PRIME introduces the novel concept of insulin signalling as a key mechanism underlying the multimorbidity of major mental and somatic illnesses. It is well known that aberrant insulin signalling causes high health and socioeconomic burden through its role in diabetes, metabolic syndrome, and obesity. We posit that the impact of ‘insulinopathies’ is still largely underestimated, since insulin multimorbidity also extends to the brain, where altered insulin signalling appears to be implicated in dementias such as Alzheimer disease and – based on our pilot work - in mental illnesses characterized by compulsivity, especially obsessive compulsive disorder and autism. We therefore further posit that insulin multimorbidity evolves throughout life, necessitating a lifespan approach.
PRIME brings together a multidisciplinary team to (1) extend our understanding of insulin multimorbidity across the lifespan, (2) understand the causal mechanisms linking somatic and mental insulin-related illnesses, (3) develop tools for early diagnosis, improved clinical care, and prevention of insulin-related lifespan multimorbidity. We will leverage the world’s largest registry, clinical cohort, and population data sets to identify and validate new insulinopathies. Through an interdisciplinary battery of innovative approaches, we will clarify the causal mechanisms linking peripheral and central insulin signalling to body-brain comorbidity, integrating across animal models and studies in humans from molecule to cell, brain, cognition, and behaviour. Our prior evidence enables PRIME to bring the new knowledge to society, based on e.g. repurposing medication and lifestyle interventions (diet/exercise monitored by mHealth assessment), identifying and validating novel drug targets, developing and testing candidate biomarkers, and by improving existing medical guidelines and policy. Furthermore, educational approaches to inform clinicians, patients, and general public will be developed.
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