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Pancreatic Fat Is Associated With Metabolic Syndrome and Visceral Fat but Not Beta-Cell Function or Body Mass Index in Pediatric Obesity
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
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2017 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 46, no 3, 358-365 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Adolescents with obesity have increased risk of type 2 diabetes and metabolic syndrome (MetS). Pancreatic fat has been related to these conditions; however, little is known about associations in pediatric obesity. The present study was designed to explore these associations further.

METHODS: We examined 116 subjects, 90 with obesity. Anthropometry, MetS, blood samples, and oral glucose tolerance tests were assessed using standard techniques. Pancreatic fat fraction (PFF) and other fat depots were quantified using magnetic resonance imaging.

RESULTS: The PFF was elevated in subjects with obesity. No association between PFF and body mass index-standard deviation score (BMI-SDS) was found in the obesity subcohort. Pancreatic fat fraction correlated to Insulin Secretion Sensitivity Index-2 and Homeostatic Model Assessment of Insulin Resistance in simple regression; however, when using adjusted regression and correcting for BMI-SDS and other fat compartments, PFF correlated only to visceral adipose tissue and fasting glucose. Highest levels of PFF were found in subjects with obesity and MetS.

CONCLUSIONS: In adolescents with obesity, PFF is elevated and associatedto MetS, fasting glucose, and visceral adipose tissue but not to beta-cellfunction, glucose tolerance, or BMI-SDS. This study demonstrates thatconclusions regarding PFF and its associations depend on the body massfeatures of the cohort.

Place, publisher, year, edition, pages
2017. Vol. 46, no 3, 358-365 p.
Keyword [en]
pancreatic fat, pediatric obesity, beta-cell function, metabolic syndrome, body mass index-standard deviation score
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-311308DOI: 10.1097/MPA.0000000000000771ISI: 000394448600018PubMedID: 27941426OAI: oai:DiVA.org:uu-311308DiVA: diva2:1059606
Funder
Swedish Research Council, 72X-14019 2012-2330 2011-4423Swedish Diabetes AssociationEU, FP7, Seventh Framework Programme, 279153
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2016-12-22 Created: 2016-12-22 Last updated: 2017-04-26Bibliographically approved
In thesis
1. Childhood Obesity and Islet Function
Open this publication in new window or tab >>Childhood Obesity and Islet Function
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The prevalence of childhood obesity and Type 2 Diabetes Mellitus (T2DM) has increased during recent decades. T2DM is accompanied with functional changes in the islets of Langerhans, which can be identified early in the pathogenesis. The aim of this thesis was to explore how metabolic changes caused by obesity early in life relate to islet function prior to overt T2DM.

To address this, Uppsala Longitudinal Study of Childhood Obesity (ULSCO) was established (paper I). Initially, the association between palmitate and insulin secretion was investigated using a translational approach with obese and lean normoglycemic juveniles and isolated human islets (paper II). Secondly, dynamics of islet-hormones insulin and glucagon, and gut-hormones glucagon like-peptide 1 (GLP-1) and glicentin (paper III) and magnetic resonance imaging of pancreatic fat fraction (PFF) (paper IV) were studied in association to glucose tolerance and beta-cell function. Finally, a novel method of analysing shape features of oral glucose tolerance test (OGTT) curves was introduced and evaluated (paper V).

Obese subjects had high prevalence of prediabetes and metabolic syndrome (MetS) (paper I). In obese pre-pubertal children with elevated palmitate levels, hyperinsulinemia was observed (paper II). In contrast, obese pubertal adolescents with similar palmitate levels showed moderate insulin levels during OGTT with delayed first phase insulin response. To explore mechanisms for these variations, isolated human islets were exposed to palmitate for different time periods in vitro. After 2 days accentuated insulin response was observed. Impaired beta-cell function and apoptosis were evident after 7 days, however. Hyperglucagonemia and disturbed GLP-1 and glicentin levels were associated with obesity and glycaemic status, with fasting glicentin being predictive of prediabetes (paper III). Furthermore, PFF was increased in obese subjects and associated to MetS and visceral adipose tissue, but not to beta-cell function (paper IV). OGTT curves were converted into geometric centres, centroids, which correlated with differences in glucose tolerance (paper V).

In conclusion, the islet function in obese children was associated with elevated levels of palmitate, but not pancreatic fat. Fasting palmitate and glicentin levels, as well as centroid analyses of OGTT curves, could potentially identify obese children at risk of prediabetes and subsequent T2DM.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 54 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1293
Keyword
type 2 diabetes mellitus, Uppsala Longitudinal Study of Childhood Obesity, palmitate, glucose-stimulated insulin secretion, hyperinsulinemia, hyperglucagonemia, GLP-1, glicentin, magnetic resonance imaging, metabolic syndrome, oral glucose tolerance test, centroid
National Category
Medical and Health Sciences
Research subject
Pediatrics
Identifiers
urn:nbn:se:uu:diva-313310 (URN)978-91-554-9801-6 (ISBN)
Public defence
2017-03-10, C2:301, BMC, Husargatan 3, Uppsala, 13:15 (English)
Opponent
Supervisors
Funder
EU, FP7, Seventh Framework Programme, 279153
Available from: 2017-02-15 Created: 2017-01-18 Last updated: 2017-02-27

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