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- Henricsson, M., et al.
(författare)
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Mortality in diabetic patients participating in an ophthalmological control and screening programme
- 1997
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Ingår i: Diabetic Medicine. - 0742-3071. ; 14:7, s. 576-583
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this follow-up study has been to assess retinopathy and change of treatment to insulin therapy as risk factors for mortality in diabetic patients participating in a control and screening programme for retinopathy. A total of 3220 diabetic patients, 483 with an age at diagnosis <30 years, and 2737 with an age at diagnosis ≤30 years, were included. Retinopathy was graded on fundus photographs using the Wisconsin Scale, and the visual acuity was assessed. The average HbA(1c) value was calculated for each patient for the previous 8 years to estimate long-term glycaemic control. Mortality data were obtained from death certificates. Two hundred and sixty-three diabetic patients (8.2 %) died during the mean follow-up time of 3.4 years, 13 (2.7 %) of those with younger-onset (<30 years) and 250 (9.1%) of those with older-onset (≤30 years) diabetes. Of them, 148 (56.3 %) died from cardiovascular and 23 (8.7 %) from cerebrovascular disorders. After adjusting for differences in age and sex, more severe retinopathy and the use of antihypertensive drugs were associated with a decreased overall survival rate as well as an increased mortality from cardiovascular and cerebrovascular diseases. A statistically significant association between HbA(tc) values in the highest quartile, i.e. ≤8.4 %, and cardiovascular and all cause mortality did not remain when retinopathy was entered into the multivariate analyses. Duration of diabetes, but not change of treatment to insulin therapy, was associated with higher cardiovascular mortality in patients whose diabetes was diagnosed after the age of 30 years. We conclude that severe retinopathy, use of antihypertensive drugs, and poor glycaemic control predicted death from cardiovascular disease in diabetic patients participating in an ophthalmological screening programme.
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| 2. |
- Schneider, K. M., et al.
(författare)
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Gut microbiota depletion exacerbates cholestatic liver injury via loss of FXR signalling
- 2021
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Ingår i: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 3:9, s. 1228-1241
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Tidskriftsartikel (refereegranskat)abstract
- Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology for which there are no approved therapeutic options. Patients with PSC display changes in gut microbiota and in bile acid (BA) composition; however, the contribution of these alterations to disease pathogenesis remains controversial. Here we identify a role for microbiota-dependent changes in BA synthesis that modulates PSC pathophysiology. In a genetic mouse model of PSC, we show that loss of microbiota-mediated negative feedback control of BA synthesis results in increased hepatic BA concentrations, disruption of bile duct barrier function and, consequently, fatal liver injury. We further show that these changes are dependent on decreased BA signalling to the farnesoid X receptor, which modulates the activity of the rate-limiting enzyme in BA synthesis, CYP7A1. Moreover, patients with advanced stages of PSC show suppressed BA synthesis as measured by serum C4 levels, which is associated with poor disease prognosis. Our preclinical data highlight the microbiota-dependent dynamics of BA metabolism in cholestatic liver disease, which could be important for future therapies targeting BA and gut microbiome interactions, and identify C4 as a potential biomarker to functionally stratify patients with PSC and predict disease outcomes. Patients with primary sclerosing cholangitis (PSC), a chronic cholestatic liver disease, display changes in the gut microbiota and in bile acid composition. Schneider, Candels and colleagues identify a role for microbiota-dependent regulation of bile acid synthesis through farnesoid X receptor signalling, which is relevant for PSC disease progression.
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| 3. |
- Alvarsson, M, et al.
(författare)
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Beneficial effects of insulin versus sulphonylurea on insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients
- 2003
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 26:8, s. 2231-2237
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - To evaluate whether treatment with insulin in recently diagnosed type 2 diabetes is advantageous compared with glibenclamide treatment. RESEARCH DESIGN AND METHODS - ▀-Cell function, glycemic control, and quality of life were monitored over 2 years in 39 patients with islet cell antibody-negative type 2 diabetes diagnosed 0-2 years before inclusion in a Swedish multicenter randomized clinical trial. Patients were randomized to either two daily injections of premixed 30% soluble and 70% NPH insulin or glibenclamide (3.5-10.5 mg daily). C-peptide-glucagon tests were performed yearly in duplicate after 2-3 days of temporary withdrawal of treatment. RESULTS - After 1 year the glucagon-stimulated C-peptide response was increased in the insulin-treated group by 0.14 ▒ 0.08 nmol/l, whereas it was decreased by 0.12 ▒ 0.08 nmol/l in the glibenclamide group, P < 0.02 for difference between groups. After 2 years, fasting insulin levels were higher after treatment withdrawal in the insulin-treated versus the glibenclamide-treated group (P = 0.02). HbA1c levels decreased significantly during the first year in both groups, however, at the end of the second year, HbA1c had deteriorated in the glibenclamide group (P < 0.01), but not in the insulin-treated group. The difference in evolution of HbA1c during the second year was significant between groups, P < 0.02 A questionnaire indicated no difference in well-being related to treatment. CONCLUSIONS - Early insulin versus glibenclamide treatment in type 2 diabetes temporarily prolongs endogenous insulin secretion and promotes better metabolic control.
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| 7. |
- Castellanos-Jankiewicz, A., et al.
(författare)
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Short Article Hypothalamic bile acid-TGR5 signaling protects from obesity
- 2021
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 33:7
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Tidskriftsartikel (refereegranskat)abstract
- Bile acids (BAs) improve metabolism and exert anti-obesity effects through the activation of the Takeda G protein-coupled receptor 5 (TGR5) in peripheral tissues. TGR5 is also found in the brain hypothalamus, but whether hypothalamic BA signaling is implicated in body weight control and obesity pathophysiology remains unknown. Here we show that hypothalamic BA content is reduced in diet-induced obese mice. Central administration of BAs or a specific TGR5 agonist in these animals decreases body weight and fat mass by activating the sympathetic nervous system, thereby promoting negative energy balance. Conversely, genetic downregulation of hypothalamic TGR5 expression in the mediobasal hypothalamus favors the development of obesity and worsens established obesity by blunting sympathetic activity. Lastly, hypothalamic TGR5 signaling is required for the anti-obesity action of dietary BA supplementation. Together, these findings identify hypothalamic TGR5 signaling as a key mediator of a top-down neural mechanism that counteracts diet induced obesity.
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| 8. |
- Diamantopoulou, S, et al.
(författare)
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ADHD symptoms and peer relations of children in a community sample: Examining associated problems, self-perceptions, and gender differences
- 2005
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Ingår i: International Journal of Behavioral Development. - 0165-0254. ; 29, s. 388-398
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Tidskriftsartikel (refereegranskat)abstract
- This study examined children's peer relations in relation to gender, symptoms of attention-deficit/hyperactivity disorder (ADHD), associated behaviour problems, prosociality, and self-perceptions, in a community sample. Six hundred and thirty-five 12-year-old children (314 girls) provided peer nominations and rated feelings of loneliness and self-perceptions regarding global self-worth and behavioural conduct. We obtained teacher ratings of ADHD symptoms, conduct and internalising problems, and prosociality. ADHD symptoms, conduct problems, internalising problems, and low levels of prosociality were all related to higher levels of peer dislike. Despite ADHD symptoms being related to more peer dislike, children with high levels of ADHD symptoms did not report more feelings of loneliness. The self-perceptions of children with high levels of ADHD were not related to peer dislike. Although high levels of ADHD symptoms were not related to peer dislike in girls, peers tolerated higher levels of ADHD symptoms among boys than among girls, providing support for the "gender appropriateness hypothesis'' regarding the impact and influence of ADHD symptomatology upon the peer relations of children within a community sample.
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| 9. |
- Fruhwürth, Stefanie, 1987, et al.
(författare)
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TREM2 is down-regulated by HSV1 in microglia and involved in antiviral defense in the brain
- 2023
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Ingår i: Science Advances. - 2375-2548. ; 9:33
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Tidskriftsartikel (refereegranskat)abstract
- Immunological control of viral infections in the brain exerts immediate protection and also long-term maintenance of brain integrity. Microglia are important for antiviral defense in the brain. Here, we report that herpes simplex virus type 1 (HSV1) infection of human induced pluripotent stem cell (hiPSC)-derived microglia down-regulates expression of genes in the TREM2 pathway. TREM2 was found to be important for virus-induced IFNB induction through the DNA-sensing cGAS-STING pathway in microglia and for phagocytosis of HSV1-infected neurons. Consequently, TREM2 depletion increased susceptibility to HSV1 infection in human microglia-neuron cocultures and in the mouse brain. TREM2 augmented STING signaling and activation of downstream targets TBK1 and IRF3. Thus, TREM2 is important for the antiviral immune response in microglia. Since TREM2 loss-of-function mutations and HSV1 serological status are both linked to Alzheimer's disease, this work poses the question whether genetic or virus-induced alterations of TREM2 activity predispose to post-infection neurological pathologies.
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| 10. |
- Hagströmer, Björn, et al.
(författare)
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Components of the Bid-Ask Spread and Variance : A Unified Approach
- 2016
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Ingår i: Journal of futures markets. - : Wiley. - 0270-7314 .- 1096-9934. ; 36:6, s. 545-563
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Tidskriftsartikel (refereegranskat)abstract
- We develop a structural model for the price formation and liquidity supply of an asset. Ourmodel facilitates decompositions of both the bid–ask spread and the return variance intocomponents related to adverse selection, inventory, and order processing costs. Furthermore,the model shows how the fragmentation of trading volume across trading venues influencesinventory pressure and price discovery. We use the model to analyze intraday price formationfor gold futures traded at the Shanghai Futures Exchange. We find that order processing costsexplain about 50% of the futures bid–ask spread, whereas the remaining 50% is equally due toasymmetric information and to inventory costs. About a third of the variance in futures returnsis attributable to microstructure noise. Trading at the spot market has a significant influence onfutures price discovery, but only a limited impact on the futures bid–ask spread.
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