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Discoveries from the study of longstanding type 1 diabetes – published online 04/03/2021

Perkins GA

Bruce A. Perkins, Leif Erik Lovblom, Sebastien O. Lanctôt, Krista Lamb, David Z. I. Cherney

Award programmes that acknowledge the remarkable accomplishments of long-term survivors with type 1 diabetes have naturally evolved into research programmes to determine the factors associated with survivorship and resistance to chronic complications. These have led to the discovery that many individuals retain insulin production and, other than for diabetic neuropathy, appear to resist the development of microvascular and macrovascular complications. In this issue, Perkins and colleagues (https://doi.org/10.1007/s00125-021-05403-9) consider the putative mechanisms underlying this phenomenon. They also discuss mechanisms that may result in the maintenance or recovery of beta cells and their function, which include: activation of specific glycolytic enzymes, such as pyruvate kinase M2; modification of AGE production and processing; novel mechanisms for modification of renin–angiotensin–aldosterone system activation, in particular those that may normalise afferent rather than efferent renal arteriolar resistance; and activation and modification of processes such as retinol binding and DNA damage checkpoint pathways. The authors conclude that these mechanisms may, in the future, serve as therapeutic targets. The figures from this review are available as a downloadable slideset.

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