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Open Access 14-07-2023 | Diabetic Retinopathy | Review

Genetics of diabetes-associated microvascular complications

Authors: Valeriya Lyssenko, Allan Vaag

Published in: Diabetologia | Issue 9/2023

Abstract

Diabetes is associated with excess morbidity and mortality due to both micro- and macrovascular complications, as well as a range of non-classical comorbidities. Diabetes-associated microvascular complications are those considered most closely related to hyperglycaemia in a causal manner. However, some individuals with hyperglycaemia (even those with severe hyperglycaemia) do not develop microvascular diseases, which, together with evidence of co-occurrence of microvascular diseases in families, suggests a role for genetics. While genome-wide association studies (GWASs) produced firm evidence of multiple genetic variants underlying differential susceptibility to type 1 and type 2 diabetes, genetic determinants of microvascular complications are mostly suggestive. Identified susceptibility variants of diabetic kidney disease (DKD) in type 2 diabetes mirror variants underlying chronic kidney disease (CKD) in individuals without diabetes. As for retinopathy and neuropathy, reported risk variants currently lack large-scale replication. The reported associations between type 2 diabetes risk variants and microvascular complications may be explained by hyperglycaemia. More extensive phenotyping, along with adjustments for unmeasured confounding, including both early (fetal) and late-life (hyperglycaemia, hypertension, etc.) environmental factors, are urgently needed to understand the genetics of microvascular complications. Finally, genetic variants associated with reduced glycolysis, mitochondrial dysfunction and DNA damage and sustained cell regeneration may protect against microvascular complications, illustrating the utility of studies in individuals who have escaped these complications.

Graphical Abstract

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Title: Genetics of diabetes-associated microvascular complications
Authors: Valeriya Lyssenko
Allan Vaag
Publication date: 14-07-2023
Publisher: Springer Berlin Heidelberg
Keywords: Diabetic Retinopathy
Diabetic Retinopathy
Hyperglycemia
Type 2 Diabetes
Published in: Diabetologia / Issue 9/2023
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-023-05964-x

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Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Graphical Abstract

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Other articles of this Issue 9/2023

Plasma proteomic signatures of a direct measure of insulin sensitivity in two population cohorts

Associations of plasma proteomics with type 2 diabetes and related traits: results from the longitudinal KORA S4/F4/FF4 Study

Further investigation of the association between diabetes status and body composition and whether this association is moderated by sex. Reply to Mai Y [letter]

The potential for genetic risk scores in type 1 diabetes

How amenable is type 2 diabetes treatment for precision diabetology? A meta-regression of glycaemic control data from 174 randomised trials

Further investigation of the association between diabetes status and body composition and whether this association is moderated by sex

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials