Developing type 2 diabetes young+lean is not as uncommon as it may seem. This phenomenon is more common in people of South Asian and East Asian ancestry, but is observed across populations. Why does this happen, how should we screen and treat young+lean T2D.
👉 Read our paper here: rdcu.be/eH0YR

Delighted to showcase @genesandhealth.bsky.social and the enormous work of teams across settings. In this piece we highlight its role in diabetes & metabolism research.
authors.elsevier.com/a/1kAgM3jDgW...

@qmulfmd.bsky.social @sarahfiner.bsky.social #SouthAsianHealth #PrecisionMedicine

Better screenshot here:

Finally putting these two extreme risk pathways together, we can identify a sub-group of SA who will develop T2D 8 years earlier with 3 kg/m2 lower BMI.

Insulin dependence: we observe increased hazards of progression to insulin dependence per SD of beta-cell dysfunction 1.08 and unfavourable fat distribution 1.108. No observable effect for higher risk of T2D due to obesity.

🔑 observation: T2D PRS is not associated with 💊 response highlighting the value of aetiological risk scores designed to represent T2D heterogeneity. Central to the goal of precision medicine. These patterns should hold regardless of ancestry.

On 💊 unsurprisingly, HbA1c response was worse for those with higher genetic risk of beta-cell dysfunction, per SD HbA1c response to SUs, TZDs and SGLT2is being 0.85, 1.56 & 1.1**% higher after treatment. SGLT2i difference surviving correction for multiple testing.

📊comparing South Asians and Europeans in #UKBiobank, SA have greater genetic risk of beta-cell dysfunction and unfavourable fat distribution, but not Obesity. In Genes & Health we show within SA groups, BB have higher risk that BP.

🧬 using the full complement of pPS representing the different aetiological pathways of T2D risk we observe the same association patterns for T2DM, GDM, and conversion of GDM to T2DM. GDM is a major risk factor for South Asian women developing early onset T2DM.

rdcu.be/d1vj0
TL;DR: partitioned polygenic scores (pPS) can help identity those at risk of early+lean onset type 2 diabetes (T2D)
Thanks to all co-authors - many not yet on Bluesky: Alice Williamson, Marghe Bigossi...@rohinimathur.bsky.social, editors and reviewers.