Diabetes

Why does Glucophage (metformin) help some people with diabetes?

Much current research is focused on insulin resistance and how it might be reversed where current treatments are ineffective. The best treatment for insulin-resistant T2D is metformin but the target of this drug is still unclear, hampering development of improved agents to replace metformin, which is not effective in all T2DM and loses potency with prolonged use.

Investigation of the molecular mechanism of metformin

Much current research is focused on insulin resistance and how it might be reversed where current treatments are ineffective. The best treatment for insulin-resistant Type 2 diabetes (T2D) is metformin but the target of this drug is still unclear, hampering development of improved agents to support metformin, which is not effective in all T2D and loses potency with prolonged use.

The genomics of cardiovascular disease and drug response in type 2 diabetes

The field of personalised medicine is being transformed by the use of whole genome technology.  We are currently studying a population of 9000 individuals with type 2 diabetes to determine the genetic factors in determining their response to a wide range of commonly used drugs such as the statin family of cholesterol lowering drugs and anti-clotting agents such as aspirin.  The use of these drugs may be limited by side effects such as muscle pain, in the case of statins, and stomach bleeding in the case of aspirin.   We have performed a whole genome scan in 8000 individuals with type 2 diab

Linking Genomics to Imaging data: Elucidation of the mechanisms of novel genes that predispose to heart disease

Genome wide studies have provided great insight into the truly polygenic nature of cardiovascular disease, with current meta-analysis being performed in populations of ~200,000 study individuals.  This has characterised around 60 loci involved in susceptibility to CAD.  This analysis combines a wide range of cardiovascular phenotypes including angina, IMT, atheroplasty and MI. So the role of these genes in individual components of cardiovascular disease such as atherosclerosis, vessel damage, heart muscle physiology etc. has not yet been elucidated.

Environmental stress and the brain

The last few decades has seen a marked increase in the incidence of both type 1 and type 2 diabetes in Western Societies resulting in a significant individual and societal health costs. Understanding those mechanisms that contribute to the development of obesity and disorders of glucose homeostasis are therefore critical areas of research. It is increasingly recognized that the brain contributes to the development of both diabetes and obesity.

Determining how BACE1 activity regulates neuronal glucose metabolism

A high proportion of the UK population is obese and this is associated with significantly increased risk of type 2 diabetes (T2D), cardiovascular disease and Alzheimer’s disease (AD).  AD is also associated with increased risk of T2D and AD patients and AD animal models demonstrate disturbances in glucose metabolism. The aspartic protease BACE1 (beta-site amyloid precursor protein (APP)-cleaving enzyme) is thought to be the primary driver for the neurodegeneration and cognitive dysfunction associated with AD.

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