were analysed. Associations between circulating levels of mid-regional pro-adrenomedullin (MR-proADM), copeptin, C-terminal pro-endothelin-1, N-terminal pro-brain natriuretic peptide (NT-proBNP), cystatin C, and all-cause mortality as well as risk of re-hospitalization due to cardiac causes were assessed using multivariable Cox regression models. A two-sided Bonferroni-corrected P-value of 0.05/5 = 0.010 was considered statistically significant. All biomarkers were related to echocardiographic measurements of cardiac dimensions and function. A total of 57 patients died (median follow-up time, 17 months). In the multivariable-adjusted Cox regression analyses, all biomarkers, except C-terminal pro-endothelin-1, were significantly associated with increased mortality: NT-proBNP [hazard ratio (HR) 1.85, 95% confidence interval (CI) 1.17-2.17; P = 4.0 × 10-4 ], MR-proADM (HR 1.94, 95% CI 1.36-2.75; P = 2.2 × 10-4 ), copeptin (HR 1.70, 95% CI 1.22-2.36; P = 0.002), and cystatin C (HR 2.11, 95% CI 1.56-2.86; P = 1.0 × 10-6 ). A total of 90 patients were re-hospitalized (median time to re-hospitalization, 5 months). In multivariable Cox regression analyses, NT-proBNP was the only biomarker that showed significant association with risk of re-hospitalization due to cardiac causes (HR 1.43, 95% CI 1.10-1.87; P = 0.009).CONCLUSIONS: Among patients hospitalized for HF, elevated plasma levels of NT-proBNP, MR-proADM, copeptin, and cystatin C are associated with higher mortality after discharge, whereas NT-proBNP is the only biomarker that predicts the risk of re-hospitalization due to cardiac causes.
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