Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2017

Enteroendocrine associations with type 2 diabetes: phenotypic risk scoring approaches for assessing complex biological systems (#333)

Amanda J Cox 1 , Ping Zhang 1 , Donald W Bowden 2 , Benedict Devereaux 3 , Peter M Davoren 4 , Allan W Cripps 1 , Nicholas P West 1
  1. Griffith University, Southport, QLD, Australia
  2. Centre for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA
  3. Digestive Diseases QLD, Chermside, QLD, Australia
  4. Diabetes and Endocrinology, Gold Coast University Hospital, Southport, QLD, Australia

Introduction: The contribution of the gut microbiota to risk for obesity-associated disease continues to be of interest. We have previously demonstrated a link between the gut and metabolic disease via associations between increases in intestinal permeability and type 2 diabetes (T2D). The potential interaction between the gut microbiota and enteroendocrine cells within the gut mucosa may provide an additional mechanism linking obesity and metabolic disease.

Objectives: The aim of the current study was examine the associations between glucagon and enteroendocrine signalling and type 2 diabetes (T2D) using a derived risk score approach.

Methods: A total of 130 individuals with T2D (age: 57.5±6.2 years (mean ± SD); BMI: 30.4±3.2; 45% female) and 161 individuals without T2D (age: 37.4±12.5 years; BMI: 25.1±3.9; 65% female) were included in the study. Circulating concentrations of glucagon, and enteroendocrine mediators ghrelin, glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP) were determined using a multiplex suspension array. Standardise scores (Z-scores) were determined and a derived enteroendocrine risk score (ERS) calculated based on summation of the individual measures. Associations between the ERS and T2D status were assessed using logistic regression models.

Results: Significant differences in the concentrations of glucagon (~35%, p<0.001), the enteroendocrine mediators (GLP-1 ~7%, p=0.01; GIP ~42%, p<0.001; Ghrelin ~11%, p=0.04) and the derived ERS (~25%; p<0.001) were observed between individuals with or without T2D. Quantification of risk across ERS tertiles revealed that individuals with an ERS in the upper tertile were 10 times more likely (CI: 3.23-32.73; p<0.001) to have T2D independent of age, sex and BMI.

Conclusions: These data support an association between enteroendocrine signalling and risk for T2D. Consideration of enteroendocrine signalling as a potential tool for classifying individuals with Metabolic Syndrome as high or low risk for T2D development appears a logical progression of this work.