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Personalisation in diabetes: a clinical CRO's perspective

Prof.
Posted by Prof. Dr. Freimut Schliess on May 20, 2015 3:03:00 PM

Background

Although regenerative medicine may deliver curative diabetes treatments in the long run, personalisation (along with the building of anti-obesogenic living and working environments) will boost the prevention and treatment of diabetes in the nearer future. Personalisalised measures will align with molecular signatures  potentially accessible by companion diagnostic tools and indicating individual risk processings, pathogenetic pathways and treatment susceptibilities. Additional dimensions of personalisation include life course-related traits and functional abilities, and meeting the peoples individual goals and preferences by taking advantage of co-creation environments. Personalisation could be another success factor pushing the market implementation of people-centered innovations in diabetes. We think that personalisation will improve both precision and sustainability of diabetes care even under the condition of societal ageing. Personalisation strategies need consideration already in early phases of clinical development.

Diversity in diabetes

Gluco-centrism: a more traditional view

Parameters addressing blood glucose homeostasis are widely used for definition of prediabetes, diagnosis of diabetes, and monitoring of diabetes treatment. Traditional endpoints in clinical trials focus on glucose-stimulated insulin secretion and the blood glucose lowering action of the hormone. However, the gluco-centric approach is limited by not entirely meeting the diversity of individual risks and molecular traits involved  in the evolution of diabetes and diabetes-related co-morbidites. Accordingly, regulators and health insurances increasingly focus on patient-relevant endpoints beyond glycaemic control when recommending anti-diabetic drugs and devices for marketing approval and reimbursement.

Heterogenous risk patterns and interacting vicious circles in diabetes

A more comprehensive view on the evolution of diabetes and its co-morbidities is depicted in Figure 1.

Circles

Figure 1. Diversity in diabetes. The model considers a heterogenous panel of risk factors and interacting vicious circles as major drivers in diabetes. In the healthy state glucose, cytokines and reactive oxygen and nitrogen species (ROS/RNOS) are key players in metabolic homeostasis and regulated by anti-hyperglycaemic, anti-inflammatory and anti-oxidative feedback loops. In the course of (pre)diabetes an auto-amplificatory exacerbation of circle activities may arise e.g. due to the cumulation of risk factors and/or defective feedbacks. In this condition increasingly irreversible transitions may account for many of the clinical manifestations of diabetes. Incident co-morbidities again aggravate diabetes. Early diversity may arise from the impact of different risk exposures on the dynamics of individual metabolic, inflammatory, and signaling networks. In advanced age functional reserves in terms of both physical and cognitive capabilities become increasingtly important for the impact of diabetes on the individuals' health outcome. 

Ambitions for personalisation in diabetes

A combined life- and disease course approach might be appropriate when aligning different dimensions of personalisation with the respective needs of diabetes prevention, treatment, and care.

People-centered diabetes prevention

Interfering with pro-diabetic transitions much before glycaemic criteria of pre-diabetes are met may be key for increasing the effectiveness of diabetes prevention. By analogy with the recently proposed “cytokine-based disease taxonomy” [1] a pre-diabetes taxonomy based on genetic and metabolic signatures may improve our understanding for diversity in diabetes prevention. Combining molecular profiling with the consideration of individual life characteristics, goals and preferences may optimise the precision fit of prevention measures. Supported by health economic modelling, target groups benefiting most from early risk assessment and specific prevention measures could be identified. Modern ICT integrating social media, telecommunication, and the internet of things and services will help to reach and motivate specific target groups for diabetes prevention.

Patient-centered diabetes treatment and co-morbidity prevention

The identification of the patient-specific diabetes signatures will promote the implementation of personalised treatments. Drugs that target endogenous islet regeneration may have a high market potential. Future insulin sensitisers may refer to a full understanding of insulin resistance in regard to its pathway-, cell type-, and tissue-specific manifestation, especially in the context of cell adaptation to an increased burden of dysfunctional biopolymers in the course of ageing. We suggest a strong commitment with the EMA geriatric medicines strategy, recommending that the specific needs of the elderly should be integrated during the development, approval and use of medicines.

Co-morbidity-adjusted care

Co-morbid people with diabetes are a quite heterogenous group of patients.  Functional reserves and cognitive performances may critically determine self-management capabilities, the benefiting from diabetes-specific interventions, and the likelihood of hospitalisation. Polypharmacy, medication non-adherence, and other treatment effect modifiers may affect the safety and efficacy of blood glucose lowering medication. Accordingly, a recent update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes points to the requirement for personalisation of glycaemic targets especially in elderly people with diabetes. Case finding algorithms will be used for identifying people with diabetes who most likely benefit from dedicated case management programs. More tools will become available that predict the interaction of drugs at the levels of pharmacokinetics, pharmacodynamics, as well as safety and tolerability. Predictions should be adjustable to the presence of common ageing traits, co-morbidities, and other life- and disease course-specific characteristics.

Impact of personalisation on early phase clinical contract research in diabetes 

Profil is a full service CRO performing early phase clinical trials with a strong focus on obesity, (pre)diabetes, and diabetes complications. Profil is ready to integrate multiple dimensions of personalisation in clinical trials. When using and expanding its people data base containing real-life and medical data of potential trial participants Profil stays in regular contact with currently more than 22,000 people representing the entire diversity of groups targeted by innovations in diabetes. Profil has a large in-house portfolio for anthropometric, metabolic and cardiovascular assessments available, and offers the control of treatment effect modifiers such as dietary and physical activity habits in clinical trials. Our active involvement in the CBmed Center for Biomarker Research in Medicine and EIT Health puts us in the position to connect our integrated service portfolio with advanced "omics" analytical platforms and the access to living labs and test beds. This enables us to implement additional levels of phenotyping and stratification. By doing patient-initiated research Profil exemplifies how patients can be directly involved in the design and implementation of clinical research projects. Thereby we pro-actively take the trend to involve patients in decision making along the lines of research and development, licensing, and health care. We think that co-creation will greatly improve tailoring of products and services in diabetes to peoples' individual needs and requirements.   

Topics: The Science behind Diabetes, Treating Diabetes