Aetiology of type 2 diabetes: an experimental medicine odyssey – published online 02/05/2025

Roy Taylor

Magnetic resonance methods have permitted the direct observation of metabolism inside organs. In this issue, Roy Taylor (https://doi.org/10.1007/s00125-025-06428-0) summarises a series of studies that resulted in a nationwide UK National Health Service programme for remission of short-duration type 2 diabetes. Initially, a research instrument was developed to test the underlying hypothesis reliably (a diet causing 10–15 kg weight loss). This allowed the removal of genetic heterogeneity by comparing the same individuals with and without diabetes. The weight loss corrected all abnormalities typical of type 2 diabetes: increased liver fat, increased liver export of glucose and lipid, and loss of acute beta cell response to food. The pathophysiology was the same whether the initial BMI was 45 kg/m2 or 27 kg/m2, indicating that individuals have a ‘personal fat threshold’. Taylor concludes that this concept explains why the weight-loss protocol is also successful in people with type 2 diabetes who have a ‘normal’ BMI—they have simply gained more weight than their genetic constitution can tolerate. The figures from this review are available as a downloadable slideset.

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