Abstract
As weight-loss surgery is an effective treatment for the glycaemic control of type 2 diabetes in obese patients, yet not all patients benefit, it is valuable to find predictive factors for this diabetic remission. This will help elucidating possible mechanistic insights and form the basis for prioritising obese patients with dysregulated diabetes for surgery where diabetes remission is of interest. In this study, we combine both clinical and genomic factors using heuristic methods, informed by prior biological knowledge in order to rank factors that would have a role in predicting diabetes remission, and indeed in identifying patients who may have low likelihood in responding to bariatric surgery for improved glycaemic control. Genetic variants from the Illumina CardioMetaboChip were prioritised through single-association tests and then seeded a larger selection from protein–protein interaction networks. Artificial neural networks allowing nonlinear correlations were trained to discriminate patients with and without surgery-induced diabetes remission, and the importance of each clinical and genetic parameter was evaluated. The approach highlighted insulin treatment, baseline HbA1c levels, use of insulin-sensitising agents and baseline serum insulin levels, as the most informative variables with a decent internal validation performance (74% accuracy, area under the curve (AUC) 0.81). Adding information for the eight top-ranked single nucleotide polymorphisms (SNPs) significantly boosted classification performance to 84% accuracy (AUC 0.92). The eight SNPs mapped to eight genes — ABCA1, ARHGEF12, CTNNBL1, GLI3, PROK2, RYBP, SMUG1 and STXBP5 — three of which are known to have a role in insulin secretion, insulin sensitivity or obesity, but have not been indicated for diabetes remission after bariatric surgery before.
Highlights
Type 2 diabetes mellitus patients are increasingly recognised to experience improved glycaemic control following bariatric surgery,[1] and a growing number of randomised control trials consistently report surgery to be more effective for controlling obese Type 2 diabetes patients than various medical/lifestyle interventions.[2]
New guidelines from the second Diabetes Surgery Summit recommend the use of bariatric surgery as an antidiabetic treatment for Type 2 diabetes patients with body mass index (BMI) ⩾ 40 kg/m2 or BMI 35.0–39.9 kg/m2 suffering from inadequately controlled hyperglycaemia, and further suggest considering surgery for patients with BMI 30.0–34.9 kg/m2 and inadequately controlled hyperglycaemia.[2]
In accordance with previous predisposes an individual to the non-remitter phenotype, whereas findings, this together suggests a higher likelihood of diabetes remission for less severe or progressed diabetes patients.[9,16,17,18] minor alleles for six of the eight single nucleotide polymorphism (SNP) are associated with higher likelihood of experiencing post-surgery diabetes remission
Summary
Type 2 diabetes mellitus patients are increasingly recognised to experience improved glycaemic control following bariatric surgery,[1] and a growing number of randomised control trials consistently report surgery to be more effective for controlling obese Type 2 diabetes patients than various medical/lifestyle interventions.[2]. Despite increased focus in this area, the precise underlying molecular mechanisms and prognostic factors of remission remain incompletely understood. Such insight would improve selection of patients for bariatric surgery, and might hint at new pharmaceutically relevant biomarkers and targets. It is of interest to investigate and identify phenotypic and genomic factors associated with surgery-induced diabetes remission. Up to 15% of patients experience minor complications and 2–6% suffer from major complications with 2.5% and Published in partnership with the Center of Excellence in Genomic Medicine Research
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
