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Lundström, E., Ljungberg, J., Andersson, J., Manell, H., Strand, R., Forslund, A., . . . Kullberg, J. (2019). Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents. Pediatric Obesity, 14(9), Article ID e12531.
Åpne denne publikasjonen i ny fane eller vindu >>Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents
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2019 (engelsk)Inngår i: Pediatric Obesity, ISSN 2047-6302, E-ISSN 2047-6310, Vol. 14, nr 9, artikkel-id e12531Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background

Despite therapeutic potential against obesity and diabetes, the associations of brown adipose tissue (BAT) with glucose metabolism in young humans are relatively unexplored.

Objectives

To investigate possible associations between magnetic resonance imaging (MRI) estimates of BAT and glucose metabolism, whilst considering sex, age, and adiposity, in adolescents with normal and overweight/obese phenotypes.

Methods

In 143 subjects (10‐20 years), MRI estimates of BAT were assessed as cervical‐supraclavicular adipose tissue (sBAT) fat fraction (FF) and T*2 from water‐fat MRI. FF and T*2 of neighbouring subcutaneous adipose tissue (SAT) were also assessed. Adiposity was estimated with a standardized body mass index, the waist‐to‐height ratio, and abdominal visceral and subcutaneous adipose tissue volumes. Glucose metabolism was represented by the 2h plasma glucose concentration, the Matsuda index, the homeostatic model assessment of insulin resistance, and the oral disposition index; obtained from oral glucose tolerance tests.

Results

sBAT FF and T*2 correlated positively with adiposity before and after adjustment for sex and age. sBAT FF, but not T*2, correlated with 2h glucose and Matsuda index, also after adjustment for sex, age, and adiposity. The association with 2h glucose persisted after additional adjustment for SAT FF.

Conclusions

The association between sBAT FF and 2h glucose, observed independently of sex, age, adiposity, and SAT FF, indicates a role for BAT in glucose metabolism, which potentially could influence the risk of developing diabetes. The lacking association with sBAT T*2 might be due to FF being a superior biomarker for BAT and/or to methodological limitations in the T*2 quantification.

Emneord
adolescent, brown adipose tissue, glucose metabolism, magnetic resonance imaging
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-380052 (URN)10.1111/ijpo.12531 (DOI)000482155600007 ()31290284 (PubMedID)
Forskningsfinansiär
Swedish Heart Lung Foundation, 2170492Swedish Research Council, 2016-01040EU, FP7, Seventh Framework Programme, 279153
Tilgjengelig fra: 2019-07-09 Laget: 2019-03-22 Sist oppdatert: 2019-10-23bibliografisk kontrollert
Weghuber, D., Boyland, E., Caroli, M., Erhardt, E., Frelut, M.-L., Forslund, A., . . . Thivel, D. (2019). Childhood Obesity: The Need to Translate Research into Daily Practice: Announcing the Annals of Nutrition and Metabolism as the Official Journal of the European Childhood Obesity Group. Annals of Nutrition and Metabolism, 74(1), 80-82
Åpne denne publikasjonen i ny fane eller vindu >>Childhood Obesity: The Need to Translate Research into Daily Practice: Announcing the Annals of Nutrition and Metabolism as the Official Journal of the European Childhood Obesity Group
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2019 (engelsk)Inngår i: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 74, nr 1, s. 80-82Artikkel i tidsskrift, Editorial material (Annet vitenskapelig) Published
sted, utgiver, år, opplag, sider
KARGER, 2019
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-379088 (URN)10.1159/000495905 (DOI)000459497900011 ()30616236 (PubMedID)
Tilgjengelig fra: 2019-03-12 Laget: 2019-03-12 Sist oppdatert: 2019-03-12bibliografisk kontrollert
Ring-Dimitriou, S., Krustrup, P., Coelho-E-Silva, M. J., Mota, J., Seabra, A., Rego, C., . . . Thivel, D. (2019). Could sport be part of pediatric obesity prevention and treatment?: Expert conclusions from the 28th European Childhood Obesity Group Congress. Journal of Sport and Health Science, 8(4), 350-352
Åpne denne publikasjonen i ny fane eller vindu >>Could sport be part of pediatric obesity prevention and treatment?: Expert conclusions from the 28th European Childhood Obesity Group Congress
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2019 (engelsk)Inngår i: Journal of Sport and Health Science, ISSN 2095-2546, E-ISSN 2213-2961, Vol. 8, nr 4, s. 350-352Artikkel i tidsskrift, Editorial material (Annet vitenskapelig) Published
sted, utgiver, år, opplag, sider
SHANGHAI UNIV SPORT, 2019
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-390435 (URN)10.1016/j.jshs.2019.01.007 (DOI)000473771300007 ()31333888 (PubMedID)
Tilgjengelig fra: 2019-08-12 Laget: 2019-08-12 Sist oppdatert: 2019-08-12bibliografisk kontrollert
Langner, T., Hedström, A., Mörwald, K., Weghuber, D., Forslund, A., Bergsten, P., . . . Kullberg, J. (2019). Fully convolutional networks for automated segmentation of abdominal adipose tissue depots in multicenter water–fat MRI. Magnetic Resonance in Medicine, 81(4), 2736-2745
Åpne denne publikasjonen i ny fane eller vindu >>Fully convolutional networks for automated segmentation of abdominal adipose tissue depots in multicenter water–fat MRI
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2019 (engelsk)Inngår i: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 81, nr 4, s. 2736-2745Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Purpose: An approach for the automated segmentation of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in multicenter water–fat MRI scans of the abdomen was investigated, using 2 different neural network architectures.

Methods: The 2 fully convolutional network architectures U‐Net and V‐Net were trained, evaluated, and compared using the water–fat MRI data. Data of the study Tellus with 90 scans from a single center was used for a 10‐fold cross‐validation in which the most successful configuration for both networks was determined. These configurations were then tested on 20 scans of the multicenter study beta‐cell function in JUvenile Diabetes and Obesity (BetaJudo), which involved a different study population and scanning device.

Results: The U‐Net outperformed the used implementation of the V‐Net in both cross‐validation and testing. In cross‐validation, the U‐Net reached average dice scores of 0.988 (VAT) and 0.992 (SAT). The average of the absolute quantification errors amount to 0.67% (VAT) and 0.39% (SAT). On the multicenter test data, the U‐Net performs only slightly worse, with average dice scores of 0.970 (VAT) and 0.987 (SAT) and quantification errors of 2.80% (VAT) and 1.65% (SAT).

Conclusion: The segmentations generated by the U‐Net allow for reliable quantification and could therefore be viable for high‐quality automated measurements of VAT and SAT in large‐scale studies with minimal need for human intervention. The high performance on the multicenter test data furthermore shows the robustness of this approach for data of different patient demographics and imaging centers, as long as a consistent imaging protocol is used.

Emneord
abdominal, adipose tissue, deep learning, fully convolutional networks, segmentation, water-fat MRI
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-364355 (URN)10.1002/mrm.27550 (DOI)000462092100044 ()30311704 (PubMedID)
Forskningsfinansiär
EU, FP7, Seventh Framework Programme, 279153
Tilgjengelig fra: 2018-10-25 Laget: 2018-10-25 Sist oppdatert: 2019-04-17bibliografisk kontrollert
Stenlid, R., Manell, H., Halldin, M., Kullberg, J., Ahlström, H., Manukyan, L., . . . Forslund, A. (2018). High DPP-4 concentrations in adolescents are associated with low intact GLP-1. Journal of Clinical Endocrinology and Metabolism, 103(8), 2958-2966
Åpne denne publikasjonen i ny fane eller vindu >>High DPP-4 concentrations in adolescents are associated with low intact GLP-1
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2018 (engelsk)Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, nr 8, s. 2958-2966Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Context: Dipeptidyl Peptidase-4 (DPP-4) metabolizes glucagon-like peptide-1 (GLP-1) and increased DPP4 levels are associated with obesity and visceral adiposity in adults.

Objective: Investigating DPP-4 levels in adolescents and association with, firstly, circulating intact GLP-1 levels and glucose tolerance, secondly, BMI, and, thirdly visceral, subcutaneous and liver fat compartments.

Design: Cross-sectional study, July 2012 to April 2015.

Setting: Pediatric obesity clinic, Uppsala University Hospital.

Patients and participants: Children and adolescents with obesity (n=59) and lean controls (n=21), age 8-18.

Main outcome measures: BMI SDS, fasting plasma concentrations of DPP-4, total and intact GLP-1, fasting and OGTT concentrations of glucose and visceral (VAT) and subcutaneous (SAT) adipose tissue volumes and liver fat fraction.

Results: Plasma DPP-4 decreased with age both in obese (41 ng/ml per year) and lean subjects (48 ng/ml per year). Plasma DPP-4 was higher in males both in the obesity and lean group. When adjusting for age and sex, plasma DPP-4 was negatively associated with intact GLP-1 at fasting, B=-12.3, 95% CI [-22.9, -1.8] and during OGTT, B=-12.1, 95% CI [-22.5, -1.7]. No associations were found between DPP-4 and plasma glucose measured at fasting or after a 2-hour OGTT. Plasma DPP-4 was 19% higher in the obese subjects. Among adipose tissue compartments the strongest association was with VAT, B=0.05, 95% CI [-0.02, 0.12].

Conclusions: In adolescents, high plasma DPP-4 concentrations are associated with low proportion of intact GLP-1, high BMI, young age and male sex. The observed associations are compatible with an increased metabolism of GLP-1 in childhood obesity.

sted, utgiver, år, opplag, sider
Endocrine Society, 2018
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-354234 (URN)10.1210/jc.2018-00194 (DOI)000442236900022 ()29850829 (PubMedID)
Forskningsfinansiär
EU, FP7, Seventh Framework Programme, 279153Swedish Diabetes Association, DIA 2016-146Ernfors Foundation, 160504Swedish Research Council, 2016-01040EXODIAB - Excellence of Diabetes Research in SwedenErik, Karin och Gösta Selanders Foundation
Tilgjengelig fra: 2018-06-19 Laget: 2018-06-19 Sist oppdatert: 2019-03-28bibliografisk kontrollert
Cen, J., Sargsyan, E., Forslund, A. & Bergsten, P. (2018). Mechanisms of beneficial effects of metformin on fatty acid-treated human islets. Journal of Molecular Endocrinology, 61(3), 91-99
Åpne denne publikasjonen i ny fane eller vindu >>Mechanisms of beneficial effects of metformin on fatty acid-treated human islets
2018 (engelsk)Inngår i: Journal of Molecular Endocrinology, ISSN 0952-5041, E-ISSN 1479-6813, Vol. 61, nr 3, s. 91-99Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Elevated levels of palmitate accentuate glucose-stimulated insulin secretion (GSIS) after short-term and cause beta-cell dysfunction after prolonged exposure. We investigated whether metformin, the first-line oral drug for treatment of T2DM, has beneficial effects on FFA-treated human islets and the potential mechanisms behind the effects. Insulin secretion, oxygen consumption rate (OCR), AMPK activation, endoplasmic reticulum (ER) stress and apoptosis were examined in isolated human islets after exposure to elevated levels of palmitate in the absence or presence of metformin. Palmitate exposure doubled GSIS after 2 days but halved after 7 days compared with control. Inclusion of metformin during palmitate exposure normalized insulin secretion both after 2 and 7 days. After 2-day exposure to palmitate, OCR and the marker of the adaptive arm of ER stress response (sorcin) were significantly raised, whereas AMPK phosphorylation, markers of pro-apoptotic arm of ER stress response (p-EIF2α and CHOP) and apoptosis (cleaved caspase 3) were not affected. Presence of metformin during 2-day palmitate exposure normalized OCR and sorcin levels. After 7-day exposure to palmitate, OCR and sorcin were not significantly different from control level, p-AMPK was reduced and p-EIF2α, CHOP and cleaved caspase 3 were strongly upregulated. Presence of metformin during 7-day culture with palmitate normalized the level of p-AMPK, p-EIF2α, CHOP and cleaved caspase 3 but significantly increased the level of sorcin. Our study demonstrates that metformin prevents early insulin hypersecretion and later decrease in insulin secretion from palmitate-treated human islets by utilizing different mechanisms.

Emneord
Metformin, palmitate, human islets, insulin secretion, mitochondrial respiration, ER stress
HSV kategori
Forskningsprogram
Medicinsk cellbiologi
Identifikatorer
urn:nbn:se:uu:diva-353691 (URN)10.1530/JME-17-0304 (DOI)000452706400005 ()30307162 (PubMedID)
Forskningsfinansiär
Swedish Diabetes Association, DIA 2016-146EU, FP7, Seventh Framework Programme, 279 153Ernfors Foundation, 170504
Tilgjengelig fra: 2018-06-27 Laget: 2018-06-27 Sist oppdatert: 2019-01-11bibliografisk kontrollert
Warnakulasuriya, L. S., Fernando, M. M. A., Adikaram, A. V. N., Thawfeek, A. R. M., Anurasiri, W.-M. L., Silva, R. R., . . . Wickramasinghe, V. P. (2018). Metformin in the Management of Childhood Obesity: A Randomized Control Trial. CHILDHOOD OBESITY, 14(8), 553-565
Åpne denne publikasjonen i ny fane eller vindu >>Metformin in the Management of Childhood Obesity: A Randomized Control Trial
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2018 (engelsk)Inngår i: CHILDHOOD OBESITY, ISSN 2153-2168, Vol. 14, nr 8, s. 553-565Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: Childhood obesity-related metabolic derangements are increasing among South Asian populations. Dietary and physical activity plans have limited effect. This study aims to assess the effectiveness of metformin in the management of obesity among 8- to 16-year-old children in Gampaha District of Sri Lanka.

Materials and Methods: A triple-blinded controlled trial was conducted on 150 obese school children. After 12-hour overnight fast, blood was drawn for fasting blood glucose (FBG) and lipid profile. Anthropometry, fat mass (FM), and blood pressure were measured. BMI and insulin resistance were calculated. Children randomly received either metformin (8-10 years-500 mg 12 hourly; 11-16 years-1 g 12 hourly) or placebo. Anthropometry and blood investigations were repeated at 6 and 12 months. Mean difference in outcome measures, adjusted for baseline values, was compared using ANCOVA.

Results: There were 84/150 boys. Metabolic syndrome was present in 25 (16.7%). A statistically significant adjusted mean reduction was observed in the metformin group compared with placebo, in weight (-0.991 vs. 1.394, p = 0.000), BMI/Age-standard deviation score (SDS; -0.287 vs. -0.116, p = 0.000), %FM/Age-SDS (-0.092 vs. 0.016, p = 0.04), systolic blood pressure (SBP; -0.415 vs. 0.015, p = 0.015), total cholesterol (-0.95 vs. -0.7, p = 0.001), low-density lipoprotein (-0.67 vs. -0.45, p = 0.001), and highly sensitive C-reactive protein (-1.36 vs. 0.08, p = 0.013) at 6 months, and in BMI/Age-SDS (-370 vs. -0.222, p = 0.001), WC/Age-SDS (-0.473 vs. -0.337, p = 0.018), SBP (-0.834 vs. -0.477, p = 0.023), and triglycerides (-0.33 vs. -0.14, p = 0.019) at 12 months.

Conclusions: Metformin compared with placebo has beneficial effects on anthropometric and metabolic indicators in the management of childhood obesity.

sted, utgiver, år, opplag, sider
MARY ANN LIEBERT, INC, 2018
Emneord
childhood obesity, metformin, Sri Lankan children
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-372384 (URN)10.1089/chi.2018.0043 (DOI)000451335700007 ()30070925 (PubMedID)
Tilgjengelig fra: 2019-01-07 Laget: 2019-01-07 Sist oppdatert: 2019-01-07bibliografisk kontrollert
Kristinsson, H., Manell, H., Dahlbom, M., Presto, J., Garedal, C., Ritzen, H., . . . Bergsten, P. (2018). The initial rise in GIP secretion during OGTT correlates with the initial suppression of glucagon secretion in adolescents with obesity and type 2 diabetes. Paper presented at 54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY. Diabetologia, 61, S247-S247
Åpne denne publikasjonen i ny fane eller vindu >>The initial rise in GIP secretion during OGTT correlates with the initial suppression of glucagon secretion in adolescents with obesity and type 2 diabetes
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2018 (engelsk)Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, s. S247-S247Artikkel i tidsskrift, Meeting abstract (Annet vitenskapelig) Published
sted, utgiver, år, opplag, sider
Springer, 2018
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-367127 (URN)000443556003095 ()
Konferanse
54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY
Tilgjengelig fra: 2018-11-30 Laget: 2018-11-30 Sist oppdatert: 2018-11-30bibliografisk kontrollert
Paulmichl, K., Ahlström, H., Bergsten, P., Brunner, S., Cadamuro, J., Dahlbom, I., . . . Weghuber, D. (2017). Association Between Non-Alcoholic Fatty Liver Disease (NAFLD) and Iron Metabolism in Obese Children and Adolescents: Results of the Beta-JUDO Study. Acta Paediatrica, 106(S470), 13-13
Åpne denne publikasjonen i ny fane eller vindu >>Association Between Non-Alcoholic Fatty Liver Disease (NAFLD) and Iron Metabolism in Obese Children and Adolescents: Results of the Beta-JUDO Study
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2017 (engelsk)Inngår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, nr S470, s. 13-13Artikkel i tidsskrift, Meeting abstract (Annet vitenskapelig) Published
sted, utgiver, år, opplag, sider
John Wiley & Sons, 2017
Emneord
Childhood, Hyperferritinemia, NAFLD, Obesity, Steatosis
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-366465 (URN)10.1111/apa.14093 (DOI)000440296300021 ()
Tilgjengelig fra: 2018-11-22 Laget: 2018-11-22 Sist oppdatert: 2018-11-22bibliografisk kontrollert
Lundström, E., Strand, R., Forslund, A., Bergsten, P., Weghuber, D., Ahlström, H. & Kullberg, J. (2017). Automated segmentation of human cervical-supraclavicular adipose tissue in magnetic resonance images. Scientific Reports, 7, Article ID 3064.
Åpne denne publikasjonen i ny fane eller vindu >>Automated segmentation of human cervical-supraclavicular adipose tissue in magnetic resonance images
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2017 (engelsk)Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikkel-id 3064Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Human brown adipose tissue (BAT), with a major site in the cervical-supraclavicular depot, is a promising anti-obesity target. This work presents an automated method for segmenting cervical-supraclavicular adipose tissue for enabling time-efficient and objective measurements in large cohort research studies of BAT. Fat fraction (FF) and R2* maps were reconstructed from water-fat magnetic resonance imaging (MRI) of 25 subjects. A multi-atlas approach, based on atlases from nine subjects, was chosen as automated segmentation strategy. A semi-automated reference method was used to validate the automated method in the remaining subjects. Automated segmentations were obtained from a pipeline of preprocessing, affine registration, elastic registration and postprocessing. The automated method was validated with respect to segmentation overlap (Dice similarity coefficient, Dice) and estimations of FF, R2* and segmented volume. Bias in measurement results was also evaluated. Segmentation overlaps of Dice = 0.93 +/- 0.03 (mean +/- standard deviation) and correlation coefficients of r > 0.99 (P < 0.0001) in FF, R2* and volume estimates, between the methods, were observed. Dice and BMI were positively correlated (r = 0.54, P = 0.03) but no other significant bias was obtained (P >= 0.07). The automated method compared well with the reference method and can therefore be suitable for time-efficient and objective measurements in large cohort research studies of BAT.

HSV kategori
Forskningsprogram
Datoriserad bildbehandling
Identifikatorer
urn:nbn:se:uu:diva-323968 (URN)10.1038/s41598-017-01586-7 (DOI)000402865000003 ()28596551 (PubMedID)
Forskningsfinansiär
Swedish Research CouncilEU, FP7, Seventh Framework Programme, 279153
Tilgjengelig fra: 2017-06-08 Laget: 2017-06-12 Sist oppdatert: 2019-04-15bibliografisk kontrollert
Organisasjoner
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0001-9109-4556