| 1. |
- Almby, Kristina E., et al.
(författare)
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Effects of Gastric Bypass Surgery on the Brain : Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:6, s. 1265-1277
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Tidskriftsartikel (refereegranskat)abstract
- While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by F-18-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.
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| 2. |
- Sarsenbayeva, Assel, et al.
(författare)
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Impaired HMG-CoA Reductase Activity Caused by Genetic Variants or Statin Exposure: Impact on Human Adipose Tissue, beta-Cells and Metabolome
- 2021
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Inhibition of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase is associated with an increased risk of new-onset type 2 diabetes. We studied the association of genetic or pharmacological HMG-CoA reductase inhibition with plasma and adipose tissue (AT) metabolome and AT metabolic pathways. We also investigated the effects of statin-mediated pharmacological inhibition of HMG-CoA reductase on systemic insulin sensitivity by measuring the HOMA-IR index in subjects with or without statin therapy. The direct effects of simvastatin (20-250 nM) or its active metabolite simvastatin hydroxy acid (SA) (8-30 nM) were investigated on human adipocyte glucose uptake, lipolysis, and differentiation and pancreatic insulin secretion. We observed that the LDL-lowering HMGCR rs12916-T allele was negatively associated with plasma phosphatidylcholines and sphingomyelins, and HMGCR expression in AT was correlated with various metabolic and mitochondrial pathways. Clinical data showed that statin treatment was associated with HOMA-IR index after adjustment for age, sex, BMI, HbA1c, LDL-c levels, and diabetes status in the subjects. Supra-therapeutic concentrations of simvastatin reduced glucose uptake in adipocytes and normalized fatty acid-induced insulin hypersecretion from beta-cells. Our data suggest that inhibition of HMG-CoA reductase is associated with insulin resistance. However, statins have a very mild direct effect on AT and pancreas, hence, other tissues as the liver or muscle appear to be of greater importance.
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| 3. |
- Toivonen, Fanni, et al.
(författare)
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Neurologic Injury in Patients Treated With Extracorporeal Membrane Oxygenation for Postcardiotomy Cardiogenic Shock
- 2021
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Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1053-0770 .- 1532-8422. ; 35:9, s. 2669-2680
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the frequency, predictors, and outcomes of neurologic injury in adults treated with postcardiotomy extracorporeal membrane oxygenation (PC-ECMO). Design: A retrospective multicenter registry study. Setting: Twenty-one European institutions where cardiac surgery is performed. Participants: A total of 781 adult patients who required PC-ECMO during 2010 to 2018 were divided into patients with neurologic injury (NI) and patients without neurologic injury (NNI). Measurements and Main Results: Baseline and operative data, in-hospital outcomes, and long-term survival were compared between the NI and the NNI groups. Predictors of neurologic injury were identified. A subgroup analysis according to the type of neurologic injury was performed. Overall, NI occurred in 19% of patients in the overall series, but the proportion of patients with NI ranged from 0% to 65% among the centers. Ischemic stroke occurred in 84 patients and hemorrhagic stroke in 47 patients. Emergency procedure was the sole independent predictor of NI. In-hospital mortality was higher in the NI group than in the NNI group (79% v 61%, p < 0.001). The one-year survival was lower in the NI group (17%) compared with the NNI group (37%). Long-term survival did not differ between patients with ischemic stroke and those with hemorrhagic stroke. Conclusion: Neurologic injury during PC-ECMO is common and associated with a dismal prognosis. There is considerable interinstitutional variation in the proportion of neurologic injury in PC-ECMO-treated adults. Well-known risk factors for stroke are not associated with neurologic injury in this setting.
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