JMIR Publications

ABSTRACT

Background:

The prevalence of obesity and diabetes in Samoa, like many other Pacific Island nations, has reached epidemic proportions. While the etiology of these conditions can be largely attributed to the rapidly changing economic and nutritional environment, a recently identified genetic variant, rs373863828 (CREBRF:c.1370G>A p.(R457Q)), is associated with increased odds of obesity, but paradoxically, decreased odds of diabetes.

Objective:

The overarching goal of the Soifua Manuia (‘Good Health’) study was to precisely characterize the impact of the CREBRF variant on metabolic (body composition, glucose homeostasis) and behavioral traits (dietary intake, physical activity, sleep, weight control behaviors) that influence energy homeostasis in 500 adults.

Methods:

A cohort of adult Samoans who participated in a genome-wide association study (GWAS) of adiposity in Samoa in 2010 were followed up, based on the presence or absence of the CREBRF variant, between August 2017 and March 2019. Over a period of 7-10 days each participant completed the main study protocol, which consisted of anthropometric measurements (weight, height, circumferences, skinfolds), body composition assessment (bioelectrical impedance and dual-energy x-ray absorptiometry), point-of-care glycated hemoglobin measurement, a fasting blood draw and oral glucose tolerance test, urine collection, blood pressure, hand grip strength, objective physical activity and sleep apnea monitoring, and questionnaire measures (e.g., health interview, cigarette and alcohol use, food frequency questionnaire, socioeconomic position, stress, social support, food and water insecurity, sleep, body image, dietary preferences). In January 2019, a sub-sample of the study participants (n=118) completed a buttock fat biopsy procedure to collect subcutaneous adipose tissue samples.

Results:

Enrollment of n=519 participants was completed in March 2019. Data analyses are ongoing, with results expected in 2020.

Conclusions:

While the genetic variant rs373863828, in CREBRF, has the largest known effect size of any identified common ‘obesity gene’, very little is currently understood about the mechanisms by which it confers increased odds of obesity, but paradoxically lowered odds of type 2 diabetes. Results from this study will provide insights into how the gene functions on a whole-body level, which could provide novel targets to prevent or treat obesity, diabetes, and associated metabolic disorders. This study represents the human arm of a comprehensive and integrated approach involving humans as well as pre-clinical models that will provide novel insights into metabolic disease.