| 1. |
|
|
| 2. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
-
A registry-based randomised trial comparing an SGLT2 inhibitor and metformin as standard treatment of early stage type 2 diabetes (SMARTEST): Rationale, design and protocol
- 2021
-
Ingår i: Journal of Diabetes and Its Complications. - : Elsevier BV. - 1056-8727 .- 1873-460X. ; 35:10
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: SGLT2 inhibitors have been shown to reduce cardiovascular and renal complications in type 2 diabetes (T2D) patients at high cardiovascular risk. Metformin is currently widely used as initial monotherapy in T2D but lacks convincing data to show that it reduces risk of complications. We aim to compare the SGLT2 inhibitor dapagliflozin and metformin as first-line T2D medication with regard to development of complications in a registry-based randomised controlled trial. Methods: The SGLT2 inhibitor or metformin as standard treatment of early stage type 2 diabetes (SMARTEST) trial will enrol 4300 subjects at 30-40 study sites in Sweden who will be randomised 1:1 to either metformin or dapagliflozin. Participants must have T2D duration <4 years, no prior cardiovascular disease, and be either drug-naive or on monotherapy for T2D. Results: The primary endpoint is a composite of all-cause death, major adverse cardiovascular events and occurrence or progression of microvascular complications (retinopathy, nephropathy, diabetic foot lesions). Secondary endpoints include individual components of the primary endpoint, start of insulin therapy, risk factor biomarkers, patient-reported outcome measures, and cost-effectiveness analysis. Outcomes will primarily be assessed using nationwide healthcare registries. Conclusions: The SMARTEST trial will investigate whether dapagliflozin is superior to metformin in preventing complications in early stage T2D. (Clinicaltrials.gov identifier NCT03982381, EudraCT 2019-001046-17).
|
|
| 3. |
- Villarejo, Arsenio, et al.
(författare)
-
Evidence for a protein transported through the secretory pathway en route to the higher plant chloroplast
- 2005
-
Ingår i: Nature Cell Biology. - : Springer Nature. - 1465-7392 .- 1476-4679. ; 7:12, s. 1224-1231
-
Tidskriftsartikel (refereegranskat)abstract
- In contrast to animal and fungal cells, green plant cells contain one or multiple chloroplasts, the organelle(s) in which photosynthetic reactions take place. Chloroplasts are believed to have originated from an endosymbiotic event and contain DNA that codes for some of their proteins. Most chloroplast proteins are encoded by the nuclear genome and imported with the help of sorting signals that are intrinsic parts of the polypeptides. Here, we show that a chloroplast-located protein in higher plants takes an alternative route through the secretory pathway, and becomes N-glycosylated before entering the chloroplast.
|
|
| 4. |
|
|
| 5. |
- de Brun, Maryam, 1991-, et al.
(författare)
-
Changing diagnostic criteria for gestational diabetes (CDC4G) in Sweden : A stepped wedge cluster randomised trial
- 2024
-
Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 21:7
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The World Health Organisation (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) has been criticised due to the limited evidence of benefits on pregnancy outcomes in different populations when switching from previously higher glycemic thresholds to the lower WHO-2013 diagnostic criteria. The aim of this study was to determine whether the switch from previous Swedish (SWE-GDM) to the WHO-2013 GDM criteria in Sweden following risk factor-based screening improves pregnancy outcomes.METHODS AND FINDINGS: A stepped wedge cluster randomised trial was performed between January 1 and December 31, 2018 in 11 clusters (17 delivery units) across Sweden, including all pregnancies under care and excluding preexisting diabetes, gastric bypass surgery, or multifetal pregnancies from the analysis. After implementation of uniform clinical and laboratory guidelines, a number of clusters were randomised to intervention (switch to WHO-2013 GDM criteria) each month from February to November 2018. The primary outcome was large for gestational age (LGA, defined as birth weight >90th percentile). Other secondary and prespecified outcomes included maternal and neonatal birth complications. Primary analysis was by modified intention to treat (mITT), excluding 3 clusters that were randomised before study start but were unable to implement the intervention. Prespecified subgroup analysis was undertaken among those discordant for the definition of GDM. Multilevel mixed regression models were used to compare outcome LGA between WHO-2013 and SWE-GDM groups adjusted for clusters, time periods, and potential confounders. Multiple imputation was used for missing potential confounding variables. In the mITT analysis, 47 080 pregnancies were included with 6 882 (14.6%) oral glucose tolerance tests (OGTTs) performed. The GDM prevalence increased from 595/22 797 (2.6%) to 1 591/24 283 (6.6%) after the intervention. In the mITT population, the switch was associated with no change in primary outcome LGA (2 790/24 209 (11.5%) versus 2 584/22 707 (11.4%)) producing an adjusted risk ratio (aRR) of 0.97 (95% confidence interval 0.91 to 1.02, p = 0.26). In the subgroup, the prevalence of LGA was 273/956 (28.8%) before and 278/1 239 (22.5%) after the switch, aRR 0.87 (95% CI 0.75 to 1.01, p = 0.076). No serious events were reported. Potential limitations of this trial are mainly due to the trial design, including failure to adhere to guidelines within and between the clusters and influences of unidentified temporal variations.CONCLUSIONS: In this study, implementing the WHO-2013 criteria in Sweden with risk factor-based screening did not significantly reduce LGA prevalence defined as birth weight >90th percentile, in the total population, or in the subgroup discordant for the definition of GDM. Future studies are needed to evaluate the effects of treating different glucose thresholds during pregnancy in different populations, with different screening strategies and clinical management guidelines, to optimise women's and children's health in the short and long term.TRIAL REGISTRATION: The trial is registered with ISRCTN (41918550).
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Fadl, Helena, 1965-, et al.
(författare)
-
Changing diagnostic criteria for gestational diabetes in Sweden-a stepped wedge national cluster randomised controlled trial-the CDC4G study protocol
- 2019
-
Ingår i: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background The optimal criteria to diagnose gestational diabetes mellitus (GDM) remain contested. The Swedish National Board of Health introduced the 2013 WHO criteria in 2015 as a recommendation for initiation of treatment for hyperglycaemia during pregnancy. With variation in GDM screening and diagnostic practice across the country, it was agreed that the shift to new guidelines should be in a scientific and structured way. The aim of the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) in Sweden () is to evaluate the clinical and health economic impacts of changing diagnostic criteria for GDM in Sweden and to create a prospective cohort to compare the many long-term outcomes in mother and baby under the old and new diagnostic approaches. Methods This is a stepped wedge cluster randomised controlled trial, comparing pregnancy outcomes before and after the switch in GDM criteria across 11 centres in a randomised manner. The trial includes all pregnant women screened for GDM across the participating centres during January-December 2018, approximately two thirds of all pregnancies in Sweden in a year. Women with pre-existing diabetes will be excluded. Data will be collected through the national Swedish Pregnancy register and for follow up studies other health registers will be included. Discussion The stepped wedge RCT was chosen to be the best study design for evaluating the shift from old to new diagnostic criteria of GDM in Sweden. The national quality registers provide data on the whole pregnant population and gives a possibility for follow up studies of both mother and child. The health economic analysis from the study will give a solid evidence base for future changes in order to improve immediate pregnancy, as well as long term, outcomes for mother and child.
|
|
| 9. |
- Husdal, Rebecka, et al.
(författare)
-
Associations between quality of work features in primary health care and glycaemic control in people with Type 2 diabetes mellitus: A nationwide survey.
- 2019
-
Ingår i: Primary care diabetes. - : Elsevier BV. - 1878-0210 .- 1751-9918. ; 13:2, s. 176-186
-
Tidskriftsartikel (refereegranskat)abstract
- To describe and analyse the associations between primary health care centres' (PHCCs') quality of work (QOW) and individual HbA1c levels in people with Type 2 diabetes mellitus (T2DM).This cross-sectional study invited all 1152 Swedish PHCCs to answer a questionnaire addressing QOW conditions. Clinical, socio-economic and comorbidity data for 230,958 people with T2DM were linked to data on QOW conditions for 846 (73.4%) PHCCs.Of the participants, 56% had controlled (≤52mmol/mol), 31.9% intermediate (53-69mmol/mol), and 12.1% uncontrolled (≥70mmol/mol) HbA1c. An explanatory factor analysis identified seven QOW features. The features having a call-recall system, having individualized treatment plans, PHCCs' results always on the agenda, and having a follow-up strategy combined with taking responsibility of outcomes/results were associated with lower HbA1c levels in the controlled group (all p<0.05). For people with intermediate or uncontrolled HbA1c, having individualized treatment plans was the only QOW feature that was significantly associated with a lower HbA1c level (p<0.05).This nationwide study adds important knowledge regarding associations between QOW in real life clinical practice and HbA1c levels. PHCCs' QOW may mainly only benefit people with controlled HbA1c and more effective QOW strategies are needed to support people with uncontrolled HbA1c.
|
|
| 10. |
- Husdal, Rebecka, et al.
(författare)
-
Organisation of primary diabetes care in people with type 2 diabetes in relation to all-cause mortality: A nationwide register-based cohort study
- 2020
-
Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 167
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To examine if personnel resources and organisational features in Swedish primary health-care centres (PHCCs) are associated to all-cause mortality (ACM) in people with type 2 diabetes mellitus (T2DM). Methods: A total of 187,570 people with T2DM registered in the Swedish National Diabetes Register (NDR) during 2013 were included in this nationwide cohort study. Individual NDR data were linked to data from a questionnaire addressing personnel resources and organisational features for 787 (68%) PHCCs as well as to individual data on socio-economic status and comorbidities. Furthermore, data on ACM were obtained and followed up until 30 January 2018. Hierarchical Cox regression analyses were applied. Results: After a median follow-up of 4.2 years, 27,136 (14.5%) participants had died. An association was found between number of whole-time-equivalent (WTE) general practitioner's (GP's) devoted to diabetes care/500 people with T2DM and lower risk of early death (hazard ratio 0.919 [95% confidence interval 0.895–0.945] per additional WTE GP; p = 0.002). No other personnel resources or organisational features were significantly associated with ACM. Conclusions: This nationwide register-based cohort study suggests that the number of WTE GPs devoted to diabetes care have an impact on the risk of early death in people with T2DM. © 2020 Elsevier B.V.
|
|
