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BETA
Berne, Christian
Alternative names
Publications (10 of 78) Show all publications
von Zur-Mühlen, B., Lundgren, T., Bayman, L., Berne, C., Bridges, N., Eggerman, T., . . . Korsgren, O. (2019). Open Randomized Multicenter Study to Evaluate Safety and Efficacy of Low Molecular Weight Sulfated Dextran in Islet Transplantation. Transplantation, 103(3), 630-637
Open this publication in new window or tab >>Open Randomized Multicenter Study to Evaluate Safety and Efficacy of Low Molecular Weight Sulfated Dextran in Islet Transplantation
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2019 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 103, no 3, p. 630-637Article in journal (Refereed) Published
Abstract [en]

Background. When transplanted human pancreatic islets are exposed to blood during intraportal infusion, an innate immune response is triggered. This instant blood-mediated inflammatory reaction (IBMIR) activates the coagulation and complement cascades and leads to the destruction of 25% of all transplanted islets within minutes, contributing to the need, in most patients, for islets from more than 1 donor. Low molecular dextran sulfate (LMW-DS) has been shown in experimental settings to inhibit IBMIR. Methods. The Clinical Islet Transplantation consortium 01 study was a phase II, multicenter, open label, active control, randomized study. Twenty-four subjects were randomized to peritransplant intraportal and systemic treatment with either LMW-DS or heparin, targeting an activated partial thromboplastin time of 150 +/- 10 seconds and 50 +/- 5 seconds, respectively. C-peptide response was measured with a mixed meal tolerance test at 75 and 365 days after transplant. Results. Low molecular dextran sulfate was safe and well tolerated with similar observed adverse events (mostly attributed to immunosuppression) as in the heparin arm. There was no difference in the primary endpoint (stimulated C-peptide 75 +/- 5 days after the first transplant) between the 2 arms (1.33 +/- 1.10 versus 1.56 +/- 1.36 ng/mL, P = 0.66). Insulin requirement, metabolic parameters, Clarke and HYPO score, quality of life, and safety were similar between the 2 treatments groups. Conclusions. Even with low dosing, LMW-DS showed similar efficacy in preventing IBMIR to promote islet engraftment when compared to "state-of-the art" treatment with heparin. Furthermore, no substantial differences in the efficacy and safety endpoints were detected, providing important information for future studies with more optimal dosing of LMW-DS for the prevention of IBMIR in islet transplantation.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2019
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-393536 (URN)10.1097/TP.0000000000002425 (DOI)000480678600034 ()30211831 (PubMedID)
Available from: 2019-09-24 Created: 2019-09-24 Last updated: 2019-09-24Bibliographically approved
Nowak, C., Hetty, S., Salihovic, S., Castillejo-Lopez, C., Ganna, A., Cook, N. L., . . . Ingelsson, E. (2018). Glucose challenge metabolomics implicates medium-chain acylcarnitines in insulin resistance. Scientific Reports, 8, Article ID 8691.
Open this publication in new window or tab >>Glucose challenge metabolomics implicates medium-chain acylcarnitines in insulin resistance
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 8691Article in journal (Refereed) Published
Abstract [en]

Insulin resistance (IR) predisposes to type 2 diabetes and cardiovascular disease but its causes are incompletely understood. Metabolic challenges like the oral glucose tolerance test (OGTT) can reveal pathogenic mechanisms. We aimed to discover associations of IR with metabolite trajectories during OGTT. In 470 non-diabetic men (age 70.6 +/- 0.6 years), plasma samples obtained at 0, 30 and 120 minutes during an OGTT were analyzed by untargeted liquid chromatography-mass spectrometry metabolomics. IR was assessed with the hyperinsulinemic-euglycemic clamp method. We applied age-adjusted linear regression to identify metabolites whose concentration change was related to IR. Nine trajectories, including monounsaturated fatty acids, lysophosphatidylethanolamines and a bile acid, were significantly associated with IR, with the strongest associations observed for medium-chain acylcarnitines C10 and C12, and no associations with L-carnitine or C2-, C8-, C14- or C16-carnitine. Concentrations of C10-and C12-carnitine decreased during OGTT with a blunted decline in participants with worse insulin resistance. Associations persisted after adjustment for obesity, fasting insulin and fasting glucose. In mouse 3T3-L1 adipocytes exposed to different acylcarnitines, we observed blunted insulin-stimulated glucose uptake after treatment with C10-or C12-carnitine. In conclusion, our results identify medium-chain acylcarnitines as possible contributors to IR.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-357687 (URN)10.1038/s41598-018-26701-0 (DOI)000434252600004 ()29875472 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation, 2013.0126Swedish Research Council, 2015-03477
Note

Tove Fall and Erik Ingelsson contributed equally to this work.

Available from: 2018-08-23 Created: 2018-08-23 Last updated: 2018-08-23Bibliographically approved
Palm, A., Berne, C., Igelström, H., Åsenlöf, P., Janson, C. & Lindberg, E. (2018). The Impact of Continuous Positive Airway Pressure on Circulating IGF-1 in Patients With Obstructive Sleep Apnea. Journal of Clinical Sleep Medicine (JCSM), 385-391
Open this publication in new window or tab >>The Impact of Continuous Positive Airway Pressure on Circulating IGF-1 in Patients With Obstructive Sleep Apnea
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2018 (English)In: Journal of Clinical Sleep Medicine (JCSM), ISSN 1550-9389, E-ISSN 1550-9397, p. 385-391Article in journal (Refereed) Published
Abstract [en]

Study Objectives: Obstructive sleep apnea (OSA) is a disease with metabolic and cardiovascular consequences and is associated with decreased serum concentrations of insulin-like growth factor-1 (IGF-1). The aim of this study was to investigate whether continuous positive airway pressure (CPAP) will increase serum IGF-1 concentration in patients with OSA. Methods: Patients with moderate to severe OSA were recruited from a sleep clinic and serum IGF-1 was measured before initiation of CPAP and at follow-up after 4.8 +/- 2.5 months. Patients adherent to CPAP treatment (usage >= 4 h/night) were compared with those considered to be nonadherent (usage < 4 h/night). Results: Complete data were obtained from 69 patients (86% male, age 56 +/- 12 years, respiratory event index 43 +/- 21 events/h, Epworth Sleepiness Scale score 12 +/- 5). In those adherent to CPAP (n = 42), there was an increase in serum IGF-1 concentration with 21.1 (95% confidence interval [CI]: 13.1 to 29.2) mu g/L compared to 4.7 (95% CI: -4.1 to 13.5) mu g/L in the nonadherent group (n = 27) (P =.0083). In a linear multivariate model adjusting for sex, age, body mass index, respiratory event index, and mean oxygen saturation during the night recording, the change in serum IGF-1 concentration was significantly associated with adherence to CPAP treatment (adjusted beta coefficient: 21.8, 95% CI: 10.2 to 33.4) and inversely associated with change in body mass index (adjusted beta coefficient: -7.1, 95% CI: -11.3 to -3.0) and change in hemoglobin A1c (adjusted beta coefficient: -1.8, 95% CI: - 33 to -0.3). Conclusions: CPAP usage >= 4 h/night is associated with increased serum IGF-1 concentration in male patients with OSA.

Keywords
adherence, continuous positive airway pressure, IGF-1, obstructive sleep apnea
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-343619 (URN)10.5664/jcsm.6982 (DOI)000427477700011 ()29458693 (PubMedID)
Funder
Swedish Research Council
Available from: 2018-02-28 Created: 2018-02-28 Last updated: 2018-09-25
Nowak, C., Salihovic, S., Ganna, A., Brandmaier, S., Tukiainen, T., Broeckling, C. D., . . . Fall, T. (2016). Effect of Insulin Resistance on Monounsaturated Fatty Acid Levels: A Multi-cohort Non-targeted Metabolomics and Mendelian Randomization Study. PLoS Genetics, 12(10), Article ID e1006379.
Open this publication in new window or tab >>Effect of Insulin Resistance on Monounsaturated Fatty Acid Levels: A Multi-cohort Non-targeted Metabolomics and Mendelian Randomization Study
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2016 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 12, no 10, article id e1006379Article in journal (Refereed) Published
Abstract [en]

Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or beta-cell responsiveness (disposition index) during an oral glucose tolerance test. These implicated bile acid, glycerophospholipid and caffeine metabolism for IR and fatty acid biosynthesis for impaired insulin secretion. In MR analysis in two separate cohorts (n = 2,613) followed by replication in three independent studies profiled on different metabolomics platforms (n = 7,824 / 8,961 / 8,330), we discovered and replicated causal effects of IR on lower levels of palmitoleic acid and oleic acid. A trend for a causal effect of IR on higher levels of tyrosine reached significance only in meta-analysis. In one of the largest studies combining "gold standard" measures for insulin responsiveness with non-targeted metabolomics, we found distinct metabolic profiles related to IR or impaired insulin secretion. We speculate that the causal effects on monounsaturated fatty acid levels could explain parts of the raised cardiovascular disease risk in IR that is independent of diabetes development.

National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-310027 (URN)10.1371/journal.pgen.1006379 (DOI)000386683300041 ()27768686 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation, 2015.0327Swedish Diabetes Association, DIA 2013-024Göran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of TechnologySwedish Heart Lung Foundation, 20120197 20150429 20070481EU, European Research Council, 33595 HEALTH-2009-2.2.1-3/242114 HEALTH-2013-2.4.2-1/602936Swedish Research Council, 2012-1397 2015-03477 M-2005-1112 2016-00250The Karolinska Institutet's Research FoundationNIH (National Institute of Health), DK U01-066134Swedish Foundation for Strategic Research
Available from: 2016-12-12 Created: 2016-12-09 Last updated: 2018-01-13Bibliographically approved
Locke, A. E., Kahali, B., Berndt, S. I., Justice, A. E., Pers, T. H., Day, F. R., . . . Speliotes, E. K. (2015). Genetic studies of body mass index yield new insights for obesity biology. Nature, 518(7538), 197-206
Open this publication in new window or tab >>Genetic studies of body mass index yield new insights for obesity biology
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2015 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, no 7538, p. 197-206Article in journal (Refereed) Published
Abstract [en]

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-244272 (URN)10.1038/nature14177 (DOI)000349190300031 ()25673413 (PubMedID)
Note

De fem sista författarna delar sistaförfattarskapet.

Available from: 2015-02-13 Created: 2015-02-13 Last updated: 2018-07-06Bibliographically approved
Shungin, D., Winkler, T. W., Croteau-Chonka, D. C., Ferreira, T., Locke, A. E., Mägi, R., . . . Mohlke, K. L. (2015). New genetic loci link adipose and insulin biology to body fat distribution. Nature, 518(7538), 187-196
Open this publication in new window or tab >>New genetic loci link adipose and insulin biology to body fat distribution
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2015 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, no 7538, p. 187-196Article in journal (Refereed) Published
Abstract [en]

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-244267 (URN)10.1038/nature14132 (DOI)000349190300030 ()25673412 (PubMedID)
Available from: 2015-02-13 Created: 2015-02-13 Last updated: 2017-12-04Bibliographically approved
Theorell-Haglöw, J., Berglund, L., Berne, C. & Lindberg, E. (2014). Both habitual short sleepers and long sleepers are at greater risk of obesity: a population-based 10-year follow-up in women. Sleep Medicine, 15(10), 1204-1211
Open this publication in new window or tab >>Both habitual short sleepers and long sleepers are at greater risk of obesity: a population-based 10-year follow-up in women
2014 (English)In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 15, no 10, p. 1204-1211Article in journal (Refereed) Published
Abstract [en]

Objective: To assess how change in sleep duration is related to subsequent obesity. Methods: In this 10-year follow-up, 4903 non-pregnant participants answered a questionnaire on sleeping habits, obesity, and lifestyle factors (questions identical to baseline questionnaire). Habitual normal sleepers were defined as sleeping 6-9 h/night at both baseline and follow-up, whereas women sleeping <6 h/night or >= 9 h/night at both occasions were defined as habitual short sleepers and habitual long sleepers, respectively. Logistic regression was used to analyze associations between changes in sleep duration, general obesity (body mass index >= 30 kg/m(2)), weight gain (>= 10 kg) and also, central obesity (waist circumference >= 88 cm), and increase in waist circumference (>= 10 cm) at follow-up. Results: Among younger women (aged <40 years) both habitual short sleepers and habitual long sleepers had a higher prevalence of general (short: 31.3%, P < 0.0001; long: 38.1%, P = 0.01) and central obesity (short: 60.5%, P = 0.01; long: 82.4%, P = 0.01) compared with habitual normal sleepers (general obesity: 8.9%; central obesity: 35.9%) at follow-up. Younger women who were short sleepers at baseline but normal sleepers at the follow-up had a higher prevalence of both general (19.3%, P = 0.01) and central obesity (45.4%, P = 0.07) compared with habitual normal sleepers at follow-up. In adjusted analyses, both habitual short [adjusted odds ratio (aOR), 6.78; 95% confidence interval (CI), 2.71-17.0] and long (aOR, 4.64; 95% CI, 1.09-19.8) sleep durations were risk factors for general obesity in younger women. In younger women habitual long sleep duration was a risk factor also for central obesity (aOR, 6.05; 95% CI, 1.19-30.7) whereas habitual short sleep duration was not (aOR, 1.93; 95% CI, 0.87-4.81). Similar results were seen also for weight gain and increased waist circumference as dependent variables. In addition, decreased sleep duration from normal to short duration was a risk factor for both weight gain (aOR, 1.85; 95% CI, 1.14-3.02) and increased waist circumference (aOR, 1.84; 95% CI, 1.20-2.81). There were no associations between changes in sleep duration and any of the measures of obesity at the follow-up in women aged >40 years at baseline. Conclusion: In younger women, both habitual short and long sleep duration was a risk factor for obesity, whereas no such relationship was seen in older women.

Keywords
Sleep duration, Obesity, Changed sleep duration, Longitudinal, Population-based, Women
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-235320 (URN)10.1016/j.sleep.2014.02.014 (DOI)000342501500004 ()
Available from: 2014-11-05 Created: 2014-10-30 Last updated: 2017-12-05Bibliographically approved
Wood, A. R., Esko, T., Yang, J., Vedantam, S., Pers, T. H., Gustafsson, S., . . . Frayling, T. M. (2014). Defining the role of common variation in the genomic and biological architecture of adult human height. Nature Genetics, 46(11), 1173-1186
Open this publication in new window or tab >>Defining the role of common variation in the genomic and biological architecture of adult human height
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2014 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 11, p. 1173-1186Article in journal (Refereed) Published
Abstract [en]

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-233669 (URN)10.1038/ng.3097 (DOI)000344131900008 ()25282103 (PubMedID)
Available from: 2014-10-07 Created: 2014-10-07 Last updated: 2018-07-06Bibliographically approved
Engström, S., Borgquist, L., Berne, C., Gahnberg, L. & Svärdsudd, K. (2013). Can costs of screening for hypertension and diabetes in dental care and follow-up in primary health care be predicted?. Upsala Journal of Medical Sciences, 118(4), 256-262
Open this publication in new window or tab >>Can costs of screening for hypertension and diabetes in dental care and follow-up in primary health care be predicted?
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2013 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 4, p. 256-262Article in journal (Refereed) Published
Abstract [en]

Aim. The purpose was to assess the direct costs of screening for high blood pressure and blood glucose in dental care and of follow-up in primary health care and, based on these data, arrive at a prediction function. Study population. All subjects coming for routine check-ups at three dental health clinics were invited to have blood pressure or blood glucose measurements; 1,623 agreed to participate. Subjects screening positive were referred to their primary health care centres for follow-up. Methods. Information on individual screening time was registered during the screening process, and information on accountable time, costs for the screening staff, overhead costs, and analysis costs for the screening was obtained from the participating dental clinics. The corresponding items in primary care, i.e. consultation time, number of follow-up appointments, accountable time, costs for the follow-up staff, overhead costs, and analysis costs during follow-up were obtained from the primary health care centres. Results. The total screening costs per screened subject ranged from (sic)7.4 to (sic)9.2 depending on subgroups, corresponding to 16.7-42.7 staff minutes. The corresponding follow-up costs were (sic)57-(sic)91. The total resource used for screening and follow-up per diagnosis was 563-3,137 staff minutes. There was a strong relationship between resource use and numbers needed to screen (NNS) to find one diagnosis (P < 0.0001, degree of explanation 99%). Conclusions. Screening and follow-up costs were moderate and appear to be lower for combined screening of blood pressure and blood glucose than for separate screening. There was a strong relationship between resource use and NNS.

Keywords
Costs, dental care, diabetes mellitus type 2, early diagnosis, high blood pressure, primary health care
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-210565 (URN)10.3109/03009734.2013.818599 (DOI)000325527300008 ()
Available from: 2013-11-13 Created: 2013-11-11 Last updated: 2017-12-06Bibliographically approved
Engström, S., Berne, C., Gahnberg, L. & Svärdsudd, K. (2013). Effectiveness of screening for diabetes mellitus in dental health care. Diabetic Medicine, 30(2), 239-245
Open this publication in new window or tab >>Effectiveness of screening for diabetes mellitus in dental health care
2013 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 30, no 2, p. 239-245Article in journal (Refereed) Published
Abstract [en]

Aims:  The aim of the present study was to test the effectiveness of opportunistic blood glucose screening in a cooperational framework between dental and primary health care.

Methods:  Altogether, 1568 subjects, age 20-75 years, with no previous history of diabetes, who came for a regular dental examination, had their non-fasting blood glucose measured with a portable blood glucose meter. Subjects with a concentration of ≥ 6.7 mmol/l (121 mg dl(-1) ) were referred to their primary healthcare centre for follow-up. The outcome, a diagnosis of diabetes mellitus, was obtained from primary healthcare centre and hospital patient records, during 3 years after screening.

 Results:  Of the 155 (9.9%) subjects who screened positive, 139 (89.7%) came to their primary healthcare centre within the 3-year follow-up period and nine (5.8%) were diagnosed as having diabetes mellitus according to the World Health Organization criteria. Of the 1413 subjects who screened negative, 1137 (80.5%) came to the primary healthcare centre and eight (0.6%) were found to have diabetes mellitus. Screening sensitivity was 52.9%, specificity 90.6% and positive predictive value 5.8%. The number of subjects needed to screen to find one case of diabetes was 196. Delineating the study population to those 40- to 75-year-olds with a BMI ≥ 25 kg/m(2) , and 30-to 75-year-olds with a BMI ≥ 30 kg/m(2) , the numbers needed to screen was reduced to 96.

Conclusions:  Cooperation between dental and primary care for high blood glucose screening and follow-up appears to be a feasible method for early diagnosis of diabetes.

National Category
Public Health, Global Health, Social Medicine and Epidemiology Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-167519 (URN)10.1111/dme.12009 (DOI)000313876500020 ()22946629 (PubMedID)
Available from: 2012-01-30 Created: 2012-01-30 Last updated: 2017-12-08Bibliographically approved
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