| 1. |
- Olafsdottir, Arndis, 1978, et al.
(författare)
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The majority of people with type 1 diabetes and multiple daily insulin injections benefit from using continuous glucose monitoring: An analysis based on the GOLD randomized trial (GOLD-5)
- 2021
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Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 23:2, s. 619-630
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Tidskriftsartikel (refereegranskat)abstract
- Aim To identify responders to continuous glucose monitoring (CGM) in relation to reductions in HbA1c and percentage of time spent in hypoglycaemia after initiation of CGM for individuals with type 1 diabetes treated with multiple daily insulin injections. Materials and Methods We analysed data from 142 participants in the GOLD randomized clinical trial. We evaluated how many lowered their HbA1c by more than 0.4% (>4.7 mmol/mol) or decreased the time spent in hypoglycaemia over 24 hours by more than 20 or 30 minutes, and which baseline variables were associated with those improvements. Results Lower reduction of HbA1c was associated with greater reduction of hypoglycaemia (r = -0.52; P < .0001). During CGM, 47% of participants lowered their HbA1c values by more than 0.4% (>4.7 mmol/mol) than with self-measurement of blood glucose, and 47% decreased the time spent in hypoglycaemia by more than 20 minutes over 24 hours. Overall, 78% either reduced their HbA1c by more than 0.4% (>4.7 mmol/mol) or the time spent in hypoglycaemia by more than 20 minutes over 24 hours, but only 14% improved both. Higher HbA1c, a lower percentage of time at less than 3.0 or 3.9 mmol/L, a lower coefficient of variation (CV) and a higher percentage of time above 13.9 mmol/L (P = .016) were associated with greater HbA1c reduction during CGM. The variables associated with a greater reduction of time in hypoglycaemia were female sex, greater time with glucose levels at less than 3.0 mmol/L, higher CV, and higher hypoglycaemia confidence as evaluated by a hypoglycaemic confidence questionnaire. Conclusion The majority of people with type 1 diabetes managed by multiple daily insulin injections benefit from CGM; some experienced reduced HbA1c while others reduced the time spent in hypoglycaemia. These factors need to be considered by healthcare professionals and decision-makers for reimbursement and diabetes guidelines.
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| 2. |
- Björnström, Karin, 1971-, et al.
(författare)
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Characterisation of the signal transduction cascade caused by propofol in rat neurons : From the GABAA receptor to the cytoskeleton
- 2008
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Ingår i: Journal of Physiology and Pharmacology. - 0867-5910 .- 1899-1505. ; 59:3, s. 617-632
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Tidskriftsartikel (refereegranskat)abstract
- The anaesthetic propofol interacts with the GABAA receptor, but its cellular signalling pathways are not fully understood. Propofol causes reorganisation of the actin cytoskeleton into ring structures in neurons. Is this reorganisation a specific effect of propofol as apposed to GABA, and which cellular pathways are involved? We used fluorescence-marked actin in cultured rat neurons to evaluate the percentage of actin rings caused by propofol or GABA in combination with rho, rho kinase (ROK), PI3-kinase or tyrosine kinase inhibitors, with or without the presence of extracellular calcium. Confocal microscopy was performed on propofol-stimulated cells and changes in actin between cellular compartments were studied with Western blot. Propofol (3 μg·ml-1), but not GABA (5 μM), caused transcellular actin ring formation, that was dependent on influx of extracellular calcium and blocked by rho, ROK, PI3-kinase or tyrosine kinase inhibitors. Propofol uses rho/ROK to translocate actin from the cytoskeleton to the membrane and its actin ring formation is dependent on an interaction site close to the GABA site on the GABAA receptor. GABA does not cause actin rings, implying that this is a specific effect of propofol.
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| 3. |
- Isaksson, Sofia Sterner, et al.
(författare)
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Discordance between mean glucose and time in range in relation to HbA1c in individuals with type 1 diabetes: results from the GOLD and SILVER trials
- 2024
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Ingår i: DIABETOLOGIA. - : SPRINGER. - 0012-186X .- 1432-0428.
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Previous studies have shown that individuals with similar mean glucose levels (MG) or percentage of time in range (TIR) may have different HbA(1c) values. The aim of this study was to further elucidate how MG and TIR are associated with HbA(1c). Methods Data from the randomised clinical GOLD trial (n=144) and the follow-up SILVER trial (n=98) of adults with type 1 diabetes followed for 2.5 years were analysed. A total of 596 paired HbA(1c)/continuous glucose monitoring measurements were included. Linear mixed-effects models were used to account for intra-individual correlations in repeated-measures data. Results In the GOLD trial, the mean age of the participants (+/- SD) was 44 +/- 13 years, 63 (44%) were female, and the mean HbA(1c) (+/- SD) was 72 +/- 9.8 mmol/mol (8.7 +/- 0.9%). When correlating MG with HbA(1c), MG explained 63% of the variation in HbA(1c) (r=0.79, p<0.001). The variation in HbA(1c) explained by MG increased to 88% (r=0.94, p value for improvement of fit <0.001) when accounting for person-to-person variation in the MG-HbA(1c) relationship. Time below range (TBR; <3.9 mmol/l), time above range (TAR) level 2 (>13.9 mmol/l) and glycaemic variability had little or no effect on the association. For a given MG and TIR, the HbA(1c) of 10% of individuals deviated by >8 mmol/mol (0.8%) from their estimated HbA(1c) based on the overall association between MG and TIR with HbA(1c). TBR and TAR level 2 significantly influenced the association between TIR and HbA(1c). At a given TIR, each 1% increase in TBR was related to a 0.6 mmol/mol lower HbA(1c) (95% CI 0.4, 0.9; p<0.001), and each 2% increase in TAR level 2 was related to a 0.4 mmol/mol higher HbA(1c) (95% CI 0.1, 0.6; p=0.003). However, neither TIR, TBR nor TAR level 2 were significantly associated with HbA(1c) when accounting for MG. Conclusions/interpretation Inter-individual variations exist between MG and HbA(1c), as well as between TIR and HbA(1c), with clinically important deviations in relatively large groups of individuals with type 1 diabetes. These results may provide important information to both healthcare providers and individuals with diabetes in terms of prognosis and when making diabetes management decisions.
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| 4. |
- Jackson, Alice M., et al.
(författare)
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Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:36, s. 3741-3752
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Patients with heart failure and preserved ejection fraction (HFpEF) frequently have difficult-to-control hypertension. We examined the effect of neprilysin inhibition on apparent resistant hypertension in patients with HFpEF in the PARAGON-HF trial, which compared the effect of sacubitril-valsartan with valsartan.Methods and results: In this post hoc analysis, patients were categorized according to systolic blood pressure at the end of the valsartan run-in (n=4795). Apparent resistant hypertension was defined as systolic blood pressure >= 14 0mmHg (>= 135 mmHg if diabetes) despite treatment with valsartan, a calcium channel blocker, and a diuretic. Apparent mineralocorticoid receptor antagonist (MRA)-resistant hypertension was defined as systolic blood pressure >= 140 mmHg (>= 135 mmHg if diabetes) despite the above treatments and an MRA. The primary outcome in the PARAGON-HF trial was a composite of total hospitalizations for heart failure and death from cardiovascular causes. We examined clinical endpoints and the safety of sacubitril-valsartan according to the hypertension category. We also examined reductions in blood pressure from the end of valsartan run-in to Weeks 4 and 16 after randomization. Overall, 731 patients (15.2%) had apparent resistant hypertension and 135 (2.8%) had apparent MRA-resistant hypertension. The rate of the primary outcome was higher in patients with apparent resistant hypertension [17.3; 95% confidence interval (CI) 15.6-19.1 per 100 person-years] compared to those with a controlled systolic blood pressure (13.4; 12.7-14.3 per 100 person-years), with an adjusted rate ratio of 1.28 (95% CI 1.05-1.57). The reduction in systolic blood pressure at Weeks 4 and 16, respectively, was greater with sacubitril-valsartan vs. valsartan in patients with apparent resistant hypertension [-4.8 (-7.0 to -2.5) and 3.9 (-6.6 to -1.3) mmHg] and apparent MRA-resistant hypertension [-8.8 (-14.0 to -3.5) and -6.3 (-12.5 to -0.1) mmHg]. The proportion of patients with apparent resistant hypertension achieving a controlled systolic blood pressure by Week 16 was 47.9% in the sacubitril-valsartan group and 34.3% in the valsartan group [adjusted odds ratio (OR) 1.78, 95% CI 1.30-2.43]. In patients with apparent MRA-resistant hypertension, the respective proportions were 43.6% vs. 28.4% (adjusted OR 2.63, 95% CI 1.18-5.89).Conclusion: Sacubitril-valsartan may be useful in treating apparent resistant hypertension in patients with HFpEF, even in those who continue to have an elevated blood pressure despite treatment with at least four antihypertensive drug classes, including an MRA.
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| 5. |
- Johansson, Martina, et al.
(författare)
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Relationships between cardiovascular risk factors and white-coat hypertension diagnosed by home blood pressure recordings in a middle-aged population
- 2021
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 39:10, s. 2009-2014
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study risk in white-coat hypertension (WCH) by measurement of coronary artery calcium score (CACS), carotid--femoral pulse-wave velocity (PWV) and carotid plaques. Methods: Cross-sectional population-based cohort with randomized selection of participants from Linkoping, Sweden. An Omron m10-IT oscillometric device was used for clinic and home blood pressures (HBP) in the morning and evening for 1 week. Results: We recruited 5029 middle-aged and mainly defined WCH as SBP at least 140 mmHg and/or DBP at least 90 mmHg with HBP less than 135/85 mmHg. There were 2680 normotensive participants and 648 had WCH after exclusion of treated participants. More women (59.5%) than men (42.8%, P < 0.001) had WCH. We found higher prevalence of CACS greater than 100 compared with less than 100 (12.4 vs. 7.2%, P < 0.001), PWV (11.5 +/- 1.5 vs. 10.4 +/- 1.3 m/s, P < 0.001) and a higher prevalence of one or more carotid plaques (59.5 vs. 48%, P < 0.001) in participants with WCH than in normotension. Participants with WCH also had more dyslipidemia and higher glucose levels. Normotensive women scored lower on nervousness than women with WCH (P = 0.022). After matching of 639 participants with WCH to normotensive participants according to age, gender and systolic HBP the prevalence of a high CACS (12.1 vs. 8.6%, P = 0.003,) PWV (11.0 +/- 0.068 vs. 11.5 +/- 0.068 m/s, estimated marginal means +/- SE, P < 0.001 by ANOVA) but not more carotid plaques (59.5 vs. 55.6%, P = 0.23), remained in the participants with WCH compared with the matched normotensive participants. Conclusion: WCH is particularly common in middle-aged women, and it displays metabolic dysfunction and increased prevalence of arteriosclerotic manifestations in both genders. As markers of increased cardiovascular risk were present also after matching normotensive and WCH participants according to systolic HBP, age and gender, the presence of WCH signals an increased cardiovascular risk burden that is not fully explained by elevated BP levels at home.
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| 6. |
- Lind, Marcus, 1976, et al.
(författare)
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Sustained Intensive Treatment and Long-term Effects on HbA(1c) Reduction (SILVER Study) by CGM in People With Type 1 Diabetes Treated With MDI
- 2021
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Ingår i: Diabetes Care. - Arlington, VA, United States : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:1, s. 141-149
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Continuous glucose monitoring (CGM) reduces HbA(1c) and time spent in hypoglycemia in people with type 1 diabetes (T1D) treated with multiple daily insulin injections (MDI) when evaluated over shorter time periods. It is unclear to what extent CGM improves and helps to maintain glucose control, treatment satisfaction, diabetes distress, hypoglycemic concerns, and overall well-being over longer periods of time. RESEARCH DESIGN AND METHODS The GOLD trial was a randomized crossover trial performed over 16 months of CGM treatment in people with T1D treated with MDI. People completing the trial (n = 141) were invited to participate in the current SILVER extension study in which 107 patients continued CGM treatment over 1 year along with the support of a diabetes nurse every 3 months. RESULTS The primary end point of the change in HbA(1c) over 1.0-1.5 years of CGM use compared with previous self-monitoring of blood glucose during GOLD showed a decrease in HbA(1c) of 0.35% (95% CI 0.19-0.50, P < 0.001). Time spent in hypoglycemia <3.0 mmol/L (54 mg/dL) and <4.0 mmol/L (72 mg/dL) decreased from 2.1% to 0.6% (P < 0.001) and from 5.4% to 2.9% (P < 0.001), respectively. Overall well-being (World Health Organization 5-item well-being index, P = 0.009), treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire, P < 0.001), and hypoglycemic confidence (P < 0.001) increased, while hypoglycemic fear (Hypoglycemia Fear Survey-Worry, P = 0.016) decreased and diabetes distress tended to decrease (Problem Areas in Diabetes Scale, P = 0.06). From randomization and screening in GOLD, HbA(1c) was lowered by 0.45% (P < 0.001) and 0.68% (P < 0.001) after 2.3 and 2.5 years, respectively. CONCLUSIONS The SILVER study supports beneficial long-term effects from CGM on HbA(1c), hypoglycemia, treatment satisfaction, well-being, and hypoglycemic confidence in people with T1D managed with MDI.
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| 7. |
- Olafsdottir, Arndis, 1978, et al.
(författare)
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A Randomized Clinical Trial of the Effect of Continuous Glucose Monitoring on Nocturnal Hypoglycemia, Daytime Hypoglycemia, Glycemic Variability, and Hypoglycemia Confidence in Persons with Type 1 Diabetes Treated with Multiple Daily Insulin Injections (GOLD-3)
- 2018
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Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert Inc. - 1520-9156 .- 1557-8593. ; 20:4, s. 274-284
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Tidskriftsartikel (refereegranskat)abstract
- Background: To evaluate the effects of continuous glucose monitoring (CGM) on nocturnal and daytime hypoglycemia in persons with type 1 diabetes treated with multiple daily insulin injections (MDI); we also evaluated factors related to differences in hypoglycemia confidence in this population. Methods: Evaluations were performed from the GOLD randomized trial, an open-label multicenter crossover randomized clinical trial (n=161) over 69 weeks comparing CGM to self-measurement of blood glucose (SMBG) in persons with type 1 diabetes treated with MDI. Masked CGM and the hypoglycemia confidence questionnaire were used for evaluations. Results: Time with nocturnal hypoglycemia, glucose levels <70mg/dL was reduced by 48% (10.2 vs. 19.6min each night, P<0.001) and glucose levels <54mg/dL by 65%. (3.1 vs. 8.9min, P<0.001). For the corresponding glucose cutoffs, daytime hypoglycemia was reduced by 40% (29 vs. 49min, P<0.001) and 54% (8 vs. 18min., P<0.001), respectively. Compared with SMBG, CGM use improved hypoglycemia-related confidence in social situations (P=0.016) and confidence in more broadly avoiding serious problems due to hypoglycemia (P=0.0020). Persons also reported greater confidence in detecting and responding to decreasing blood glucose levels (thereby avoiding hypoglycemia) during CGM use (P=0.0033) and indicated greater conviction that they could more freely live their lives despite the risk of hypoglycemia (P=0.022). Conclusion: CGM reduced time in both nocturnal and daytime hypoglycemia in persons with type 1 diabetes treated with MDI and improved hypoglycemia-related confidence, especially in social situations, thus contributing to greater well-being and quality of life. Trial registration: ClinicalTrials.gov, number NCT02092051.
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| 8. |
- Sandberg, Klas, 1961-
(författare)
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Effects of exercise in different phases after stroke
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Stroke is a complex disease that can vary in severity. After a stroke, patients often have long-term disabilities that require major rehabilitation efforts. Evaluation of treatment and methods are important for development of effective rehabilitation after stroke. Various forms of physiotherapy interventions have been tested in different phases after stroke, but there are still questions about timing and forms of exercise. In this work, aerobic exercise with an ergometer cycle and an in-bed cycle were used as models for intervention in subacute and acute phase after stroke. Exercise has been evaluated both after discharge from hospital and in hospital care. Aim: The overall aim of the dissertation was to study the effects of exercise in different phases after stroke of varying severity.Method: Two studies were performed in Swedish stroke units during 2013- 2018. Both studies were randomized controlled trials focusing on the effects of exercise in different phases after stroke. Study A included 56 patients with mild stroke from one hospital. Patients were discharged from the hospital and enrolled to intervention in median 22.5 days after stroke onset. All patients received usual care in a stroke unit according to national guidelines, and the intervention group received additionally aerobic exercise for 1 hour 2 times per week for 12 weeks post-discharge. The session included 2x8 minutes of intense aerobic exercise on an ergometer cycle. In study A, the effects of exercise were evaluated by aerobic exercise, walking distance and hemodynamic responses and compared to usual care.Study B included 52 patients in the acute phase of moderate to severe stroke from two hospitals. Patients were enrolled to intervention 2 days after onset, and all patients received usual care. In addition to usual care, one group received in-bed cycle exercise 20 minutes daily, 5 days per week for 3 weeks. In study B, the effects of exercise were evaluated by walking distance and hemodynamic responses and compared to usual care.Results: Study A showed that intensive aerobic exercise twice weekly for 12 weeks during the subacute phase of mild stroke improved the patient’s aerobic capacity and walking distance after the intervention period. The study also showed that exaggerated blood pressure reactions associated with exercise were common in the subacute phase but not significantly affected by participation in a 12-week exercise period.Study B showed that the addition of in-bed cycle exercise in the acute phase after more severe stroke was not superior to usual care with regards to walking distance after 3 months. From baseline to post-intervention, systolic blood pressure decreased significantly to a similar extent in both groups, but the exercise group seemed to normalize their blood pressure response to exercise to a greater extent than patients in the control group.Conclusion: For patients with mild symptoms, aerobic exercise initiated 3 weeks after stroke onset was beneficial for aerobic capacity and walking distance. In the acute phase after stroke, starting two days after onset, 3 weeks 4 of in-bed cycle exercise was not superior to usual care with regards to walking distance after 3 months. Exercise-related exaggerated blood pressure reactions were common in the subacute phase but not affected by participation in a 12- week exercise period. An effect of the in-bed cycle exercise in the acute phase after stroke seemed to be that patients randomized to the intervention normalized their blood pressure reaction in connection with exercise.
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| 9. |
- Sandberg, Klas, 1961-, et al.
(författare)
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Effects of In-Bed Cycle Exercise in Patients With Acute Stroke : A Randomized Controlled Trial
- 2020
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Ingår i: Archives of Rehabilitation Research and Clinical Translation. - : Elsevier. - 2590-1095. ; 2:4
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the effects of in-bed cycle exercise in addition to usualcare in patients with acute stroke, National Institutes of Health Stroke Scale (NIHSS) 7-42,regarding walking ability, functional outcomes, and inpatient care days.Design: Randomized controlled trial.Setting: Hospital care.Participants: Patients (NZ56) with stroke NIHSS 7-42 were recruited 24-48 hours after strokeonset from 2 stroke units in Sweden.Interventions: Both groups received usual care. The intervention group also received 20 minutes bed cycling 5 days per week with a maximum of 15 sessions.Main Outcome Measures: The primary outcome was median change in walking ability measuredwith the 6-minute walk test (6MWT). Secondary outcome measures included the median change inmodified Rankin Scale (mRS), Barthel Index (BI) for activities of daily living, and inpatient care days.Measurements were performed at baseline, post intervention (3 weeks), and at 3-month follow-up.Results: There was no significant difference in change of walking ability (6MWT) from baseline tofollow-up between the intervention and control groups (median, 105m [interquartile range [IQR,220m] vs 30m [IQR, 118m], respectively, PZ.147, dZ0.401). There were no significant differencesbetween groups regarding mRS, BI, or inpatient care days. Patients with less serious stroke (NIHSS 7-12) seemed to benefit from the intervention.Conclusion: Although this study may have been underpowered, patients with stroke NIHSS 7-42 didnot benefit from in-bed cycle exercise in addition to usual care after acute stroke. A larger study isneeded to confirm our results.
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| 10. |
- Sandberg, Klas, et al.
(författare)
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Hemodynamic responses to In-Bed Cycle Exercise in the acute phase after moderate to severe stroke : A randomized controlled trial
- 2021
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Ingår i: The Journal of Clinical Hypertension. - : Wiley. - 1524-6175 .- 1751-7176. ; 23:5, s. 1077-1084
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Tidskriftsartikel (refereegranskat)abstract
- Hemodynamic responses to exercise in the acute phase after moderate to severe stroke have remained poorly investigated. The aim of this randomized controlled study, in which 52 (32 women) patients with moderate to severe stroke were randomized to three weeks of 20 minutes in-bed cycle exercise 5 days per week or to usual care, was to explore the systolic blood pressure (SBP) response to exercise and to evaluate the impact of the intervention on the resting and post-test systolic and diastolic blood pressures and heart rate, and on the systolic blood pressure response to exercise. We found that resting SBP decreased from baseline to post-intervention in both the intervention group (147.7 +/- 18.1 mmHg to 125.3 +/- 17.1 mmHg, P < .001) and in the control group (147.8 +/- 23.7 mmHg to 131.4 +/- 14.8 mmHg, P < .001) without a significant difference between the groups (interaction P = .308). However, there was a significant difference (interaction P = .010) regarding how. SBP (change in SBP from pre-test to post-test) changed from baseline to post-intervention. In the intervention group, Delta SBP increased from -1.0 +/- 15.0 mmHg to 8.5 +/- 9.4 mmHg, P = .009, whereas in the control group, Delta SBP decreased from 7.1 + 10.9 mmHg to 4.5 + 11.8 mmHg, P = .395. We conclude that patients randomized to in-bed cycle exercise seemed to normalize their blood pressure response to exercise to a larger extent than patients in the control group.
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