Disease Studies

Type-II Diabetes Complications

Type-II diabetes-related complications create some of the most significant health and economic burdens in developed and developing countries. Complications associated with type-II diabetes include renal failure, neuropathies, blindness and cardiovascular impacts including heart disease, stroke, ulcers and amputations. They account for 80% of the huge diabetes treatment costs, and are directly responsible for poor quality of life for patients, with higher long-term social care costs and mortality rates.

We identified 20 genes most closely associated with the risk of developing type-II diabetes complications. We then built combinatorial risk scores that predict which type of complications a type-II diabetes patient is likely to experience.



Methodology

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.

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Results/Findings

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)
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