Per M Thorsby - Academia.edu (original) (raw)
Papers by Per M Thorsby
Scandinavian Journal of Clinical and Laboratory Investigation, Apr 3, 2014
Transmembrane protein 27 (Tmem27), which is expressed in pancreatic β-cells, plays an important r... more Transmembrane protein 27 (Tmem27), which is expressed in pancreatic β-cells, plays an important role in insulin secretion and pancreatic β-cell proliferation. Analysis of the INS-1 cell proteome using stable isotope labeling by amino acids in cell culture (SILAC) in combination with LC-MS identified Tmem27 as the one of most robustly (up to seven-fold) upregulated proteins after treatment with the active metabolite of vitamin D, 1,25-(OH)2D3. Furthermore, we report that Tmem27 which is cleaved and released from, i.e. pancreatic β-cells, is present in human serum and its levels are significantly lower in subjects with autoimmune diabetes as compared to healthy individuals (13% of the levels). Additionally, Tmem27 correlated positively (0.70) with C-peptide serum levels in healthy subjects. Our data indicate that Tmem27 could be of potential value as a serum marker for the pathogenesis of diabetes and as such may warrant the development of measurement methods with lower limit of detection for its further validation.
Endocrine reviews, 2009
Context: Infusion of insulin acutely stimulates leptin production and chronic insulin treatment i... more Context: Infusion of insulin acutely stimulates leptin production and chronic insulin treatment is associated with elevated serum leptin levels and body weight in subjects with type 2 diabetes. Objective: The objective of the study was to investigate the relationship between insulin administration, leptin levels, and weight gain in subjects with type 2 diabetes. Design: This was a post hoc analysis of two randomized, controlled trials. Setting: The study was conducted at an outpatient clinic. Subjects: Subjects included 35 (study 1) and 32 (study 2) poorly controlled oral hypoglycemic agent (OHA)-treated type 2 diabetic subjects. Intervention: Study 1: subjects were investigated during a hyperinsulinemic, euglycemic glucose clamp and 12 months after being randomly allocated to start insulin or continue on OHAs. Study 2: 1 yr treatment with either OHAs and lifestyle intervention or insulin with or without concomitant lifestyle intervention. Main outcome measure: Changes in serum leptin levels during clamp and during 1 yr of treatment in relationship to changes in body weight. Results: Study 1: during acute insulin infusion leptin levels increased by 10% (P Ͻ 0.001). During 1 yr of insulin therapy, mean body weight increased by 6%, whereas the fasting leptin levels increased by 108% (both P Ͻ 0.001). The weight gain observed at 1 yr correlated with the increase in leptin levels observed during the clamp (r ϭ 0.62, P ϭ 0.003). Study 2: mean body weight increased by 4% (P Ͻ 0.01), whereas leptin levels increased by 56% (P Ͻ 0.001) during 1 yr of insulin treatment and the increase in leptin preceded the increase in body weight. Conclusions: Significant correlations were observed between insulin's effect on serum leptin levels and the increase in weight that accompanied insulin therapy.
Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke, 2004
BACKGROUND A few case reports suggest that the use of androgenic anabolic steroids may be associa... more BACKGROUND A few case reports suggest that the use of androgenic anabolic steroids may be associated with myocardial infarction. MATERIAL AND METHODS Case report. RESULTS We report the case of a 27-year-old male body builder with acute myocardial infarction due to occlusion of the proximal left anterior descending coronary artery. He was treated with primary angioplasty with stent implantation and intra-aortic balloon support, but still developed a large myocardial infarction as determined by both echocardiography and myocardial perfusion tomography. The patient had been using androgenic anabolic steroids regularly for ten years. There was no family history of heart disease or lipid disorder. INTERPRETATION The actual frequency of myocardial infarction and even sudden death among users of anabolic steroids is presumably underreported in the medical literature. A causal relationship is not established, but a pathogenic role is plausible. Use of androgenic anabolic steroids has been a...
Background: Immigrants from South Asia to Western countries have a high prevalence of type 2 diab... more Background: Immigrants from South Asia to Western countries have a high prevalence of type 2 diabetes mellitus (T2DM). We explored pathogenic factors that might contribute to the high risk of T2DM in Pakistani immigrants to Norway. Methods: A cross-sectional study was performed in 18 Pakistani and 21 Norwegian men and women with T2DM (age 29-45 years), recruited from two hospital outpatient clinics. Anthropometrics and a two-step euglycemic, hyperinsulinemic clamp with measurements of non-esterified fatty acids (NEFA) during clamp, was performed in all patients. Insulin sensitivity, given as the Glucose Infusion Rate (GIR) and Insulin Sensitivity Index (ISI), was calculated from the two euglycemic clamp steps. Fasting adipokines and inflammatory mediators were measured. Continuous variables between groups were compared using Student's t test or Mann-Whitney U test as appropriate. Spearman's correlation coefficient and multiple linear regression analyses were used. Results: Despite having a lower BMI, Pakistani patients were more insulin resistant than Norwegian patients, during both low and high insulin infusion rates, after adjustment for sex and % body fat: median (interquartile range) GIR (low insulin) : 339.8(468.0) vs 468.4(587.3) µmol/m 2 /min (p=0.060), ISI (low insulin) : 57.1(74.1) vs 79.7(137.9) µmol/m 2 /min (p=0.012), GIR (high insulin) : 1661.1(672.3) vs 2055.6(907.0) µmol/m 2 /min (p=0.042), ISI (high insulin) : 14.2(7.3) vs 20.7(17.2) µmol/m 2 /min (p=0.014). Pakistani patients had lower percentage NEFA suppression 30 minutes into clamp hyperinsulinemia than Norwegians: 41.9(90.6)% vs 71.2(42.1)%,(p=0.042). The relationship of ISI to BMI, leptin and interleukin1-receptor antagonist also differed between Norwegians and Pakistanis. Conclusions: Compared with Norwegian patients, Pakistani patients with T2DM had lower insulin sensitivity, affecting both glucose and lipid metabolism. The relation of insulin sensitivity to BMI and some adipokines also differed between the groups.
Antioxidants
There is a need for feasible and non-invasive diagnostics in perinatal asphyxia. Metabolomics is ... more There is a need for feasible and non-invasive diagnostics in perinatal asphyxia. Metabolomics is the study of small molecular weight products of cellular metabolism that may, directly and indirectly, reflect the level of oxidative stress. Saliva analysis is a novel approach that has a yet unexplored potential in metabolomics in perinatal asphyxia. The aim of this review was to give an overview of metabolomics studies of oxidative stress in perinatal asphyxia, particularly searching for studies analyzing non-invasively collected biofluids including saliva. We searched the databases PubMed/Medline and included 11 original human and 4 animal studies. In perinatal asphyxia, whole blood, plasma, and urine are the most frequently used biofluids used for metabolomics analyses. Although changes in oxidative stress-related salivary metabolites have been reported in adults, the utility of this approach in perinatal asphyxia has not yet been explored. Human and animal studies indicate that, in...
Psychoneuroendocrinology
The diagnosis of fetal anomaly can be a major stressor to the expectant mother. Current understan... more The diagnosis of fetal anomaly can be a major stressor to the expectant mother. Current understanding of the relationship between psychological stress and cortisol in pregnancy is limited. This study examined: (1) differences in the ratio of serum cortisol to cortisol binding globulin (SC/CBG) and cortisone levels among women with and without a diagnosis of fetal anomaly, (2) the association between self-reported stress and cortisol from mid to late pregnancy, and (3) the Jo ur na l P re -p ro of
Journal of Nutritional Science
The aim of the study was to investigate the effect of prebiotic fibres on appetite-regulating hor... more The aim of the study was to investigate the effect of prebiotic fibres on appetite-regulating hormones, subjective feeling of appetite and energy intake in subjects with type 2 diabetes. Data presented are secondary outcomes of a study investigating the effect of prebiotics on glucagon-like peptide-1 and glycaemic regulation. We conducted a randomised and placebo-controlled crossover trial to evaluate the effects of 16 g/d of inulin-type fructans or a control supplement (maltodextrin) for 6 weeks in randomised order, with a 4-week washout period in-between, on appetite in thirty-five men and women with type 2 diabetes. Data were collected at visits before and after each treatment: plasma concentration of the satiety-related peptides ghrelin and peptide YY (PYY) were assessed during a standardised mixed meal. The subjective sensation of appetite was evaluated in response to an ad libitum lunch by rating the visual analogue scale. Twenty-nine individuals (twelve women) were included i...
Sleep
Study Objectives Narcolepsy type 1 (NT1) is associated with hypocretin neuron loss. However, ther... more Study Objectives Narcolepsy type 1 (NT1) is associated with hypocretin neuron loss. However, there are still unexplained phenotypic NT1 features. We investigated the associations between clinical and sleep phenotypic characteristics, the NT1-associated P2RY11 polymorphism rs2305795, and P2Y11 protein levels in T lymphocytes in patients with NT1, their first-degree relatives and unrelated controls. Methods The P2RY11 SNP was genotyped in 100 patients (90/100 H1N1-(Pandemrix)-vaccinated), 119 related and 123 non-related controls. CD4 and CD8 T lymphocyte P2Y11 protein levels were quantified using flow cytometry in 167 patients and relatives. Symptoms and sleep recording parameters were also collected. Results We found an association between NT1 and the rs2305795 A allele (OR = 2, 95% CI (1.3, 3.0), p = 0.001). T lymphocyte P2Y11 protein levels were significantly lower in patients and relatives homozygous for the rs2305795 risk A allele (CD4: p = 0.012; CD8: p = 0.007). The nocturnal s...
Sleep
Study Objectives Narcolepsy type 1 (NT1) may be complicated by comorbidities. We aimed to study t... more Study Objectives Narcolepsy type 1 (NT1) may be complicated by comorbidities. We aimed to study the extent of obesity and other medical comorbidities in a Norwegian population of NT1 patients with debut of symptoms after the 2009 H1N1 influenza epidemic and vaccination campaign. We also aimed to explore factors associated with obesity. Methods Ninety-one patients (48 children and 43 adults) were included in this cross-sectional study, 80 of whom were H1N1-vaccinated. All participants were hospitalized and underwent sleep investigation and physical examination, and completed a semi-structured clinical interview. Results In children, 16 females (70%) and 10 males (40%) were classified as overweight or obese. Twenty children (42%) had a co-existing medical disorder. Medical comorbidity was significantly positively associated with BMI in children (p = .032). In adults, 19 females (58%) and 7 males (70%) were classified as overweight or obese. Twenty-six adults (61%) had a co-existing me...
Sleep
Study Objectives To explore HLA (human leukocyte antigen) in post-H1N1 narcolepsy type 1 patients... more Study Objectives To explore HLA (human leukocyte antigen) in post-H1N1 narcolepsy type 1 patients (NT1), first-degree relatives and healthy controls, and assess HLA associations with clinical and sleep parameters in patients and first-degree relatives. Methods Ninety post-H1N1 NT1 patients and 202 of their first-degree relatives were HLA-genotyped (next generation sequencing) and phenotyped (semi-structured interviews, Stanford Sleep Questionnaire, polysomnography, multiple sleep latency test). HLA allele distributions were compared between DQB1*06:02-heterozygous individuals (77 patients, 59 parents, 1230 controls). A subsample (74 patients, 114 relatives) was investigated for associations between HLA-loci and continuous sleep variables using logistic regression. Identified candidate HLA-loci were explored for HLA allele associations with hypnagogic hallucinations and sleep paralysis in 90 patients, and patient allele findings were checked for similar associations in 202 relatives....
Sleep
Study Objectives: To assess white matter involvement in H1N1-vaccinated hypocretin deficient pati... more Study Objectives: To assess white matter involvement in H1N1-vaccinated hypocretin deficient patients with narcolepsy type 1 (NT1) compared with first-degree relatives (a potential risk group) and healthy controls. Methods: We compared four diffusion tensor imaging-based microstructural indices (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], and axial diffusivity [AD]) in 57 patients with NT1 (39 females, mean age 21.8 years, 51/57 H1N1-vaccinated, 57/57 HLA-DQB1*06:02-positive, 54/54 hypocretin-deficient), 54 first-degree relatives (29 females, mean age 19.1 years, 37/54 H1N1-vaccinated, 32/54 HLA-DQB1*06:02-positive), and 55 healthy controls (38 females, mean age 22.3 years). We tested for differences between these groups, for parametric effects (controls > first-degree relatives > patients) and associations in patients (cerebrospinal fluid [CSF] hypocretin-1 and disease duration) and first-degree relatives (HLA-DQB1*06:02 and H1N1-vaccination). We employed tract-based spatial statistics and used permutation testing and threshold-free cluster enhancement for inference. Results: Patients with NT1 had a widespread, bilateral pattern of significantly lower FA compared with first-degree relatives and healthy controls. Additionally, patients with NT1 also exhibited significantly higher RD and lower AD in several focal white matter clusters. The parametric model showed that first-degree relatives had intermediate values. Full sample of patients with NT1 showed no significant associations with disease duration or CSF hypocretin-1. Conclusions: Our study suggests widespread abnormal white matter involvement far beyond the already known focal hypothalamic pathology in NT1, possibly reflecting the combined effects of the loss of the widely projecting hypothalamic hypocretin neurons, and/or secondary effects of wake/sleep dysregulation. These findings demonstrate the importance of white matter pathology in NT1.
Bone
In observational studies, vitamin D deficiency is a risk factor for low bone density and future f... more In observational studies, vitamin D deficiency is a risk factor for low bone density and future fractures, whereas a causal relation has been difficult to show in randomized controlled trials (RCTs). Similarly, vitamin D deficiency has been associated with increased bone turnover, but RCTs with vitamin D have not shown conclusive effects. This could be due to inclusion of vitamin D sufficient subjects and low vitamin D doses. In the present study 399 subjects with mean baseline serum 25-hydroxyvitamin D (25(OH)D) 34.0 nmol/L completed a four months intervention with vitamin D 3 20,000 IU per week versus placebo. Mean serum 25(OH)D increased to 89.0 nmol/L in the vitamin D group and decreased slightly in the placebo group. A small, but significant, decrease in the bone formation marker procollagen of type 1 amino-terminal propeptide (P1NP) was seen in the vitamin D group as compared to the placebo group (mean delta P1NP-1.2 pg/mL and 1.5 ng/mL, respectively, P < 0.01). No significant effects were seen on serum carboxyl-terminal telopeptide of type 1 collagen (CTX-1), Dickkopf-1, sclerostin, tumor necrosis factor-alpha, osteoprotegerin, receptor activator of nuclear factor ĸB ligand, or leptin. Subgroup analyses on subjects with low baseline serum 25(OH)D did not yield additional, significant results. In subjects with high baseline serum parathyroid hormone (PTH) > 6.5 pmol/L and post-intervention decrease in PTH, the decrease in P1NP was more pronounced, they also exhibited significantly reduced serum CTX-1 and increased serum sclerostin. In conclusion, supplementation with vitamin D appears to suppress bone turnover, possibly mediated by PTH reduction. Our findings need to be confirmed in even larger cohorts with vitamin D insufficient subjects.
Sleep
Study Objectives To assess brain activation patterns in response to fun-rated and neutral-rated m... more Study Objectives To assess brain activation patterns in response to fun-rated and neutral-rated movies we performed functional magnetic resonance imaging (fMRI) during a humor-paradigm in narcolepsy type 1 (NT1) patients with cataplexy (muscle atonia triggered by emotions) and controls. Methods The fMRI-humor-paradigm consisted of short movies (25/30 with a humorous punchline; 5/30 without a humorous punchline [but with similar build-up/anticipation]) rated by participants based on their humor experience. We included 41 NT1 patients and 44 controls. Group-level inferences were made using permutation testing. Results Permutation testing revealed no group differences in average movie ratings. fMRI analysis found no group differences in brain activations to fun-rated movies. Patients showed significantly higher activations compared to controls during neutral-rated movies; including bilaterally in the thalamus, pallidum, putamen, amygdala, hippocampus, middle temporal gyrus, cerebellum,...
Endocrine Connections
Immunoassays of steroid hormones are still used in the diagnosis and monitoring of patients with ... more Immunoassays of steroid hormones are still used in the diagnosis and monitoring of patients with congenital adrenal hyperplasia. However, cross-reactivity between steroids can give rise to falsely elevated steroid levels. Here we compare the use of immunoassays and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the monitoring of patients with classic 21-hydroxylase deficiency (21OHD). Steroid profiles in different mutation groups (genotypes) were also compared. Fifty-five patients with classic 21OHD (38 women) were studied. Blood samples were collected in the morning after an overnight medication fast. LC-MS/MS and immunoassays were employed to assay 17-hydroxyprogesterone (17OHP), testosterone and androstenedione. In addition, 21-deoxycortisol (21DF), 11-deoxycortisol (11DF), corticosterone, deoxycorticosterone, cortisone and cortisol were analyzed by LC-MS/MS. Testosterone, androstenedione and 17OHP levels were consistently lower (by about 30-50%) when measured by LC...
Scandinavian journal of clinical and laboratory investigation, 2017
Minimally invasive surgery seems to reduce hormonal stress response to surgery, but has not previ... more Minimally invasive surgery seems to reduce hormonal stress response to surgery, but has not previously been examined in major abdominal vascular surgery. Aortic cross-clamping time and operation time is known to be longer in the totally laparoscopic aortobifemoral bypass (LABF) as compared to open aortobifemoral bypass (OABF). The main objective of our study was to measure the hormonal stress response during surgery and aortic cross-clamping in patients undergoing a totally laparoscopic versus an open aortobifemoral bypass. This was a sub-study of a larger randomized controlled multicentre trial. Thirty consecutive patients with severe aortoiliac occlusive disease were randomized to either a laparoscopic (LABF) or an open (OABF) procedure. The surgical stress response was measured by perioperative monitoring of adrenocorticotropic hormone (ACTH), aldosterone, metanephrine and cortisol at eight different time-points. During surgery. there was an increase in all humoral stress markers...
Objective: To determine the relationship between serum total 25-hydroxyvitamin D (25(OH)D), direc... more Objective: To determine the relationship between serum total 25-hydroxyvitamin D (25(OH)D), directly measured free 25(OH) D and calculated free 25(OH)D with regard to vitamin D-binding protein (DBP) phenotypes, sex, BMI, age and season, and their interrelationship to vitamin D supplementation. Design, patients and interventions: A randomized controlled trial with 20 000 IU of vitamin D3 per week or placebo for 12 months was designed. A total of 472 subjects, 236 in each of the intervention groups, were included in the analyses. Main outcome measures: Baseline serum concentrations and increases in serum total 25(OH)D, directly measured free 25(OH)D, calculated free 25(OH)D and DBP. Results: Serum total 25(OH)D and DBP concentrations were significantly lower in subjects with the phenotype Gc2/Gc2 compared to phenotypes with the Gc1S allele, and lower in males compared to females. When using directly measured free 25(OH)D, the differences related to DBP phenotypes and sexes were clearl...
Gene
BACKGROUND Studies have shown that vitamin D can enhance glucose-stimulated insulin secretion (GS... more BACKGROUND Studies have shown that vitamin D can enhance glucose-stimulated insulin secretion (GSIS) and change the expression of genes in pancreatic β-cells. Still the mechanisms linking vitamin D and GSIS are unknown. MATERIAL AND METHODS We used an established β-cell line, INS1E. INS1E cells were pre-treated with 10 nM 1,25(OH)2vitamin D or 10 nM 25(OH)vitamin D for 72 hours and stimulated with 22 mM glucose for 60 minutes. RNA was extracted for gene expression analysis. RESULTS Expression of genes affecting viability, apoptosis and GSIS changed after pre-treatment with both 1,25(OH)2vitamin D and 25(OH)vitamin D in INS1E cells. Stimulation with glucose after pre-treatment of INS1E cells with 1,25(OH)2vitamin D resulted in 181 differentially expressed genes, whereas 526 genes were differentially expressed after pre-treatment with 25(OH)vitamin D. CONCLUSION Vitamin D metabolites may affect pancreatic β-cells and GSIS through changed gene expression for genes involved in β-cell function and viability.
Scandinavian Journal of Clinical and Laboratory Investigation, Apr 3, 2014
Transmembrane protein 27 (Tmem27), which is expressed in pancreatic β-cells, plays an important r... more Transmembrane protein 27 (Tmem27), which is expressed in pancreatic β-cells, plays an important role in insulin secretion and pancreatic β-cell proliferation. Analysis of the INS-1 cell proteome using stable isotope labeling by amino acids in cell culture (SILAC) in combination with LC-MS identified Tmem27 as the one of most robustly (up to seven-fold) upregulated proteins after treatment with the active metabolite of vitamin D, 1,25-(OH)2D3. Furthermore, we report that Tmem27 which is cleaved and released from, i.e. pancreatic β-cells, is present in human serum and its levels are significantly lower in subjects with autoimmune diabetes as compared to healthy individuals (13% of the levels). Additionally, Tmem27 correlated positively (0.70) with C-peptide serum levels in healthy subjects. Our data indicate that Tmem27 could be of potential value as a serum marker for the pathogenesis of diabetes and as such may warrant the development of measurement methods with lower limit of detection for its further validation.
Endocrine reviews, 2009
Context: Infusion of insulin acutely stimulates leptin production and chronic insulin treatment i... more Context: Infusion of insulin acutely stimulates leptin production and chronic insulin treatment is associated with elevated serum leptin levels and body weight in subjects with type 2 diabetes. Objective: The objective of the study was to investigate the relationship between insulin administration, leptin levels, and weight gain in subjects with type 2 diabetes. Design: This was a post hoc analysis of two randomized, controlled trials. Setting: The study was conducted at an outpatient clinic. Subjects: Subjects included 35 (study 1) and 32 (study 2) poorly controlled oral hypoglycemic agent (OHA)-treated type 2 diabetic subjects. Intervention: Study 1: subjects were investigated during a hyperinsulinemic, euglycemic glucose clamp and 12 months after being randomly allocated to start insulin or continue on OHAs. Study 2: 1 yr treatment with either OHAs and lifestyle intervention or insulin with or without concomitant lifestyle intervention. Main outcome measure: Changes in serum leptin levels during clamp and during 1 yr of treatment in relationship to changes in body weight. Results: Study 1: during acute insulin infusion leptin levels increased by 10% (P Ͻ 0.001). During 1 yr of insulin therapy, mean body weight increased by 6%, whereas the fasting leptin levels increased by 108% (both P Ͻ 0.001). The weight gain observed at 1 yr correlated with the increase in leptin levels observed during the clamp (r ϭ 0.62, P ϭ 0.003). Study 2: mean body weight increased by 4% (P Ͻ 0.01), whereas leptin levels increased by 56% (P Ͻ 0.001) during 1 yr of insulin treatment and the increase in leptin preceded the increase in body weight. Conclusions: Significant correlations were observed between insulin's effect on serum leptin levels and the increase in weight that accompanied insulin therapy.
Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke, 2004
BACKGROUND A few case reports suggest that the use of androgenic anabolic steroids may be associa... more BACKGROUND A few case reports suggest that the use of androgenic anabolic steroids may be associated with myocardial infarction. MATERIAL AND METHODS Case report. RESULTS We report the case of a 27-year-old male body builder with acute myocardial infarction due to occlusion of the proximal left anterior descending coronary artery. He was treated with primary angioplasty with stent implantation and intra-aortic balloon support, but still developed a large myocardial infarction as determined by both echocardiography and myocardial perfusion tomography. The patient had been using androgenic anabolic steroids regularly for ten years. There was no family history of heart disease or lipid disorder. INTERPRETATION The actual frequency of myocardial infarction and even sudden death among users of anabolic steroids is presumably underreported in the medical literature. A causal relationship is not established, but a pathogenic role is plausible. Use of androgenic anabolic steroids has been a...
Background: Immigrants from South Asia to Western countries have a high prevalence of type 2 diab... more Background: Immigrants from South Asia to Western countries have a high prevalence of type 2 diabetes mellitus (T2DM). We explored pathogenic factors that might contribute to the high risk of T2DM in Pakistani immigrants to Norway. Methods: A cross-sectional study was performed in 18 Pakistani and 21 Norwegian men and women with T2DM (age 29-45 years), recruited from two hospital outpatient clinics. Anthropometrics and a two-step euglycemic, hyperinsulinemic clamp with measurements of non-esterified fatty acids (NEFA) during clamp, was performed in all patients. Insulin sensitivity, given as the Glucose Infusion Rate (GIR) and Insulin Sensitivity Index (ISI), was calculated from the two euglycemic clamp steps. Fasting adipokines and inflammatory mediators were measured. Continuous variables between groups were compared using Student's t test or Mann-Whitney U test as appropriate. Spearman's correlation coefficient and multiple linear regression analyses were used. Results: Despite having a lower BMI, Pakistani patients were more insulin resistant than Norwegian patients, during both low and high insulin infusion rates, after adjustment for sex and % body fat: median (interquartile range) GIR (low insulin) : 339.8(468.0) vs 468.4(587.3) µmol/m 2 /min (p=0.060), ISI (low insulin) : 57.1(74.1) vs 79.7(137.9) µmol/m 2 /min (p=0.012), GIR (high insulin) : 1661.1(672.3) vs 2055.6(907.0) µmol/m 2 /min (p=0.042), ISI (high insulin) : 14.2(7.3) vs 20.7(17.2) µmol/m 2 /min (p=0.014). Pakistani patients had lower percentage NEFA suppression 30 minutes into clamp hyperinsulinemia than Norwegians: 41.9(90.6)% vs 71.2(42.1)%,(p=0.042). The relationship of ISI to BMI, leptin and interleukin1-receptor antagonist also differed between Norwegians and Pakistanis. Conclusions: Compared with Norwegian patients, Pakistani patients with T2DM had lower insulin sensitivity, affecting both glucose and lipid metabolism. The relation of insulin sensitivity to BMI and some adipokines also differed between the groups.
Antioxidants
There is a need for feasible and non-invasive diagnostics in perinatal asphyxia. Metabolomics is ... more There is a need for feasible and non-invasive diagnostics in perinatal asphyxia. Metabolomics is the study of small molecular weight products of cellular metabolism that may, directly and indirectly, reflect the level of oxidative stress. Saliva analysis is a novel approach that has a yet unexplored potential in metabolomics in perinatal asphyxia. The aim of this review was to give an overview of metabolomics studies of oxidative stress in perinatal asphyxia, particularly searching for studies analyzing non-invasively collected biofluids including saliva. We searched the databases PubMed/Medline and included 11 original human and 4 animal studies. In perinatal asphyxia, whole blood, plasma, and urine are the most frequently used biofluids used for metabolomics analyses. Although changes in oxidative stress-related salivary metabolites have been reported in adults, the utility of this approach in perinatal asphyxia has not yet been explored. Human and animal studies indicate that, in...
Psychoneuroendocrinology
The diagnosis of fetal anomaly can be a major stressor to the expectant mother. Current understan... more The diagnosis of fetal anomaly can be a major stressor to the expectant mother. Current understanding of the relationship between psychological stress and cortisol in pregnancy is limited. This study examined: (1) differences in the ratio of serum cortisol to cortisol binding globulin (SC/CBG) and cortisone levels among women with and without a diagnosis of fetal anomaly, (2) the association between self-reported stress and cortisol from mid to late pregnancy, and (3) the Jo ur na l P re -p ro of
Journal of Nutritional Science
The aim of the study was to investigate the effect of prebiotic fibres on appetite-regulating hor... more The aim of the study was to investigate the effect of prebiotic fibres on appetite-regulating hormones, subjective feeling of appetite and energy intake in subjects with type 2 diabetes. Data presented are secondary outcomes of a study investigating the effect of prebiotics on glucagon-like peptide-1 and glycaemic regulation. We conducted a randomised and placebo-controlled crossover trial to evaluate the effects of 16 g/d of inulin-type fructans or a control supplement (maltodextrin) for 6 weeks in randomised order, with a 4-week washout period in-between, on appetite in thirty-five men and women with type 2 diabetes. Data were collected at visits before and after each treatment: plasma concentration of the satiety-related peptides ghrelin and peptide YY (PYY) were assessed during a standardised mixed meal. The subjective sensation of appetite was evaluated in response to an ad libitum lunch by rating the visual analogue scale. Twenty-nine individuals (twelve women) were included i...
Sleep
Study Objectives Narcolepsy type 1 (NT1) is associated with hypocretin neuron loss. However, ther... more Study Objectives Narcolepsy type 1 (NT1) is associated with hypocretin neuron loss. However, there are still unexplained phenotypic NT1 features. We investigated the associations between clinical and sleep phenotypic characteristics, the NT1-associated P2RY11 polymorphism rs2305795, and P2Y11 protein levels in T lymphocytes in patients with NT1, their first-degree relatives and unrelated controls. Methods The P2RY11 SNP was genotyped in 100 patients (90/100 H1N1-(Pandemrix)-vaccinated), 119 related and 123 non-related controls. CD4 and CD8 T lymphocyte P2Y11 protein levels were quantified using flow cytometry in 167 patients and relatives. Symptoms and sleep recording parameters were also collected. Results We found an association between NT1 and the rs2305795 A allele (OR = 2, 95% CI (1.3, 3.0), p = 0.001). T lymphocyte P2Y11 protein levels were significantly lower in patients and relatives homozygous for the rs2305795 risk A allele (CD4: p = 0.012; CD8: p = 0.007). The nocturnal s...
Sleep
Study Objectives Narcolepsy type 1 (NT1) may be complicated by comorbidities. We aimed to study t... more Study Objectives Narcolepsy type 1 (NT1) may be complicated by comorbidities. We aimed to study the extent of obesity and other medical comorbidities in a Norwegian population of NT1 patients with debut of symptoms after the 2009 H1N1 influenza epidemic and vaccination campaign. We also aimed to explore factors associated with obesity. Methods Ninety-one patients (48 children and 43 adults) were included in this cross-sectional study, 80 of whom were H1N1-vaccinated. All participants were hospitalized and underwent sleep investigation and physical examination, and completed a semi-structured clinical interview. Results In children, 16 females (70%) and 10 males (40%) were classified as overweight or obese. Twenty children (42%) had a co-existing medical disorder. Medical comorbidity was significantly positively associated with BMI in children (p = .032). In adults, 19 females (58%) and 7 males (70%) were classified as overweight or obese. Twenty-six adults (61%) had a co-existing me...
Sleep
Study Objectives To explore HLA (human leukocyte antigen) in post-H1N1 narcolepsy type 1 patients... more Study Objectives To explore HLA (human leukocyte antigen) in post-H1N1 narcolepsy type 1 patients (NT1), first-degree relatives and healthy controls, and assess HLA associations with clinical and sleep parameters in patients and first-degree relatives. Methods Ninety post-H1N1 NT1 patients and 202 of their first-degree relatives were HLA-genotyped (next generation sequencing) and phenotyped (semi-structured interviews, Stanford Sleep Questionnaire, polysomnography, multiple sleep latency test). HLA allele distributions were compared between DQB1*06:02-heterozygous individuals (77 patients, 59 parents, 1230 controls). A subsample (74 patients, 114 relatives) was investigated for associations between HLA-loci and continuous sleep variables using logistic regression. Identified candidate HLA-loci were explored for HLA allele associations with hypnagogic hallucinations and sleep paralysis in 90 patients, and patient allele findings were checked for similar associations in 202 relatives....
Sleep
Study Objectives: To assess white matter involvement in H1N1-vaccinated hypocretin deficient pati... more Study Objectives: To assess white matter involvement in H1N1-vaccinated hypocretin deficient patients with narcolepsy type 1 (NT1) compared with first-degree relatives (a potential risk group) and healthy controls. Methods: We compared four diffusion tensor imaging-based microstructural indices (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], and axial diffusivity [AD]) in 57 patients with NT1 (39 females, mean age 21.8 years, 51/57 H1N1-vaccinated, 57/57 HLA-DQB1*06:02-positive, 54/54 hypocretin-deficient), 54 first-degree relatives (29 females, mean age 19.1 years, 37/54 H1N1-vaccinated, 32/54 HLA-DQB1*06:02-positive), and 55 healthy controls (38 females, mean age 22.3 years). We tested for differences between these groups, for parametric effects (controls > first-degree relatives > patients) and associations in patients (cerebrospinal fluid [CSF] hypocretin-1 and disease duration) and first-degree relatives (HLA-DQB1*06:02 and H1N1-vaccination). We employed tract-based spatial statistics and used permutation testing and threshold-free cluster enhancement for inference. Results: Patients with NT1 had a widespread, bilateral pattern of significantly lower FA compared with first-degree relatives and healthy controls. Additionally, patients with NT1 also exhibited significantly higher RD and lower AD in several focal white matter clusters. The parametric model showed that first-degree relatives had intermediate values. Full sample of patients with NT1 showed no significant associations with disease duration or CSF hypocretin-1. Conclusions: Our study suggests widespread abnormal white matter involvement far beyond the already known focal hypothalamic pathology in NT1, possibly reflecting the combined effects of the loss of the widely projecting hypothalamic hypocretin neurons, and/or secondary effects of wake/sleep dysregulation. These findings demonstrate the importance of white matter pathology in NT1.
Bone
In observational studies, vitamin D deficiency is a risk factor for low bone density and future f... more In observational studies, vitamin D deficiency is a risk factor for low bone density and future fractures, whereas a causal relation has been difficult to show in randomized controlled trials (RCTs). Similarly, vitamin D deficiency has been associated with increased bone turnover, but RCTs with vitamin D have not shown conclusive effects. This could be due to inclusion of vitamin D sufficient subjects and low vitamin D doses. In the present study 399 subjects with mean baseline serum 25-hydroxyvitamin D (25(OH)D) 34.0 nmol/L completed a four months intervention with vitamin D 3 20,000 IU per week versus placebo. Mean serum 25(OH)D increased to 89.0 nmol/L in the vitamin D group and decreased slightly in the placebo group. A small, but significant, decrease in the bone formation marker procollagen of type 1 amino-terminal propeptide (P1NP) was seen in the vitamin D group as compared to the placebo group (mean delta P1NP-1.2 pg/mL and 1.5 ng/mL, respectively, P < 0.01). No significant effects were seen on serum carboxyl-terminal telopeptide of type 1 collagen (CTX-1), Dickkopf-1, sclerostin, tumor necrosis factor-alpha, osteoprotegerin, receptor activator of nuclear factor ĸB ligand, or leptin. Subgroup analyses on subjects with low baseline serum 25(OH)D did not yield additional, significant results. In subjects with high baseline serum parathyroid hormone (PTH) > 6.5 pmol/L and post-intervention decrease in PTH, the decrease in P1NP was more pronounced, they also exhibited significantly reduced serum CTX-1 and increased serum sclerostin. In conclusion, supplementation with vitamin D appears to suppress bone turnover, possibly mediated by PTH reduction. Our findings need to be confirmed in even larger cohorts with vitamin D insufficient subjects.
Sleep
Study Objectives To assess brain activation patterns in response to fun-rated and neutral-rated m... more Study Objectives To assess brain activation patterns in response to fun-rated and neutral-rated movies we performed functional magnetic resonance imaging (fMRI) during a humor-paradigm in narcolepsy type 1 (NT1) patients with cataplexy (muscle atonia triggered by emotions) and controls. Methods The fMRI-humor-paradigm consisted of short movies (25/30 with a humorous punchline; 5/30 without a humorous punchline [but with similar build-up/anticipation]) rated by participants based on their humor experience. We included 41 NT1 patients and 44 controls. Group-level inferences were made using permutation testing. Results Permutation testing revealed no group differences in average movie ratings. fMRI analysis found no group differences in brain activations to fun-rated movies. Patients showed significantly higher activations compared to controls during neutral-rated movies; including bilaterally in the thalamus, pallidum, putamen, amygdala, hippocampus, middle temporal gyrus, cerebellum,...
Endocrine Connections
Immunoassays of steroid hormones are still used in the diagnosis and monitoring of patients with ... more Immunoassays of steroid hormones are still used in the diagnosis and monitoring of patients with congenital adrenal hyperplasia. However, cross-reactivity between steroids can give rise to falsely elevated steroid levels. Here we compare the use of immunoassays and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the monitoring of patients with classic 21-hydroxylase deficiency (21OHD). Steroid profiles in different mutation groups (genotypes) were also compared. Fifty-five patients with classic 21OHD (38 women) were studied. Blood samples were collected in the morning after an overnight medication fast. LC-MS/MS and immunoassays were employed to assay 17-hydroxyprogesterone (17OHP), testosterone and androstenedione. In addition, 21-deoxycortisol (21DF), 11-deoxycortisol (11DF), corticosterone, deoxycorticosterone, cortisone and cortisol were analyzed by LC-MS/MS. Testosterone, androstenedione and 17OHP levels were consistently lower (by about 30-50%) when measured by LC...
Scandinavian journal of clinical and laboratory investigation, 2017
Minimally invasive surgery seems to reduce hormonal stress response to surgery, but has not previ... more Minimally invasive surgery seems to reduce hormonal stress response to surgery, but has not previously been examined in major abdominal vascular surgery. Aortic cross-clamping time and operation time is known to be longer in the totally laparoscopic aortobifemoral bypass (LABF) as compared to open aortobifemoral bypass (OABF). The main objective of our study was to measure the hormonal stress response during surgery and aortic cross-clamping in patients undergoing a totally laparoscopic versus an open aortobifemoral bypass. This was a sub-study of a larger randomized controlled multicentre trial. Thirty consecutive patients with severe aortoiliac occlusive disease were randomized to either a laparoscopic (LABF) or an open (OABF) procedure. The surgical stress response was measured by perioperative monitoring of adrenocorticotropic hormone (ACTH), aldosterone, metanephrine and cortisol at eight different time-points. During surgery. there was an increase in all humoral stress markers...
Objective: To determine the relationship between serum total 25-hydroxyvitamin D (25(OH)D), direc... more Objective: To determine the relationship between serum total 25-hydroxyvitamin D (25(OH)D), directly measured free 25(OH) D and calculated free 25(OH)D with regard to vitamin D-binding protein (DBP) phenotypes, sex, BMI, age and season, and their interrelationship to vitamin D supplementation. Design, patients and interventions: A randomized controlled trial with 20 000 IU of vitamin D3 per week or placebo for 12 months was designed. A total of 472 subjects, 236 in each of the intervention groups, were included in the analyses. Main outcome measures: Baseline serum concentrations and increases in serum total 25(OH)D, directly measured free 25(OH)D, calculated free 25(OH)D and DBP. Results: Serum total 25(OH)D and DBP concentrations were significantly lower in subjects with the phenotype Gc2/Gc2 compared to phenotypes with the Gc1S allele, and lower in males compared to females. When using directly measured free 25(OH)D, the differences related to DBP phenotypes and sexes were clearl...
Gene
BACKGROUND Studies have shown that vitamin D can enhance glucose-stimulated insulin secretion (GS... more BACKGROUND Studies have shown that vitamin D can enhance glucose-stimulated insulin secretion (GSIS) and change the expression of genes in pancreatic β-cells. Still the mechanisms linking vitamin D and GSIS are unknown. MATERIAL AND METHODS We used an established β-cell line, INS1E. INS1E cells were pre-treated with 10 nM 1,25(OH)2vitamin D or 10 nM 25(OH)vitamin D for 72 hours and stimulated with 22 mM glucose for 60 minutes. RNA was extracted for gene expression analysis. RESULTS Expression of genes affecting viability, apoptosis and GSIS changed after pre-treatment with both 1,25(OH)2vitamin D and 25(OH)vitamin D in INS1E cells. Stimulation with glucose after pre-treatment of INS1E cells with 1,25(OH)2vitamin D resulted in 181 differentially expressed genes, whereas 526 genes were differentially expressed after pre-treatment with 25(OH)vitamin D. CONCLUSION Vitamin D metabolites may affect pancreatic β-cells and GSIS through changed gene expression for genes involved in β-cell function and viability.