Glucagon, NAFLD and Amino Acids - an Evidence Map

Background: Health systems are not only confronted with the growing worldwide childhood obesity epidemic, but also associated comorbidities. These subsequently cause variations in distinct metabolic pathways, such as hepatic fat accumulation, which leads to non-alcoholic fatty liver disease (NAFLD). The aim of this evidence map is to systematically evaluate the literature and to identify research gaps on the glucagon induced amino acid turnover and its metabolic interaction with NAFLD. Methods: A systematic literature search was conducted in April 2020 to identify research using three electronic databases. Two independent reviewers screened titles and abstracts, according to prespecified eligibility criteria, as well as full-text articles. Quantitative studies of either humans or animals, at all age, were included. Studies were required to contain at least two of the main research areas, being glucagon, amino acid metabolism and NAFLD. Data was independently extracted by two reviewers and summarized according to study design, publication year, comorbidities, age, sex, sample size, intervention, study duration and control group. Conflicts were resolved by discussion or a third reviewer. Results: Twenty-nine references were finally included. The publication years dated back until 1965 and showed a great increase from 2012 to 2020. All studies were carried out among adults, only 1 study focused on adolescents. The most common comorbidity was obesity. In total there were 13 animal studies and 16 human studies. The study designs in the human experiments differed immensely. The hyperinsulinemic-euglycemic clamp and the oral glucose tolerance test were the most used experimental methods to evaluate metabolic changes. Thirteen studies focused on metabolic effects due to NAFLD, however only 2 studies focused on the interaction of NAFLD, glucagon and the amino acid metabolism, both being non-human studies. The other 14 studies focused on metabolomics, beta cell function or just on one topic of the research area and not as an interaction on one another. Conclusion: Research on the interaction of NAFLD, glucagon and the amino acid metabolisms in human studies is sparse and completely lacking in pediatrics. Furthermore, longitudinal studies such as studies focusing on hyperglucagonemia independent of diabetes but related to NAFLD present an unambiguous research gap.