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- Ahlin, Sofie, 1985, et al.
(författare)
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A new sensitive and accurate model to predict moderate to severe obstructive sleep apnea in patients with obesity
- 2019
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Ingår i: Medicine (United States). - : Ovid Technologies (Wolters Kluwer Health). - 0025-7974 .- 1536-5964. ; 98:32
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Tidskriftsartikel (refereegranskat)abstract
- Obstructive sleep apnea (OSA) has a high prevalence in patients with obesity. Only patients with clinical symptoms of OSA are admitted to polysomnography; however, many patients with OSA are asymptomatic. We aimed to create and validate a population-based risk score that predicts the severity of OSA in patients with obesity. We here report the cross-sectional analysis at baseline of an ongoing study investigating the long-term effect of bariatric surgery on OSA. One-hundred sixty-one patients of the Obesity Center of the Catholic University Hospital in Rome, Italy were included in the study. The patients underwent overnight cardiorespiratory monitoring, blood chemistry analyses, hepatic ultrasound, and anthropometric measurements. The patients were divided into 2 groups according OSA severity assessed by the apnea-hypopnea index (AHI): AHI < 15 = no or mild and AHI >= 15 moderate to severe OSA. A statistical prediction model was created and validated. C statistics was used to evaluate the discrimination performance of the model. The prevalence of OSA was 96.3% with 74.5% of the subjects having moderate/severe OSA. Sex, body mass index, diabetes, and age were included in the final prediction model that had excellent discrimination ability (C statistics equals to 83%). An OSA risk chart score for clinical use was created. Patients with severe obesity are at a very high risk for moderate or severe OSA in particular if they are men, older, more obese, and/or with type 2 diabetes. The OSA risk chart can be useful for general practitioners and patients as well as for bariatric surgeons to select patients with high risk of moderate to severe OSA for further polysomnography.
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- Leusen, JHW, et al.
(författare)
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Disturbed interaction of p21-rac with mutated p67-phox causes chronic granulomatous disease
- 1996
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 184:4, s. 1243-1249
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Tidskriftsartikel (refereegranskat)abstract
- Chronic granulomatous disease (CGD) is characterized by the failure of phagocytic leukocytes to generate superoxide, needed for the intracellular killing of microorganisms. This is caused by mutations in any one of the four subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In a rare, autosomal recessive form of CGD, a 67-kD cytosolic component of this enzyme (p67-phox) is missing. We here report on a patient with a mutation in the p67-phox gene that leads to expression of a nonfunctional p67-phox protein. The purified granulocytes of this patient failed to produce superoxide and contained about half of the normal amount of p67-phox. Analysis of the cDNA and genomic DNA of this patient showed that the patient is a compound heterozygote for a triplet nucleotide deletion in the p67-phox gene, predicting an in-frame deletion of lysine 58 in the p67-phox protein and a larger deletion of 11-13 kb in the other allele. Interestingly, the 58Lys deletion in p67-phox disrupts the interaction with p21-rac1, a ras-related protein involved in the activation of the NADPH oxidase. In contrast to normal neutrophils, in which p47-phox and p67-phox translocate to the plasma membrane upon cell activation, the cells of the patient did not show this translocation, indicating that an interaction between p67-phox and p21-rac1 is essential for translocation of these cytosolic proteins and activation of the NADPH oxidase. Moreover, this CGD patient represents the first case of disease caused by a disturbed binding of a ras-related protein to its target protein.
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- Ahlin, Sofie, 1985, et al.
(författare)
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Metabolite Changes After Metabolic Surgery – Associations to Parameters Reflecting Glucose Homeostasis and Lipid Levels
- 2021
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To test the hypothesis that adipose tissue gene expression patterns would be affected by metabolic surgery and we aimed to identify genes and metabolic pathways as well as metabolites correlating with metabolic changes following metabolic surgery. Materials and Methods: This observational study was conducted at the Obesity Unit at the Catholic University Hospital of the Sacred Heart in Rome, Italy. Fifteen patients, of which six patients underwent Roux-en-Y gastric bypass and nine patients underwent biliopancreatic diversion, were included. The participants underwent an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Small polar metabolites were analyzed with a two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS). Gene expression analysis of genes related to metabolism of amino acids and fatty acids were analyzed in subcutaneous adipose tissue. All procedures were performed at study start and at follow-up (after 185.3 ± 72.9 days). Results: Twelve metabolites were significantly changed after metabolic surgery. Six metabolites were identified as 3-indoleacetic acid, 2-hydroxybutyric acid, valine, glutamic acid, 4-hydroxybenzeneacetic acid and alpha-tocopherol. The branched chain amino acids displayed a significant decrease together with a decrease in BCAT1 adipose tissue mRNA levels. Changes in the identified metabolites were associated to changes in lipid, insulin and glucose levels. Conclusions: Our study has identified metabolites and metabolic pathways that are altered by metabolic surgery and may be used as biomarkers for metabolic improvement. Copyright © 2021 Ahlin, Cefalo, Bondia-Pons, Trošt, Capristo, Marini, Romero, Zorzano, Gastaldelli, Mingrone and Nolan.
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- Klintman, Marie, et al.
(författare)
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The Prognostic Value of Mitotic Activity Index (MAI), Phosphohistone H3 (PPH3), Cyclin B1, Cyclin A, and Ki67, Alone and in Combinations, in Node-Negative Premenopausal Breast Cancer
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Proliferation, either as the main common denominator in genetic profiles, or in the form of single factors such as Ki67, is recommended for clinical use especially in estrogen receptor-positive (ER) patients. However, due to high costs of genetic profiles and lack of reproducibility for Ki67, studies on other proliferation factors are warranted. The aim of the present study was to evaluate the prognostic value of the proliferation factors mitotic activity index (MAI), phosphohistone H3 (PPH3), cyclin B1, cyclin A and Ki67, alone and in combinations. In 222 consecutive premenopausal node-negative breast cancer patients (87% without adjuvant medical treatment), MAI was assessed on whole tissue sections (predefined cut-off >= 10 mitoses), and PPH3, cyclin B1, cyclin A, and Ki67 on tissue microarray (predefined cut-offs 7th decile). In univariable analysis (high versus low) the strongest prognostic proliferation factor for 10-year distant disease-free survival was MAI (Hazard Ratio (HR)=3.3, 95% Confidence Interval (CI): 1.8-6.1), followed by PPH3, cyclin A, Ki67, and cyclin B1. A combination variable, with patients with MAI and/or cyclin A high defined as high-risk, had even stronger prognostic value (HR=4.2, 95% CI: 2.2-7). When stratifying for ER-status, MAI was a significant prognostic factor in ER-positive patients only (HR=7.0, 95% CI: 3.1-16). Stratified for histological grade, MAI added prognostic value in grade 2 (HR=7.2, 95% CI: 3.1-38) and grade 1 patients. In multivariable analysis including HER2, age, adjuvant medical treatment, ER, and one proliferation factor at a time, only MAI (HR=2.7, 95% CI: 1.1-6.7), and cyclin A (HR=2.7, 95% CI: 1.2-6.0) remained independently prognostic. In conclusion this study confirms the strong prognostic value of all proliferation factors, especially MAI and cyclin A, in all patients, and more specifically in ER-positive patients, and patients with histological grade 2 and 1. Additionally, by combining two proliferation factors, an even stronger prognostic value may be found.
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- Mingrone, G., et al.
(författare)
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Insulin sensitivity depends on the route of glucose administration
- 2020
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 63, s. 1382-1395
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis The small intestine plays an important role in hepatic and whole-body insulin sensitivity, as shown by bariatric surgery. Our goal was to study whether routes and dose of glucose administration have an acute impact on insulin sensitivity. The primary endpoint of this proof-of-concept study was the difference in insulin-mediated metabolic clearance rate (MCR/I) of glucose between the oral and intravenous routes of glucose administration. Secondary endpoints were differences in insulin effect on proteolysis, ketogenesis, lipolysis and glucagon levels. Methods In this parallel cohort study, we administered multiple oral glucose loads to 23 participants (aged between 18 and 65 years) with morbid obesity and with normal or impaired glucose tolerance or type 2 diabetes. In a different session, we administered isoglycaemic intravenous glucose infusions (IGIVI) to match the plasma glucose levels observed during the oral challenges. Glucose rate of appearance (R-a) and disappearance (R-d) and endogenous glucose production (EGP) were calculated by infusing [6,6-H-2(2)]glucose with or without oral [U-C-13(6)]glucose. Plasma small polar metabolites were measured by gas chromatography and time-of-flight mass spectrometry. Lipids were measured by ultra-HPLC and quadrupole mass spectrometry. Glucagon-like peptide-1, insulin, C-peptide and glucagon were also measured. Participants, caregivers, people doing measurements or examinations, and people assessing the outcomes were unblinded to group assignment. Results Glucose MCR/I was significantly higher during IGIVI than during oral glucose administration, independently of glycaemic status (12 +/- 6 for IGIVI vs 7.4 +/- 3 ml min(-1) kg(-1) per nmol/l for oral, p< 0.001 from paired t test). Insulin secretion was higher during oral administration than during IGIVI (p< 0.001). The disposition index was significantly lower during the oral procedure: 4260 +/- 1820 vs 5000 +/- 2360 (ml min(-1) kg(-1) (nmol/l)(-1) pmol/min; p = 0.005). Insulin clearance was significantly higher when glucose was infused rather than ingested (2.53 +/- 0.82 vs 2.16 +/- 0.49 l/min in intravenous and oral procedure, respectively, p = 0.006). The efficacy of insulin in inhibiting lipolysis and proteolysis was decreased after oral glucose loads. A heat map diagram showed a different pattern for the metabolites between the two routes of glucose administration. Conclusions/interpretation Our study shows that insulin sensitivity depends on the route of glucose administration, the oral route leading to increased insulin secretion and compensatory insulin resistance compared with the intravenous route. The efficacy of insulin in blocking lipolysis and protein breakdown is lower after oral glucose loads vs the intravenous route. Our findings suggest that, while the glucose-mediated incretin release is followed by an increase in insulin release, the effect of the released insulin is limited by an increase in insulin resistance.
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