Uppsala Longitudinal Study of Childhood Obesity: Protocol Description

Abstract

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.

Hyperglucagonemia in youth is associated with high plasma free fatty acids, visceral adiposity, and impaired glucose tolerance

“…After fasting overnight, subjects underwent a standard OGTT, as previously described . Briefly, subjects drank a glucose solution at a dose of 1.75 g glucose/kg body weight, maximum 75 g glucose.…”

Initial hyperinsulinemia and subsequent β-cell dysfunction is associated with elevated palmitate levels

“…Subjects were 3-18 y old, with approximately the same number of males and females. All subjects had normal fasting glucose levels ( Table 1) and were part of the Uppsala Longitudinal Study of Childhood Obesity cohort (40). Prepubertal and pubertal subjects are referred to as "children" and "adolescents", respectively.…”

“…Blood was sampled as previously described (40). In short, blood was drawn from a peripheral vein using a stationary catheter.…”

“…OGTT was conducted as previously described (40). In brief, after drinking a glucose solution (1.75 g glucose per kilogram body mass, maximum 75 g), blood samples were collected after 5, 10, 30, 60, 90, and 120 min.…”

Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents

“…To evaluate glucose metabolism, each subject underwent an oral glucose tolerance test (OGTT), from which measurements of plasma glucose and insulin levels were obtained. The OGTT was performed according to a previously described procedure . Additional information on handling and analyses of the blood samples is provided in the Data S1.…”