| 1. |
- Fryk, Emanuel, et al.
(författare)
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Microdialysis and proteomics of subcutaneous interstitial fluid reveals increased galectin-1 in type 2 diabetes patients
- 2016
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Ingår i: Metabolism-Clinical and Experimental. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 65:7, s. 998-1006
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To identify a potential therapeutic target for type 2 diabetes by comparing the subcutaneous interstitial fluid from type 2 diabetes patients and healthy men. Methods. Proteomics was performed on the interstitial fluid of subcutaneous adipose tissue obtained by microdialysis from 7 type 2 diabetes patients and 8 healthy participants. 851 proteins were detected, of which 36 (including galectin-1) showed significantly altered expression in type 2 diabetes. We also measured galectin-1 expression in: (1) adipocytes isolated from adipose tissue biopsies from these participants; (2) subcutaneous adipose tissue of 24 obese participants before, during and after 16 weeks on a very low calorie diet (VLCD); and (3) adipocytes isolated from 6 healthy young participants after 4 weeks on a diet and lifestyle intervention to promote weight gain. We also determined the effect of galectin-1 on glucose uptake in human adipose tissue. Results. Galectin-1 protein levels were elevated in subcutaneous dialysates from type 2 diabetes compared with healthy controls (p < 0.05). In agreement, galectin-1 mRNA expression was increased in adipocytes from the type 2 diabetes patients (p < 0.05). Furthermore, galectin-1 mRNA expression was decreased in adipose tissue after VLCD (p < 0.05) and increased by overfeeding (p < 0.05). Co-incubation of isolated human adipocytes with galectin-1 reduced glucose uptake (p < 0.05) but this was independent of the insulin signal. Conclusion. Proteomics of the interstitial fluid in subcutaneous adipose tissue in vivo identified a novel adipokine, galectin-1, with a potential role in the pathophysiology of type 2 diabetes. (C) 2016 Elsevier Inc. All rights reserved.
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| 2. |
- Kos, K., et al.
(författare)
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Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose : Regulation of SPARC in human adipose tissue
- 2009
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 58:8, s. 1780-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Matricellular Secreted Protein, Acidic and Rich in Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose tissue collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human adipose tissue is influenced by glucose metabolism and adipokines. RESEARCH DESIGN AND METHODS: Serum and adipose tissue biopsies were obtained from morbidly obese nondiabetic subjects undergoing bariatric surgery and lean control subjects for analysis of metabolic markers, SPARC, and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet of 1,883 kJ (450 kcal)/day for 16 weeks and serial subcutaneous-abdominal-adipose tissue (SCAT) biopsies (weight loss: 28 +/- 3.7 kg). Another six lean subjects underwent fast-food-based hyperalimentation for 4 weeks (weight gain: 7.2 +/- 1.6 kg). Finally, visceral adipose tissue explants were cultured with recombinant leptin, insulin, and glucose, and SPARC mRNA and protein expression determined by Western blot analyses. RESULTS: SPARC expression in human adipose tissue correlated with fat mass and was higher in SCAT. Weight loss induced by very-low-calorie diet lowered SPARC expression by 33% and increased by 30% in adipose tissue of subjects gaining weight after a fast-food diet. SPARC expression was correlated with leptin independent of fat mass and correlated with homeostasis model assessment-insulin resistance. In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein. CONCLUSIONS: Our data suggest that SPARC expression is predominant in subcutaneous fat and its expression and secretion in adipose tissue are influenced by fat mass, leptin, insulin, and glucose. The profibrotic effects of SPARC may contribute to metabolic dysregulation in obesity.
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| 3. |
- af Geijerstam, Peder, Doktorand, 1983-, et al.
(författare)
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A low dose of daily licorice intake affects renin, aldosterone, and home blood pressure in a randomized crossover trial
- 2024
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Ingår i: American Journal of Clinical Nutrition. - : ELSEVIER SCIENCE INC. - 0002-9165 .- 1938-3207. ; 119:3, s. 682-691
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundLicorice, through the effects of glycyrrhizic acid (GA), raises blood pressure (BP). The World Health Organization has suggested that 100 mg GA/d would be unlikely to cause adverse effects, but of 13 previously published studies none have been randomized and controlled and independently quantified the GA content.ObjectiveOur aim was to analyze the effects on home BP of a daily licorice intake containing 100 mg GA.MethodsHealthy volunteers were randomly assigned to start with either licorice or a control product in a nonblinded, 2 × 2 crossover study. Home BP was measured daily, and blood samples were collected at the end of each 2-wk period.ResultsThere were 28 participants and no dropouts. The median age was 24.0 y (interquartile range 22.8–27.0 y). During the licorice compared with control intake period, the systolic home BP increased [mean difference: 3.1 mm Hg (95% confidence interval [CI]: 0.8, 5.4 mm Hg) compared with −0.3 mm Hg (95% CI: −1.8, 1.3 mm Hg); P = 0.018] and renin and aldosterone were suppressed [mean change: −30.0% (95% CI: −56.7%, −3.3%) compared with 15.8% (95% CI: −12.8%, 44.4%); P = 0.003; and −45.1% (95% CI: −61.5%, −28.7%) compared with 8.2% (95% CI: −14.7%, 31.1%); P <0.001, respectively]. In the quartile of participants with the most pronounced suppression of renin and aldosterone, N-terminal prohormone of brain natriuretic peptide concentration increased during the licorice compared with control period [mean change: 204.1% (95% CI: −11.6%, 419.7%) compared with 72.4% (95% CI: −52.2%, 197.1%); P = 0.016].ConclusionsWe found licorice to be more potent than previously known, with significant increases in BP, after a daily intake of only 100 mg GA. Thus, the safe limit of intake of this substance might need to be reconsidered.
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| 4. |
- af Geijerstam, Peder, Doktorand, 1983-
(författare)
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Home Blood Pressure in Health and Disease
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hypertension is the most common preventable cause of premature all-cause mortality, primarily from cardiovascular disease (CVD). Individuals with dysglycemia, including prediabetes and diabetes, are at increased risk. Licorice intake raises blood pressure (BP) through the effects of glycyrrhizic acid (GA), but the true limit of safe intake is uncertain. Home BP has several benefits over BP measured at a clinic, including a higher predictive value for CVD. By combining office and home BP, it is possible to diagnose masked hypertension (MH), in which home but not office BP is elevated, and white coat hypertension (WCH), in which office but not home BP is elevated. The aim of this thesis was to advance our knowledge on home BP in relation to dysglycemia, markers of CVD, and licorice intake. The first 3 papers used data from the Linköping cohort of the prospective Swedish CArdioPulmonary bioImage Study (SCAPIS). Study IV was a randomized controlled cross-over study. Data was obtained from questionnaires, blood samples and office and home BP measurements. In studies I-III, pulse wave velocity (PWV), coronary artery calcium score (CACS), and carotid artery plaques as markers of CVD were also included. In Study I, we examined 5025 men and women aged 50-64 years old for the relation between dysglycemia and home BP. Both the systolic office and home BP measurements were positively as-sociated with dysglycemia. Participants with dysglycemia vs normoglycemia more often had MH. The findings were in line with previous research and strengthened the association between dysglycemia and MH. In Study II, we examined the associations between MH and markers of CVD in 4122 individuals without BP-lowering treatment. Of participants, 4.2% had MH, and these were more often men and had higher BMI than those with normotension. Participants with MH also had higher odds for CACS ≥100, an as-sociation which has previously been suggested as a trend.In Study III, we examined the relation between soluble P-se-lectin (sP-selectin) as a measure of thrombotic activity, plasma high-sensitivity C-reactive protein (hsCRP) as a measure of inflammation, and home BP in 4548 participants. Both markers were higher in each hypertension phenotype compared with sustained normotension. The quartile of participants with the highest sP-se-lectin values had higher odds for CACS ≥100 and carotid artery plaques. The association between sP-selectin and sustained hyper-tension was novel and not affected by adjustments for hsCRP. In Study IV, 28 healthy participants aged 18-30 years old were evaluated for the effects of a daily intake of licorice containing 100 mg of GA compared with a control product for 2 weeks. During the licorice intake period, the systolic home BP increased with 3.1 mmHg, and the suppression of serum aldosterone and plasma renin levels indicated that this was due to the licorice intake. In conclusion, this thesis further strengthens the idea that both home and office BP measurements have values beyond that of the other, and that home BP may be most valuable in individuals with dysglycemia and obesity, and in men. Finally, licorice may be more potent than previously known, suggesting the need for increased awareness.
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| 5. |
- af Geijerstam, Peder, Doktorand, 1983-, et al.
(författare)
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P-selectin and C-reactive protein in relation to home blood pressure and coronary calcification: a SCAPIS substudy
- 2024
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Soluble P-selectin (sP-selectin) and high-sensitivity C-reactive protein (hsCRP) have previously been associated with hypertension, but the relation with out-of-office blood pressure (BP) and coronary artery calcification score is unknown. We aimed to examine the relationship between sP-selectin, hsCRP and home BP, as well as coronary artery calcification score and carotid artery plaques.Methods: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), 5057 randomly selected participants were evaluated with office and home BP using the semi-automatic Omron M10-IT device. For this cross-sectional study, participants with sP-selectin <4 standard deviations above mean and hsCRP <5 mg/l, representing low-grade inflammation, were included. Using generalized linear models, these inflammatory markers were evaluated in relation to BP classifications, as well as coronary artery calcification score and carotid artery plaques.Results: Of participants, 4548 were included in the analyses. The median age was 57.2 (53.4–61.2) years, and 775 (17.0%) reported taking medication for hypertension. Participants in the highest quartile of sP-selectin [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.40–1.98, P < 0.001] and hsCRP [OR 2.25, (95% CI 1.89–2.60), P < 0.001] were more likely to have sustained hypertension. Participants in the highest quartile of hsCRP were also more likely to have masked hypertension, OR (95% CI) 2.31 (1.72–3.10), P < 0.001 and carotid artery plaques, OR (95% CI) 1.21 (1.05–1.38), P = 0.007.Conclusion: Increased sP-selectin and hsCRP were independently associated with sustained hypertension. These findings indicate an association between hypertension and platelet activity, as expressed by sP-selectin.
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| 6. |
- Agebratt, Christian, et al.
(författare)
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A Randomized Study of the Effects of Additional Fruit and Nuts Consumption on Hepatic Fat Content, Cardiovascular Risk Factors and Basal Metabolic Rate
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1, s. e0147149-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundFruit has since long been advocated as a healthy source of many nutrients, however, the high content of sugars in fruit might be a concern.ObjectivesTo study effects of an increased fruit intake compared with similar amount of extra calories from nuts in humans.MethodsThirty healthy non-obese participants were randomized to either supplement the diet with fruits or nuts, each at +7 kcal/kg bodyweight/day for two months. Major endpoints were change of hepatic fat content (HFC, by magnetic resonance imaging, MRI), basal metabolic rate (BMR, with indirect calorimetry) and cardiovascular risk markers.ResultsWeight gain was numerically similar in both groups although only statistically significant in the group randomized to nuts (fruit: from 22.15±1.61 kg/m2 to 22.30±1.7 kg/m2, p = 0.24 nuts: from 22.54±2.26 kg/m2 to 22.73±2.28 kg/m2, p = 0.045). On the other hand BMR increased in the nut group only (p = 0.028). Only the nut group reported a net increase of calories (from 2519±721 kcal/day to 2763±595 kcal/day, p = 0.035) according to 3-day food registrations. Despite an almost three-fold reported increased fructose-intake in the fruit group (from 9.1±6.0 gram/day to 25.6±9.6 gram/day, p<0.0001, nuts: from 12.4±5.7 gram/day to 6.5±5.3 gram/day, p = 0.007) there was no change of HFC. The numerical increase in fasting insulin was statistical significant only in the fruit group (from 7.73±3.1 pmol/l to 8.81±2.9 pmol/l, p = 0.018, nuts: from 7.29±2.9 pmol/l to 8.62±3.0 pmol/l, p = 0.14). Levels of vitamin C increased in both groups while α-tocopherol/cholesterol-ratio increased only in the fruit group.ConclusionsAlthough BMR increased in the nut-group only this was not linked with differences in weight gain between groups which potentially could be explained by the lack of reported net caloric increase in the fruit group. In healthy non-obese individuals an increased fruit intake seems safe from cardiovascular risk perspective, including measurement of HFC by MRI.
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| 7. |
- Al-Karkhi, Isam, et al.
(författare)
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Comparisons of automated blood pressures in a primary health care setting with self-measurements at the office and at home using the Omron i-C10 device
- 2015
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Ingår i: Blood Pressure Monitoring. - : Lippincott Williams & Wilkins. - 1359-5237 .- 1473-5725. ; 20:2, s. 98-103
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We aimed to compare blood pressure (BP) levels recorded using the semiautomatic oscillometric Omron i-C10 BP device in patients with or without hypertension in three different settings: (a) when used by a doctor or a nurse at the office (OBP); (b) when used for self-measurement by the patient at the office (SMOBP); and (c) when used for 7 consecutive days at home (HBP).MATERIALS AND METHODS: A total of 247 individuals were invited to participate, but 78 of these individuals declined and a further seven were excluded, leaving a final cohort of 162 participants.RESULTS: The mean OBP was higher than HBP (difference 8.1±14/3.1±8.8 mmHg, P<0.0001) and so was SMOBP compared with HBP (difference 7.0±13/4.2±7.3 mmHg, P<0.0001). Sixteen participants (9.9%) had at least 10 mmHg higher systolic SMOBP than OBP and 28 (17%) participants had at least 10 mmHg lower systolic SMOBP than OBP. Participants who were current smokers had a larger mean difference between systolic OBP and SMOBP than nonsmokers (OBP-SMOBP in smokers: 6.6±9.4 mmHg, OBP-SMOBP in nonsmokers: 0.5±9.2 mmHg, P=0.011 between groups).CONCLUSION: Self-measurement of BP in the office does not preclude an increase in BP when levels in the individual patients are compared with HBP using the same equipment. Thus, SMOBP with a semiautomatic device does not lead to a reduction in the white-coat effect in the same manner as fully automatic devices.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.
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| 8. |
- Albinsson-Stenholm, Erina, et al.
(författare)
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Subjects with high fasting insulin also have higher postprandial GLP-1 and glucagon levels than controls with lower insulin
- 2019
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Ingår i: Nutrition Research. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0271-5317 .- 1879-0739. ; 72, s. 111-120
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about postprandial release of serum ghrelin, glucagon, and glucagon-like peptide-1 (GLP-1) in relation with differing fasting insulin levels. We hypothesized that these hormones are affected by insulin resistance, and hence, we compared different postprandial responses of GLP-1, glucagon, and ghrelin in subjects with relatively high (RHI) or relatively low (RLI) fasting insulin levels. The trial was a randomized crossover study with 4 different meal conditions. Fourteen nonobese or obese, healthy, men and 14 women were randomly assigned to the order of supervised intake of a 750 kcal drink with the same protein contents but with 20 energy-percent (E%) or 55 E% from carbohydrates, and the remaining energy from fat. Participants were also randomized to consume the drinks as 1 large beverage or as five 150-kcal portions every 30 minutes. The 28 subjects were divided into 2 equally sized groups based on fasting insulin levels. Statistics were done with general linear mixed model. Fasting insulin levels were 3-fold higher in the group with RHI compared with the RLI group (RHI: 1004 +/- 510 pg/mL, RLI: 324 +/- 123 pg/mL, P amp;lt; .0005). Serum GLP-1 was highest in the RHI group after both single meals and after 5 drinks and following high- and low-carbohydrate meals (both P amp;lt;= .002), and this was the case also for glucagon levels (both P amp;lt;= .018), whereas ghrelin levels did not differ between groups. Thus, subjects with RHI displayed both higher postprandial serum GLP-1 and glucagon than the participants with RLI, suggesting that glucagon could play a role in the advent of dysglycemia by insulin resistance. (C) 2019 Elsevier Inc. All rights reserved.
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| 9. |
- Barmano, Neshro, 1980-, et al.
(författare)
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The association between alcohol consumption, cardiac biomarkers, left atrial size and re-ablation in patients with atrial fibrillation referred for catheter ablation
- 2019
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Ingår i: PLOS ONE. - San Francisco, CA, United States : Public Library of Science. - 1932-6203. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundInformation on alcohol consumption in patients undergoing radiofrequency ablation (RFA) of atrial fibrillation (AF) is often limited by the reliance on self-reports. The aim of this study was to describe the long-term alcohol consumption, measured as ethyl glucuronide in hair (hEtG), in patients undergoing RFA due to AF, and to examine potential associations with cardiac biomarkers, left atrial size and re-ablation within one year after the initial RFA.MethodsThe amount of hEtG was measured in patients referred for RFA, and a cut-off of 7 pg/mg was used. N-terminal pro B-type natriuretic peptide (NT-proBNP) and the mid-regional fragment of pro atrial natriuretic peptide (MR-proANP) were examined and maximum left atrium volume index (LAVI) was measured. The number of re-ablations was examined up to one year after the initial RFA. Analyses were stratified by gender, and adjusted for age, systolic blood pressure, body mass index, presence of heart failure and heart rhythm for analyses regarding NT-proBNP, MR-proANP and LAVI and heart rhythm being replaced by type of AF for analyses regarding re-ablation.ResultsIn total, 192 patients were included in the study. Median (25th– 75th percentile) NT-proBNP in men with hEtG ≥ 7 vs. < 7 pg/mg was 250 (96–695) vs. 130 (49–346) pg/ml (p = 0.010), and in women it was 230 (125–480) vs. 230 (125–910) pg/ml (p = 0.810). Median MR-proANP in men with hEtG ≥ 7 vs. < 7 pg/mg was 142 (100–224) vs. 117 (83–179) pmol/l (p = 0.120) and in women it was 139 (112–206) vs. 153 (93–249) pmol/l (p = 0.965). The median of maximum LAVI was 30.1 (26.7–33.9) vs. 25.8 (21.4–32.0) ml/m2 (p = 0.017) in men, and 25.0 (18.9–29.6) vs. 25.7 (21.7–34.6) ml/m2 (p = 0.438) in women, with hEtG ≥ 7 vs. < 7 pg/ml, respectively. Adjusted analyses showed similar results, except for MR-proANP turning out significant in men with hEtG ≥ 7 vs. < 7 pg/mg (p = 0.047). The odds ratio of having a re-ablation was 3.5 (95% CI 1.3–9.6, p = 0.017) in men with hEtG ≥ 7 vs. < 7 pg/mg, while there was no significant difference in women.ConclusionsIn male patients with AF and hEtG ≥ 7 pg/mg, NT-proBNP and MR-proANP were higher, LA volumes larger, and there was a higher rate of re-ablations, as compared to men with hEtG < 7 pg/mg. This implies that men with an alcohol consumption corresponding to an hEtG-value ≥ 7, have a higher risk for LA remodelling that could potentially lead to a deterioration of the AF situation.
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| 10. |
- Bergström, Göran, 1964, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 11. |
- Blomstrand, Peter, et al.
(författare)
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Left ventricular diastolic function, assessed by echocardiography and tissue Doppler imaging, is a strong predictor of cardiovascular events, superior to global left ventricular longitudinal strain, in patients with type 2 diabetes
- 2015
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16:9, s. 1000-1007
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of the study was to determine whether left ventricular systolic function, in terms of global left ventricular longitudinal strain (GLS), and diastolic function, expressed as the ratio between early diastolic transmitral flow and mitral annular motion velocities (E/e'), can predict cardiovascular events in patients with diabetes mellitus type 2.Methods and results: We prospectively investigated 406 consecutive patients, aged 55-65 years, with diabetes mellitus, who participated in the CARDIPP study. Echocardiography, pulse pressure (pp), and glycosylated haemoglobin (HbA1c) were analysed. Twelve cases of myocardial infarction and seven cases of stroke were identified during the follow-up period of 67 +/- 17 months. Univariate Cox regression analysis showed that E/e' was a strong predictor of cardiovascular events (hazards ratio 1.12; 95% confidence interval 1.06-1.18, P < 0.001). E/e' was prospectively associated with cardiovascular events independent of age, sex, GLS, left ventricular ejection fraction (LVEF), pp, and HbA1c in multivariate analysis. Receiver operating characteristic curves showed that E/e' and HbA1c were the strongest predictors for cardiovascular events, both having an area under the curve (AUC) of 0.71 followed by LVEF with an AUC of 0.65 and GLS of 0.61. In a Kaplan-Meyer analysis, the cumulative probability of an event during the follow-up period was 8.6% for patients with an E/e' ratio >15 compared with 2.6% for patients with E/e' <= 15, P = 0.011.Conclusion: In middle-aged patients with type 2 diabetes, E/e' is a strong predictor of myocardial infarction and stroke, comparable with HbA1c and superior to GLS and LVEF.
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| 12. |
- Blomstrand, Peter, et al.
(författare)
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Overweight and obesity impair left ventricular systolic function as measured by left ventricular ejection fraction and global longitudinal strain
- 2018
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Ingår i: Cardiovascular Diabetology. - : BioMed Central. - 1475-2840. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- AimsObesity is associated with type 2 diabetes mellitus, left ventricular diastolic dysfunction and heart failure but it is unclear to which extent it is related to left ventricular systolic dysfunction. The aim of the study was to explore the effects of overweight and obesity on left ventricular systolic function in patients with type 2 diabetes mellitus and a control group of non-diabetic persons.MethodsWe prospectively investigated 384 patients with type 2 diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL studies. The participants were grouped according to body mass index (normal weight < 25 kg/m2, overweight 25–29 kg/m2, and obesity ≥ 30 kg/m2). Echocardiography was performed at the beginning of the study and after 4-years in the patient group.ResultsUnivariable and multivariable regression analysis revealed that variations in left ventricular ejection fraction, global longitudinal strain, left ventricular mass and diastolic function expressed as E/é (the ratio between early diastolic mitral flow and annular motion velocities) all are related to body mass index. The mean and standard deviation of left ventricular ejection fraction and global longitudinal strain values were 57% (8%) vs. − 18.6% (2.3%) for normal weight patients, 53% (8%) vs. − 17.5% (2.3%) for overweight, and 49% (9%) vs. − 16.2% (3.0%) for obese (p < 0.05 vs. p < 0.05). Corresponding results in the control group were 58% (6%) vs. − 22.3% (3.0%), 55% (7%) vs. − 20.8% (3.1%) and 54% (8%) − 19.6% (4.0%) (p < 0.05 vs. p < 0.05). Patients who gained weight from baseline to follow-up changed left ventricular ejection fraction (median and interquartile range) by − 1.0 (9.0) % (n = 187) and patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0) % (n = 179) (p < 0.05).ConclusionOverweight and obesity impair left ventricular ejection fraction and global longitudinal strain in both patients with type 2 diabetes mellitus and non-diabetic persons.
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| 13. |
- Brynhildsen, Jan, et al.
(författare)
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Leptin and adiponectin in cord blood from children of normal weight, overweight and obese mothers
- 2013
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Ingår i: Acta Paediatrica. - : Wiley-Blackwell. - 0803-5253 .- 1651-2227. ; 102:6, s. 620-624
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Tidskriftsartikel (refereegranskat)abstract
- Aim To study cord blood concentrations of adiponectin and leptin in children born by normal weight, overweight and obese mothers and to study these parameters in relation to a weight gain intervention programme for obese mothers. Methods Ten millilitre cord blood was collected and analysed for leptin and adiponectin concentrations in children with gestational age andgt;37weeks born by 60 normal weight, 45 overweight and 145 obese mothers. 82 obese mothers took part in a weight gain intervention programme. Results Concentrations of leptin and adiponectin were higher in cord blood from children of overweight and obese mothers compared with children of normal weight mothers (leptin: Md 13.2, 30, 3 and 90.2ng/mL respectively, pandlt;0.001; adiponectin 35.9, 205.4, 213.8ng/L pandlt;0.001). No differences were found between overweight and obese mothers. The weight gain intervention programme for obese pregnant women had significant effects on the weight gain during pregnancy but had no effects on cord blood serum concentrations of leptin and adiponectin. Conclusion Cord blood leptin and adiponectin concentrations were higher in children born by overweight or obese women compared with children of normal weight mothers. A weight gain intervention programme for obese pregnant women did not affect these results. Intrauterine exposition to high concentrations of leptin and adiponectin may play a role in weight development later in life.
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| 14. |
- Carlsson, Axel C., et al.
(författare)
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Association of soluble tumor necrosis factor receptors 1 and 2 with nephropathy, cardiovascular events, and total mortality in type 2 diabetes
- 2016
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) contribute to experimental diabetic kidney disease, a condition with substantially increased cardiovascular risk when present in patients. Therefore, we aimed to explore the levels of sTNFRs, and their association with prevalent kidney disease, incident cardiovascular disease, and risk of mortality independently of baseline kidney function and microalbuminuria in a cohort of patients with type 2 diabetes. In pre-defined secondary analyses we also investigated whether the sTNFRs predict adverse outcome in the absence of diabetic kidney disease.METHODS: The CARDIPP study, a cohort study of 607 diabetes patients [mean age 61 years, 44 % women, 45 cardiovascular events (fatal/non-fatal myocardial infarction or stroke) and 44 deaths during follow-up (mean 7.6 years)] was used.RESULTS: Higher sTNFR1 and sTNFR2 were associated with higher odds of prevalent kidney disease [odd ratio (OR) per standard deviation (SD) increase 1.60, 95 % confidence interval (CI) 1.32-1.93, p < 0.001 and OR 1.54, 95 % CI 1.21-1.97, p = 0.001, respectively]. In Cox regression models adjusting for age, sex, glomerular filtration rate and urinary albumin/creatinine ratio, higher sTNFR1 and sTNFR2 predicted incident cardiovascular events [hazard ratio (HR) per SD increase, 1.66, 95 % CI 1.29-2.174, p < 0.001 and HR 1.47, 95 % CI 1.13-1.91, p = 0.004, respectively]. Results were similar in separate models with adjustments for inflammatory markers, HbA1c, or established cardiovascular risk factors, or when participants with diabetic kidney disease at baseline were excluded (p < 0.01 for all). Both sTNFRs were associated with mortality.CONCLUSIONS/INTERPRETATIONS: Higher circulating sTNFR1 and sTNFR2 are associated with diabetic kidney disease, and predicts incident cardiovascular disease and mortality independently of microalbuminuria and kidney function, even in those without kidney disease. Our findings support the clinical utility of sTNFRs as prognostic markers in type 2 diabetes.
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| 15. |
- Carlsson, Axel C., et al.
(författare)
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The association between endostatin and kidney disease and mortality in patients with type 2 diabetes
- 2016
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Ingår i: Diabetes & Metabolism. - : Elsevier BV. - 1262-3636 .- 1878-1780. ; 42:5, s. 351-357
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Tidskriftsartikel (refereegranskat)abstract
- Aim. - Circulating endostatin, a biologically active derivate of collagen XVIII, is considered to be a marker of kidney disease and a risk factor for its related mortality. However, less is known of the role of endostatin in diabetes and the development of diabetic nephropathy. For this reason, our study investigated the associations between circulating endostatin and the prevalence and progression of kidney disease, and its mortality risk in patients with type 2 diabetes (T2D). Methods. - This was a cohort study of 607 patients with T2D (mean age: 61 years, 44% women). Estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, was used to assess the patients' kidney function decline and mortality. Results. - Of the total study cohort, 20 patients declined by >= 20% in eGFR over 4 years, and 44 died during the follow-up (mean duration: 6.7 years). At baseline, participants with diabetic nephropathy (defined as eGFR < 60 mL/min/1.73 m(2)) and/or microalbuminuria [defined as a urinary albumin-to-creatinine ratio (ACR) > 3 g/mol] had higher median levels of endostatin than those without nephropathy (62.7 mu g/L vs 57.4 mu g/L, respectively; P = 0.031). In longitudinal analyses adjusted for age, gender, baseline eGFR and ACR, higher endostatin levels were associated with a higher risk of decline (>= 20% in eGFR, OR per 1 SD increase: 1.73, 95% CI: 1.13-2.65) and a higher risk of mortality (HR per 1 SD increase: 1.57, 95% CI: 1.19-2.07). Conclusion. - In patients with T2D, circulating endostatin levels can predict the progression of kidney disease and mortality independently of established kidney disease markers. The clinical usefulness of endostatin as a risk marker in such patients merits further studies.
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| 16. |
- Charitakis, Emmanouil, et al.
(författare)
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Symptom burden, Metabolic profile, Ultrasound findings, Rhythm, neurohormonal activation, haemodynamics and health-related quality of life in patients with atrial Fibrillation (SMURF) : a protocol for an observational study with a randomised interventional component
- 2015
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Ingår i: BMJ Open. - : BMJ Publishing Group. - 2044-6055. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with an estimated prevalence of 1.5-2%. It is an independent risk factor for ischaemic stroke and is estimated to cause about 20-25% of all stroke cases. AF has a great impact on health-related quality of life (HRQoL); however, one unresolved issue related to AF is the wide variation in its symptoms.METHODS AND ANALYSIS: The symptom burden, metabolic profile, ultrasound findings, rhythm, neurohormonal activation, haemodynamics and HRQoL in patients with AF (Symptom burden, Metabolic profile, Ultrasound findings, Rhythm, neurohormonal activation, haemodynamics and health-related quality of life in patients with atrial Fibrillation, SMURF) study is a prospective observational, cohort study, with a randomised interventional part. The aim of the study is to investigate, in patients with AF, the relationship between symptom burden and metabolic aspects, atrial function and different neurohormones, and the effect of radiofrequency ablation (RFA). The interventional part of the study will give an insight into the neurohormonal and intracardiac pressure changes directly after initiation of AF. Consecutive patients with symptomatic AF accepted for treatment with RFA for the first time at Linköping University Hospital are eligible for participation. The enrolment started in January 2012, and a total of 200 patients are to be included into the study, with 45 of them being enrolled into the interventional study with initiation of AF. The sample size of the interventional study is based on a small pilot study with 5 patients induced to AF while 2 served as controls. The results indicated that, in order to find a statistically significant difference, there was a need to include 28 patients; for safety reasons, 45 patients will be included.ETHICS AND DISSEMINATION: The SMURF study is approved by the Regional Ethical Review Board at the Faculty of Health Sciences, Linköping, Sweden. The results will be presented through peer-review journals and conference presentation.TRIAL REGISTRATION NUMBER: NCT01553045; Pre-results.
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| 17. |
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| 18. |
- Dahlén, Elsa M, et al.
(författare)
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Sagittal abdominal diameter is a more independent measure compared with waist circumference to predict arterial stiffness in subjects with type 2 diabetes - a prospective observational cohort study
- 2013
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Ingår i: Cardiovascular Diabetology. - : BioMed Central. - 1475-2840. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAnthropometric measurements are useful in clinical practice since they are non-invasive and cheap. Previous studies suggest that sagittal abdominal diameter (SAD) may be a better measure of visceral fat depots. The aim of this study was to prospectively explore and compare how laboratory and anthropometric risk markers predicted subclinical organ damage in 255 patients, with type 2 diabetes, after four years.MethodsBaseline investigations were performed in 2006 and were repeated at follow-up in 2010. Carotid intima-media thickness (IMT) was evaluated by ultrasonography and aortic pulse wave velocity (PWV) was measured with applanation tonometry over the carotid and femoral arteries at baseline and at follow-up in a cohort of subjects with type 2 diabetes aged 55–65 years old.ResultsThere were significant correlations between apolipoprotein B (apoB) (r = 0.144, p = 0.03), C - reactive protein (CRP) (r = 0.172, p = 0.009) at baseline and IMT measured at follow-up. After adjustment for sex, age, treatment with statins and Hba1c, the associations remained statistically significant. HbA1c, total cholesterol or LDL-cholesterol did not correlate to IMT at follow-up. Baseline body mass index (BMI) (r = 0.130, p = 0.049), waist circumference (WC) (r = 0.147, p = 0.027) and sagittal Abdominal Diameter (SAD) (r = 0.184, p = 0.007) correlated to PWV at follow-up. Challenged with sex, SBP and HbA1c, the association between SAD, not WC nor BMI, and PWV remained statistically significant (p = 0.036). In a stepwise linear regression, entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV.ConclusionsWe conclude that apoB and CRP, but not LDL-cholesterol predicted subclinical atherosclerosis. Furthermore, SAD was more independent in predicting arterial stiffness over time, compared with WC, in middle-aged men and women with type 2 diabetes.
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| 19. |
- Dahlqvist Leinhard, Olof, et al.
(författare)
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Quantification of abdominal fat accumulation during hyperalimentation using MRI
- 2009
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Ingår i: Proceedings of the ISMRM Annual Meeting (ISMRM'09), 2009. - Berkeley, CA, USA : International Society for Magnetic Resonance in Medicine. ; , s. 206-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- There is an increasing demand for imaging methods that can be used for automatic, accurate and quantitative determination of the amounts of abdominal fat. Such methods are important as they will allow the evaluation of some of the risk factors underlying the ’metabolic syndrome’. The metabolic syndrome is becoming common in large parts of the world, and it appears that a dominant risk factor for developing this syndrome is abdominal obesity. Subjects that are afflicted with the metabolic syndrome are exposed to a high risk for developing a large range of diseases such as type 2 diabetes, cardiac failure, and stroke. The aim of this work
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| 20. |
- Danielsson, Anna, et al.
(författare)
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Attenuation of insulin-stimulated insulin receptor substrate-1 serine 307 phosphorylation in insulin resistance of type 2 diabetes
- 2005
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Ingår i: Journal of biological chemistry. - 0021-9258 .- 1083-351X. ; 280:41, s. 34389-3492
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance is a primary characteristic of type 2 diabetes and likely causally related to the pathogenesis of the disease. It is a result of defects in signal transduction from the cell surface receptor of insulin to target effects. We found that insulin-stimulated phosphorylation of serine 307 (corresponding to serine 302 in the murine sequence) in the immediate downstream mediator protein of the insulin receptor, insulin receptor substrate-1 (IRS1), is required for efficient insulin signaling and that this phosphorylation is attenuated in adipocytes from patients with type 2 diabetes. Inhibition of serine 307 phosphorylation by rapamycin mimicked type 2 diabetes and reduced the sensitivity of IRS1 tyrosine phosphorylation in response to insulin, while stimulation of the phosphorylation by okadaic acid, in cells from patients with type 2 diabetes, rescued cells from insulin resistance. EC50 for insulin-stimulated phosphorylation of serine 307 was about 0.2 nM with a t1/2 of about 2 min. The amount of IRS1 was similar in cells from non-diabetic and diabetic subjects. These findings identify a molecular mechanism for insulin resistance in non-selected patients with type 2 diabetes.
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| 21. |
- Danielsson, Anna, et al.
(författare)
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Insulin resistance in human adipocytes occurs downstream of IRS1 after surgical cell isolation but at the level of phosphorylation of IRS1 in type 2 diabetes
- 2005
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 272:1, s. 141-151
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance is a cardinal feature of type 2 diabetes and also a consequence of trauma such as surgery. Directly after surgery and cell isolation, adipocytes were insulin resistant, but this was reversed after overnight incubation in 10% CO2 at 37 °C. Tyrosine phosphorylation of the insulin receptor and insulin receptor substrate (IRS)1 was insulin sensitive, but protein kinase B (PKB) and downstream metabolic effects exhibited insulin resistance that was reversed by overnight incubation. MAP-kinases ERK1/2 and p38 were strongly phosphorylated after surgery, but was dephosphorylated during reversal of insulin resistance. Phosphorylation of MAP-kinase was not caused by collagenase treatment during cell isolation and was present also in tissue pieces that were not subjected to cell isolation procedures. The insulin resistance directly after surgery and cell isolation was different from insulin resistance of type 2 diabetes; adipocytes from patients with type 2 diabetes remained insulin resistant after overnight incubation. IRS1, PKB, and downstream metabolic effects, but not insulin-stimulated tyrosine phosphorylation of insulin receptor, exhibited insulin resistance. These findings suggest a new approach in the study of surgery-induced insulin resistance and indicate that human adipocytes should recover after surgical procedures for analysis of insulin signalling. Moreover, we pinpoint the signalling dysregulation in type 2 diabetes to be the insulin-stimulated phosphorylation of IRS1 in human adipocytes.
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| 22. |
- Danielsson, Anna, et al.
(författare)
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Phosphorylation of IRS1 at serine 307 and serine 312 in response to insulin in human adipocytes
- 2006
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 0006-291X. ; 342:4, s. 1183-1187
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Tidskriftsartikel (refereegranskat)abstract
- Feedback control in insulin signaling involves serine phosphorylation of insulin receptor substrate-1 (IRS1). By analyzing the insulin-induced phosphorylation of IRS1 at serine 307, serine 312, and tyrosine in the same primary human adipocytes, we now report that negative feedback phosphorylation of serine 312 (corresponding to murine serine 307) required relatively high concentrations of insulin (EC50 = 3 nM) for a long time (t1/2 ca. 30 min) and reduced the steady-state tyrosine phosphorylation, without affecting the cellular concentration, of IRS1. In contrast, positive feedback phosphorylation of serine 307 was a rapid (t1/2 ca. 2 min) event at physiological concentrations of insulin (EC50 = 0.2 nM).
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| 23. |
- Danielsson, Anna, et al.
(författare)
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Short-Term Overeating Induces Insulin Resistance in Fat Cells in Lean Human Subjects
- 2009
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Ingår i: Molecular Medicine. - : Springer Science and Business Media LLC. - 1076-1551 .- 1528-3658. ; 15:7-8, s. 228-234
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance and type 2 diabetes (T2D) are closely linked to obesity. Numerous prospective studies have reported on weight gain, insulin resistance, and insulin signaling in experimental animals, but not in humans. We examined insulin signaling in adipocytes from lean volunteers, before and at the end of a 4-wk period of consuming a fast-food, high-calorie diet that led to weight gain. We also examined adipocytes from patients with T2D. During the high-calorie diet, subjects gained 10% body weight and 19% total body fat, but stayed lean (body mass index = 24.3 kg/m2) and developed moderate systemic insulin resistance. Similarly to the situation in T2D subjects, in subjects on the high-calorie diet, the amount of insulin receptors was reduced and phosphorylation of IRS1 at tyrosine and at serine-307 (human sequence, corresponding to murine serine-302) were impaired. The amount of insulin receptor substrate protein-1 (IRS1) and the phosphorylation of IRS1 at serine-312 (human sequence, corresponding to murine serine-307) were unaffected by the diet. Unlike the T2D subjects, in subjects on the high-calorie diet, likely owing to the ongoing weight-gain, phosphorylation of MAP-kinases ERK1/2 became hyperresponsive to insulin. To our knowledge this study is the first to investigate insulin signaling during overeating in humans, and it demonstrates that T2D effects on intracellular insulin signaling already occur after 4 wks of a high-calorie diet and that the effects in humans differ from those in laboratory animals.
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| 24. |
- Davidson, Lee Ti, et al.
(författare)
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Association of physiological stress markers at the emergency department to readmission and death within 90 days: a prospective observational study
- 2023
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 128:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Predicting the risk of readmission or death in patients at the emergency department (ED) is essential in identifying patients who would benefit the most from interventions. We aimed to explore the prognostic value of mid-regional proadrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin, and high-sensitivity troponin T (hs-TnT) to identify patients with a higher risk of readmission and death among patients presenting with chest pain (CP) and/or shortness of breath (SOB) in the ED.Methods: This single-center prospective observational study included non-critically ill adult patients with a chief complaint of CP and/or SOB who visited the ED at Linköping University Hospital. Baseline data and blood samples were collected, and patients were followed up for 90 days after inclusion. The primary outcome was a composite of readmission and/or death from non-traumatic causes within 90 days of inclusion. Binary logistic regression was used and receiver operating characteristics (ROC) curves were constructed to determine the prognostic performance for predicting readmission and/or death within 90 days.Results: A total of 313 patients were included and 64 (20.4%) met the primary endpoint. MR-proADM > 0.75 pmol/L (odds ratio [OR]: 2.361 [95% confidence interval [CI]: 1.031 – 5.407], P = 0.042) and multimorbidity (OR: 2.647 [95% CI: 1.282 – 5.469], P = 0.009) were significantly associated with readmission and/or death within 90 days. MR-proADM increased predictive value in the ROC analysis to age, sex, and multimorbidity (P = 0.006).Conclusions: In non-critically ill patients with CP and/or SOB in the ED, MR-proADM and multimorbidity may be helpful for the prediction of the risk of readmission and/or death within 90 days.
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| 25. |
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