Metabolic Disease & Diabetes Research
Corticosteroid Hormones in CVD
High blood pressure is the major risk factor for coronary disease, heart failure and stroke, which are estimated to be responsible for 7 million excess deaths each year worldwide. Of the various factors contributing to blood pressure homeostasis, the steroids aldosterone and cortisol play a crucial role. These hormones are made in the adrenal gland by the enzymes aldosterone synthase and 11β-hydroxylase and are encoded by the CYP11B2 and CYP11B1 genes respectively. Using a translational research approach integrating basic molecular biology, in vitro cell biology and human investigations, our studies have advanced our understanding of adrenal steroid synthesis regulation and the contribution of steroids to cardiovascular dysfunction.
Cardiovascular effects of metformin
Metformin has been used to control blood sugar in type 2 diabetes for more than 50 years. Its protective properties on the heart have been recognised in recent years, including in our own work and collaborations. We are now conducting clinical trials to see whether metformin’s beneficial effects extend to other conditions.
Metformin is widely regarded to have cardioprotective effects in type 2 diabetes which may be mediated via a number of mechanisms including activation of endothelial AMP kinase (see Vascular, Pathophysiology and Therapy – Coordinated regulation of metabolism and vascular health).
Cardiovascular Effects of Pre-eclampsia
Pre-eclampsia affects 2 to 5% of pregnant women worldwide and is associated with considerable morbidity and mortality for both the mother and the foetus. The condition is characterised by high blood pressure and excretion of protein in the urine. Pre-eclampsia can only be treated by delivery of the baby, which is again associated with risks to mother and the newborn. Early detection of women at risk for pre-eclampsia would allow better monitoring and preventative therapy, but currently no routinely applicable and reliable markers exist that predict development of the condition. In our research we aim to detect novel biomarkers of pre-eclampsia and study the effect of pre-eclampsia on future cardiovascular risk.
Scotland has an internationally recognised reputation for routinely collected health data. A subtheme involving many of the researchers in the Institute involves analysis of anonymised health data to answer a series of questions regarding the health of people with diabetes. Staff at the BHF Glasgow CRC work with colleagues in health economics in Glasgow and the other 3 major academic centres in Scotland to use these data for the benefit of patients in work based around the Scottish Diabetes Research Network Epidemiology group and Wellcome funded Scottish Health Informatics Programme. Dr Lindsay is chairperson of the Scottish Diabetes Research Network Epidemiology group and Professor Petrie previous lead of SDRN. Publications from this Scotland wide collaboration are included below1-6.
Glasgow Biomarker Laboratory
The Glasgow Biomarker Laboratory is an internationally recognised group, specialising in blood-based biomarker research and associated epidemiology. The team is an off-shoot of the DREAM theme (link) research team at the BHF Glasgow Cardiovascular Research Centre, University of Glasgow. We have a wide range of experience and a proven track history of measuring a vast range of blood-based biomarkers to a high standard, and asking the right questions to translate that data into results of clinical relevance.
Lifestyle & Obesity
Cardiovascular disease, diabetes and obesity are, to a large extent, diseases of 'lifestyle', in that how active we are and what we eat over our life-course markedly influences our risk of developing these conditions. Lifestyle interventions also provide the cornerstone to the management of obesity and cardio-metabolic disease.
We are interested in understanding the mechanics by which activity and diet modulate disease risk and progression; novel lifestyle interventions for risk reduction and disease management; how maternal obesity impacts on pregnancy outcome and offspring health; and how lifestyle, genetic background and early life events interact to modulate disease risk.
Metabolic health in pregnancy
Metabolic and endocrine conditions present during pregnancy have important effects on maternal and fetal health. It is recognised that conditions occurring during pregnancy, including gestational diabetes and pre-eclampsia, are important indicators of long term risk of metabolic disease - including hypertension and type 2 diabetes. Maternal obesity adversely affects maternal metabolism and is a contributing factor to such adverse pregnancy outcomes. Work in this area includes a number of national and international collaborations as well as projects shared with the School of Medicine.
Proteomics of diabetic nephropathy
Diabetes affects more than 6% of the British population, and the expenditure on patients with diabetes accounts for 15% of the UK health care budget. Almost 90% of patients have type 2 diabetes, and absolute numbers are expected to rise in parallel to the current obesity and metabolic syndrome epidemic. Recent advances in treatment have led to reduced mortality but, due to prolonging the duration of diabetes, have increased the likelihood of development of diabetic complications. Major complications are micro and macrovascular disease, which are highly interconnected. Diabetic nephropathy (DN) is a major microvascular complication of diabetes but is associated with substantial macrovascular disease and thereby cardiovascular morbidity and mortality. Already at early stages of DN, cardiovascular morbidity is increased, and it is further aggravated once end stage renal disease (ESRD) occurs.
Vascular Function in Pregnancy
During pregnancy the mother adapts her metabolism and physiology in a number of ways to help support and feed her fetus. In early pregnancy, maternal fat is laid down and in later pregnancy, the fats stored in adipose tissue are mobilised to provide the mother and baby with essential nutrients and fuels for energy. The maternal blood vessels also adapt and can become more responsive to signals allowing them to relax and this helps provide good blood flow to the placenta. The mechanisms by which these adaptations are achieved are not well understood. Furthermore, in obese pregnancy and pregnancies complicated by preeclampsia, intrauterine growth restriction and gestational diabetes, the metabolic and blood vessel adaptation to pregnancy is not optimal leading to hypertension, poor placental blood perfusion, failure to respond properly to hormones such as insulin. This can have immediate consequences for the health of mother and baby, but also may impact on their future health.