| 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. |
- Bastholm Rahmner, Pia, et al.
(författare)
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Physicians perceptions of possibilities and obstacles prior to implementing a computerised drug prescribing support system
- 2004
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Ingår i: International journal of health care quality assurance incorporating leadership in helath services. - : Emerald. - 1366-0756 .- 2051-3135. ; 17:4, s. 173-179
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Tidskriftsartikel (refereegranskat)abstract
- Seeks to identify physicians' perceptions of possibilities and obstacles prior to implementing a computerised drug prescribing support system. Details a descriptive, qualitative study, with semi-structured individual interviews of 21 physicians in the Accident and Emergency Department of South Stockholm General Hospital. Identifies four descriptive categories for possibilities and obstacles. Concludes that gaining access to patient drug history enables physicians to carry out work in a professional way – a need the computerised prescription support system was not developed for and thus cannot fulfil. Alerts and producer-independent drug information are valuable in reducing workload. However, technical prerequisites form the base for a successful implementation. Time must be given to adapt to new ways of working.
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| 3. |
- 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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| 4. |
- Alonso, Lorena, et al.
(författare)
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TIGER : The gene expression regulatory variation landscape of human pancreatic islets
- 2021
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 37:2
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) identified hundreds of signals associated with type 2 diabetes (T2D). To gain insight into their underlying molecular mechanisms, we have created the translational human pancreatic islet genotype tissue-expression resource (TIGER), aggregating >500 human islet genomic datasets from five cohorts in the Horizon 2020 consortium T2DSystems. We impute genotypes using four reference panels and meta-analyze cohorts to improve the coverage of expression quantitative trait loci (eQTL) and develop a method to combine allele-specific expression across samples (cASE). We identify >1 million islet eQTLs, 53 of which colocalize with T2D signals. Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identify eight cASE colocalizations, among which we found a T2D-associated SLC30A8 variant. We make all data available through the TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translates into therapeutic insight and precision medicine for T2D.
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| 5. |
- Andre, M, et al.
(författare)
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Ion energization mechanisms at 1700 km in the auroral region
- 1998
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Ingår i: JOURNAL OF GEOPHYSICAL RESEARCH-SPACE PHYSICS. - : AMER GEOPHYSICAL UNION. ; 103:A3, s. 4199-4222
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Observations obtained by the Freja satellite at altitudes around 1700 km in the high-latitude magnetosphere are used to study ion energization perpendicular to the geomagnetic field. Investigations of ions, electrons, plasma densities, electric and magnet
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| 6. |
- Chriett, S., et al.
(författare)
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SCRT1 is a novel beta cell transcription factor with insulin regulatory properties
- 2021
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 521
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Tidskriftsartikel (refereegranskat)abstract
- Here we show that scratch family transcriptional repressor 1 (SCRT1), a zinc finger transcriptional regulator, is a novel regulator of beta cell function. SCRT1 was found to be expressed in beta cells in rodent and human islets. In human islets, expression of SCRT1 correlated with insulin secretion capacity and the expression of the insulin (INS) gene. Furthermore, SCRT1 mRNA expression was lower in beta cells from T2D patients. siRNA-mediated Scrt1 silencing in INS-1832/13 cells, mouse- and human islets resulted in impaired glucose-stimulated insulin secretion and decreased expression of the insulin gene. This is most likely due to binding of SCRT1 to E-boxes of the Ins1 gene as shown with ChIP. Scrt1 silencing also reduced the expression of several key beta cell transcription factors. Moreover, Scrt1 mRNA expression was reduced by glucose and SCRT1 protein was found to translocate between the nucleus and the cytosol in a glucose-dependent fashion in INS-1832/13 cells as well as in a rodent model of T2D. SCRT1 was also regulated by a GSK3β-dependent SCRT1-serine phosphorylation. Taken together, SCRT1 is a novel beta cell transcription factor that regulates insulin secretion and is affected in T2D.
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| 7. |
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| 8. |
- 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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| 9. |
- Marklund, Göran, et al.
(författare)
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Observations of the electric field fine structure associated with the westward traveling surge and large-scale auroral spirals
- 1998
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 103:A3, s. 4125-4144
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Tidskriftsartikel (refereegranskat)abstract
- The characteristics of the fine scale electric field associated with the westward traveling surge and large-scale auroral spirals and surges are investigated using high-resolution electric field, magnetic field, particle and UV imager observations from four eveningside auroral oval crossings by the Freja satellite. Three of the crossings were associated with signatures of auroral substorms and one crossing went directly through the head of a surge close in time and space to substorm onset. Three passes were adjacent to auroral spiral formations, one poleward of and one equatorward of such forms and one through the multiple arc region near the front of an extended region of auroral activity. The ambient electric field was found to intensify in the direction toward the spiral head (or the center of the auroral activity region) over a region comparable to the size of the visible auroral forms. These results confirm previous findings that the spiral or surge head is associated with negative space charge and an intense upward field-aligned current. The fourth pass, directly through the surge head reveals a very complicated structure of the surge region. Narrowly structured, intense (up to 700 mV/m) and mostly converging electric fields associated with intense electron precipitation (of both high and medium energies) and balanced field-aligned currents (up to 30 μA/m2) are seen near the edge of the surge head and adjacent to auroral structures in the wake. These narrow regions are embedded within more extended regions of intense high-energy electron precipitation but very weak electric fields and field-aligned currents. According to some existing models of the surge, a pronounced westward electric field component and a southward polarisation electric field is expected within the entire high-conductivity region but evidence in support of this was not found in the data. Rather, these suggest that a significant part of the upward surge current is closed by distributed downward field-aligned currents from the near surroundings. The Freja electric field is typically seen to intensify at the edges of or in-between bright auroral structures and to decrease within the arcs similar to what is observed in the ionosphere. The surge electric field is, however, much more intense than previously observed or anticipated at these altitudes with characteristics rather similar to those observed in the auroral acceleration region. Since the particle data indicate that most of the acceleration takes place above Freja altitudes, it seems as if Freja traversed the lower part of the auroral acceleration region associated with the surge.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Shcherbina, L, et al.
(författare)
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Endogenous beta-cell CART regulates insulin secretion and transcription of beta-cell genes
- 2017
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 447, s. 52-60
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Tidskriftsartikel (refereegranskat)abstract
- Impaired beta-cell function is key to the development of type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART) is an islet peptide with insulinotropic and glucagonostatic properties. Here we studied the role of endogenous CART in beta-cell function. CART silencing in INS-1 (832/13) beta-cells reduced insulin secretion and production, ATP levels and beta-cell exocytosis. This was substantiated by reduced expression of several exocytosis genes, as well as reduced expression of genes important for insulin secretion and processing. In addition, CART silencing reduced the expression of a network of transcription factors essential for beta-cell function. Moreover, in RNAseq data from human islet donors, CARTPT expression levels correlated with insulin, exocytosis genes and key beta-cell transcription factors. Thus, endogenous beta-cell CART regulates insulin expression and secretion in INS-1 (832/13) cells, via actions on the exocytotic machinery and a network of beta-cell transcription factors. We conclude that CART is important for maintaining the beta-cell phenotype.
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| 15. |
- Andersson, L, et al.
(författare)
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Electron signatures and Alfven waves
- 2002
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 107:A9
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Tidskriftsartikel (refereegranskat)abstract
- [1] We identify two distinct electron populations associated with Alfven waves in the Freja data set using the high time resolution state of the art electron detector. One of the populations, detected together with an Alfven wave, is field-aligned and can be seen as trapped within the wave. The other electron population is detected before the wave and consists of electrons which have left the wave at a point with a velocity higher than the local Alfven speed. In the paper, the electrons leaving wave are modeled for different density profiles and are compared with the observed data. Depending on the density profile, the model can produce the same energy-time and pitch angle-time dispersion that is observed in the Freja data. The conclusion of the paper is that the Alfven wave can explain the observed particle signatures. It is shown that the Alfven wave acceleration can create electron signatures similar to inverted-V structures. The density distribution along a flux tube has an important role in the type of particle signatures that can be detected at low altitudes.
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| 16. |
- Andersson, L., Wahlund, J.E., Clemmons, J., Gustavsson, B. and Eliasson, L.
(författare)
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Electromagnetic waves and bursty electron acceleration: implications from Freja.
- 2001
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Ingår i: Annales Geophysicae. ; 20:2, s. 139-150
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Tidskriftsartikel (refereegranskat)abstract
- Dispersive Alfven wave activity is identified in four dayside auroral oval events measured by the Freja satellite. The events are characterized by ion injection, bursty electron precipitation below about 1 keV, transverse ion heating and broadband extreme
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| 17. |
- Andre, M, et al.
(författare)
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Ion energization mechanisms at 1700 km in the auroral region
- 1998
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Ingår i: JOURNAL OF GEOPHYSICAL RESEARCH-SPACE PHYSICS. - 0148-0227. ; 103:A3, s. 4199-4222
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Tidskriftsartikel (refereegranskat)abstract
- Observations obtained by the Freja satellite at altitudes around 1700 km in the high-latitude magnetosphere are used to study ion energization perpendicular to the geomagnetic field. Investigations of ions, electrons, plasma densities, electric and magnetic wave fields, and field-aligned currents are used to study O+ heating mechanisms. Three ion heating events are studied in detail, and 20 events are used in a detailed statistical study. More than 200 events are classified as belonging to one of four major types of ion heating and are ordered as a function of magnetic local time. The most common types of ion heating are associated with broadband low-frequency electric wave fields occurring at all local times. These waves cover frequencies from below one up to several hundred hertz and correspond to the most intense O+ energization. Heating by these waves at frequencies of the order of the O+ gyrofrequency at 25 Hz seems to be the important energization mechanism, causing O+ ion mean energies up to hundreds of eV. The broadband waves are associated with Alfven waves with frequencies up to at least a few hertz and with field-aligned currents. Other types of O+ energization events are less common. During these events the ions are heated by waves near the lower hybrid frequency or near half the proton gyrofrequency. These waves are generated by auroral electrons or in a few cases by precipitating ions.
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| 18. |
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| 19. |
- 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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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Christensen, Gitte L., et al.
(författare)
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Bone morphogenetic protein 4 inhibits insulin secretion from rodent beta cells through regulation of calbindin1 expression and reduced voltage-dependent calcium currents
- 2015
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 58:6, s. 1282-1290
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Type 2 diabetes is characterised by progressive loss of pancreatic beta cell mass and function. Therefore, it is of therapeutic interest to identify factors with the potential to improve beta cell proliferation and insulin secretion. Bone morphogenetic protein 4 (BMP4) expression is increased in diabetic animals and BMP4 reduces glucose-stimulated insulin secretion (GSIS). Here, we investigate the molecular mechanism behind this inhibition. Methods BMP4-mediated inhibition of GSIS was investigated in detail using single cell electrophysiological measurements and live cell Ca2+ imaging. BMP4-mediated gene expression changes were investigated by microarray profiling, quantitative PCR and western blotting. Results Prolonged exposure to BMP4 reduced GSIS from rodent pancreatic islets. This inhibition was associated with decreased exocytosis due to a reduced Ca2+ current through voltage-dependent Ca2+ channels. To identify proteins involved in the inhibition of GSIS, we investigated global gene expression changes induced by BMP4 in neonatal rat pancreatic islets. Expression of the Ca2+-binding protein calbindin1 was significantly induced by BMP4. Overexpression of calbindin1 in primary islet cells reduced GSIS, and the effect of BMP4 on GSIS was lost in islets from calbindin1 (Calb1) knockout mice. Conclusions/interpretation We found BMP4 treatment to markedly inhibit GSIS from rodent pancreatic islets in a calbindin1-dependent manner. Calbindin1 is suggested to mediate the effect of BMP4 by buffering Ca2+ and decreasing Ca2+ channel activity, resulting in diminished insulin exocytosis. Both BMP4 and calbindin1 are potential pharmacological targets for the treatment of beta cell dysfunction.
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| 24. |
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| 25. |
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| 26. |
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| 27. |
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| 28. |
- 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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| 29. |
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| 30. |
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| 31. |
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| 32. |
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Margolin, S, et al.
(författare)
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CYP2D6 and adjuvant tamoxifen: possible differences of outcome in pre- and post-menopausal patients
- 2013
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Ingår i: Pharmacogenomics. - : Future Medicine Ltd. - 1744-8042 .- 1462-2416. ; 14:6, s. 613-622
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Previous studies on CYP2D6 activity and the effect of adjuvant tamoxifen in breast cancer are inconsistent. We analyzed the impact of the CYP2D6 polymorphism in pre- and post-menopausal patients that were adherent to tamoxifen treatment for at least a year. Materials & methods: A total of 382 breast cancer patients prescribed adjuvant tamoxifen for 5 years constituted the study-base. Clinical information, including compliance and outcome, was retrieved from medical records. Comprehensive CYP2D6 genotyping was performed and translated into predicted metabolic activity. Results & conclusion: In patients adherent to tamoxifen for at least one year (n = 313) there was an association between reduced CYP2D6 activity (≤50% of normal) and recurrence (p = 0.025) and breast cancer-specific mortality (p = 0.034). In a multivariable analysis, CYP2D6 remained an independent predictor of outcome. In a subgroup analysis, the effect of CYP2D6 seemed to derive mainly from premenopausal patients, which represents a new finding that needs validation in a larger study sample. Original submitted 13 November 2012; Revision submitted 1 March 2013
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| 37. |
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| 38. |
- 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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| 39. |
- Mishin, V M, et al.
(författare)
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A study of the CDAW 9C substorm of May 3, 1986, using magnetogram inversion technique 2, and a substorm scenario with two active phases
- 1997
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Ingår i: JOURNAL OF GEOPHYSICAL RESEARCH-SPACE PHYSICS. - 0148-0227. ; 102:A9, s. 19845-19859
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Tidskriftsartikel (refereegranskat)abstract
- One of the CDAW 9C substorms is investigated in this paper using the database reported by Hones et al. and supplemented with magnetogram inversion technique (MIT) 2 data. These latter have provided information about the dynamics of the open tail magnetic Aux, current systems in the ionosphere, and the size and dynamics of the current wedge. We have identified the growth: expansion, and recovery phases of this substorm, with characteristics expected from a generally accepted scenario. However, specific signatures were observed in the interval (0919-0935) UTI i.e., between the growth and expansion phases, indicating the concurrent development of the substorm onset and corresponding instabilities in the innermost current sheet, and small-scale cross-tail current disruptions without the open tail reconnection. In addition to signatures of small-scale dipolarization, an increase of the open tail magnetic flux, and a current system of the type close to DP 2 were observed at (0919-0935) UT, which is more likely to suggest predominance of the tail-stretching process than magnetic collapse, This fact was interpreted in tel ms of a relevant simple model as a signature of the growth of the energy input from the solar wind which ensures the observable disturbance power. Hence the disturbance st (0919-0935) UT was more likely a driven one than an unloading one. The aforementioned signatures make it possible to identify the interval (0919-0935) UT as the ''phase of multiple onsets'' or: (equivalently) the ''first active phase,'' which was previously defined by Mishin [1991., and references therein] as one of the four standard phases of a typical substorm (in addition to the expansion phase). Thus the case study supports the substorm scenario with two active phases and, accordingly, with two different kinds of physics, This case study illustrates also the informativity of MIT 2 data and their ability to effectively complement the database traditionally used in substorm studies.
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| 40. |
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| 41. |
- 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-SPACE PHYSICS. - : AMER GEOPHYSICAL UNION. - 0148-0227. ; 101:A6, s. 13179-13193
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)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 energizati
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| 42. |
- 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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| 43. |
- 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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| 44. |
- Pettus, J., et al.
(författare)
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Rates of Hypoglycemia Predicted in Patients with Type 2 Diabetes on Insulin Glargine 300 U/ml Versus First- and Second-Generation Basal Insulin Analogs: The Real-World LIGHTNING Study
- 2019
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Ingår i: Diabetes Therapy. - : Springer Science and Business Media LLC. - 1869-6953 .- 1869-6961. ; 10:2, s. 617-633
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe LIGHTNING study applied conventional and advanced analytic approaches to model, predict, and compare hypoglycemia rates of people with type 2 diabetes (T2DM) on insulin glargine 300 U/ml (Gla-300) with those on first-generation (insulin glargine 100 U/ml [Gla-100]; insulin detemir [IDet]) or second-generation (insulin degludec [IDeg]) basal-insulin (BI) analogs, utilizing a large real-world database.MethodsData were collected between 1 January 2007 and 31 March 2017 from the Optum Humedica US electronic health records [EHR] database. Patient-treatments, the period during which a patient used a specific BI, were analyzed for patients who switched from a prior BI or those who newly initiated BI therapy. Data were analyzed using two approaches: propensity score matching (PSM) and a predictive modeling approach using machine learning.ResultsA total of 831,456 patients with T2DM receiving BI were included from the EHR data set. Following selection, 198,198 patient-treatments were available for predictive modeling. The analysis showed that rates of severe hypoglycemia (using a modified definition) were approximately 50% lower with Gla-300 than with Gla-100 or IDet in insulin-naive individuals, and 30% lower versus IDet in BI switchers (all p<0.05). Similar rates of severe hypoglycemia were predicted for Gla-300 and IDeg, regardless of prior insulin experience. Similar results to those observed in the overall cohorts were seen in analyses across subgroups at a particularly high risk of hypoglycemia.PSM (performed on 157,573 patient-treatments) revealed comparable reductions in HbA(1c) with Gla-300 versus first- and second-generation BI analogs, alongside lower rates of severe hypoglycemia with Gla-300 versus first-generation BI analogs (p<0.05) and similar rates versus IDeg in insulin-naive and BI-switcher cohorts.ConclusionsBased on real-world data, predicted rates of severe hypoglycemia with Gla-300 tended to be lower versus first-generation BI analogs and similar versus IDeg in a wide spectrum of patients with T2DM.FundingSanofi, Paris, France.
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| 45. |
- Salunkhe, V.A., et al.
(författare)
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MiR-335 regulates exocytotic proteins and affects glucose-stimulated insulin secretion through decreased Ca2+-dependent exocytosis in beta cells
- 2015
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 58:Suppl. 1, s. 128-128
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Konferensbidrag (refereegranskat)abstract
- Background and aims: Ca2+-induced exocytosis is essential for insulin to be secreted from beta-cells, and in islets from type-2 diabetic (T2D) donors the expression of several genes coding for exocytotic proteins is reduced. Largely this phenomenon cannot be explained by polymorphism; rather it is likely due to epigenetic factors like microRNAs (miRNAs). Indeed, previous studies have identified a number of miRNAs with differential expression in the islets from T2D donors and the Goto- Kakizaki (GK) rat. One of the upregulatedmiRNAs in the GK rat is miR- 335, predicted to target several exocytotic genes amongst those Stxbp1 is a validated target. Here we aim to investigate whether miR-335 regulates the expression of exocytotic genes and affects insulin secretion and exocytosis in beta-cells. Materials and methods: Insulin secretion was measured by radio immuno assay. Exocytosis and docking of insulin granules was studied by capacitance measurements using the patch-clamp technique and by TIRF microscopy. Rat miR-335 was overexpressed using chemicallymodified mature microRNA mimic in INS-1 832/13 beta-cells by transfection. Gene knockdown was performed with RNAi. Protein and mRNA levels were analysed with Western Blot and RT-qPCR, respectively. Results: Overexpression of miR-335 (OE335) in INS-1 832/13 cells reduced insulin secretion at 16.7 mM glucose compared to control cells (SCR) (n=3; p
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| 46. |
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| 50. |
- Tattikota, Sudhir G, et al.
(författare)
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Argonaute2 Mediates Compensatory Expansion of the Pancreatic β Cell.
- 2014
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 19:1, s. 122-134
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic β cells adapt to compensate for increased metabolic demand during insulin resistance. Although the microRNA pathway has an essential role in β cell proliferation, the extent of its contribution is unclear. Here, we report that miR-184 is silenced in the pancreatic islets of insulin-resistant mouse models and type 2 diabetic human subjects. Reduction of miR-184 promotes the expression of its target Argonaute2 (Ago2), a component of the microRNA-induced silencing complex. Moreover, restoration of miR-184 in leptin-deficient ob/ob mice decreased Ago2 and prevented compensatory β cell expansion. Loss of Ago2 during insulin resistance blocked β cell growth and relieved the regulation of miR-375-targeted genes, including the growth suppressor Cadm1. Lastly, administration of a ketogenic diet to ob/ob mice rescued insulin sensitivity and miR-184 expression and restored Ago2 and β cell mass. This study identifies the targeting of Ago2 by miR-184 as an essential component of the compensatory response to regulate proliferation according to insulin sensitivity.
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