Research > Diabetes & Metabolism
Research Focus:
Pathogenesis of Type 2 diabetes. Mechanisms underlying insulin resistance, beta-cell failure, and new mechanisms for the treatment of these defects in pre-diabetes and diabetes. The team is headed by Prof John Nolan.
Main Achievements:
This group is focused on the integrative physiology of obesity, insulin resistance and Type 2 diabetes. We have established a clinical investigation group (the Metabolic Research Unit), currently based in Hospital 5, adjacent to and integrated with the Diabetes Day Centre. This group conducts metabolic studies in human subjects, and clinical trials. We are now developing the biochemical and molecular extension of these clinical studies at the IMM. The group has been successfully funded since 1997 from a variety of sources including HRB, HEA (PRTLI), EU and industry. Dr Maria Byrne (Research Senior Lecturer, Consultant Endocrinologist) and Dr Vivion Crowley (Consultant Chemical Pathologist) have recently joined the group.
Populations:
St James's is one of the busiest diabetes centres in Ireland with 6,000 patients, and 1,000 new patients per year. We have established studies in the following populations:
- Type 2 Diabetes
- Patients with severe insulin resistance
- Diabetes and Haemochromatosis
- Type 1 Diabetes
- First degree relatives of patients with diabetes
- Pre-diabetes (IGT and IFG)
- Healthy Controls
- Children and adolescents
- Early onset Type 2 diabetes (before age 25)
Techniques:
We have established a range of techniques in the clinical investigation of fuel metabolism, including:
- Glucose clamp: A gold standard method to measure insulin sensitivity
- IVGTT: This method allows a model-based calculation of insulin secretion and sensitivity
- Muscle and adipose tissue biopsy: can be combined with the clamp, to analyse signalling, gene expression, protein expression
- Glucose Turnover: Using isotopic tracers
- Exercise Physiology: We have an exercise unit, run by graduate student Nicole Mag, where we can study the metabolic effects of varying forms of exercise in a range of settings and patient groups
In addition group members have experience in a variety of molecular biology techniques, including PCR, real-time RT-PCR, Sequencing, SNP/RFLP genotyping, plasmid-based cloning/subcloning, cell culture, retroviral transduction and microarray analysis.
Cellular and Molecular Mechanisms:
- Insulin signalling in diabetes and obesity, pre and post aerobic exercise
- Prospective case-control study in Type 2 diabetes as a basis for candidate gene and SNP analysis (in progress, with Dr Vivion Crowley)
- Genetic characterization of subjects with severe insulin resistance (SIR) and early onset severe obesity (in collaboration with paediatrics, and Dr Vivion Crowley)
- Genetic characterization of families with MODY (Dr Maria Byrne)
Collaborations:
This group collaborates widely within TCD and locally, and is involved in several international research collaborations. Within TCD/SJH, we collaborate with:
- Psychological Medicine: Eating disorder behaviour in early onset obesity
- Surgery: Total pancreatectomy; surgery for morbid obesity
- Hepatology: Mechanisms of diabetes in haemochromatosis
- Nutrition: Metabolic and molecular responses to diet intervention
- Emergency Medicine: Risk analysis at the Chest Pain Assessment Unit
- Engineering & Computer Science: Mathematical modelling and electronic records
- Physiology: Exercise physiology
We are involved in the following EU integrated research grants:
- EGIR-RISC: A 20-centre prospective study in healthy volunteers of the relationship between insulin resistance and the evolution of atherosclerosis, diabetes, hypertension, and obesity. 1,100 subjects recruited to date, 100 at St James's
- DIABESITY: Framework 6 project focused on the identification of drug targets for the treatment of diabetes and obesity. This group comprises the leading groups in the field of diabetes and obesity genetics throughout Europe. The project spans areas from human and animal physiology through neuropeptides, appetite and energy balance to molecular mechanisms pre and post interventions