Type-II Diabetes Complications

We analyzed a UK Biobank dataset using the PrecisionLife® combinatorial analytics platform. We compared cases with type-II diabetes associated complications (such as ketoacidosis, nephropathy, and retinopathy) against the oldest available set of gender- and BMI-matched controls who had diabetes but had not (yet) developed any complications.

Having stratified patients into distinct complication-specific subtypes, we identified individual genes and biological mechanisms associated with each. These high resolution disease insights enable novel drug discovery, the development of combinatorial risk scores and biomarkers to distinguish the patient subgroups and predict individual risk.

These can be used to identify at-risk patients and inform targeted lifestyle and therapeutic interventions, to prevent development of these complications. This could result in better patient outcomes, and reduce the huge health and economic burden caused by diabetes complications.

We found significant genetic differences between the case and control populations, indicating that there is a subset of diabetic patients with genetic features that predispose them to severe diabetes and related complications, independent of lifestyle and environmental factors.

Heatmap showing the frequency of diabetes-related complications for five type 2 diabetes case clusters from UK Biobank

Our analysis revealed several SNPs and genes that were highly associated with the development of specific diabetes related complications. The diabetes complication subpopulations for which genetic signatures were identified included:

• general (five genes associated with an increase in all complications)
• acute (ketoacidosis/coma – five genes)
• neurological (six genes)
• peripheral (circulatory/angiopathy issues – eight genes)
• renal (four genes)
• ophthalmic (seven genes)
• type 1 diabetes (four genes associated with a mis-diagnosed cohort)