uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Alternative names
Publications (10 of 42) Show all publications
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.
Open this publication in new window or tab >>Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents
Show others...
2019 (English)In: Pediatric Obesity, ISSN 2047-6302, E-ISSN 2047-6310, Vol. 14, no 9, article id e12531Article in journal (Refereed) 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.

Keywords
adolescent, brown adipose tissue, glucose metabolism, magnetic resonance imaging
National Category
Pediatrics Medical Image Processing
Identifiers
urn:nbn:se:uu:diva-380052 (URN)10.1111/ijpo.12531 (DOI)000482155600007 ()31290284 (PubMedID)
Funder
Swedish Heart Lung Foundation, 2170492Swedish Research Council, 2016-01040EU, FP7, Seventh Framework Programme, 279153
Available from: 2019-07-09 Created: 2019-03-22 Last updated: 2019-10-23Bibliographically approved
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
Open this publication in new window or tab >>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
Show others...
2019 (English)In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 74, no 1, p. 80-82Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
KARGER, 2019
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-379088 (URN)10.1159/000495905 (DOI)000459497900011 ()30616236 (PubMedID)
Available from: 2019-03-12 Created: 2019-03-12 Last updated: 2019-03-12Bibliographically approved
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
Open this publication in new window or tab >>Could sport be part of pediatric obesity prevention and treatment?: Expert conclusions from the 28th European Childhood Obesity Group Congress
Show others...
2019 (English)In: Journal of Sport and Health Science, ISSN 2095-2546, E-ISSN 2213-2961, Vol. 8, no 4, p. 350-352Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
SHANGHAI UNIV SPORT, 2019
National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:uu:diva-390435 (URN)10.1016/j.jshs.2019.01.007 (DOI)000473771300007 ()31333888 (PubMedID)
Available from: 2019-08-12 Created: 2019-08-12 Last updated: 2019-08-12Bibliographically approved
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
Open this publication in new window or tab >>Fully convolutional networks for automated segmentation of abdominal adipose tissue depots in multicenter water–fat MRI
Show others...
2019 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 81, no 4, p. 2736-2745Article in journal (Refereed) 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.

Keywords
abdominal, adipose tissue, deep learning, fully convolutional networks, segmentation, water-fat MRI
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-364355 (URN)10.1002/mrm.27550 (DOI)000462092100044 ()30311704 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 279153
Available from: 2018-10-25 Created: 2018-10-25 Last updated: 2019-04-17Bibliographically approved
Manell, H., Kristinsson, H., Kullberg, J., Ubhayasekera, S. J., Mörwald, K., Staaf, J., . . . Bergsten, P. (2019). Hyperglucagonemia in youth is associated with high plasma free fatty acids, visceral adiposity and impaired glucose tolerance. Pediatric Diabetes, 20(7), 880-891
Open this publication in new window or tab >>Hyperglucagonemia in youth is associated with high plasma free fatty acids, visceral adiposity and impaired glucose tolerance
Show others...
2019 (English)In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 20, no 7, p. 880-891Article in journal (Refereed) Published
Abstract [en]

Objective: To delineate mechanisms for fasting hyperglucagonemia in childhood obesity bystudying the associations between fasting plasma glucagon concentrations and plasmalipid parameters and fat compartments.

Methods: Cross-sectional study of children and adolescents with obesity (n=147) and leancontrols (n=43). Differences in free fatty acids (FFA), triglycerides, insulin and fatcompartments (quantified by magnetic resonance imaging) across quartiles of fastingplasma glucagon concentration were analysed. Differences in OGTT glucagonresponse was tested in high vs low FFAs, triglycerides and insulin. Human islets ofLangerhans were cultured at 5.5 mmol/l glucose and in the absence or presence of aFFA mixture with total FFA concentration of 0.5 mmol/l and glucagon secretionquantified.

Results: In children with obesity, the quartile with the highest fasting glucagon had higherinsulin (201±174 vs 83±39 pmol/l, p<0.01), FFAs (383±52 vs 338±109 μmol/l,p=0.02), triglycerides (1.5±0.9 vs 1.0±0.7 mmol/l, p<0.01), visceral adipose tissuevolume (1.9±0.8 vs 1.2±0.3 dm3, p<0.001) and a higher prevalence of impairedglucose tolerance (41% vs 8%, p=0.01) than the lowest quartile. During OGTT,children with obesity and high insulin had a worse suppression of glucagon during thefirst 10 minutes after glucose intake. Glucagon secretion was 2.6-fold higher in isletstreated with FFAs than in those not treated with FFAs.4

Conclusion: Hyperglucagonemia in childhood obesity is associated with hyperinsulinemia, highplasma FFAs, high plasma triglycerides, visceral adiposity and impaired glucosetolerance. The glucagonotropic effect of FFAs on isolated human islets provides apotential mechanism linking high fasting plasma FFAs and glucagon levels.

Keywords
Childhood obesity, glucagon, free fatty acids, insulin, visceral adiposity, impaired glucose tolerance, type 2 diabetes
National Category
Pediatrics Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-380313 (URN)10.1111/pedi.12890 (DOI)000476081000001 ()31271247 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 279153EXODIAB - Excellence of Diabetes Research in SwedenErnfors FoundationErik, Karin och Gösta Selanders FoundationSwedish Research Council, 2015-4870Swedish Diabetes Association
Available from: 2019-03-26 Created: 2019-03-26 Last updated: 2019-12-06Bibliographically approved
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
Open this publication in new window or tab >>High DPP-4 concentrations in adolescents are associated with low intact GLP-1
Show others...
2018 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, no 8, p. 2958-2966Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
Endocrine Society, 2018
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-354234 (URN)10.1210/jc.2018-00194 (DOI)000442236900022 ()29850829 (PubMedID)
Funder
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
Available from: 2018-06-19 Created: 2018-06-19 Last updated: 2019-03-28Bibliographically approved
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
Open this publication in new window or tab >>Mechanisms of beneficial effects of metformin on fatty acid-treated human islets
2018 (English)In: Journal of Molecular Endocrinology, ISSN 0952-5041, E-ISSN 1479-6813, Vol. 61, no 3, p. 91-99Article in journal (Refereed) 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.

Keywords
Metformin, palmitate, human islets, insulin secretion, mitochondrial respiration, ER stress
National Category
Endocrinology and Diabetes Pharmacology and Toxicology
Research subject
Medical Cell Biology
Identifiers
urn:nbn:se:uu:diva-353691 (URN)10.1530/JME-17-0304 (DOI)000452706400005 ()30307162 (PubMedID)
Funder
Swedish Diabetes Association, DIA 2016-146EU, FP7, Seventh Framework Programme, 279 153Ernfors Foundation, 170504
Available from: 2018-06-27 Created: 2018-06-27 Last updated: 2019-01-11Bibliographically approved
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
Open this publication in new window or tab >>Metformin in the Management of Childhood Obesity: A Randomized Control Trial
Show others...
2018 (English)In: CHILDHOOD OBESITY, ISSN 2153-2168, Vol. 14, no 8, p. 553-565Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
MARY ANN LIEBERT, INC, 2018
Keywords
childhood obesity, metformin, Sri Lankan children
National Category
Endocrinology and Diabetes Pediatrics
Identifiers
urn:nbn:se:uu:diva-372384 (URN)10.1089/chi.2018.0043 (DOI)000451335700007 ()30070925 (PubMedID)
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-01-07Bibliographically approved
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
Open this publication in new window or tab >>The initial rise in GIP secretion during OGTT correlates with the initial suppression of glucagon secretion in adolescents with obesity and type 2 diabetes
Show others...
2018 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, p. S247-S247Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2018
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-367127 (URN)000443556003095 ()
Conference
54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY
Available from: 2018-11-30 Created: 2018-11-30 Last updated: 2018-11-30Bibliographically approved
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
Open this publication in new window or tab >>Association Between Non-Alcoholic Fatty Liver Disease (NAFLD) and Iron Metabolism in Obese Children and Adolescents: Results of the Beta-JUDO Study
Show others...
2017 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no S470, p. 13-13Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
Childhood, Hyperferritinemia, NAFLD, Obesity, Steatosis
National Category
Pediatrics
Identifiers
urn:nbn:se:uu:diva-366465 (URN)10.1111/apa.14093 (DOI)000440296300021 ()
Available from: 2018-11-22 Created: 2018-11-22 Last updated: 2018-11-22Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-9109-4556

Search in DiVA

Show all publications