Diabetes and Stratified Medicine

The impact of cardio-respiratory fitness on an individual’s metabolic response to prolonged sitting and light activity breaks.

• Principle Investigators and Co-Investigators: Matthew McCarthy, Dr Thomas Yates, Professor Melanie Davies, Professor Kamlesh Khunti, Dr Charlotte Edwardson
• Funded by: by The Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical research unit and University of Leicester

Research consistently shows that sitting for long periods of time is bad for our metabolic health and can leave us vulnerable to a plethora of unfavourable health outcomes such as diabetes, cardiovascular disease and metabolic syndrome.

Interrupting our sitting time with frequent bouts of light intensity activity such as walking has been documented as a viable strategy to protect against this detrimental impact.

Cross sectional research has recently highlighted the potential ability of cardio-respiratory fitness to moderate an individual’s metabolic response to both sedentary behaviour and light activity breaks. This leads us to the notion that high fitness levels could potentially protect individuals from the deleterious impacts of prolonged sedentary behaviours, leaving light activity breaks far less required in high fitness individuals.

However, an  absence of randomised control trials assessing the ‘extent’ to which fitness moderates these relationships is yet be verified in an objective manner and warrants further intervention based investigation.

Outcomes and impacts

Certain occupations do not allow for regular interruptions in sitting time (for instance, long distance drivers), therefore it is vital that we explore the protective role of fitness in more detail. If fitness can fully or substantially protect against the deleterious impacts of prolonged sitting, then people with unavoidable sedentary occupations can engage in exercise outside of working hours in order to build resilience. This would empower individuals who would otherwise be resigned to the fact that their unavoidable sitting habits are putting them in danger. In light of this research, future physical activity and sedentary behaviour interventions may be tailored to the fitness level of the individual in question.

An acute bout of HIT on glycaemic responses in south Asian compared to white Europeans with IGR

• Principle Investigators and Co-Investigators: Charlotte Jelleyman, Dr Thomas Yates, Professor Melanie Davies, Prof Kamlesh Khunti, Dr James King
• External Collaborators: Loughborough University
• Funded by Leicester-Loughborough Diet, Lifestyle and PA BRU

High-intensity interval training has been proposed as a novel, time efficient mode of exercise training that could be recommended as an alternative to continuous moderate exercise in the general guidelines for physical activity. HIT is purported to stimulate the same if not greater health adaptations as traditional exercise training and a number of studies have reported a beneficial influence of HIT on T2DM related outcomes such as insulin sensitivity and glucose response to a challenge. To date, the majority of research has been conducted in populations of white European descent and has not distinguished between responses of individuals of different ethnicities, a factor recently identified as a potential confounder. This experiment will look at the effect of a single bout of HIT on levels of blood glucose in response to a meal as well as the subsequent regulation throughout the day in white Europeans and south Asians with impaired glucose regulation.

Outcomes and impacts

It is increasingly clear that one size does not fit all when it comes to recommendations for health and behaviour. It is therefore important to quantify differences in the metabolic response to health behaviour between population groups. Such an understanding will enable recommendations and lifestyle programmes to be specific to the population they are targeting. This study will provide a greater insight into the potential therapeutic impact of completing HIT and whether this is influenced by ethnic origin.

Sedentary behaviour in older adults: investigating a new therapeutic paradigm

• Principle Investigators and Co-Investigators: Dr Thomas Yates, Professor Melanie Davies, Professor Kamlesh Khunti, Dr Charlotte Edwardson
• External Collaborators: University of Glasgow and Loughborough University
• Funded by MRC-LLHW

Sedentary behaviour, referring to all non-exercise sitting based activity, is closely linked to the risk of developing chronic disease. Breaking sedentary behaviour with light bouts of movement or standing improves metabolic health, particularly the amount of glucose and fat in the blood following a meal. However, the rate of improvement has been hypothesised to differ between ethics groups. This project will look at the effect of breaking sedentary behaviour with standing or walking on levels of insulin and glucose in the blood in white Europeans and South Asian older adults and whether the response is meaningfully influenced by ethnic origin.

Outcomes and impacts

It is increasingly clear that one size does not fit all when it comes to recommendations for health and behaviour. It is therefore important to quantify differences in the metabolic response to health behaviour between population groups. Such an understanding will enable recommendations and lifestyle programmes to be specific to the population they are targeting. Our study will provide a greater insight into the potential therapeutic role of reducing sedentary behaviours in older adults and whether this is influenced by ethnic origin.

Pre-diabetes and Type 2 diabetes: Risk-assessment tools for early detection and prevention

• Principle Investigators and Co-Investigators: Dr Laura Gray, Professor Melanie Davies, Professor Kamlesh Khunti
• Funded by Diabetes UK and NIHR CLARHC

Key publications:

• Gray L.J, Khunti K, Wilmot EG, Yates T, Davies MJ (2014) External validation of two diabetes risk scores in a young UK South Asian population. Diabetes Research and Clinical Practice.
• Gray L.J, Khunti K, Edwardson C, Goldby S, Henson J, Morris DH, Sheppard D, Webb D, Williams S, Yates T, Davies MJ (2012) Implementation of the automated Leicester Practice Risk Score in two diabetes prevention trials provides a high yield of people with abnormal glucose tolerance. Diabetologia 55 (12), 3238-3244.
• Gray L.J, Davies MJ, Hiles S, Taub N, Webb DR, Srinivasan BT, Khunti K (2012) Detection of Impaired Glucose Regulation and/or Type 2 Diabetes Mellitus, using primary care electronic data, in a multiethnic UK community setting. Diabetologia. 55(4):959-66.
• Gray L.J, Taub NA, Khunti K, Gardiner E, Hiles S, Webb DR, Srinivasan BT, Davies MJ (2010) The Leicester Risk Assessment score for detecting undiagnosed Type 2 diabetes and impaired glucose regulation for use in a multiethnic UK setting. Diabetic Medicine. 27(8) 887-895.

Around 2.5 million people in the UK have Type 2 diabetes, with many more in a pre-diabetic state. Both conditions are hard to detect and frequently remain undiagnosed and untreated for years. The cost burden to the NHS of eventual treatment is estimated at £10 billion; 80% of which is spent on complications that are, with good care, avoidable. Targeted diabetes prevention programmes could aid in prevalence reduction and associated costs. Leicester’s Diabetes Research Centre has developed two risk scores, both suitable for use with an ethnically diverse UK population, to detect these conditions: a self-assessment questionnaire and a general practice database tool.

Outcomes and impacts

Recommended by NICE, they have been used successfully in varied settings. Since July 2011, around 650,000 people have completed the self-assessment score online and more than 60,000 through other means. The self-assessment score can also be completed with the help of a pharmacist at Boots and Tesco stores nationally.

Modelling work by NICE showed that utilising risk scores in a screening programme is cost-effective and is likely to be cost-saving in those from black and minority ethnic backgrounds. Work carried out by the Centre shows that the cost per case detected is lowered significantly, from £350 to around £200, by incorporating risk scores.

The effectiveness of community initiated screening for undiagnosed type 2 diabetes: The PRISM Study

• Principle Investigators and Co-Investigators: PI-Prof Kamlesh Khunti, Co-Is- Andy Willis, Dr Helen Eborall, Dr laura Gray, Dr Margaret Stone, Prof Melanie Davies
• Funded by: CLAHRC LNR, Leicester City PCT, Merck Sharp & Dohme

There has been an increase in efforts in the last decade, towards early detection of type 2 diabetes to address the growing prevalence of the disease, and increased cost of treating complications. In order to increase the uptake of screening, tests are offered opportunistically using point of care or non-invasive tests in community settings such as faith centres and pharmacies. There is limited evidence of the effectiveness of this method of screening as it is difficult to collect follow up (diagnostic) data on participants who are referred to their GP for a confirmatory test.

This study is testing out two community pharmacy based methods of screening for diabetes: 1) Leicester self-assessment risk score, 2) Leicester self-assessment risk score followed by a finger prick HbA1c test. This study has been designed as a two arm randomised controlled trial and is being conducted in Lincoln County and Leicester City.

Outcomes and impacts

Collecting data on feasibility of screening including; screening yield (number of participants diagnosed with type 2 diabetes and impaired glucose regulation) will provide a quantitative measure of feasibility. It is anticipated that this data will be used to inform a cost-effectiveness analysis of the screening to provide data which can be compared to similar analyses of other screening methods for type 2 diabetes.

In addition to the qualitative outcomes the study team have conducted a qualitative study including analysis of semi-structured interview transcripts to gather participating pharmacists’ views and experiences of providing the screening service. The results of this analysis provide valuable data on pharmacists’ views on feasibility and acceptability of the screening including barriers and facilitators to implementation which will be valuable in the designing of future community based screening interventions.