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Uppsala Longitudinal Study of Childhood Obesity: Protocol Description
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
Vise andre og tillknytning
2014 (engelsk)Inngår i: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 133, nr 2, s. E386-E393Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND AND OBJECTIVE: The prevalence of childhood obesity has risen considerably on a global scale during the past decades, and the condition is associated with increased risk of morbidity. The objective is to describe the Uppsala Longitudinal Study of Childhood Obesity (ULSCO) cohort, including some baseline data, and outline addressed research areas that aim at identifying factors implicated in and contributing to development of obesity and obesity-related diseases, including type 2 diabetes. METHODS: Severely obese and lean control subjects are examined at enrollment and at subsequent annual visits by using detailed questionnaires, anthropometric measurements, indirect calorimetry, and functional tests such as oral glucose tolerance tests. Some subjects undergo additional characterization with MRI, subcutaneous fat biopsies, frequent blood sampling, and hyperglycemic clamps. Biological samples are obtained and stored in a biobank. RESULTS: Active recruitment started in 2010, and standard operating procedures have been established. A high participation rate and annual follow-ups have resulted in a cohort exceeding 200 subjects, including 45 lean controls (as of October 2013). Initial research focus has been on traits of the metabolic syndrome, hyperinsulinemia and identifying risk factors for type 2 diabetes. CONCLUSIONS: The ULSCO cohort serves as an important resource in defining and understanding factors contributing to childhood obesity and development of obesity-related diseases. Given the comprehensive characterization of the cohort, factors contributing to disease development and progression can be identified. Such factors are further evaluated for their mechanistic role and significance, and noncommunicable metabolic diseases are especially addressed and considered.

sted, utgiver, år, opplag, sider
2014. Vol. 133, nr 2, s. E386-E393
Emneord [en]
childhood obesity, cohort, MRI, pediatric, type 2 diabetes mellitus, ULSCO
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-227577DOI: 10.1542/peds.2013-2143ISI: 000333413600041OAI: oai:DiVA.org:uu-227577DiVA, id: diva2:730840
Tilgjengelig fra: 2014-06-30 Laget: 2014-06-27 Sist oppdatert: 2017-12-05bibliografisk kontrollert
Inngår i avhandling
1. Childhood Obesity and Islet Function
Åpne denne publikasjonen i ny fane eller vindu >>Childhood Obesity and Islet Function
2017 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2017. s. 54
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1293
Emneord
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
HSV kategori
Forskningsprogram
Pediatrik
Identifikatorer
urn:nbn:se:uu:diva-313310 (URN)978-91-554-9801-6 (ISBN)
Disputas
2017-03-10, C2:301, BMC, Husargatan 3, Uppsala, 13:15 (engelsk)
Opponent
Veileder
Forskningsfinansiär
EU, FP7, Seventh Framework Programme, 279153
Tilgjengelig fra: 2017-02-15 Laget: 2017-01-18 Sist oppdatert: 2017-02-27

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