Future Roadmaps for Precision Medicine Applied to Diabetes: Rising to the Challenge of Heterogeneity

Table 1

Opportunities and limitations in diabetes research.

Models in diabetes research		Utility	Limitations	Facilitators	Future potential
Human	Populations	(i) GWAS for risk variants in polygenic disease and new gene discovery studies for monogenic disease; (ii) Risk and treatment stratification using biomarkers and clinical features; (iii) Clinical trials of new/repurposed treatments	(i) Large-scale bioinformatics support and data management/storage required with cost implications; (ii) Ethical implications of use and long-term storage of genetic data; (iii) Functional and clinical interpretation of genetic data is challenging particularly for vast quantities	(i) High throughput genomic sequencing techniques, e.g., NGS; (ii) Data sharing via human gene/disease/clinical databases, clinical trial data access; (iii) Integration of research into clinical practice, e.g., 100,000 Genomes Project; (iv) Electronic health records	+++
	Beta cells	(i) Mapping pathways and regulatory networks in combination with molecular genetic data; (ii) Determining the role of immunological/environmental factors	(i) Difficult to obtain large numbers of specimens from cadaveric donors; (ii) Does not capture multisystem physiology and so may not be fully translatable to the whole organism	(i) High throughput genomic sequencing techniques, e.g., NGS; (ii) Improved interpretation of GWAS findings; (iii) Advances in laboratory techniques	++
Animal	Induced	(i) Can provide some supporting evidence of disease causality or association for genetic/environmental factor(s) being studied	(i) Differences in aetiology and natural history of disease between animals and humans limit clinical translation/utility; (ii) Not useful for testing therapeutic interventions as differences in animal and human responses	(i) Advances in molecular genetic techniques including genetic manipulation	−/+
	Spontaneous	(i) May help generate hypotheses about factors involved in disease aetiology/pathophysiology			−/+

NGS = next-generation sequencing; GWAS = genome-wide association study; +++ = excellent potential for future advances; ++ = good potential; + = possible potential; − = limited potential.