| 1. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 2. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 3. |
- Hahn, Robert, et al.
(författare)
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A simple intravenous glucose tolerance test for assessment of insulin sensitivity
- 2011
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Ingår i: Theoretical Biology and Medical Modelling. - : BioMed Central. - 1742-4682. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe aim of the study was to find a simple intravenous glucose tolerance test (IVGTT) that can be used to estimate insulin sensitivity.MethodsIn 20 healthy volunteers aged between 18 and 51 years (mean, 28) comparisons were made between kinetic parameters derived from a 12-sample, 75-min IVGTT and the Mbw (glucose uptake) obtained during a hyperinsulinemic euglycemic glucose clamp. Plasma glucose was used to calculate the volume of distribution (Vd) and the clearance (CL) of the injected glucose bolus. The plasma insulin response was quantified by the area under the curve (AUCins). Uptake of glucose during the clamp was corrected for body weight (Mbw).ResultsThere was a 7-fold variation in Mbw. Algorithms based on the slope of the glucose-elimination curve (CL/Vd) in combination with AUCins obtained during the IVGTT showed statistically significant correlations with Mbw, the linearity being r2 = 0.63-0.83. The best algorithms were associated with a 25-75th prediction error ranging from -10% to +10%. Sampling could be shortened to 30-40 min without loss of linearity or precision.ConclusionSimple measures of glucose and insulin kinetics during an IVGTT can predict between 2/3 and 4/5 of the insulin sensitivity.
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| 4. |
- Hahn, Robert G, et al.
(författare)
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Preoperative insulin resistance reduces complications after hip replacement surgery in non-diabetic patients.
- 2013
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Ingår i: BMC Anesthesiology. - : Springer Science and Business Media LLC. - 1471-2253 .- 1471-2253. ; 13:1, s. 39-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Insulin resistance negatively affects the outcome of surgery in patients with type 2 diabetes. This association is often believed to be present in other patient populations as well, but studies are lacking on the influence of preoperative insulin resistance on the clinical course of surgery in non-diabetic patients.METHODS: Sixty non-diabetic patients with a mean age of 68 years underwent a 75-min intravenous glucose tolerance test (IVGTT) one day before and after elective hip replacement surgery. Patients were regarded to be either insulin resistant (< median insulin sensitivity) or not (> median insulin sensitivity). Hypotensive events occurring in the postoperative care unit and complications in the orthopedic ward were recorded. Fatigue and well-being were assessed via questionnaires.RESULTS: A total of 52 patients were included in the final analysis. Insulin resistance before surgery was associated with a lower risk of arterial hypotension in the postoperative care unit (systolic pressure < 80 mmHg; P < 0.05) and with fewer complications in the orthopedic ward (mean 1.9 versus 1.2 per operation, P < 0.01), particularly with respect to nausea/vomiting (P < 0.04) and arterial hypotension (P < 0.05). Fewer of these patients had more than one complication (23% versus 58%, P < 0.001), while no statistical link between preoperative insulin resistance and fatigue or well-being was evident. Insulin resistance, when measured one day postoperatively, did not correlate with the number of complications.CONCLUSIONS: Preoperative insulin resistance offers some benefit in the postoperative period and early convalescence in non-diabetic patients who undergo hip replacement surgery.
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| 5. |
- Hahn, Robert, et al.
(författare)
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Plasma volume expansion from the intravenous glucose tolerance test before and after hip replacement surgery
- 2013
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Ingår i: Theoretical Biology and Medical Modelling. - : Springer Science and Business Media LLC. - 1742-4682. ; 10:48
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHyperosmotic glucose is injected intravenously when an intravenous glucose tolerance test (IVGTT) is initiated. The extent and time period of plasma volume expansion that occurs in response to the glucose load has not been studied in the perioperative setting.MethodsTwenty-two non-diabetic patients aged between 57 and 76 years (mean 68) underwent an IVGTT, during which 0.3 g/kg of glucose 30% (1 ml/kg) was injected as a bolus over one minute, one day before and two days after hip replacement surgery. Twelve blood samples were collected over 75 minutes from each patient. The turnover of both the exogenous glucose and the injected fluid volume was calculated by means of mass balance and volume kinetic analysis.ResultsThe IVGTT raised plasma glucose by 9 mmol/L and the plasma volume by 8%. The extracellular fluid volume increased by 320 (SD 60) ml of which 2/3 could be accounted for in the plasma. The half-life of the exogenous glucose averaged 30 minutes before surgery and 36 minutes postoperatively (P < 0.02). The glucose elimination governed 86% of the decay of the plasma volume expansion, which occurred with a half-life of 12 minutes before to 21 minutes after the surgery (median, P < 0.001).ConclusionHyperosmotic glucose translocated intracellular water to the plasma volume rather than to the entire extracellular fluid volume. The preferential re-distribution acts to dilute the plasma concentrations used to quantify insulin sensitivity and ß-cell function from an IVGTT. The greater-than-expected plasma dilution lasted longer after than before surgery.
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| 6. |
- Holleboom, Adriaan G, et al.
(författare)
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Heterozygosity for a Loss-of-Function Mutation in GALNT2 Improves Plasma Triglyceride Clearance in Man
- 2011
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Ingår i: Cell Metabolism. - : Elsevier. - 1550-4131 .- 1932-7420. ; 14:6, s. 811-8
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified GALNT2 as a candidate gene in lipid metabolism, but it is not known how the encoded enzyme ppGalNAc-T2, which contributes to the initiation of mucin-type O-linked glycosylation, mediates this effect. In two probands with elevated plasma high-density lipoprotein cholesterol and reduced triglycerides, we identified a mutation in GALNT2. It is shown that carriers have improved postprandial triglyceride clearance, which is likely attributable to attenuated glycosylation of apolipoprotein (apo) C-III, as observed in their plasma. This protein inhibits lipoprotein lipase (LPL), which hydrolyses plasma triglycerides. We show that an apoC-III-based peptide is a substrate for ppGalNAc-T2 while its glycosylation by the mutant enzyme is impaired. In addition, neuraminidase treatment of apoC-III which removes the sialic acids from its glycan chain decreases its potential to inhibit LPL. Combined, these data suggest that ppGalNAc-T2 can affect lipid metabolism through apoC-III glycosylation, thereby establishing GALNT2 as a lipid-modifying gene.
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| 7. |
- Jamal, Sophie A., et al.
(författare)
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Effects of Denosumab on Fracture and Bone Mineral Density by Level of Kidney Function
- 2011
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 26:8, s. 1829-1835
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Tidskriftsartikel (refereegranskat)abstract
- The incidences of osteoporosis and chronic kidney disease (CKD) both increase with increasing age, yet there is a paucity of data on treatments for osteoporosis in the setting of impaired kidney function. We examined the efficacy and safety of denosumab (DMAb) among subjects participating in the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6Months (FREEDOM) Study. We estimated creatinine clearance (eGFR) using Cockcroft-Gault and classified levels of kidney function using the modified National Kidney Foundation classification of CKD. We examined incident fracture rates; changes in bone mineral density (BMD), serum calcium, and creatinine; and the incidence of adverse events after 36 months of follow-up in subjects receiving DMAb or placebo, stratified by level of kidney function. We used a subgroup interaction term to determine if there were differences in treatment effect by eGFR. Most (93%) women were white, and the mean age was 72.3 +/- 5.2 years; 73 women had an eGFR of 15 to 29mL/min; 2817, between 30 to 59mL/min; 4069, between 60 to 89mL/min, and 842 had an eGFR of 90mL/min or greater. None had stage 5 CKD. Fracture risk reduction and changes in BMD at all sites were in favor of DMAb. The test for treatment by subgroup interaction was not statistically significant, indicating that treatment efficacy did not differ by kidney function. Changes in creatinine and calcium and the incidence of adverse events were similar between groups and did not differ by level of kidney function. It is concluded that DMAb is effective at reducing fracture risk and is not associated with an increase in adverse events among patients with impaired kidney function.
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| 8. |
- Karlsson, Helen, 1961-, et al.
(författare)
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Two-dimensional gel electrophoresis and mass spectrometry in studies of nanoparticle-protein interactions
- 2012
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Ingår i: Gel electrophoresis-Advanced Techniques. - Rijeka, Croatia : In Tech. - 9789535104575 ; , s. 327-358
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Over the years a number of epidemiological studies have shown that PM from combustion sources such as motor vehicles contributes to respiratory and cardiovascular morbidity and mortality.Especially so do the ultra-fine particles (UFPs) with a diameter less than 0.1 micrometer.UFPs from combustion engines are capable to translocate over the alveolar–capillary barrier. When nano-sized PM (nanoparticles, NP), which are small enough to enter the blood stream, do so they are likely to interact with plasma proteins and this protein-NP interaction will probably affect the fate of and the effects caused by the NPs in the human body. Here, by using a proteomic approach, we present results showing that several proteins indeed are associated to NPs that have in vitro been introduced to human blood plasma.
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| 9. |
- Levels, Johannes HM, et al.
(författare)
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High-density Lipoprotein proteome dynamics in human endotoxemia
- 2011
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Ingår i: Proteome Science. - : BiOMed Central. - 1477-5956. ; 9:34
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Tidskriftsartikel (refereegranskat)abstract
- Background: A large variety of proteins involved in inflammation, coagulation, lipid-oxidation and lipid metabolism have been associated with high-density lipoprotein (HDL) and it is anticipated that changes in the HDL proteome have implications for the multiple functions of HDL. Here, SELDI-TOF mass spectrometry (MS) was used to study the dynamic changes of HDL protein composition in a human experimental low-dose endotoxemia model. Ten healthy men with low HDL cholesterol (0.7+/-0.1 mmol/L) and 10 men with high HDL cholesterol levels (1.9+/-0.4mmol/L) were challenged with endotoxin (LPS) intravenously (1ng/kg bodyweight). We previously showed that subjects with low HDL cholesterol are more susceptible to an inflammatory challenge. The current study tested the hypothesis that this discrepancy may be related to differences in the HDL proteome.Results: Plasma drawn at 7 time-points over a 24 hour time period after LPS challenge was used for direct capture of HDL using antibodies against apolipoprotein A-I followed by subsequent SELDI-TOF MS profiling. Upon LPS administration, profound changes in 21 markers (adjusted p-value<0.05) were observed in the proteome in both study groups. These changes were observed 1 hour after LPS infusion and sustained up to 24 hours, but unexpectedly were not different between the 2 study groups. Hierarchical clustering of the protein spectra at all time points of all individuals revealed 3 distinct clusters, which were largely independent of baseline HDL cholesterol levels but correlated with paraoxonase 1 activity. The acute phase protein serum amyloid A-1/2 (SAA-1/2) was clearly upregulated after LPS infusion in both groups and comprised both native and N-terminal truncated variants that were identified by two-dimensional gel electrophoresis and mass spectrometry. Individuals of one of the clusters were distinguished by a lower SAA-1/2 response after LPS challenge and a delayed time-response of the truncated variants.Conclusions: This study shows that the semi-quantitative differences in the HDL proteome as assessed by SELDI-TOF MS cannot explain why subjects with low HDL cholesterol are more susceptible to a challenge with LPS than those with high HDL cholesterol. Instead the results indicate that hierarchical clustering could be useful to predict HDL functionality in acute phase responses towards LPS.
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| 10. |
- Lewerin, Catharina, 1961, et al.
(författare)
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Low holotranscobalamin and cobalamins predict incident fractures in elderly men: the MrOS Sweden.
- 2014
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 25:1, s. 131-140
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Tidskriftsartikel (refereegranskat)abstract
- In a population-based study on cobalamin status and incident fractures in elderly men (n=790) with an average follow-up of 5.9years, we found that low levels of metabolically active and total cobalamins predict incident fractures, independently of body mass index (BMI), bone mineral density (BMD), plasma total homocysteine (tHcy), and cystatin C.
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| 11. |
- Ljunggren, Stefan A, et al.
(författare)
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Persistent organic pollutants distribution in lipoprotein fractions in relation to cardiovascular disease and cancer
- 2014
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Ingår i: Environment International. - Kidlington : Pergamon-Elsevier Science Ltd. - 0160-4120 .- 1873-6750. ; 65, s. 93-99
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Tidskriftsartikel (refereegranskat)abstract
- Persistent organic pollutants (POPS) are lipophilic environmental toxins that have been associated with cardiovascular disease (CVD) and cancer. The aim of this study was to investigate the concentrations of POPs in human high and low/very low-density lipoproteins (HDL and LDL/VLDL) and the possible association with CVD and cancer occurrence in individuals living in a contaminated area. Lipoproteins from 28 individuals (7 healthy controls, 8 subjects with cancer, 13 subjects with CVD) were isolated and the fraction-specific concentration of 20 different POPs was analyzed by high resolution gas chromatography/high resolution mass spectrometry. The activity of Paraoxonase 1 (PON1), an anti-oxidant in HDL, was determined in plasma of these 28 subjects and additional 50 subjects from the same area excluding diseases other than cancer or CVD. Fourteen polychlorinated biphenyls (PCBs) and three organochlorine pesticides were detected, and especially highly chlorinated PCBs were enriched in lipoproteins. Significantly higher concentrations of POPs were found among individuals with CVD or cancer compared to controls. Principal component analyses showed that POP concentrations in HDL were more associated with CVD, while POP concentrations in LDL/VLDL were more associated with cancer. PON1 activity was negatively correlated to sumPCB and a co-variation between decreased arylesterase-activity, increased PCB concentrations and CVD was found. This study shows that POPs are present in lipoproteins and were more abundant in individuals with CVD or cancer compared to healthy controls. The results also indicate that PCB exposure is accompanied by reduced PON1 activity that could impair the HDL function to protect against oxidation. (C) 2014 Elsevier Ltd. All rights reserved.
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| 12. |
- Ljunggren, Stefan, et al.
(författare)
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Accuracy and precision of commonly used methods for quantifying surgery-induced insulin resistance : Prospective observational study
- 2014
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Ingår i: European Journal of Anaesthesiology. - : Lippincott Williams & Wilkins. - 0265-0215 .- 1365-2346. ; 31:2, s. 110-116
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Insulin resistance develops in the perioperative setting and has an adverse influence on postoperative recovery and well-being.OBJECTIVES: To evaluate the effectiveness of commonly used methods for quantifying surgery-induced insulin resistance.DESIGN: Prospective observational study.SETTING: Surgery department and orthopaedic ward at two regional hospitals.PATIENTS: Twenty-two patients (mean age 68 years) scheduled for elective hip replacement.INTERVENTIONS: A short seven-sample intravenous glucose tolerance test (IVGTT) followed by a euglycaemic hyperinsulinaemic glucose clamp 1 day before and 2 days after the surgery.MAIN OUTCOME MEASURES: Insulin resistance shown by dynamic tests (the IVGTT and the glucose clamp) were compared to static tests [the quantitative insulin sensitivity check index (QUICKI) and the homeostatic model assessment-insulin resistance (HOMA-IR)], which use only the plasma glucose and insulin concentrations at baseline.RESULTS: The linear correlation coefficients for the relationship between insulin resistance as obtained with the glucose clamp and the other methods before or after surgery were 0.76 (IVGTT), 0.58 (QUICKI) and -0.65 (HOMA). The prediction errors (precision) averaged 18, 29 and 31%, respectively. Surgery-induced insulin resistance amounted to 45% (glucose clamp), 26% (IVGTT), 4% (QUICKI) and 3% (HOMA).CONCLUSION: Despite reasonably good linear correlations, the static tests grossly underestimated the degree of insulin resistance that developed in response to surgery.
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| 13. |
- Ljunggren, Stefan, et al.
(författare)
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ApoA-I mutations, L202P and K131del, in HDL from heterozygotes with low HDL-C
- 2014
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Ingår i: PROTEOMICS - Clinical Applications. - : Wiley-Blackwell. - 1862-8346 .- 1862-8354. ; 8:3-4, s. 241-250
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Mutations in apolipoprotein A-I (apoA-I) may affect plasma high-density lipoprotein (HDL) cholesterol levels and the risk for cardiovascular disease but little is known about the presence and effects of circulating apoA-I variants. This study investigates whether the apoA-I mutations, apoA-I(L202P) and apoA-I(K131del) , are present on plasma HDL particles derived from heterozygote carriers and whether this is associated to changes in HDL protein composition.EXPERIMENTAL DESIGN: Plasma HDL of heterozygotes for either apoA-I(L202P) or apoA-I(K131del) and family controls was isolated using ultracentrifugation. HDL proteins were separated by 2DE and analyzed by MS.RESULTS: ApoA-I peptides containing apoA-I(L202P) or apoA-I(K131del) were identified in HDL from heterozygotes. The apoA-I(L202P) mutant peptide was less abundant than wild-type peptide while the apoA-I(K131del) mutant peptide was more abundant than wild-type peptide in the heterozygotes. Two-dimensional gel electrophoresis analyses indicated that, compared to controls, HDL in apoA-I(L202P) carriers contained less apoE and more zinc-α-2-glycoprotein while HDL from the apoA-I(K131del) heterozygotes contained more alpha-1-antitrypsin and transthyretin.CONCLUSIONS AND CLINICAL RELEVANCE: Both apoA-I(L202P) and apoA-I(K131del) were identified in HDL. In heterozygotes, these mutations have markedly differential effects on the concentration of wild-type apoA-I in the circulation, as well as the HDL proteome, both of which might affect the clinical phenotype encountered in the heterozygous carriers.
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| 14. |
- Ljunggren, Stefan, et al.
(författare)
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Changes in Human Liportein Composition in Patients with Acute Coronary Syndrome
- 2011
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Ingår i: Atherosclerosis Supplements. - : Elsevier. - 1567-5688 .- 1878-5050. ; 12:1, s. 14-14
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The protein composition of lipoproteins may serve as biomarkers or reveal underlying mechanisms during different states of disease. Here we have analysed the protein composition of LDL and HDL from patients with acute coronary syndrome (ACS) and patients receiving statins after previous ACS. Plasma samples were obtained from males, namely 12 healthy donors, 9 patients with ACS and 7 stable patients receiving statin treatment after previous ACS. LDL and HDL were isolated by two-step density ultracentrifugation. LDL proteins were analysed with two-dimensional gel electrophoresis and mass spectrometry. Paraoxonase 1 (PON-1) in HDL was analyzed with SDSPAGE/Western Blot.Concentrations of apo A-IV, a1-antitrypsin and transthyretin were significantly increased (P < 0.05) in LDL from patients with ACS compared to healthy controls. In patients receiving statins, a1-antitrypsin remained increased while serum amyloid A4 was decreased. By western blot analysis, a non-significant increase in PON-1 was found in HDL from patients with ACS. Interestingly, a truncated form of PON-1 was detected in all patients with ACS but not in any of the controls.In conclusion, we confirm previous findings that LDL-associated transthyretin is a possible biomarker of myocardial infarction. Moreover, the increased concentration of the inflammatory marker a1-antitrypsin in LDL from both ACS patients and stable patients after ACS indicate that the enrichment does not only reflect an acute phase response. The presence of a truncated form of the antioxidant protein PON-1 in HDL may explain previous findings showing increased amounts but lower activity of PON-1 in patients with ACS.
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| 15. |
- Ljunggren, Stefan
(författare)
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Fluid and nutrition support before total hip replacement surgery
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Surgical trauma results in a variety of physiological reactions in the body, including transient insulin resistance. The effect of surgery on postoperative wellbeing has been linked to this insulin resistance, which can be prevented through the ingestion of carbohydrate-rich liquid before surgery. The aim of this Thesis is to improve the clinical usefulness of the intravenous glucose tolerance test (IVGTT) by shortening the sampling time from 3 hours to 75 minutes and to use the IVGTT, and two other simple tests (QUICKI and HOMA-IR), to study whether most or all of the beneficial effects of the carbohydrate drink on postoperative insulin resistance can be explained by the water component of the drink. Study I: Twenty healthy volunteers underwent a 75-min IVGTT. Insulin resistance was then assessed using the hyperinsulinemic glucose clamp technique, regarded as the gold- standard method. The resultant measurements of plasma glucose and insulin concentrations during the IVGTT were combined, using a variety of algorithms, allowing the insulin resistance, as measured by the clamp, to be predicted in 2/3 and 4/5 of subjects. Study II: Sixty non-diabetic patients scheduled for hip replacement surgery were randomized into preoperative fasting (control), drink flavored water (placebo) or carbohydrate-rich liquid group. An IVGTT was performed the day before surgery, immediately afterwards, and the day after the surgery. No statistically significant differences were found with regard to glucose clearance, insulin resistance, postoperative complications or wellbeing between the three study groups. Study III: A double-blind clinical trial was performed in which twenty-three non-diabetic patients underwent both an IVGTT and a hyperinsulinemic glucose clamp test on the day before and two days after hip replacement surgery. Half of the patients received a carbohydrate-rich liquid before the surgery; the other half received a placebo. There was a similar development of insulin resistance in both groups, but those who received a carbohydrate-rich liquid showed an increase in β-cell activity. Study IV: Twenty-two patients from Study III were used to compare the insulin resistance results obtained from two dynamic tests (our short 7-sample IVGTT and the glucose clamp) and two static tests (QUICKI and HOMA-IR). The static tests showed slightly weaker linearity and larger residual errors compared to IVGTT in estimating insulin resistance before and after surgery. More importantly, they greatly underestimated the degree of surgery-induced insulin resistance, suggesting that they should not be used for that purpose. Conclusions: The simplified IVGTT results strongly correlated with those obtained used the hyperinsulinemic glucose clamp technique, which makes its use possible in the clinical setting. There was no statistical difference in surgery-induced insulin resistance between those who had received a carbohydrate-rich beverage or flavored water prior to hip replacement surgery. In addition, similar outcomes were seen in patients who had received a pretreatment carbohydrate-rich beverage, water or fasted preoperatively with regard to well-being and complications. HOMA and QUICKI should not be used to assess surgery-induced changes in insulin resistance.
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| 16. |
- Ljunggren, Stefan, et al.
(författare)
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Insulin sensitivity and beta-cell function after carbohydrate oral loading in hip replacement surgery : A double-blind, randomised controlled clinical trial
- 2014
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Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 33:3, s. 392-398
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Surgery initiates a series of physiological stress processes in the body, inducing transient insulin resistance. Preoperative carbohydrate treatment can reduce the latter phenomenon. We investigated the effects of carbohydrate loading on insulin sensitivity and beta-cell function after elective hip replacement.METHODS: Twenty-three nondiabetic patients (mean age of 68 years) who underwent elective hip replacement surgery participated in this double-blind controlled study. The patients were randomised to a nutrition group, which ingested a carbohydrate-rich fluid (50 kcal/100 ml) (Preop(®)), or a control group (tap water flavoured with lemon) 800 ml + 400 ml before the surgery. The insulin response (beta-cell function) and the insulin sensitivity were measured with an intravenous glucose tolerance test (IVGTT) and a hyperinsulinaemic euglycaemic glucose clamp, respectively, one day before and two days after the surgery.RESULTS: Insulin sensitivity decreased by 51% (median; 25-75th percentiles 35-61) after ingesting Preop(®) and by 39% (21-51) after ingesting in the control group (n.s.). The postoperative IVGTT in the nutrition group was followed by a significantly larger area under the curve (AUC) for plasma insulin (+54% versus the preoperative IVGTT) compared to the control group (+7%). This difference was already apparent during the first phase (0-10 min) of insulin secretion (+20 and -21%, respectively; P < 0.05).CONCLUSIONS: The patients randomised to the carbohydrate oral fluid or the water prior to the surgery demonstrated a significant but similar decrease in insulin sensitivity. The carbohydrates increased the beta-cell function as a compensatory response to the disposition index, resulting in a smaller reduction in surgery-induced insulin resistance compared to the tap water. The study was registered at http://www.clinicaltrials.gov (NCT01774084).
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| 17. |
- Ljunggren, Stefan, et al.
(författare)
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Oral nutrition or water loading before hip replacement surgery; a randomized clinical trial
- 2012
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Ingår i: Trials. - : BioMed Central. - 1745-6215. ; 13:97
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSurgery induces insulin resistance that might be alleviated by a nutritional drink given preoperatively. The authors hypothesized that some of the beneficial effects of the drink could be attributed to the volume component (approximately 1 L) rather than to the nutrients.MethodsSixty patients scheduled for elective total hip replacement under spinal anesthesia were recruited to a clinical trial, and randomly allocated to preoperative fasting, to oral ingestion of tap water, or to oral ingestion of a carbohydrate drink. An intravenous glucose tolerance test calculated glucose clearance and insulin sensitivity on the day before surgery, in the postoperative ward, and on the day after surgery. Other parameters were stress (cortisol in plasma and urine), muscle catabolism (urinary 3-methylhistidine), and wellbeing.ResultsFifty-seven patients completed the study. In the postoperative ward, the glucose clearance and the insulin response had decreased from the previous day by 23% and 36%, respectively. Insulin sensitivity did not decrease until the next morning (−48%) and was due to an increased insulin response (+51%). Cortisol excretion was highest on the day of surgery, while 3-methylhistidine increased 1 day later. Follow-up on the third postoperative day showed an average of 1.5 complications per patient. Wellbeing was better 2 weeks after than before the surgery. None of the measured parameters differed significantly between the study groups.ConclusionsPreoperative ingestion of tap water or a nutritional drink had no statistically significant effect on glucose clearance, insulin sensitivity, postoperative complications, or wellbeing in patients undergoing elective hip surgery.
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| 18. |
- Vimaleswaran, Karani S, et al.
(författare)
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Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study.
- 2014
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Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595 .- 2213-8587. ; 2:9, s. 719-29
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Tidskriftsartikel (refereegranskat)abstract
- Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of −0·29 mm Hg in diastolic blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87–0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
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