Advancing a causal role of type 2 diabetes and its components in developing macro‐ and microvascular complications via genetic studies

Abstract

The role of diabetes in developing microvascular and macrovascular complications has been subject to extensive research. Despite multiple observational and genetic studies, the causal inference of diabetes (and associated risk factors) on those complications remains incomplete. In this review, we focused on type 2 diabetes, as the major form of diabetes, and investigated the evidence of causality provided by observational and genetic studies. We found that genetic studies based on Mendelian randomization provided consistent evidence of causal inference of type 2 diabetes on macrovascular complications; however, the evidence for causal inference on microvascular complications has been somewhat limited. We also noted high BMI could be causal for several diabetes complications, notable given high BMI is commonly upstream of type 2 diabetes and the recent calls to target weight loss more aggressively. We emphasize the need for further studies to identify type 2 diabetes components that mostly drive the risk of those complications. Even so, the genetic evidence summarized broadly concurs with the need for a multifactorial risk reduction approach in type 2 diabetes, including addressing excess adiposity.

Features of Non-Alcoholic Beer on Cardiovascular Biomarkers. Can It Be a Substitute for Conventional Beer?

“…Several diabetes-related conditions contribute to increased cardiovascular risk. Among them, insulin resistance and hyperglycemia are the main drivers of atherothrombotic events leading to poor cardiovascular health [ 31 , 32 ]. Taking this into account, it is interesting to analyze the effect of beer intake on parameters related to glycemic control.…”

Blood Pressure as a Key Mediator in the Link Between Type 2 Diabetes and Heart Failure: Insights from Mendelian Randomization

“…Two prior studies reported con icting results on the T2D-HF link. Mordi et al [28] (2021) found mediating variables slightly reduced the T2D-HF effect, while Ahmed et al [29] (2023) noted BMI and SBP nulli ed it. Our MR analysis reconciles these differences, con rming and bolstering the T2D-HF link based on recent evidence and extending past MR research.…”

“…Concerning weight management, a prior study [29] indicated that BMI mediate the relationship between T2D and HF. However, this association has limitations as individuals with similar BMIs may have differing metabolic and CVD risk pro les [35].…”

Stellar science: Basic science has lift off!

“…Rory McCrimmon, 9 this year's Dorothy Hodgkin Lecture recipient, has written an engaging overview of his prize lecture in which he has provided mechanistic insights into recurrent hypoglycaemia in diabetes. We are confident that the articles in this special issue, which are a mixture of primary research, 1–5,7 and state of the art reviews, 6,8,9 are accessible to non‐specialists and will be enjoyed by a wide readership.…”

“…The most outstanding basic science diabetes researchers in the UK are awarded five‐year RD Lawrence Fellowships after competitive interview. Three of the current RD Lawrence Fellows (Benoit Hastoy and Quan Zhang 7 and Hanieh Yaghootkar 8 ) contributed articles that emphasise their expertise in the regulation of beta‐cell exocytosis 7 and genetic studies of vascular complications of diabetes 8 . The Diabetes UK Dorothy Hodgkin Lecture is awarded annually to internationally recognised basic science researchers in recognition of Hodgkin's achievement in determining the crystal structure of insulin.…”