Using crop genetics to understand the importance of dietary resistant starches for maintaining healthy glucose homeostasis

Type 2 diabetes is a major and increasing problem worldwide and is particularly prevalent among the aging population. Over 2.5 million individuals in the UK are affected, costing the NHS around £10 billion per year (almost 10% of its budget). The risk of diabetes is thought to increase with age because of poor control of blood glucose levels. This in turn is due to a progressive decline in the capacity of cells in the pancreas (beta-cells) to secrete insulin, the hormone that controls glucose levels. The decline in beta-cell function can be accelerated by a poor diet and lifestyle, thus increasing the risk of developing type 2 diabetes.
There is much evidence that diets rich in a type of carbohydrate called resistant starch have a positive impact on controlling of blood glucose levels, and hence reduce susceptibility to type 2 diabetes. Resistant starch, as the name suggests, is not completely digested in upper parts of the digestive tract, and so is fermented by bacteria in the colon. The products of fermentation, known as short-chain fatty acids, are thought to improve beta-cell function and thus insulin secretion. There are a variety of fruits and vegetables that contain various amounts of resistant starch, but UK diets are generally low in resistant starch. Thus there is great potential to reduce the incidence of type 2 diabetes in the long term by promoting the widespread consumption of resistant starch. However, very little is known about why particular types of starch are resistant to digestion and whether resistant starches from different food sources differ in their capacity to improve beta-cell function. Plugging these gaps in our knowledge will help the development of strategies to increase the amount of resistant consumed in the UK diet, thus helping to reduce the rates of onset of type 2 diabetes.

Our aim is to study systematically which features of starch structure are important in making it resistant to digestion and in allowing it to improve beta cell function. As well as studying resistant starch itself, we will study the influence of the type of food in which the starch is contained, and the way in which the food is cooked prior to consumption. Our study will focus on peas, as they are a range of naturally occurring variants or mutants known to contain different types of resistant starch. These seeds, and starch extracted from them, will be digested in an artificial gut, allowing us to assess which features of the starch and the food are important for maximum fermentation in the colon. In parallel, selected types of peas will be fed to human volunteers to determine the digestibility of the starch in vivo, together with a full spectrum of short and medium term physiological responses relevant to beta-cell function and control of blood glucose levels to be monitored.

We will also study the best way to process/prepare the peas, as some resistant starch can behave differently, so that they can be used in a wide range of foods.

This project will provide new insights into the relationship between resistant starch and susceptibility to type 2 diabetes. Importantly it will also inform crop breeders about which genes in crop plants are associated with types of starch that provide the best protection against type 2 diabetes. This will immediately allow the directed breeding of peas that provide maximal protection against this disease. It will also increase the flexibility of peas by investigating the use of pea flour in commonly consumed foods.

Our aim is to develop a systematic basis for increasing the intake of resistant starch in the diet in order to protect the function of insulin-secreting pancreatic beta-cells and improve blood glucose homeostasis in an ageing population. Age related declines in beta-cell function and glucose homeostasis increase susceptibility to type 2 diabetes, the incidence of which has doubled in the UK since 1996. We and others have shown that carbohydrates such as resistant starch that escape digestion in the small intestine lead to improved insulin sensitivity and first phase insulin response. We propose that short chain fatty acids liberated by colonic carbohydrate fermentation causes receptor-mediated improvements in beta-cell function. In this project we will define which starches and food matrices are most effective in protecting beta-cell function and discover the basis of this protection. The results will underpin development of a roadmap for increasing the most effective types of resistant starch in the diet via a concerted approach involving crop breeding and food processing.
Our project utilises a suite of genetically-defined natural mutants of peas, representing two types of resistant starch in a variety of genetic backgrounds. Experiments with static and dynamic digestion models will examine starch digestibility and colonic fermentability in raw and processed materials and purified starch. Selected samples will be physically characterised to establish which starch/matrix features determine digestibility and fermentability, which will be confirmed in human studies. In parallel we will carry out human trials on selected peas to assess effectiveness in beta-cell protection. Volunteers aged 55 - 65 will be used to assess physiological functions related to susceptibility to diabetes including measures of insulin release, gut hormones, colonic microbiota and the microbiota activity.

This project addresses one of UKs major diet-related health challenges. It has huge potential for long term impact on a wide range of stakeholders from consumers to policy makers. In addition to the academic beneficiaries listed, the outputs of the research will impact on the following stakeholder groups:-

Food Industry: The outputs from this project will enable the food industry to develop a new generation of foods targeted at reducing the incidence of type 2 diabetes through improved delivery of functional carbohydrates to the colon. Further research will allow the generic design principles to be incorporated into a wide range of food and beverages. Results from the project will inform efforts to ensure that new resistant-starch foods have consumer acceptability comparable to currently-available foods, making it more convenient for consumers to adopt healthier options. Food with high nutritional impact is a growing sector of the food industry and robust scientific evidence of positive health benefits arising from this and future projects will support health claims and further growth and give the UK food industry a competitive advantage.
Consumers: Individual consumers will have new knowledge regarding the health benefits of certain foods, together with a wider choice of manufactured foods with specific, proven health benefits. Care must be taken with the health communication aspects as consumption of these foods may only be effective as part of a healthy balanced diet. In the long term, the benefits of reducing the prevalence of diabetes will impact on lifelong health and wellbeing of individuals and improve the quality of life into old age.
Pharmaceutical Industry: The generic principles involved in this research are expected to stimulate further research to improve the targeted delivery of carbohydrates, polymers and other therapeutic and health promoting compounds to the colon.
National Health Service and Government: The number of individuals diagnosed with type 2 diabetes in the UK has roughly doubled since 1996 to about 2.6 million, with over 70% of cases being over the age of 55. Older diabetes patients often develop complications including heart disease, stroke, blindness, kidney disease and amputations leading to disability and premature mortality. The direct cost to the NHS and other health care providers for treating type 2 diabetes and related conditions is around £10 billion per year (approx. 10% of the NHS budget). The total cost of diabetes to the nation including direct care, loss of working days due to sickness and loss of productivity is estimated to be £23.7 billion. Any reduction in the prevalence of diabetes would have a huge impact through fewer hospital admissions, fewer surgical interventions and fewer prescriptions, hence lower health costs. The basic knowledge generated from this project and further research targeted at foods which would naturally deliver fermentable starch to the colon, will also help Government agencies to develop dietary advice for individuals at risk from developing diabetes in later life.

To maximise impact, we will assemble an Advisory Panel composed of various stakeholders including academics beneficiaries, end users and industry (see Pathways to Impact). The panel will meet three times during the project to review progress and advise on future directions, application and exploitation. In addition, two further open meetings will be held at the end of the project to consult with a broader group of stakeholders.