| 1. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 2. |
- Hageman, S., et al.
(författare)
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SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 42:25, s. 2439-2454
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Tidskriftsartikel (refereegranskat)abstract
- Aims The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40-69 years in Europe. Methods and results We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65-0.68) to 0.81 (0.76-0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low- risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries. Conclusion SCORE2-a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations-enhances the identification of individuals at higher risk of developing CVD across Europe.
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| 3. |
- Axelsson, Annika, et al.
(författare)
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Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion, but the mechanisms underlying insulin secretion failure are not completely understood. Here, we show that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with T2D. These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. We identify Sox5 as a regulator of the module. Sox5 knockdown induces gene expression changes similar to those observed in T2D and diabetic animals and has profound effects on insulin secretion, including reduced depolarization-evoked Ca 2+-influx and β-cell exocytosis. SOX5 overexpression reverses the expression perturbations observed in a mouse model of T2D, increases the expression of key β-cell genes and improves glucose-stimulated insulin secretion in human islets from donors with T2D. We suggest that human islets in T2D display changes reminiscent of dedifferentiation and highlight SOX5 as a regulator of β-cell phenotype and function.
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| 4. |
- Jain, Ruchi, et al.
(författare)
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Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual beta-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D.
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| 5. |
- Muskiet, M H A, et al.
(författare)
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Exenatide twice-daily does not affect renal function or albuminuria compared to titrated insulin glargine in patients with type 2 diabetes mellitus: A post-hoc analysis of a 52-week randomised trial.
- 2019
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Ingår i: Diabetes research and clinical practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 153, s. 14-22
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Tidskriftsartikel (refereegranskat)abstract
- To compare the effects of long-term treatment with the GLP-1RA exenatide twice-daily versus titrated insulin glargine (iGlar) on renal function and albuminuria in type 2 diabetes (T2DM) patients.We post-hoc evaluated renal outcome-data of 54 overweight T2DM patients (mean ±SD age 60±8years, HbA1c 7.5±0.9%, eGFR 86±16mL/min/1.73m2, median [IQR] urinary albumin-to-creatinine-ratio (UACR) 0.75 [0.44-1.29]mg/mmol) randomised to exenatide 10µg twice-daily or titrated iGlar on-top-of metformin for 52-weeks. Renal efficacy endpoints were change in creatinine clearance (CrCl) and albuminuria (urinary albumin-excretion [UAE] and UACR) based on 24-h urines, collected at baseline and Week-52. eGFR and exploratory endpoints were collected throughout the intervention-period, and after a 4-week wash-out.HbA1c-reductions were similar with exenatide (mean±SEM -0.80±0.10%) and iGlar (-0.79±0.14%; treatment-difference 0.02%; 95% CI -0.31 to 0.42%). Change from baseline to Week-52 in CrCl, UAE or UACR did not statistically differ; only iGlar reduced albuminuria (P<0.05; within-group). eGFR decreased from baseline to Week-4 with exenatide (-3.9±2.1mL/min/1.73m2; P=0.069) and iGlar (-2.7±1.2mL/min/1.73m2; P=0.034), without treatment-differences in ensuing trajectory. Exenatide versus iGlar reduced bodyweight (-5.4kg; 2.9-7.9; P<0.001), but did not affect blood pressure, lipids or plasma uric acid.Among T2DM patients without overt nephropathy, one-year treatment with exenatide twice-daily does not affect renal function-decline or onset/progression of albuminuria compared to titrated iGlar.ClinicalTrials.gov ID: NCT00097500.
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| 6. |
- Ostergaard, H. B., et al.
(författare)
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Development and Validation of a Lifetime Risk Model for Kidney Failure and Treatment Benefit in Type 2 Diabetes 10-Year and Lifetime Risk Prediction Models
- 2022
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Ingår i: Clinical Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1555-9041 .- 1555-905X. ; 17:12, s. 1783-1791
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives: Individuals with type 2 diabetes are at a higher risk of developing kidney failure. The objective of this study was to develop and validate a decision support tool for estimating 10-year and lifetime risks of kidney failure in individuals with type 2 diabetes as well as estimating individual treatment effects of preventive medication. Design, setting, participants, & measurements: The prediction algorithm was developed in 707,077 individuals with prevalent and incident type 2 diabetes from the Swedish National Diabetes Register for 2002-2019. Two Cox proportional regression functions for kidney failure (first occurrence of kidney transplantation, long-term dialysis, or persistent eGFR < 15 ml/min per 1.73 m(2)) and all-cause mortality as respective end points were developed using routinely available predictors. These functions were combined into life tables to calculate the predicted survival without kidney failure while using all-cause mortality as the competing outcome. The model was externally validated in 256,265 individuals with incident type 2 diabetes from the Scottish Care Information Diabetes database between 2004 and 2019. Results: During a median follow-up of 6.8 years (interquartile range, 3.2-10.6), 8004 (1%) individuals with type 2 diabetes in the Swedish National Diabetes Register cohort developed kidney failure, and 202,078 (29%) died. The model performed well, with c statistics for kidney failure of 0.89 (95% confidence interval, 0.88 to 0.90) for internal validation and 0.74 (95% confidence interval, 0.73 to 0.76) for external validation. Calibration plots showed good agreement in observed versus predicted 10-year risk of kidney failure for both internal and external validation. Conclusions: This study derived and externally validated a prediction tool for estimating 10-year and lifetime risks of kidney failure as well as life years free of kidney failure gained with preventive treatment in individuals with type 2 diabetes using easily available clinical predictors.
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| 7. |
- Ostergaard, H. B., et al.
(författare)
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Estimating individual lifetime risk of incident cardiovascular events in adults with Type 2 diabetes: an update and geographical calibration of the DIAbetes Lifetime perspective model (DIAL2)
- 2023
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 30:1, s. 61-69
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Tidskriftsartikel (refereegranskat)abstract
- Aims The 2021 European Society of Cardiology cardiovascular disease (CVD) prevention guidelines recommend the use of (lifetime) risk prediction models to aid decisions regarding intensified preventive treatment options in adults with Type 2 diabetes, e.g. the DIAbetes Lifetime perspective model (DIAL model). The aim of this study was to update the DIAL model using contemporary and representative registry data (DIAL2) and to systematically calibrate the model for use in other European countries. Methods and results The DIAL2 model was derived in 467 856 people with Type 2 diabetes without a history of CVD from the Swedish National Diabetes Register, with a median follow-up of 7.3 years (interquartile range: 4.0-10.6 years) and comprising 63 824 CVD (including fatal CVD, non-fatal stroke and non-fatal myocardial infarction) events and 66 048 non-CVD mortality events. The model was systematically recalibrated to Europe's low- and moderate-risk regions using contemporary incidence data and mean risk factor distributions. The recalibrated DIAL2 model was externally validated in 218 267 individuals with Type 2 diabetes from the Scottish Care Information-Diabetes (SCID) and Clinical Practice Research Datalink (CPRD). In these individuals, 43 074 CVD events and 27 115 non-CVD fatal events were observed. The DIAL2 model discriminated well, with C-indices of 0.732 [95% confidence interval (CI) 0.726-0.739] in CPRD and 0.700 (95% CI 0.691-0.709) in SCID. Conclusion The recalibrated DIAL2 model provides a useful tool for the prediction of CVD-free life expectancy and lifetime CVD risk for people with Type 2 diabetes without previous CVD in the European low- and moderate-risk regions. These long-term individualized measures of CVD risk are well suited for shared decision-making in clinical practice as recommended by the 2021 CVD ESC prevention guidelines.
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| 8. |
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| 9. |
- Andersson, H., et al.
(författare)
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Transcriptional profiling of the peripheral blood response during tularemia
- 2006
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 7:6, s. 503-513
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Tidskriftsartikel (refereegranskat)abstract
- Tularemia is a febrile disease caused by the highly contagious bacterium Francisella tularensis. We undertook an analysis of the transcriptional response in peripheral blood during the course of ulceroglandular tularemia by use of Affymetrix microarrays comprising 14,500 genes. Samples were obtained from seven individuals at five occasions during 2 weeks after the first hospital visit and convalescent samples 3 months later. In total, 265 genes were differentially expressed, 95 of which at more than one time point. The differential expression was verified with real-time quantitative polymerase chain reaction for 36 genes (R(2)=0.590). The most prominent changes were noted in samples drawn on days 2-3 and a considerable proportion of the upregulated genes appeared to represent an interferon-gamma-induced response and also a proapoptotic response. Genes involved in the generation of innate and acquired immune responses were found to be downregulated, presumably a pathogen-induced event. A logistic regression analysis revealed that seven genes were good predictors of the early phase of tularemia. This is the first description of the transcriptional host response to ulceroglandular tularemia and the study has identified gene subsets relevant to the pathogenesis of the disease and subsets that may serve as early diagnostic biomarkers.
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| 10. |
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| 11. |
- Berkelmans, G. F. N., et al.
(författare)
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Population median imputation was noninferior to complex approaches for imputing missing values in cardiovascular prediction models in clinical practice
- 2022
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier BV. - 0895-4356. ; 145, s. 70-80
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare the validity and robustness of five methods for handling missing characteristics when using cardiovascular disease risk prediction models for individual patients in a real-world clinical setting.& nbsp;Study design and setting: The performance of the missing data methods was assessed using data from the Swedish National Diabetes Registry (n = 419,533) with external validation using the Scottish Care Information ? diabetes database (n = 226,953). Five methods for handling missing data were compared. Two methods using submodels for each combination of available data, two imputation methods: conditional imputation and median imputation, and one alternative modeling method, called the naive approach, based on hazard ratios and populations statistics of known risk factors only. The validity was compared using calibration plots and c-statistics.& nbsp;Results: C-statistics were similar across methods in both development and validation data sets, that is, 0.82 (95% CI 0.82-0.83) in the Swedish National Diabetes Registry and 0.74 (95% CI 0.74-0.75) in Scottish Care Information-diabetes database. Differences were only observed after random introduction of missing data in the most important predictor variable (i.e., age).& nbsp;Conclusion: Validity and robustness of median imputation was not dissimilar to more complex methods for handling missing values, provided that the most important predictor variables, such as age, are not missing. (C)& nbsp;2022 Elsevier Inc. All rights reserved.
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| 12. |
- Boehm, M. H., et al.
(författare)
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Observations of an upward-directed electron beam with the perpendicular temperature of the cold ionosphere
- 1995
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 22, s. 2103-2106
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Tidskriftsartikel (refereegranskat)abstract
- The Freja TESP electron spectrometer has repeatedly observed similar to 100 eV - 1 keV upward-directed, anti-field-aligned electron beams near 1700 km altitude in the auroral zone. A particularly intense event, at energies up to 2 keV, is described. The beam perpendicular temperature T perpendicular to(e)), was as low as 0.1-0.2 eV at 100-200 eV parallel energy. The 10-15 s period of upward fluxes was coincident with a low density (similar to 10 cm(-3)) period and a similar to 5 keV ion conic. Strong low frequency waves and the lack of any downward motion in the simultaneously observed ion conic suggest a strong element of wave acceleration, while electric field and ion loss cone measurements provide limited evidence of potential acceleration to a fraction of the observed energies.
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| 13. |
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| 14. |
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| 15. |
- Efe, C., et al.
(författare)
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Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis
- 2019
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 114:7, s. 1101-1108
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%). DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.
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| 16. |
- Eliasson, Björn, 1959, et al.
(författare)
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Hyperinsulinaemia impairs gastrointestinal motility and slows carbohydrate absorption
- 1995
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Ingår i: Diabetologia. - 0012-186X. ; 38:1, s. 79-85
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Tidskriftsartikel (refereegranskat)abstract
- Experimental euglycaemic hyperinsulinaemia (insulin levels 46 +/- 4 mU/l) impaired the post-absorptive gastrointestinal motility in healthy individuals; the effect being particularly pronounced in the upper gastrointestinal tract (stomach and proximal duodenum). The postprandial gastric emptying, measured with a standardized 99mTc labelled meal, was also significantly delayed (t50 increased by 38% or 32 min). This was combined with a slower carbohydrate absorption (delay in peak blood glucose level about 40 min). Furthermore, during experimental hyperinsulinaemia higher blood glucose levels were seen at 120 min than at 60 min after food ingestion. This was not seen in any subject in the control study where only 0.9% NaCl was infused. Blood levels of the motility-stimulating hormone, motilin, were significantly lower during experimental hyperinsulinaemia. Thus, experimental hyperinsulinaemia impairs the gastrointestinal motility in both the postabsorptive and postprandial states. This effect is combined with a delayed carbohydrate absorption. Hyperinsulinaemia per se may thus lead to alterations in carbohydrate absorption and can also contribute to the gastrointestinal disturbances in diabetes.
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| 17. |
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| 18. |
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| 19. |
- Eliasson, H., et al.
(författare)
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Modeling of high power impulse magnetron sputtering discharges with graphite target
- 2021
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Ingår i: Plasma sources science & technology. - : IOP Publishing Ltd. - 0963-0252 .- 1361-6595. ; 30:11
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Tidskriftsartikel (refereegranskat)abstract
- The ionization region model (IRM) is applied to model a high power impulse magnetron sputtering discharge in argon with a graphite target. Using the IRM, the temporal variation of the various species and the average electron energy, as well as internal parameters such as the ionization probability, back-attraction probability, and the ionized flux fraction of the sputtered species, is determined. It is found that thedischarge develops into working gas recycling and most of the discharge current at the cathode target surface is composed of Ar+ ions, which constitute over 90% of the discharge current, while the contribution of the C+ ions is always small (<5%), even for peak current densities close to 3 A cm(-2). For the target species, the time-averaged ionization probability is low, or 13-27%, the ion back-attraction probability during the pulse is high (>92%), and the ionized flux fraction is about 2%. It is concluded that in the operation range studied here it is a challenge to ionize carbon atoms, that are sputtered off of a graphite target in a magnetron sputtering discharge, when depositing amorphous carbon films.
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| 20. |
- Erlandson, R. E., et al.
(författare)
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Freja observations of electromagnetic ion cyclotron ELF waves and transverse oxygen ion acceleration on auroral field lines
- 1994
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Ingår i: Geophysical Research Letters. - 0094-8276. ; 21:17, s. 1855-1858
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Tidskriftsartikel (refereegranskat)abstract
- Extremely low-frequency (ELF) magnetic and electric field plasma wave emissions were recorded on 2 October 1993 on auroral field lines by the Magnetic Field Experiment during Freja orbit 4770. The ELF wave frequencies were below the local oxygen gyrofrequency (25 Hz) and between the helium and proton gyrofrequencies (100 to 400 Hz). The ELF waves, interpreted as electromagnetic ion cyclotron (EMIC) waves, were observed in a region of inverted-v-type electron precipitation. The EMIC waves were correlated over time with auroral and lower energy (≈ 100 eV) electrons, which are both possible sources of free energy, and also with transversely accelerated oxygen ions. The waves above the helium gyrofrequency were more closely correlated with the transverse oxygen ion acceleration than the waves below the oxygen gyrofrequency. These observations are consistent with a scenario in which electron beams generate EMIC waves, which then produce transverse oxygen ion acceleration through a gyroresonant interaction.
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| 21. |
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| 22. |
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| 23. |
- Lee, S. D., et al.
(författare)
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IDOL regulates systemic energy balance through control of neuronal VLDLR expression
- 2019
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Ingår i: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 1:11
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Tidskriftsartikel (refereegranskat)abstract
- Liver X receptors limit cellular lipid uptake by stimulating the transcription of inducible degrader of the low-density lipoprotein receptor (IDOL), an E3 ubiquitin ligase that targets lipoprotein receptors for degradation. The function of IDOL in systemic metabolism is incompletely understood. Here we show that loss of IDOL in mice protects against the development of dietinduced obesity and metabolic dysfunction by altering food intake and thermogenesis. Unexpectedly, analysis of tissue-specific knockout mice revealed that IDOL affects energy balance, not through its actions in peripheral metabolic tissues (liver, adipose tissue, endothelium, intestine, and skeletal muscle) but by controlling lipoprotein receptor abundance in neurons. Single-cell RNA sequencing of the hypothalamus demonstrated that IDOL deletion altered gene expression linked to the control of metabolism. Finally, we identified very low-density lipoprotein receptor (VLDLR) rather than low-density lipoprotein receptor (LDLR) as the primary mediator of the effects of IDOL on energy balance. These data identify a role for the neuronal IDOL-VLDLR pathway in metabolic homoeostasis and diet-induced obesity.
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| 24. |
- Matikainen, N., et al.
(författare)
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Fructose intervention for 12 weeks does not impair glycemic control or incretin hormone responses during oral glucose or mixed meal tests in obese men
- 2017
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Ingår i: Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753. ; 27:6, s. 534-542
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are affected early on in the pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies consistently link high fructose consumption to insulin resistance but whether fructose consumption impairs the incretin response remains unknown. Methods and results: As many as 66 obese (BMI 26-40 kg/m(2)) male subjects consumed fructose-sweetened beverages containing 75 g fructose/day for 12 weeks while continuing their usual lifestyle. Glucose, insulin, GLP-1 and GIP were measured during oral glucose tolerance test (OGTT) and triglycerides (TG), GLP-1, GIP and PYY during a mixed meal test before and after fructose intervention. Fructose intervention did not worsen glucose and insulin responses during OGTT, and GLP-1 and GIP responses during OGTT and fat-rich meal were unchanged. Postprandial TG response increased significantly, p = 0.004, and we observed small but significant increases in weight and liver fat content, but not in visceral or subcutaneous fat depots. However, even the subgroups who gained weight or liver fat during fructose intervention did not worsen their glucose, insulin, GLP-1 or PYY responses. A minor increase in GIP response during OGTT occurred in subjects who gained liver fat (p = 0.049). Conclusion: In obese males with features of metabolic syndrome, 12 weeks fructose intervention 75 g/day did not change glucose, insulin, GLP-1 or GIP responses during OGTT or GLP-1, GIP or PYY responses during a mixed meal. Therefore, fructose intake, even accompanied with mild weight gain, increases in liver fat and worsening of postprandial TG profile, does not impair glucose tolerance or gut incretin response to oral glucose or mixed meal challenge. (C) 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
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| 25. |
- Matikainen, N., et al.
(författare)
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Minor contribution of endogenous GLP-1 and GLP-2 to postprandial lipemia in obese men
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Context. Glucose and lipids stimulate the gut-hormones glucagon-like peptide (GLP)-1, GLP-2 and glucose-dependent insulinotropic polypeptide (GIP) but the effect of these on human postprandial lipid metabolism is not fully clarified. Objective. To explore the responses of GLP-1, GLP-2 and GIP after a fat-rich meal compared to the same responses after an oral glucose tolerance test (OGTT) and to investigate possible relationships between incretin response and triglyceride-rich lipoprotein (TRL) response to a fat-rich meal. Design. Glucose, insulin, GLP-1, GLP-2 and GIP were measured after an OGTT and after a fat-rich meal in 65 healthy obese (BMI 26.5-40.2 kg/m2) male subjects. Triglycerides (TG), apoB48 and apoB100 in TG-rich lipoproteins (chylomicrons, VLDL1 and VLDL2) were measured after the fat-rich meal. Main Outcome Measures. Postprandial responses (area under the curve, AUC) for glucose, insulin, GLP-1, GLP-2, GIP in plasma, and TG, apoB48 and apoB100 in plasma and TG-rich lipoproteins. Results. The GLP-1, GLP-2 and GIP responses after the fat-rich meal and after the OGTT correlated strongly (r = 0.73, p<0.0001; r = 0.46, p<0.001 and r = 0.69, p<0.001, respectively). Glucose and insulin AUCs were lower, but the AUCs for GLP-1, GLP-2 and GIP were significantly higher after the fat-rich meal than after the OGTT. The peak value for all hormones appeared at 120 minutes after the fat-rich meal, compared to 30 minutes after the OGTT. After the fat-rich meal, the AUCs for GLP-1, GLP-2 and GIP correlated significantly with plasma TG- and apoB48 AUCs but the contribution was very modest. Conclusions. In obese males, GLP-1, GLP-2 and GIP responses to a fat-rich meal are greater than following an OGTT. However, the most important explanatory variable for postprandial TG excursion was fasting triglycerides. The contribution of endogenous GLP-1, GLP-2 and GIP to explaining the variance in postprandial TG excursion was minor. Copyright © 2016 Matikainen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 26. |
- Norqvist, P, et al.
(författare)
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Ion cyclotron heating in the dayside magnetosphere
- 1996
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 101:A6, s. 13179-13193
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Tidskriftsartikel (refereegranskat)abstract
- Observations of waves and particles obtained by the Freja satellite at altitudes around 1700 km in the dayside high-latitude magnetosphere are used to study ion energization. We find that ions, including O+, during several events of intense ion energization can be heated perpendicularly to the geomagnetic field to mean energies df up to about 20 eV via the process of cyclotron resonance by broadband waves around the ion gyrofrequencies. There is a good correlation between such broadband waves and the ion energization. The waves show no spectral features at the O+ gyrofrequency. The observed wave amplitudes are used as an input to a Monte Carlo simulation to obtain the observed ion energies. The waves around the ion gyrofrequencies may be generated either by field-aligned electrons or by nonlinear processes transferring energy from waves with lower frequencies. Not only the mean energy but also the shape of the particle distribution agrees with the cyclotron resonance heating mechanism. Other mechanisms, such as heating by lower hybrid waves or by a slowly varying electric field, are investigated but are found to be less important than cyclotron heating in this region of space.
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| 27. |
- Ozgumus, T., et al.
(författare)
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Reduced expression of OXPHOS and DNA damage genes is linked to protection from microvascular complications in long-term type 1 diabetes: the PROLONG study
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes is a chronic autoimmune disease requiring insulin treatment for survival. Prolonged duration of type 1 diabetes is associated with increased risk of microvascular complications. Although chronic hyperglycemia and diabetes duration have been considered as the major risk factors for vascular complications, this is not universally seen among all patients. Persons with long-term type 1 diabetes who have remained largely free from vascular complications constitute an ideal group for investigation of natural defense mechanisms against prolonged exposure of diabetes. Transcriptomic signatures obtained from RNA sequencing of the peripheral blood cells were analyzed in non-progressors with more than 30 years of diabetes duration and compared to the patients who progressed to microvascular complications within a shorter duration of diabetes. Analyses revealed that non-progressors demonstrated a reduction in expression of the oxidative phosphorylation (OXPHOS) genes, which were positively correlated with the expression of DNA repair enzymes, namely genes involved in base excision repair (BER) machinery. Reduced expression of OXPHOS and BER genes was linked to decrease in expression of inflammation-related genes, higher glucose disposal rate and reduced measures of hepatic fatty liver. Results from the present study indicate that at transcriptomic level reduction in OXPHOS, DNA repair and inflammation-related genes is linked to better insulin sensitivity and protection against microvascular complications in persons with long-term type 1 diabetes.
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| 28. |
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| 31. |
- Taskinen, M. R., et al.
(författare)
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Adverse effects of fructose on cardiometabolic risk factors and hepatic lipid metabolism in subjects with abdominal obesity
- 2017
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 282, s. 187-201
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 The Association for the Publication of the Journal of Internal Medicine Background: Overconsumption of dietary sugars, fructose in particular, is linked to cardiovascular risk factors such as type 2 diabetes, obesity, dyslipidemia and nonalcoholic fatty liver disease. However, clinical studies have to date not clarified whether these adverse cardiometabolic effects are induced directly by dietary sugars, or whether they are secondary to weight gain. Objectives: To assess the effects of fructose (75 g day −1 ), served with their habitual diet over 12 weeks, on liver fat content and other cardiometabolic risk factors in a large cohort (n = 71) of abdominally obese men. Methods: We analysed changes in body composition, dietary intake, an extensive panel of cardiometabolic risk markers, hepatic de novo lipogenesis (DNL), liver fat content and postprandial lipid responses after a standardized oral fat tolerance test (OFTT). Results: Fructose consumption had modest adverse effects on cardiometabolic risk factors. However, fructose consumption significantly increased liver fat content and hepatic DNL and decreased β-hydroxybutyrate (a measure of β-oxidation). The individual changes in liver fat were highly variable in subjects matched for the same level of weight change. The increase in liver fat content was significantly more pronounced than the weight gain. The increase in DNL correlated positively with triglyceride area under the curve responses after an OFTT. Conclusion: Our data demonstrated adverse effects of moderate fructose consumption for 12 weeks on multiple cardiometabolic risk factors in particular on liver fat content despite only relative low increases in weight and waist circumference. Our study also indicates that there are remarkable individual differences in susceptibility to visceral adiposity/liver fat after real-world daily consumption of fructose-sweetened beverages over 12 weeks.
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| 32. |
- Yamauchi, M, et al.
(författare)
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Dynamic response of the cusp morphology to the solar wind : A case study during passage of the solar wind plasma cloud on February 21, 1994
- 1996
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 101:A11, s. 24675-24687
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Tidskriftsartikel (refereegranskat)abstract
- On February 21, 1994, both Geotail and LMP 8 satellites detected an interplanetary plasma cloud with intense interplanetary magnetic field (IMF>50 nT) and high dynamic pressure (> 50 nPa). During this interval the Freja satellite detected intense cusp-like plasma injections in four out of six dayside traversals. The first two traversals are carefully studied, During the first traversal the overall morphology of the ion injection is characterized by a ''multiple-injection'' signature over a wide magnetic local time (MLT) range, whereas it is characterized by a ''single-injection'' signature with narrow injection region at 8 MLT in the second traversal, The solar wind conditions were also quite different between these two periods: while both dynamic and magnetic pressures stayed high during entire period, the dynamic beta was much higher during the first Freja traversal than during the second traversal. Between these two traversals, the cusp plasma injection is detected by the Sondre Stromfjord radar. The radar signature of the plasma injection is identified using the satellite particle data when the satellite and the radar were conjugate (the satellite's footprint was in the radar's field of view.) The cusp position and dynamics observed by the Sondre Stromfjord radar again show a very good correlation to the solar wind condition, especially to the dynamic pressure. The result indicates the following. (1) During southward IMF the cusp morphology differs for conditions of high or low solar wind dynamic pressure. High dynamic pressure widens the cusp (with multiple injections), whereas high magnetic pressure narrows it (with single injection), The effect of the IMF on the cusp locations and morphology becomes dominant only when the dynamic pressure is not very high, (2) Such a morphological difference reflects dynamic pressure more than dynamic beta during southward IMF at least during times of high solar wind dynamic pressure. (3) The cusp morphology responds very quickly to the changes in the solar wind conditions.
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| 37. |
- Akerblom, H., et al.
(författare)
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Association of Gastric Bypass Surgery With Risk of Developing Diabetic Retinopathy Among Patients With Obesity and Type 2 Diabetes in Sweden: An Observational Study
- 2021
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Ingår i: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 139:2, s. 200-205
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Knowledge of the incidence and progression of diabetic retinopathy (DR) after gastric bypass surgery (GBP) in patients with obesity and diabetes could guide the management of these patients. OBJECTIVE To investigate the incidence of diabetic ocular complications in patients with type 2 diabetes after GBP compared with the incidence of diabetic ocular complications in a matched cohort of patients with obesity and diabetes who have not undergone GBP. DESIGN, SETTING, AND PARTICIPANTS Data from 2 nationwide registers in Sweden, the Scandinavian Obesity Surgery Registry and the National Diabetes Register, were used for this cohort study. A total of 5321 patients with diabetes from the Scandinavian Obesity Surgery Registry who had undergone GBP from January 1, 2007, to December 31, 2013, were matched with 5321 patients with diabetes from the National Diabetes Register who had not undergone GBP, based on sex, age, body mass index (BMI), and calendar time (2007-2013). Follow-up data were obtained until December 31, 2015. Statistical analysis was performed from October 5, 2018, to September 30, 2019. EXPOSURE Gastric bypass surgery. MAIN OUTCOMES AND MEASURES Incidence of new DR and other diabetic ocular complications. RESULTS The study population consisted of 5321 patients who had undergone GBP (3223 women [60.6%]; mean [SD] age, 49.0 [9.5] years) and 5321 matched controls (3395 women [63.8%]; mean [SD] age, 47.1 [11.5] years). Mean (SD) follow-up was 4.5 (1.6) years. The mean (SD) BMI and hemoglobin A1c concentration at baseline were 42.0 (5.7) and 7.6%(1.5%), respectively, in the GBP group and 40.9 (7.3) and 7.5%(1.5%), respectively, in the control group. The mean (SD) duration of diabetes was 6.8 (6.3) years in the GBP group and 6.4 (6.4) years in the control group. The risk for new DR was reduced in the patients who underwent GBP (hazard ratio, 0.62 [95% CI, 0.49-0.78]; P <.001). The dominant risk factors for development of DR at baseline were diabetes duration, hemoglobin A1c concentration, use of insulin, glomerular filtration rate, and BMI. CONCLUSIONS AND RELEVANCE This nationwide matched cohort study suggests that there is a reduced risk of developing new DR associated with GBP, and no evidence of an increased risk of developing DR that threatened sight or required treatment. (c) 2021 American Medical Association. All rights reserved.
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| 38. |
- Alenius Dahlqvist, Jenny, 1972-, et al.
(författare)
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Sinus node dysfunction in patients with Fontan circulation: could heart rate variability be a predictor for pacemaker implantation?
- 2019
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Ingår i: Pediatric Cardiology. - : Springer Science and Business Media LLC. - 0172-0643 .- 1432-1971. ; 40:4, s. 685-693
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Tidskriftsartikel (refereegranskat)abstract
- Sinus node dysfunction (SND) causes significant morbidity in patients after Fontan surgery. Heart rate variability (HRV) reflects the autonomic regulation of the heart, and changes in HRV have been associated with SND in adults. We aimed to study whether changes in HRV could be detected in 24-h electrocardiographic (ECG) recordings in Fontan patients with SND. We compared HRV results from two patient groups; patients with Fontan circulation who later required a pacemaker due to severe SND (n = 12) and patients with Fontan circulation and SND, without indication for pacemaker treatment (n = 11), with two control groups; patients with Fontan circulation without SND (n = 90) and healthy controls (n = 66). The Poincare plot index SD2 (representing changes in heart rate over 24-h) and the very low-frequency (VLF) HRV component were significantly higher in both SND groups, both compared with healthy controls and patients with Fontan circulation without SND. In SND patients with pacemakers, SD2 and VLF were slightly reduced compared to SND patients without pacemaker (p = 0.06). In conclusion, in Fontan patients with SND the HRV is significantly higher compared to healthy controls and Fontan patients without SND. However, in patients with severe SND requiring pacemaker, SD2 and VLF tended to be lower than in patients with SND without pacemaker, which could indicate a reduced diurnal HRV in addition to the severe bradycardia. This is a small study, but our results indicate that HRV analysis might be a useful method in the follow-up of Fontan patients regarding development of SND.
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| 39. |
- Amer, Ahmed, 1984-, et al.
(författare)
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The Ugandan version of the Pediatric Evaluation of Disability Inventory (PEDI-UG). Part II : Psychometric properties
- 2018
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Ingår i: Child Care Health and Development. - : John Wiley & Sons. - 0305-1862 .- 1365-2214. ; 44:4, s. 562-571
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Pediatric Evaluation of Disability Inventory (PEDI) has been recommended as a gold standard in paediatric rehabilitation. A Ugandan version of PEDI (PEDI-UG) has been developed by culturally adapting and translating the original PEDI. The aim of this study was to investigate the psychometric properties of the PEDI-UG in Ugandan children by testing the instrument's rating scale functioning, internal structure, and test-retest reliability.Methods: Two hundred forty-nine Ugandan children (125 girls) aged 6 months to 7.5 years (Mean = 3.4, SD = 1.9) with typical development were tested using the PEDI-UG. Forty-nine children were tested twice to assess test-retest reliability. Validity was investigated by Rasch analysis and reliability by intraclass correlation coefficient.Results: The PEDI-UG domains showed good unidimensionality based on principal component analysis of residuals. Most activities (95%) showed acceptable fit to the Rasch model. Six misfit items were deleted from the Functional Skills scales and one from the Caregiver Assistance scales. The category steps on the Caregiver Assistance scales' rating scale were reversed but functioned well when changed from a 6-point to 4-point rating scale. The reliability was excellent; intraclass correlation coefficient was 0.87-0.92 for the domains of the Functional Skills scales and 0.86-0.88 for the domains of the Caregiver Assistance scales.Conclusion: The PEDI-UG has good to excellent psychometric properties and provides a valid measure of the functional performance of typically developing children from the age of 6 months to 7.5 years in Uganda. Further analysis of all items, including misfit and deleted items, in children with functional disability is recommended.
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| 40. |
- Amer, Ahmed, et al.
(författare)
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Validity and test-retest reliability of the Ugandan version of the Pediatric Evaluation of Disability Inventory (PEDI-UG) in children and youth with cerebral palsy
- 2023
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Ingår i: Child Care Health and Development. - : John Wiley & Sons. - 0305-1862 .- 1365-2214. ; 49:3, s. 464-484
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Validity of the Ugandan version of the Pediatric Evaluation of Disability Inventory (PEDI-UG) was previously investigated on typically developing children. This study aimed to investigate the validity, test-retest reliability and minimal detectable change (MDC) of the PEDI-UG in children and youth (C&Y) with cerebral palsy (CP).METHOD: A cross-sectional study design with 118 C&Y with CP (44.7% girls) aged 10 months-22.5 years were included in the study; 37 of them completed the PEDI-UG twice to investigate test-retest reliability, determined by calculating the intraclass correlation coefficient (ICC). Additionally, data from 249 typically developing children were used for differential item functioning (DIF) analysis. The validity of the PEDI-UG was investigated by Rasch analysis. The Kruskal-Wallis test and Spearman's correlation coefficient were calculated to investigate associations between PEDI-UG scores and external classification systems.RESULTS: The principal component analysis of residuals indicated unidimensionality in all domains. The ICC values were excellent (0.98-0.99), and the MDCs were less than 6 and 13 (on a 0-100 scale) for the functional skills and caregiver assistance parts, respectively. The four-category caregiver assistance rating scale fulfilled the criteria for the analysis of rating scale functioning. In total, 78 of 189 items in the functional skills domain and two items in the caregiver assistance domain demonstrated DIF between C&Y with CP and TD children. The Kruskal-Wallis test (p<0.05) and Spearman's correlation (coefficients of -0.93 to -0.78) supported the validity of PEDI-UG.CONCLUSION: The current diagnose-specific version of PEDI-UG demonstrates evidence for validity as a measure of ability in C&Y with CP in Uganda and other similar settings, being a promising tool for use in clinical practice and research. Conversion tables and MDC values are provided to facilitate clinical adoption of the measure.
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| 41. |
- Andersson, Sofia A, et al.
(författare)
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Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes.
- 2012
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 364:1-2, s. 36-45
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Tidskriftsartikel (refereegranskat)abstract
- Reduced insulin release has been linked to defect exocytosis in β-cells. However, whether expression of genes suggested to be involved in the exocytotic process (exocytotic genes) is altered in pancreatic islets from patients with type 2 diabetes (T2D), and correlate to insulin secretion, needs to be further investigated. Analysing expression levels of 23 exocytotic genes using microarray revealed reduced expression of five genes in human T2D islets (χ(2)=13.25; p<0.001). Gene expression of STX1A, SYT4, SYT7, SYT11, SYT13, SNAP25 and STXBP1 correlated negatively to in vivo measurements of HbA1c levels and positively to glucose stimulated insulin secretion (GSIS) in vitro in human islets. STX1A, SYT4 and SYT11 protein levels correspondingly decreased in human T2D islets. Moreover, silencing of SYT4 and SYT13 reduced GSIS in INS1-832/13 cells. Our data support that reduced expression of exocytotic genes contributes to impaired insulin secretion, and suggest decreased expression of these genes as part of T2D pathogenesis.
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| 42. |
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| 43. |
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| 45. |
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| 46. |
- Axelsson, K. F., et al.
(författare)
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Fracture Risk After Gastric Bypass Surgery : A Retrospective Cohort Study
- 2018
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Ingår i: Osteoporosis International. - : Springer London. - 0937-941X .- 1433-2965. ; 29:Suppl. 1, s. S491-S491
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: Gastric bypass surgery constitutes the most common and effective bariatric surgery to treat obesity. Gastric bypass leads to bone oss but fracture risk following surgery has been insufficiently studied. Our objective was to investigate if gastric bypass surgery in obese patients, with and without diabetes, was associated with fracture risk, and if the fracture risk was associated with post-surgery weight loss or insufficient calcium and vitamin D supplementation.Methods: Using large databases, 38 971 obese patients undergoing gastric bypass were identified, 7758 with diabetes and 31 213 without. Through multivariable 1:1 propensity score matching, well-balanced controls were identified. The risk of fracture and fall injury was investigated using Cox proportional hazards and flexible parameter models. Fracture risk according to weight loss and degree of calcium and vitamin D supplementation one year post-surgery was investigated.Results: 77 942 patients had a median and total follow-up time of 3.1 (IQR 1.7-4.6) and 251 310 person-years, respectively. Gastric bypass was associated with increased risk of any fracture, in patients with diabetes and without diabetes using a multivariable Cox model (HR 1.26, 95%CI 1.05-1.53 and HR 1.32, 95%CI 1.18-1.47, respectively). The risk of fall injury without fracture was also increased after gastric bypass, both in patients with (HR 1.26 95%CI 1.04-1.52) and without diabetes (HR 1.24 95%CI 1.12-1.38). Weight loss or degree of calcium and vitamin D supplementation after gastric bypass were not associated with fracture risk.Conclusions: Gastric bypass was associated with an increased risk of fracture and fall injury. Weight loss or calcium and vitamin D supplementation following surgery were not associated with fracture risk. These findings indicate that gastric bypass increases fracture risk, which could at least partly be due to increased susceptibility to falls.
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| 47. |
- Bacos, Karl, et al.
(författare)
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Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26-74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D. DNA methylation correlates with islet expression of multiple genes, including FHL2, ZNF518B, GNPNAT1 and HLTF. Silencing these genes in β-cells alter insulin secretion. Together, we demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D.
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