Understanding diabetes heterogeneity: key steps towards precision medicine in diabetes.

Diabetes is a highly heterogeneous condition; yet, it is diagnosed by measuring a single blood-borne metabolite, glucose, irrespective of aetiology. Although pragmatically helpful, disease classification can become complex and limit advances in research and medical care. Here, we describe diabetes heterogeneity, highlighting recent approaches that could facilitate management by integrating three disease models across all forms of diabetes, namely, the palette model, the threshold model and the gradient model. Once diabetes has developed, further worsening of established diabetes and the subsequent emergence of diabetes complications are kept in check by multiple processes designed to prevent or circumvent metabolic dysfunction. The impact of any given disease risk factor will vary from person-to-person depending on their background, diabetes-related propensity, and environmental exposures. Defining the consequent heterogeneity within diabetes through precision medicine, both in terms of diabetes risk and risk of complications, could improve health outcomes today and shine a light on avenues for novel therapy in the future.
Competing Interests: Declaration of interests RDL is on the Advisory Boards of Diamyd and Provention and has received educational grants from Novo Nordisk, Eli Lily, Sanofi, Astra Zeneca, and MSD. RCWM has received research funding from AstraZeneca, Bayer, Novo Nordisk, Pfizer, Roche Diagnostics (HK), and Tricida for carrying out clinical trials, and has received speaker honorarium or consultancy in advisory boards from AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic, Merck, and Kyowa Kirin. All proceeds have been donated to the Chinese University of Hong Kong to support diabetes research. RCWM is a cofounder of GemVCare, a diabetes technology start-up, established through support from the Hong Kong Government Technology Start-up Support Scheme for Universities (TSSSU). PWF has received consulting fees from Zoe, and is an employee of the Novo Nordisk Foundation, a non-profit, philanthropic, enterprise foundation. The views expressed in this Series paper do not necessarily reflect those of the institutions to which the authors are affiliated. ERP has received honoraria for speaking from Lilly, Novo Nordisk, and Illumina. All other authors declare no competing interests.
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