Identification of those at high risk of having IGR/T2DM
All participating GP practices will receive a Practice Pack giving them general information and contact numbers for the study. All practices will have an induction visit from the project lead and research assistant who will provide training and support.
An automated risk score will be used to identify those at high risk of IGR/T2DM using data routinely stored on individual GP practice computer databases. Various risk scores have been developed and validated for identifying T2DM . Scores available to date have not been validated for the UK multiethnic population and do not additionally pick up those with IGR. Therefore we will use a score developed using data from a previous screening study carried out in Leicester . This score has been amended to take into account ethnicity using the percentage of South Asians within the practice as a proxy for individual ethnicity.
Before the risk tool is applied to a practice database the quality of the data completion is assessed. If the quality level of Body Mass Index (BMI) data recorded is less than 40% practices will be asked to increase this before the risk tool can be used. The score will be calculated for all members of a participating practice. The practice list will then be ranked by risk score with those with the highest scores having the highest risk. The top 10% of patients with the highest score will be invited initially for screening. This 10% limit can be increased to generate further invitations and increase inclusion in the study if required. Where the top 10% of the risk score identifies fewer than 500, all patients within the top 10% will be invited. Where the number of eligible patients identified in the top 10% is greater than 500, the first 500 patients within the top 10% will be invited. If the response rate to initial invitations is insufficient a second mailing of invitations will be conducted. A computer programme will be written to automate the process and produce an excel spreadsheet listing risk scores in descending order.
The invitation will include a patient information sheet and a reply sheet, so patients can register their interest in taking part in the study. A self addressed envelope will be provided for returning of slips. Patients will also be given the number of a dedicated phone line to contact if they are interested and/or require further information. Written informed consent will be taken from all participants and participants will be able to withdraw from the study at any time.
Baseline screening visit
Participants will be asked to fast for 8 hours prior to attending the screening appointment and to bring a list of prescribed medications with them. Before beginning the overnight fast participants are asked to consume their regular evening meal and take any medication as normal. All participants receive a standard 75 g OGTT following informed consent being taken. Those patients who do not wish to have an OGTT will be discontinued from the study and return to their GP for routine care. Plasma samples are obtained immediately before (fasting plasma glucose) and 120 minutes after the glucose challenge (two hours post challenge glucose) along with fasting samples for serum urea and electrolytes, liver function, lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), and HbA1c. A number of biomarkers will also be measured including: tumor necrosis factor-α, interleukin-6, leptin, adiponectin, resistin, hs-CRP, and PAI-1. Insulin resistance will be measured using HOMA-IR. Levels of vitamin D and C will also be measured.
Results will be relayed via written correspondence and copied to participant and general practitioner. All biochemical measurements will be performed in-house at the University Hospitals of Leicester NHS Trust, UK. Glucose samples will be taken in fluoride oxalate test tubes and placed immediately in a portable 4 litre 4°C refrigerator. HbA1c% will be analysed by a DCCT aligned Biorad Variant HPLC II system (Bio-Rad laboratories, Hemel Hempstead, UK). The imprecision coefficient of variation of this machinery is <0.1%, and the reference intervals fit with national recommendations valid for carriers of variant Hb S, C and Q. Samples will be processed within a maximum of two hours, using an Abbott Aeroset clinical chemistry analyser (Abbott laboratories, Maidenhead, UK), which employs the hexokinase enzymatic method. This machinery has an imprecision coefficient of variation of 1.61%. Serum total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides will be measured by means of enzymatic techniques (Dade Behring Dimension analyser, Newark, USA). Plasma creatinine will be analysed with kinetic colorimetric methods. Plasma levels of urea and electrolytes, bilirubin, alanine aminotransferase, alkaline phosphatase and thyroid stimulating hormone will be analysed by means of the Dade Behring Dimension analyser.
Participants will be categorised according to World Health Organisation (WHO) criteria . Diabetes will be defined as a fasting blood glucose of greater or equal to 7 mmoll-1 and/or 2 hour plasma glucose of greater than or equal to 11.1 mmoll-1. Anyone who has an OGTT result in the diabetes range will be recalled as soon as possible for a second, confirmatory test for diabetes. Those found to have diabetes at baseline will discontinue the study and receive standard diabetes care from their general practitioner; those found to have diabetes during follow up will remain in the study (but not receive OGTTs, further follow up education or support phone calls) and again be referred to their general practitioner for their diabetes care. In this study IGR or ‘pre-diabetes’ will be defined as IFG and/or IGT. IFG will be defined as a fasting blood glucose concentration of between 6.1 and 6.9 mmoll-1 inclusive and IGT as a 2-hour blood glucose concentration of between 7.8 and 11 mmoll-1 inclusive.
Anthropometric measurements will be performed by trained staff using standard operating procedures. BMI will be calculated after the body weight (kg) and height (m) are measured, weight to be measured in light clothing without shoes to the nearest 0.5 kg. Waist circumference will be measured with a soft tape on standing participants, mid-way between the lowest rib and iliac crest to the nearest 0.1 cm. Hip circumference will be measured over the widest part of the gluteal region, and the waist-to-hip ratio calculated. Three blood pressure recordings will be obtained from the right arm of the patient in a sitting position after 3 minutes of rest, at 1 minute intervals, and then the mean value will be calculated of the second and third reading discounting the first. Seven day step count will be assessed by giving all participants a sealed piezoelectric pedometer (NL-800). Participants will be asked to wear the pedometer, fitted to their trunks (placed on right anterior axillary line) for seven consecutive days during waking hours. Participants will be provided with a stamped addressed envelope to return the pedometers to the study co-ordinators.
A trained nurse will collect data on previous and current medical history, medication and family history using a standard form. Self completed questionnaires will be used to assess smoking status, alcohol consumption, occupation, sleep habits and ethnicity. Social deprivation will be determined by assigning an Index of Multiple Deprivation (IMD) score to participant postcodes . IMD scores are publicly available continuous measures of compound social and material deprivation which are calculated using a variety of data including current income, employment, health, education, and housing.
The following validated questionnaires will also be collected
The Dietary Instrument for Nutrition Education or DINE food frequency questionnaire will be used to assess dietary fat and fibre intake 
The Health State Descriptive System to assess quality of life, known as 15D 
The Hospital Anxiety and Depression HADS – validated for depression and anxiety relating to diagnosis of condition and the care provided thereafter 
The Brief Illness Perception Questionnaire or BIPQ designed to quickly assess cognitive and emotional representations of illness 
The International Physical Activity Questionnaire (short form) (IPAQ) to obtain internationally comparable data on health–related physical activity 
Patients will also self-report on two questions concerning sleeping pattern (how many hours sleep did you get last night? And on average, how many hours do you sleep in 24 hours) .