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- Lundkvist, Per, et al.
(författare)
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Predictive biomarkers of rapidly developing insulin deficiency in children with type 1 diabetes
- 2024
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Ingår i: BMJ Open Diabetes Research & Care. - : BMJ Publishing Group Ltd. - 2052-4897. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The rate of progression to complete insulin deficiency varies greatly in type 1 diabetes. This constitutes a challenge, especially when randomizing patients in intervention trials aiming to preserve beta cell function. This study aimed to identify biomarkers predictive of either a rapid or slow disease progression in children with new-onset type 1 diabetes.Research design and methods A retrospective, longitudinal cohort study of children (<18 years) with type 1 diabetes (N=46) was included at diagnosis and followed until complete insulinopenia (C-peptide <0.03 nmol/L). Children were grouped into rapid progressors (n=20, loss within 30 months) and slow progressors (n=26). A sex-matched control group of healthy children (N=45) of similar age was included for comparison. Multiple biomarkers were assessed by proximity extension assay (PEA) at baseline and follow-up.Results At baseline, rapid progressors had lower C-peptide and higher autoantibody levels than slow. Three biomarkers were higher in the rapid group: carbonic anhydrase 9, corticosteroid 11-beta-dehydrogenase isozyme 1, and tumor necrosis factor receptor superfamily member 21. In a linear mixed model, 25 proteins changed over time, irrespective of group. One protein, a coxsackievirus B–adenovirus receptor (CAR) increased over time in rapid progressors. Eighty-one proteins differed between type 1 diabetes and healthy controls. Principal component analysis could not distinguish between rapid, slow, and healthy controls.Conclusions Despite differences in individual proteins, the combination of multiple biomarkers analyzed by PEA could not distinguish the rate of progression in children with new-onset type 1 diabetes. Only one marker was altered significantly when considering both time and group effects, namely CAR, which increased significantly over time in the rapid group. Nevertheless, we did find some markers that may be useful in predicting the decline of the C-peptide. Moreover, these could potentially be important for understanding type 1 diabetes pathogenesis.
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| 2. |
- Bratt, Ola, 1963, et al.
(författare)
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The Swedish national guidelines on prostate cancer, part 1: early detection, diagnostics, staging, patient support and primary management of non-metastatic disease
- 2022
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 56:4, s. 265-273
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Tidskriftsartikel (refereegranskat)abstract
- Objective There is now an unprecedented amount of evidence to consider when revising prostate cancer guidelines. We believe that there is a value in publishing summaries of national clinical guidelines in English for others to read and comment on. Methods This is part 1 of a summary of the Swedish prostate cancer guidelines that were published in June 2022. It covers the early detection, diagnostics, staging, patient support and management of the non-metastatic disease. Part 2 covers recurrence after local treatment and management of the metastatic disease. Results The 2022 Swedish guidelines include several new recommendations: rectal iodine-povidone to reduce post-biopsy infections, external beam radiation with focal boost to the tumour, use of a pre-rectal spacer to reduce rectal side effects after external beam radiotherapy in some expert centres, 6 months' concomitant and adjuvant rather than neoadjuvant and concomitant hormonal treatment together with radiotherapy for unfavourable intermediate and high-risk disease, and adjuvant abiraterone plus prednisolone together with a GnRH agonist for a subgroup of men with very high-risk disease. The Swedish guidelines differ from the European by having more restrictive recommendations regarding genetic testing and pelvic lymph node dissection, the risk group classification, recommending ultra-hypofractionated (7 fractions) external radiotherapy for intermediate and selected high-risk cancers, by not recommending any hormonal treatment together with radiotherapy for favourable intermediate-risk disease, and by recommending bicalutamide monotherapy instead of a GnRH agonist for some patient groups. Conclusions The 2022 Swedish prostate cancer guidelines include several new recommendations and some that differ from the European guidelines.
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| 3. |
- Bratt, Ola, 1963, et al.
(författare)
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The Swedish national guidelines on prostate cancer, part 2: recurrent, metastatic and castration resistant disease
- 2022
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 56:4, s. 278-284
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Tidskriftsartikel (refereegranskat)abstract
- Objective There is now an unprecedented amount of evidence to consider when revising prostate cancer guidelines. We believe that there is a value in publishing summaries of national clinical guidelines in English for others to read and comment on. Methods This is part 2 of a summary of the Swedish prostate cancer guidelines that were published in June 2022. This part covers recurrence after local treatment and management of metastatic and castration resistant disease. Part 1 covers early detection, diagnostics, staging, patient support and management of non-metastatic disease. Results The 2022 Swedish guidelines include several new recommendations. Among these is a recommendation of a period of observation with repeated PSA tests for patients with approximately 10 years' life expectancy who experience a BCR more than 2-5 years after radical prostatectomy, to allow for estimating the PSA doubling time before deciding whether to give salvage radiotherapy or not. Recent results from the PEACE-1 trial led to the recommendation of triple-treatment with a GnRH agonist, abiraterone plus prednisolone and 6 cycles of docetaxel for patients with high-volume metastatic disease who are fit for chemotherapy. The Swedish guidelines differ from the European ones by having more restrictive recommendations about genetic testing of and high-dose zoledronic acid or denosumab treatment for men with metastatic prostate cancer, and by recommending considering bicalutamide monotherapy for selected patients with low-volume metastatic disease. Conclusions The 2022 Swedish prostate cancer guidelines include several new recommendations and some that differ from the European guidelines.
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| 4. |
- Grönberg, Annika, 1970-
(författare)
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Predictors of long-term glycemic control, pancreatic function and BMI trajectory in children with type 1 diabetes
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The maintenance of normal metabolic control underpins all management of insulin dependent diabetes whether in terms of preserved beta-cell function, body composition, or family support. The hypothesis of this work was that preserved C-peptide predicts better glycemic control and lowers risk of severe hypoglycemia. It was additionally investigated whether Body Mass Index (BMI) and family structure contributes to the prediction of long-term glycemic control. Objectives: This thesis aimed to 1) identify the factors associated with residual C peptide production at least 10 years after diagnosis, 2) evaluate the association of BMI trajectory and long-term glycemic control, 3) identify early characteristics associated with rapid or slow decline of beta-cell function and how it affects the clinical course, and 4) investigate the relations of family structure at diagnosis and long-term glycemic control. Methods: Data from four cohorts were used: In the Uppsala cohort, measurement of long-term residual C-peptide was undertaken using ultrasensitive C-peptide ELISA in 73 children and adolescents <25 years, BMI trajectory prior diagnosis was evaluated in 295 children, while family structure at diagnosis was evaluated in 215 children in relation to glycemic control. In the Linköping cohort, stimulated C-peptide was assessed by mixed meal tolerance test in 50 children. Results: The cohort studies showed that better early glycemic control predicted long term residual C-peptide and that long term residual C-peptide, in turn, was protective against severe hypoglycemia. Additionally, BMI trajectory was predicted by BMI prior to the presentation of type 1 diabetes. There was no association with glycemic outcome. Children living in a whole family had a lower probability of long-term dysglycemia. Conclusions: Residual C-peptide is important for better glycemic control and to reduce complications in children with type 1 diabetes. Family structure, but not BMI trajectory, contributes to the prediction of long-term glycemic control. However, more research is needed to understand how to preserve the beta-cell function in children and to target and support families in those children with early deteriorating glycemic control to reduce future complications.
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| 5. |
- Johansson, Magnus, 1976-, et al.
(författare)
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Prolactin treatment improves engraftment and function of transplanted pancreatic islets
- 2009
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 150:4, s. 1646-1653
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Tidskriftsartikel (refereegranskat)abstract
- Transplantation of pancreatic islets is clinically used to treat type 1 diabetes, but requires multiple donors. Previous experimental studies have demonstrated that transplanted islets have a low blood vessel density, which leads to a hypoxic microenvironment. The present study tested the hypothesis that experimental prolactin pretreatment, a substance which seems to stimulate angiogenesis in endogenous islets, would increase graft blood vessel density, thereby improving transplantation outcome. Pancreatic islets from C57BL/6 mice were incubated with prolactin (500 ng/ml) or vehicle during the last 24 h of culture before syngeneic transplantation beneath the renal capsule, or recipients were injected with prolactin or vehicle for the first 7 days after transplantation. One month post-transplantation, graft vascular density, blood flow, oxygen tension, endocrine volume and function was evaluated. Also human islets were incubated with prolactin or vehicle before experimental transplantation and investigated for vascular engraftment. Vascular engraftment of syngeneically transplanted mouse islets was improved by both in vivo and in vitro prolactin pretreatment. Moreover, prolactin pretreatment in vitro of islets used for transplantation improved recovery from diabetes in a minimal islet mass model. Interestingly, also human islets subjected to prolactin treatment before experimental transplantation demonstrated improved revascularization, blood perfusion and oxygen tension when evaluated one month post-transplantation. We conclude that prolactin may improve engraftment of transplanted pancreatic islets. The protocol with pretreatment of islets ex vivo could minimize the risk of side effects when used in the clinical setting.
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| 6. |
- Johansson, Åsa, 1981-, et al.
(författare)
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Angiostatic factors normally restrict islet endothelial cell proliferation and migration : implications for islet transplantation
- 2009
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 22:12, s. 1182-1188
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Tidskriftsartikel (refereegranskat)abstract
- New blood vessel formation in transplanted islets occurs within 7-14 days posttransplantation through both the expansion of donor islet endothelium and ingrowth of blood vessels from the implantation organ. However, several studies indicate that although the islets attract recipient blood vessels, the formed intra-islet vascular network is insufficient, which affects islet posttransplant function. This study aimed to develop an in vitro model to investigate the migration and proliferation properties of isolated liver and islet endothelium. Rat islet or liver endothelium was purified using Bandeiraea simplicifolia (BS-1)-coated Dynabeads. The liver endothelium displayed an increased migration towards islet-conditioned medium, and this chemo-attractant effect was fully prevented by adding a neutralizing vascular endothelial growth factor (VEGF)-antibody. In contrast, islet-produced VEGF failed to induce islet endothelial cell migration and only had marginal effects on islet endothelial cell proliferation. These properties could, however, be activated through blocking the effects of either endostatin, thrombospondin-1 or α1-antitrypsin. In conclusion, VEGF may attract recipient blood vessels towards intrahepatically transplanted islets, but intra-islet vascular expansion is hampered by angiostatic factors present within the islets and the islet endothelium. Inhibition of these early after transplantation may provide a strategy to restore the islet vascular network and improve islet graft function.
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