| 1. |
- Nyström, Thomas, et al.
(author)
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Evaluation of Effects of Continuous Glucose Monitoring on Physical Activity Habits and Blood Lipid Levels in Persons With Type 1 Diabetes Managed With MDI: An Analysis Based on the GOLD Randomized Trial (GOLD 8)
- 2024
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In: Journal of diabetes science and technology. - : SAGE Publications. - 1932-2968. ; 18:1, s. 89-98
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Journal article (peer-reviewed)abstract
- Background: People with type 1 diabetes generally view it easier to exercise when having continuous information of the glucose levels. We evaluated whether patients with type 1 diabetes managed with multiple daily insulin injections (MDI) exercised more after initiating continuous glucose monitoring (CGM) and whether the improved glycemic control and well-being associated with CGM translates into improved blood lipids and markers of inflammation. Method: The GOLD trial was a randomized cross-over trial over 16 months where patients used either CGM or capillary self-monitoring of blood glucose (SMBG) over six months, with a four-month wash-out period between the two treatment periods. We compared grade of physical activity, blood lipids, apolipoproteins, and high-sensitivity C-reactive protein (hsCRP) levels during CGM and SMBG. Results: There were 116 patients with information of physical activity estimated by the International Physical Activity Questionnaire (IPAQ) during both CGM and SMBG. No changes were found during CGM or SMBG, IPAQ scores 3305 versus 3878 (P =.16). In 136 participants with information of blood lipid levels with no change in lipid-lowering medication during the two treatment periods, HbA1c differed by 4.2 mmol/mol (NGSP 0.39%) between SMBG and CGM treatment (P <.001). No significant changes existed in low-density lipoprotein, high-density lipoprotein, triglycerides, total cholesterol, apolipoprotein A1, apolipoprotein B1, or hsCRP, during CGM and SMBG. Conclusion: Although many patients experience it easier to perform physical activity when monitoring glucose levels with CGM, it does not influence the amount of physical activity in persons with type 1 diabetes. Blood lipids, apolipoprotein, and hsCRP levels were similar during CGM and SMBG.
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| 2. |
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| 3. |
- Holmer, Magnus
(author)
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Aspects of diagnosis, prognosis and treatment of nonalcoholic fatty liver disease
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally. NAFLD is caused by obesity, often in combination with type 2 diabetes mellitus (T2D). Lifestyle modifications that lead to weight loss, primarily diet change, is the only treatment proven to reverse steatosis and nonalcoholic steatohepatitis (NASH). The projects included in this thesis explore different aspects of epidemiology, pathophysiology, and treatment of NAFLD. A significant number of NAFLD patients will develop cirrhosis, and NAFLD has become a leading cause for the need of a liver transplantation in several parts of the world. We first performed a population-based cohort study including 4609 patients from the Nordic Liver Transplant Registry who were listed for liver transplantation between 1994 to 2015. We observed that NAFLD is increasing as a cause of severe liver disease in the Nordic countries. Common genetic variants have been linked to more advanced forms of NAFLD in cross- sectional studies. How these polymorphisms affect the long-term risk of progressive disease is less known. Study 2 was a cohort study on 546 patients with NAFLD and 5,234 reference individuals matched on age, sex, and municipality. DNA samples were collected from all subjects with NAFLD. Genetic variants previously associated with NAFLD, NASH, and fibrosis were determined from blood samples or stored biopsies. Long-term outcomes were collected from national patient registers during a median follow-up of 20 years. The main finding was an association of the G/G genotype of the patatin-like phospholipase domain containing 3 (PNPLA3 rs738409) gene with an increased prevalence of NASH at baseline and the risk of developing severe liver disease during follow-up. More research is needed to establish the role of adipose tissue in the pathogenesis of NAFLD and NASH. In study 3 we collected subcutaneous adipose tissue (SAT) from 32 patients with NAFLD and 15 healthy controls matched on BMI. We studied the association between SAT morphology and NASH or fibrosis. We found that subjects with NAFLD have hypertrophic SAT adipocytes compared to controls. Using RNA-sequencing of SAT, we explored genes that were differently expressed in subjects with NASH and compared our results to those seen in previous studies on morbidly obese subjects. The final study of this thesis was an open label randomized controlled trial on 74 patients with NAFLD. We compared the efficacy of a low-carb high-fat diet (the LCHF diet), intermittent calorie restriction (the 5:2 diet) and standard diet recommendations on reduction of hepatic steatosis. Liver fat content was measured with magnetic resonance spectroscopy at baseline and after 12 weeks of treatment. The main finding was that the LCHF and the 5:2 diets were equally effective in reducing steatosis. Both were superior to the standard treatment given to the control group. The results of this thesis have implications on several aspects of NAFLD epidemiology, pathogenesis, and treatment.
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| 4. |
- Holmer, Magnus, et al.
(author)
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Effect of common genetic variants on the risk of cirrhosis in non-alcoholic fatty liver disease during 20 years of follow-up
- 2022
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In: Liver international (Print). - : Wiley. - 1478-3223 .- 1478-3231. ; 42:12, s. 2769-2780
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Journal article (peer-reviewed)abstract
- Background and Aims Several genotypes associate with a worse histopathological profile in patients with non-alcoholic fatty liver disease (NAFLD). Whether genotypes impact long-term outcomes is unclear. We investigated the importance of PNPLA3, TM6SF2, MBOAT7 and GCKR genotype for the development of severe outcomes in NAFLD. Method DNA samples were collected from 546 patients with NAFLD. Advanced fibrosis was diagnosed by liver biopsy or elastography. Non-alcoholic steatohepatitis (NASH) was histologically defined. Additionally, 5396 controls matched for age, sex and municipality were identified from population-based registers. Events of severe liver disease and all-cause mortality were collected from national registries. Hazard ratios (HRs) adjusted for age, sex, body mass index and type 2 diabetes were estimated with Cox regression. Results In NAFLD, the G/G genotype of PNPLA3 was associated with a higher prevalence of NASH at baseline (odds ratio [OR] 3.67, 95% CI = 1.66-8.08), but not with advanced fibrosis (OR 1.81, 95% CI = 0.79-4.14). After up to 40 years of follow-up, the PNPLA3 G/G genotype was associated with a higher rate of severe liver disease (adjusted hazard ratio [aHR] 2.27, 95% CI = 1.15-4.47) compared with the C/C variant. NAFLD patients developed cirrhosis at a higher rate than controls (aHR 9.00, 95% CI = 6.85-11.83). The PNPLA3 G/G genotype accentuated this rate (aHR 23.32, 95% = CI 9.14-59.47). Overall mortality was not affected by any genetic variant. Conclusion The PNPLA3 G/G genotype is associated with an increased rate of cirrhosis in NAFLD. Our results suggest that assessment of the PNPLA3 genotype is of clinical relevance in patients with NAFLD to individualize monitoring and therapeutic strategies.
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| 5. |
- Holmer, Magnus, et al.
(author)
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Extended lymph node dissection in patients with urothelial cell carcinoma of the bladder: can it make a difference?
- 2009
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In: World Journal of Urology. - : Springer Science and Business Media LLC. - 1433-8726 .- 0724-4983. ; 27, s. 521-526
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Journal article (peer-reviewed)abstract
- OBJECTIVE: We compared extended and limited lymph node dissections performed during radical cystectomy with regard to impact on survival and time to recurrence in bladder cancer patients. METHODS: We analyzed 170 patients who underwent radical cystectomy for urothelial carcinoma between January 1997 and December 2005. From 1997 to 2000, 69 of the patients were subjected to limited lymph dissection that included perivesical nodes and nodes in the obturator fossa. In 2001-2005, the remaining 101 patients underwent extended lymph dissection that included perivesical nodes; nodes in the obturator fossa; the internal, external, and common iliac nodes; and the presacral nodes. RESULTS: Tumors penetrating the bladder wall (pT3 and pT4a) were more common in the extended than in the limited dissection group (48 and 33%, respectively). The median numbers of lymph nodes removed in the two groups were 37 and 8, respectively. Lymph node metastases were detected in 38% of the extended dissection patients but only in 17% of the limited dissection patients. There was no significant difference in survival or time to recurrence between the two groups. Subgroup analyses showed a significantly longer time to recurrence (HR 0.45, 95% CI 0.22-0.93; P = 0.032) in patients with non-organ-confined disease who underwent extended lymph node dissection. In a multivariate analysis adjusting for tumor stage, lymph node status, age, sex, and adjuvant chemotherapy, there was a significantly improved survival (HR 0.47, 95% CI 0.25-0.88; P = 0.018) and time to recurrence (HR 0.42, 95% CI 0.23-0.79; P = 0.007) in the patients with extended lymph node dissections. CONCLUSIONS: Extended lymph node dissection did not improve disease-specific survival, but was in multivariate analysis related to significantly improved disease-specific survival and prolonged time to recurrence in radical cystectomy patients. These results should be interpreted cautiously, since they might have been affected by stage migration and the shorter follow-up in the extended dissection group.
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| 6. |
- Isaksson, Sofia Sterner, et al.
(author)
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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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In: DIABETOLOGIA. - : SPRINGER. - 0012-186X .- 1432-0428.
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Journal article (peer-reviewed)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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| 7. |
- Jansson, Tomas, et al.
(author)
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An ultrasonic method for detection of fluid properties in the paranasal sinuses
- 2005
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In: Proceedings of the International Federation for Medical & Biomedical Engineering. 13th Nordic Baltic Conference on Biomedical Engineering and Medical Physics. - 9173059102 ; , s. 115-116
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Conference paper (peer-reviewed)abstract
- We propose a method for detection of the degree of infection in the paranasal sinuses utilizing a previously published method whereby the viscosity in a sealed container may be measured using an ultrasound Doppler method. As ultrasound propagates in a liquid medium, due to attenuation, the resulting pressure gradient will cause the liquid to move in the propagation direction - the wellknown effect of acoustic streaming. The streaming velocity will, for a given acoustic output, be proportional to the viscosity of the fluid. In this study, we verify that acoustic streaming can be induced in an anthropomorphic sinus phantom cast from a human cranium. The sinus phantom was made from agar with added graphite providing sound attenuation prior to the sinus cavity corresponding to an in vivo situation. A number of water-glycerol solutions with scattering particles, were prepared to mimic a clinically interesting range of viscosities (7-47 mPas). Using a 4.2 MHz continuous wave Doppler probe, clearly detectable Doppler shifts in the range of 6.5 to 20 Hz were recorded. A linear relationship was found between the Doppler shifts and 1/viscosity (R2=0.94, corrected for the square-law dependence of sound speed variation due to varying glycerol concentration)
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| 8. |
- Jansson, Tomas, et al.
(author)
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Ultrasound Doppler for improved diagnosis of disease in the paranasal sinuses
- 2005
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In: Proceedings - IEEE Ultrasonics Symposium. - 1051-0117. - 0780393821 ; 2, s. 839-841
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Conference paper (peer-reviewed)abstract
- We propose a method to improve the diagnosis of infection in the paranasal sinuses, distinguishing between mucous and serous cases. The method utilizes a previously published method whereby the viscosity in a sealed container may be measured using an ultrasound Doppler method. As ultrasound propagates in a liquid medium, due to attenuation, the resulting pressure gradient will cause the liquid to move in the propagation direction - the wellknown effect of acoustic streaming. The streaming velocity will, for a given acoustic output, be proportional to the viscosity of the fluid. In this study, we verify that acoustic streaming can be induced in an anthropomorphic sinus phantom cast from a human cranium. The sinus phantom was made from agar with added graphite providing sound attenuation prior to the sinus cavity corresponding to an in vivo situation. A number of water-glycerol solutions with scattering particles, were prepared to mimic a clinically interesting range of viscosities (7-47 mPas). Using a 4.2 MHz continuous wave Doppler probe, clearly detectable mean Doppler shifts in the range of 6.5 to 20 Hz were recorded A linear relationship was found between the Doppler shifts and 1/viscosity (R2=0.94, corrected for the square-law dependence of sound speed variation due to varying glycerol concentration).
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| 9. |
- Jönsson, Peter, et al.
(author)
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Feasibility of measuring acoustic streaming for improved diagnosis of rhinosinusitis
- 2008
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In: Ultrasound in Medicine and Biology. - : Elsevier BV. - 0301-5629. ; 34:2, s. 228-238
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Journal article (peer-reviewed)abstract
- No noninvasive methods exist currently with the capability of distinguishing between various stages of a sinus infection. We studied a method based on induced acoustic streaming in the accumulated fluid within the maxillary sinuses. The hypothesis was that acoustic streaming will not be induced at clinically acceptable intensity levels in infectious mucous fluid because of its high viscosity, whereas detected acoustic streaming is a strong indication that the sinus content is a noninfectious serous fluid. As a model, an anthropomorphic sinus phantom with bovine cortical bone to mimic the bone surrounding the maxillary sinus was constructed. Milk (1.5% fat content) was used as model fluid. From fluid and bone attenuation measurements, an ultrasound frequency of about 5 MHz was estimated to produce the highest acoustic streaming in the sinus phantom. Simulations of the acoustic streaming in a sealed cavity also showed that the width of the ultrasound beam should be about half the size of the cavity to optimize the streaming velocity. With a 4.9-MHz continuous-wave transducer operating at a spatial peak temporal average intensity of 640 mW/cm(2), an acoustic streaming velocity of 0.19 cm/s was generated and detected in the sinus phantom.
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| 10. |
- Liedberg, Fredrik, et al.
(author)
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Preoperative staging of locally advanced bladder cancer before radical cystectomy using 3 tesla magnetic resonance imaging with a standardized protocol
- 2013
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In: Scandinavian Journal of Urology. - : Informa UK Limited. - 2168-1813 .- 2168-1805. ; 47:2, s. 108-112
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Journal article (peer-reviewed)abstract
- Objective. The correlation between clinical tumour stage and pathological tumour stage in radical cystectomy specimens in locally advanced bladder cancer is suboptimal. Radiological methods have so far been of limited value in preoperative staging; however, the resolution with magnetic resonance imaging (MRI) has improved with further technical developments of the method. The aim of this study was to compare tumour stage at MRI with pathological tumour stage in the cystectomy specimen. Material and methods. Prospectively, 53 patients with invasive bladder cancer were preoperatively investigated with 3 tesla (3T) MRI using a standardized protocol. 3T MRI was performed at a standardized bladder volume. Clinical tumour stage, tumour stage at MRI and pathological tumour stage groups (Ta, Cis, T1/T2a, T2b/T3a, T3b/T4a), were compared, and sensitivity and specificity for organ-confined and non-organ-confined disease (stage T3a or above or lymph-node metastases) were analysed. Results. MRI overestimated tumour stage in 23 out of 47 patients (49%), whereas six patients (13%) were understaged. In the three groups of patients (those with the same stage group at MRI as in the cystectomy specimen, overestimated tumour stage and understaged patients), the time interval between transurethral resection of the bladder (TURB) and MRI did not differ significantly. Conclusions. Preoperative MRI overestimated tumour stage in almost half of the patients investigated in this study. Postoperative changes could have contributed to such overstaging with MRI.
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