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UNIGE – Faculty of Medicine


A life without insulin

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The challenge

Millions suffer from type 1 diabetes (T1D); a condition caused by insulin deficiency. Untreated T1D is characterized by hyperglycaemia, hyperketonaemia, (and many other defects) and is lethal within a few months of diagnosis. Insulin therapy is the only option for T1D patients. Yet, this therapy is unable to restore metabolic homeostasis.

Despite insulin therapy, T1D patients remain at high risk of life-threatening ketoacidosis (a drop in blood pH due to uncontrolled fat breakdown), insulin-induced hypoglycaemia and cardiovascular complications that lead to stroke, blindness and a considerable reduction of lifespan. Therapies used alongside insulin also present significant safety concerns, namely increased risk of ketoacidosis and hypoglycaemia.

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The solution

Recently, a research team at the Department of Cell Physiology and Metabolism from the UNIGE Faculty of medicine demonstrated in their Lab that insulin independent mechanisms present in mammalian organisms can be harnessed to greatly improve metabolism in insulin deficiency.

« [...] insulin independent mechanisms present in mammalian organisms can be harnessed to greatly improve metabolism in insulin deficiency »

To this end, they have identified a secreted protein capable of improving metabolism in T1D. They found that increased circulating recombinant of this protein greatly ameliorates and, in some instances, even normalizes the severe lipid, glucose and ketogenic imbalances in rodent models of T1D and doubled their lifespan. Importantly, this was achieved without causing hypoglycaemia. Hence, co-treatment between this protein and lower doses of insulin represents a solution to reduce insulin needs and achieve better metabolic outcomes in T1D patients.

The aim of this project is to demonstrate that those enhanced proteins and reduced insulin therapy are safe and achieve the same metabolic outcome as full-dose insulin therapy. This would greatly improve the life quality of T1D patients reducing side effects while improving metabolic control. Results from experiments proposed herein will allow pursuing their therapeutic strategy and undertake a first in human stage 1 clinical trial, enabling this protein to become a realistic next-generation agent for improvement of T1D clinical practice.

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