Grant: CIHR Fellowship

Type 2 diabetes (T2D) impacts more than 3 million Canadians and 385 million people worldwide. Obesity, which increases the risk of T2D, has also reached epidemic proportions, impacting ~30% of the population. Despite numerous treatment options many obese and/or T2D patients suffer from a decreased quality of life. Defects in the insulin-secreting beta cells are critical for the development of obesity/T2D. Elevated fasting insulin (hyperinsulinemia) is a pre-requisite for the development of obesity. Interestingly, obesity and its complications can be prevented in mice that are genetically protected from diet-induced hyperinsulinemia, suggesting that a reduction in insulin levels is beneficial to the metabolic health of an individual with obesity/T2D. While glucose is the main driver of acute insulin release, other dietary macronutrients can also potentiate insulin secretion. However, insulin release in response to these macronutrients is different between individuals. This could explain why 'low-carb' diets that aim to keep insulin levels low are only effective in a subset of the population. Thus, the goal of our study is to understand these variations, and identify pathways that determine the sensitivity of individuals to various macronutrients. We will characterize human islet functional responses to dietary macronutrients by measuring insulin release. The responses will be compared to the unique genetic profile of the donor. Multi-scale modeling will used to predict obesity and diabetes risk. The proposed final outcome will be the development of a model that will allow us to predict, based on a person's genetics, whether they will be an insulin hypersecretor in response to any macronutrient. This will form the basis for a clinical trial in conjunction with the Institute for Personalized Therapeutic Nutrition, a Vancouver based-entity that is being co-founded by Prof. Johnson for the purpose of translating this work and existing evidence-based guidelines.