Pathways and Levers for prevention of Multi-morbidity from Young and Middle Adulthood

Multimorbidity is the presence of two or even several more major health condition at the same time within a single person. It is a growing problem in the United Kingdom in part of the combination of increasing lifespans with unhealthy lifestyles. Although multimorbidity is most common in older age, poor diet, physical inactivity, and obesity in young adulthood and middle-age are likely important causes of the tendency to multimorbidity. We suspect that 3 conditions in particular - diabetes, hypertension, and depression - cause a large portion of multimorbidity because of the way that they work together to affect so many systems of the body. If this is the case, then programmes for focused lifestyle interventions could make a big difference in preventing multimorbidity. Unfortunately, it is difficult to know how these conditions in young and middle-age affect multimorbidity and what works to prevent it because no studies track population across many stage of life, while measuring the impact of interventions. This research progamme will tackle these questions with 3 parts. First, it will use long-term data from the UK and London populations to uncover the most common combinations of diseases occurring and whether there are particular steps and pathways in their formation. After finding those combinations and estimating how rapidly they develop at different times in life, we will construct a new computer-based model, called a "life-course simulation model" that can identify the optimal times in life, combinations of behaviors, risk factors, and diseases that cause the greatest illness over life. The computer model will also examine the effect of different ways of preventing the accumulation of multimorbidity, such as using focused support to change lifestyle in people at risk for hypertension, diabetes, and depression. The third part of the research programme will use these data and the computer model to measure the effect of two National Health Service initiatives that support people at risk of diabetes or with diabetes to change lifestyle diabetes. Since lifestyle behaviors are also crucial to hypertension, depression, and other conditions, these "natural experiments" may have a big effect on multimorbidity as well. This work will require a team with expertise in diverse areas - including medical care, epidemiology, behaviour change, mathematics, and computer modeling. This study will answer important questions about what types of conditions are causing the most multimorbidity and what are the best ways to act to prevent them. The computer model and research that results will give doctors, health planners, and the public new way to improve health in communities for the years to come. The work will be first-of-its-kind in the way that it assesses chronic conditions as they form in combination from young adulthood to older adulthood. It will also be new in the way it uses computer models and natural experiments in combination to find out what works best to reduce multimorbidity.

Although multimorbidity (MM) has its greatest burden in older adulthood, its genesis lies in risk factors and conditions of middle-age and early adulthood. We hypothesize that 3 conditions in particular - hypertension, type 2 diabetes, and depression - are key leverage points in the progression to MM because they often emerge in young or middle-adulthood, have disproportionate effects on other conditions, yet can be altered by multi-component lifestyle interventions. We will build a multi-disciplinary research programme to characterize and quantify the progression of MM from its inception, prioritise sub-populations and risk levels for action, and determine the impact of major public health interventions.

We will accomplish this goal through 3 integrated work streams: First, an epidemiological work stream will characterize the phenotypes, progression and sequence of MM across life stages using a combination of a priori and agnostic data-driven analyses. Second, we will develop an individual-based, life-course simulation model (LCSM) that quantifies MM progression and identifies the 'leverage points', subgroups, and interventions for action. Third, we will conduct natural experimental studies of ongoing NHS lifestyle-based initiatives and integrate these findings with the LCSM to estimate long-term intervention impact on MM.

This work will be innovative and unprecedented for MM in its focus on young and middle-adulthood, its use of individual-based modelling to capture the multiple interactions between conditions, its study of impact of lifestyle interventions, and in its use of natural experiments to study public health initiatives. We expect our research findings and infrastructure to guide MM prevention and management policies while building an infrastructure for long-term MM surveillance. A consolidator phase is necessary because of the complexity of each of the 3 work streams and the need for pilot analyses to organize and refine study protocols