Examining the Feasibility of Conducting a Randomised Control Trial to Evaluate the Effectiveness of a Focused 15-minute One-to-one Consultation to Improve Blood Glucose Control in Pre-diabetes
Phase: NA
Conditions: Pre-Diabetes
Sponsor: Aberystwyth University

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Title: Examining the feasibility of conducting a randomised control trial to evaluate the 
effectiveness of a focussed 15-minute one-to-one consultation to improve blood glucose control 
in pre-diabetes 
 
Research Reference Number (IRAS): 239910 
Protocol Version Number and Date: 02 27/02/2018  
Sponsor: Aberystwyth University    
 
Key trial contacts  
Chief Investigator 
Mr Nick Gregory (BSc, MPhil) 
Carwyn James Building 
Aberystwyth University 
SY23 3FD 
nig5@aber.ac.uk 
07825538040 
Academic Supervisors  
Dr Rhys Thatcher 
Carwyn James Building 
Aberystwyth University 
SY23 3FD 
ryt@aber.ac.uk 
01970 628630 
 
Dr Simon Payne 
Carwyn James Building 
Aberystwyth University 
SY23 3FD 
smp14@aber.ac.uk 
01970 628629 
Sponsor 
Mr Mitchell Parker 
Aberystwyth University 
SY23 3FL 
ethics@aber.ac.uk 
01970 621789 
Key Protocol Contributors 
Mr Sam Chapman  
Carwyn James Building 
Aberystwyth University 
SY23 3FD 
sac37@aber.ac.uk 
 
Dr Thomas Wilson 
Aberystwyth University 
SY23 3FL 

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tpw2@aber.ac.uk 
 
Dr Heather Cox 
Church Surgery 
Portland Street 
Aberystwyth 
Heather.Cox@wales.nhs.uk  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Protocol Contents  
 
Page: 
Abbreviations 
5 
Study Abstract 
6 
1. Study Flow Chart 
7 
2. Background and Rationale 
8 
3. Assessment and Management of Risk 
9 
4. Objectives and Outcome Measures 
11 
5. Study Design  
12 
6. Study Setting:  
12 
7. Participant Eligibility 
13 
8. Inclusion and Exclusion Criteria 
13 
9. Participant Identification and Recruitment 
13 
10. Screening 
14 
11. Study Payment 
14 
12. Consent 
14 
13. Study Procedures 
15 
14. Randomisation Procedure 
19 
15. Baseline Data 
20 
16. Clinical Study Assessments (Frequency and Duration)  
21 
17. Qualitative Assessments (Frequency and Duration)  
22 
18. Withdrawal Criteria  
23 
19. Storage and Analysis of Clinical Samples 
23 

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20. End of Trial  
23 
21. Statistics and Data Analysis 
24 
22. Sample Size Calculation 
24 
23. Planned Recruitment Rate 
24 
24. Data Management  
25 
25. Monitoring, Audit and Inspection   
26 
26. Ethical and Regulatory Considerations 
26 
27. Dissemination Policy 
26 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Abbreviations  
Glycated Haemoglobin 
HbA1c 
Body Mass Index 
BMI 
General Practitioner  
GP 
Wellbeing Assessment Research Unit  
WARU 
National Health Service  
NHS 
International Physical Activity Questionnaire  
IPAQ 
Intervention  
INT 
Control 
CON 
Institute of Biological, Environmental and Rural Sciences  
IBERS 
Flow Infusion Electrospray-High Resolution Mass Spectrometry  FIE-HRMS 
Flow Infusion Electrospray- Mass Spectrometry 
FIE-MS 
Gas Chromatography-Mass Spectrometry 
GC-MS 
Statistical Package for the Social Sciences  
SPSS 
Analysis of Variance  
ANOVA 
Principal Component Analysis  
PCA 
 
 
 
 
 
 
 
 
 
 

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Study Abstract  
This research will assess the feasibility of conducting a randomised control trial to evaluate the 
effectiveness of a 15-minute one-to-one consultation to improve blood glucose control in pre-
diabetes. The consultation will take the form of a 15-minute one-to-one consultation between a 
health-care practitioner and the patient in a primary care setting. Patients with a glycated 
haemoglobin (HbA1c) of between 42 and 47 mmol·mol-1 will be identified in general practise 
and will be eligible to participate. They will attend testing sessions at baseline (before the 
consultation), and at three months and six months post consultation. BMI, waist and hip girth, 
blood pressure and body composition will be recorded and blood analysed for HbA1c, 
cholesterol (total and HDL) and dietary components. For a three-week period following each 
visit, urine will be collected, a 5-ml sample on nine occasions, and physical activity will be 
recorded in a sub group of participants. Urine will be analysed by flow infusion electrospray 
mass spectrometry (FIE-MS) to determine the metabolic content, providing an indication of the 
diet over the three-week sampling period. The research objectives are to assess the effectiveness 
of recruitment strategy and willingness of patients to engage in, and adhere to, the research 
process; to determine the impact of consultation on health outcome measures, including HbA1c, 
and to establish participant and practitioner perspectives of the consultation. 

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1. Study Flow Chart 
 
 
 
 
 

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2. Background and Rationale 
Pre-diabetes is defined as a higher than normal blood glucose concentration and is associated 
with an increased risk of developing diabetes; of those identified as pre-diabetic 5 – 10% will 
develop diabetes within 12 months while a similar percentage will revert to normal blood glucose 
levels (Tabak et al., 2012). Furthermore, those with pre-diabetes are at an increased risk of 
developing a range of complications (e.g. Ford et al., 2010). It has been reported that the 
prevalence of pre-diabetes in England increased dramatically between 2003 and 2011, with the 
prevalence in those over the age of 16 years, increasing from 11.6% to 35.3% (Mainous et al., 
2014). If unchecked the increase in the diabetic and pre-diabetic populations will pose an 
unsustainable burden on the health care service. It is widely accepted that diet and physical 
activity play an important role in reducing the risk of developing diabetes. The Diabetes 
Prevention Program Research Group has shown that diabetes may be preventable by lifestyle 
intervention targeting diet and exercise (Knowler et al., 2002). Despite this, three in every four 
adults in the UK are not consuming the recommended five portions of fruit and vegetables per 
day and one in every three are not reaching the minimum recommendations for physical activity 
(Statistics on Obesity, Physical Activity and Diet, 2017), figures which go some way to explain 
the increase in prevalence of pre-diabetes. In 2015 a North Ceredigion GP Cluster initiated a pre-
diabetes intervention which targeted patient education and lifestyle modification (Thatcher & 
Gregory, 2017. Welsh Endocrine and Diabetes Society, Spring Meeting, Cardiff). The 
intervention comprised of a 30-minute one-to-one consultation with a practice nurse for those 
identified as having a glycated haemoglobin (HbA1c) of between 42 and 47 mmol·mol-1. The 30-
minute consultation included the collection of baseline data on diet and exercise and stressed the 
importance of avoiding developing diabetes and what steps could be taken to avoid this. The 
design did not include a control group, as such, direct comparisons with usual care cannot be 
made, however, twelve months post the consultation there were statistically significant 

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reductions in BMI, waist circumference and HbA1c. Of the 130 participants who had an HbA1c 
of between 42 and 47 mmol·mol-1 at the start of the study 79 remained in the pre-diabetic range 
while 44 fell below 42 mmol·mol-1, none progressed to >47 mmol·mol-1 and there were no 
follow up data for seven. The current proposal will develop the initial work done by the GP 
Cluster and inform the development of a randomised control trial. As the consultation will no 
longer involve collecting baseline data (see ‘Plan of investigation’) the time required has been 
reduced from 30 minutes to 15 minutes. Feedback from participants on the consultation will be 
used to inform the development of the consultation in relation to content and mode of delivery. 
 
3. Assessment and Management of Risk  
Blood Sampling:  
A 6 mL blood sample will be collected during each visit to the Well-being Assessment Research 
Unit (WARU). All blood samples will be collected within a Category 2 laboratory. Blood 
sampling carries a small risk of bruising or infection however members of the research team 
responsible for collecting blood samples are trained in venepuncture and have an abundance of 
previous venepuncture experience from previous research projects. Therefore with good practice, 
the risk is minimal. Blood samples will be labelled anonymously and stored appropriately.  
 
Randomisation:  
Participants will be randomised into either the 'Intervention' or 'No intervention' group following 
the baseline visit to WARU. Whilst half of the cohort will not receive the intervention, usual GP 
care will not be withheld at any point   
 
 

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Participant Burden:  
(A) Participation in the study will result in some additional burden to participant's daily lives 
although every effort has been made to keep this to a minimum. The research team will be as 
accommodating as possible when booking participants in for visits to the WARU.  
(B) The collection of urine in the home (for the purposes of dietary analysis) has been tested 
rigorously in previous studies by Aberystwyth University. Previous work has shown the urine 
collection and storage process to be acceptable, easily conducted and understandable by a cohort 
of 16 free living individuals. Participants are asked to collect 3 urine samples per week for 3 
weeks following each visit to the WARU. All samples are to be collected by participants the first 
time they urinate in the morning and therefore should not result in additional disruption to their 
day. The urine collection tubes will be coded anonymously with individual participant numbers 
and refrigerated by the participant in sealed containers until returned to the WARU by free post 
or in person depending on participant preference. In total, 27 urine samples will be collected 
across a period of 6 months.             
(C) A randomly allocated sub-group of participants will be asked to wear a physical activity 
monitor (ActiGraph) for one week following each visit to the WARU. The monitors can simply 
be worn around the waist like a belt and will not interfere with daily life when worn. Participants 
will be asked to wear the monitor throughout the day from the time they get out of bed until they 
return to bed. They do not need to wear the monitor whilst washing. Participants will be asked to 
record the times they do not wear the monitor during the day using a simple recording sheet 
provided by the research team. The ActiGraph can be returned to the WARU by free post or in 
person depending on participant preference.  
The research team will be available to assist participants via email, telephone or in person with 
queries relating to the dietary monitoring protocol and/or physical activity monitoring protocol.    

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Autonomy:  
Participants will be made aware at the outset of the study that their participation is voluntary and 
are free to withdraw at any time without giving prior notice or reason for withdrawal. Non 
participation in the study or withdrawing on-going participation from the study will not 
compromise any current or future care participants receive from the UK National Health Service 
or future involvement in studies conducted by Aberystwyth University.  
 
Confidentiality:  
Participating GP surgeries will only be informed of their patient's participation in the study 
following receipt of informed consent. All data storage and handling will follow the principles of 
good clinical practice. All human tissue samples will be labelled anonymously and stored in 
accordance with the Human Tissue Act (2004).     
      
4. Objectives and Outcome Measures  
Primary Objectives:  
The primary aim of the research is to assess the feasibility of conducting a randomised control 
trial to evaluate the effectiveness of a focused 15-minute one-to-one consultation in a primary 
care setting with a health-care professional to improve blood glucose control in pre-diabetes. 
The study aims to quantify the following:  
- the number of patients with an HbA1c between 42 and 47 mmolmol-1 during the recruitment 
phase  
- the percentage of patients eligible to participate who gave consent to be part of the study 
- the percentage of patients who completed baseline testing; 3 month; and 6 month testing 
 

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Secondary Objectives 
Secondary research questions aim to determine the impact of the consultation on the following 
measures at 3 and 6 months:  
HbA1c 
Cholesterol 
BMI 
Waist and hip girth 
Blood pressure 
Body composition 
Physical activity level  
Dietary habits 
 
5. Study Design  
This feasibility study will use a randomised control design to assess the effectiveness of a 15 
minute one to one consultation compared to no treatment.  
 
6. Study Setting:  
All research activity included in the baseline, 3 month and 6 month visits will be completed 
within the Carwyn James Building, Aberystwyth University. The 15 minute pre-diabetes 
consultations will take place within Church Surgery, Aberystwyth.  
  
 
 
 
 

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7. Participant Eligibility 
Participants will be eligible for participation if they are registered with Church Surgery and have 
an HbA1c (recorded within the last year) of between 42 and 47 mmol-1. 
 
8. Inclusion and Exclusion Criteria 
 
9. Participant Identification and Recruitment  
Patients registered with a mid-Wales general practice who are considered at risk of developing 
diabetes will be identified on surgery’s patient database systems based on a body mass index 
(BMI) > 25 kg/m2 or an existing glycated haemoglobin (HbA1c; recorded within the last 12 
months) of between  42 mmol·mol-1 and 47 mmol·mol-1. Database searches will be completed by 
trained surgery employees. Patients identified as being at risk of diabetes based on BMI (without 
a < 12 month HbA1c) will be invited by letter to their registered surgery to have their blood 
tested for HbA1c. Eligible patients, with HbA1c between 42 mmol·mol-1 and 47 mmol·mol-1, 
will be informed by their surgery via a second letter that they are at increased risk of diabetes and 
informed of the study. The letter will include key information relating to diabetes, steps that can 
Inclusion Criteria 
Exclusion Criteria 
Age > 18, < 80 
Under judicial control 
Able to provide consent 
Unable to understand and follow instructions 
due to cognition or language problems or 
provide consent 
Registered with a mid-Wales GP surgery 
 
 
HbA1c between 42 mmol·mol-1 and 47 
mmol·mol-1 
 

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be taken to avoid developing diabetes, information on the purpose and procedures of the research 
study and contact information for the research team. Patients wishing to confirm their interest in 
participating or to receive further information can do so via telephone, email or visiting the 
university research facility in person.  
 
10. Screening  
Potential participants will initially be screened on patient records to identify those with a body 
mass index (BMI) > 25 kg/m2 or an existing glycated haemoglobin (HbA1c; recorded within the 
last 12 months) of between 42 mmol·mol-1 and 47 mmol·mol-1. Screening will be completed by 
trained surgery employees. Patients identified as being at risk of diabetes based on BMI (without 
a < 12 month HbA1c) will be invited by letter to their registered surgery to have their blood 
tested for HbA1c. Patients contacted for screening who do not respond will not be contacted 
again. A record of contacts made is kept on the patient database.    
 
11. Study Payment  
Participants will not receive payment or expenses for participating in the study.  
 
12. Consent 
Further information regarding the study can be sought via telephone, email or visiting the 
university research facility in person. Any questions the participant may have can be asked at any 
point prior to giving consent using any of these methods. Patients are free to withhold consent 
without giving reason. In accordance with the Welsh Language Act 1993, all correspondence will 
be translated into Welsh.  For patients confirming their involvement, verbal and written informed 
consent will be sought in person at the start of their first visit to the Well-being Assessment 
Research Unit (WARU) before being inducted into the study (> 24 hours between receipt of the 

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study invite letter & participant information sheet and signing informed consent). Those who 
decline involvement will receive usual care from their GP.  
 
13. Study Procedures  
Participants will be required to visit the WARU (Carywn James Building, Penglais Campus, 
Aberystwyth University, SY23 3FD) on 3 separate occasions, for baseline, 3 month and 6 month 
testing. During the baseline visit, the procedures and protocol of the study will be explained and 
informed consent will be received. Participant’s height (Holtain Ltd, Crymych, UK) and body 
mass (wearing loose fitting clothing; Seca 899, Hamburg, Germany) will be collected to calculate 
body mass index (BMI) and waist and hip girth recorded (Seca 201, Seca Gmbh & Co, Hamburg, 
Germany). Next, participants will be asked to sit quietly for 10 minutes in the laboratory before 
blood pressure is recorded from the upper non-dominant arm (Omron M3, Omron Healthcare 
Ltd, Milton Keynes, UK). Participants will remain seated prior to a 6 mL blood sample being 
obtained from the antecubital vein and collected into a heparinised vacutainer (BD Vacutainer 
Systems, Plymouth, UK), with minimal stasis, using standard venepuncture methods performed 
by a trained member of the research team. Should patients HbA1c be outside the required values 
during the baseline visit, they will be informed and will take no further part in the research. 
WARU will inform the participant's GP if their HbA1c is indicative of diabetes. Body 
composition will be analysed using bioelectrical impedance (Bodystat 1500, Bodystat Ltd, 
Douglas, British Isles).  
 
 
 
 

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Upon completion of this phase of data collection, participants will be provided with a series of 
validated questionnaires to complete (to be completed at every visit unless otherwise stated). 
These include; the International Physical Activity Questionnaire- Short Form (IPAQ-SF), Food 
Frequency Questionnaire (FFQ; EPIC-Norfolk; baseline and 6 months), SF-36 (36-
Item Short Form Survey Instrument) and components of the Personal Diabetes Questionnaire 
(baseline). Participants will complete the questionnaires unassisted although members of the 
research team will be available to answer any questions the participant may have relating to the 
questionnaires. Lastly, participants will receive instructions on the use of the urine collection kit 
for dietary monitoring (see below) and the ActiGraph for physical activity monitoring (if 
randomised; see below). Participants will then be free to leave the laboratory. An additional 
acceptability questionnaire designed by the research team will be given to participants at the end 
of the 6 month visit and will include questions relating to the WARU visits, 15 minute 
consultation (if received), urine collection and ActiGraph use. Visits will last between 
approximately 120 minutes and 150 minutes depending on the time taken for participants to 
complete the relevant questionnaires.     
 
Following completion of the baseline visit, participants will be randomised into either the 
intervention group (INT) or the control group (CON). Randomisation will be achieved using a 
minimisation software package (Minim) and will ensure that there will be only minor differences 
between groups in the variables used in the allocation process. Participants in INT will receive a 
focussed 15 minute one to one consultation with a practice nurse at their registered general 
practice. The consultation derives from the original 30 minute protocol employed during a 
previous study conducted by the present research team (Thatcher and Gregory, 2017) which used 
104 GP-registered patients. The first half of the 30 minute consultation in that study (led by 
general practise) collected baseline data (height, weight, waist circumference, blood pressure) 

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and the second half provided patients with lifestyle advice on preventing diabetes. The 
consultation to be used in the proposed study does not require general practise to collect baseline 
data and therefore the consultation time has been reduced from 30 minute to 15 minutes. The 
consultation will provide the participant with one to one information regarding the benefits of 
physical activity and healthy eating. Emphasis will placed on the importance of achieving at least 
150 minutes of moderate physical activity each week as well as adhering to healthy dietary 
habits, based on the NHS Eatwell Guide (Eatwell Guide, 2016). Furthermore, participants will 
have the opportunity to discuss prediabetes with a trained practice nurse and ask any questions 
they may have. Participants placed in CON will not receive the consultation and will only attend 
visits to the WARU. Due to logistical and financial implications, a subgroup of participants will 
also be randomised for additional physical activity monitoring. 5 participants from INT and 5 
from CON will receive an Actigraph (see below for further information on the Actigraph).         
 
Dietary Monitoring:  
Metabolic fingerprinting and metabolic profiling of human urine is able to provide a 
comprehensive and quantitative snapshot of dietary exposure for 12 – 24 hrs prior to urine 
collection. While a single sample snapshot is not representative of an individuals' habitual dietary 
exposure, a series of snapshots over a prolonged time period can give a robust overview of an 
individual’s nutritional health. Previous work by IBERS has demonstrated a community based 
urine collection protocol (n = 16) as a successful and non-disruptive method for monitoring 
habitual diet. Participants will be provided with a urine collection kit consisting of; of 14 cm 
non-sterile urine collection straws 4 mL additive free evacuated vacutainer tubes and a125 mL 
collection container. Once urine has been collected, the sealed vacutainer tubes will be stored in 
an absorbent pouch within a sealed leak-proof bag and kept in the refrigerator. All urine storage 
equipment and instructions are fully compliant with the UN3373 standard for Category B 

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biological substances. Participants will receive instructions to fill the collection container with a 
mid-stream urine sample (in order to minimise the possibility of bacterial contamination from 
urethral contaminants; Gilbert, 2006). Any excess urine produced which is not collected in the 
container should be deposited within the lavatory. The tip of the transfer straw will be submerged 
into the urine and a 4mL vacutainer tube inserted into the transfer straw to draw the urine into the 
vacutainer. Any remaining urine in the container will be deposited within the lavatory. The 
collection container can be rinsed with tap water after each urine sample and reused for each 
sample collected. Vacutainer tubes will be labelled with anonymous information including 
participant number, sample number, weekday/weekend sample and week number. Samples will 
be stored in a refrigerator at 4ºC for a maximum of 10 days before the sample are returned to the 
lab either in person or by free post for freezing at -80ºC to await analysis.  Participants will 
record the collection details of their urine samples onto a sample collection sheet (see 
appendices) which notes the sample number and the date and time of collection. Participants will 
collect 3 samples a week for 3 weeks following each WARU visit. Participants must collect two 
urine samples within the week on non-consecutive days (e.g. Tuesday & Thursday) and collect a 
third sample on either day of the weekend (Saturday/Sunday). In total, participants will collect 27 
urine samples during their participation in the study. Urine samples will be analysed using 
laboratory based Flow Infusion High Resolution Mass Spectrometry (FIE-HRMS) which is an 
established method for dietary analysis using urine samples.   
 
Physical Activity Monitoring:    
Physical activity and sedentary lifestyle will be determined using ActiGraph (ActiGraph LLC, 
Pensacola, FL, USA) following baseline, 3 months and 6 month WARU visits. Participants will 
be provided with written and verbal instructions on how to operate the device. Participants will 
choose one week within the three week urine collection period to wear the ActiGraph. 

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Participants can choose any day within the week to begin wearing the ActiGraph but must then 
wear it for the following 7 days unless unfeasible to do so (e.g. swimming, bathing or 
showering). In this instance, participants will record at what time and the amount of time they are 
not wearing the ActiGraph. Should participants forget to wear the device; the same procedure 
will be followed.  Should participants miss a whole day; they must record for an extra day 
directly after the 7th day. An additional sheet will be provided for participants to record any time 
when the device is not worn. Participants do not need to wear the ActiGraph when sleeping 
although they must record the time they go to sleep and at what time they wake up. Participants 
must fit the ActiGraph in the morning as soon as it is feasible to do so. Participants can return the 
ActiGraph at the end of the 7 day recording period either in person or be post.       
 
14. Randomisation Procedure 
Randomisation will be achieved using a minimisation software package (Minim) and will ensure 
that there will be only minor differences between groups in the variables used in the allocation 
process. Participant details will be recorded after the first visit and inputted into the 
randomisation package. Following randomisation of the first participant, remaining participants 
will be randomly allocated into either the intervention or control based upon age (ages 60 + in 
both groups / equal distribution of sex and BMI 30 kg/m2 + in both groups). Randomisation will 
be conducted primarily by the academic supervisor. Church surgery will be informed of the 
patients who have been randomised to receive the intervention and referral arrangements made.    
 
 
 

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15. Baseline Data  
The data to be collected at baseline and in subsequent visits are directly related to pre-diabetes or 
to factors which contribute to diabetes risk (e.g. dietary habits and physical activity).  
 
-Blood test: (non-fasted) measure of glycated haemoglobin, cholesterol and metabolites 
indicative of dietary intake  
-Anthropometry: Measures body weight and size. Being overweight is a risk factor associated 
with diabetes 
-Blood pressure: cardiovascular health is detrimentally affected by poor lifestyle and diabetes 
risk 
-Body composition Provides an analysis of fat mass and percentage body fat  
-Urine collection: Allows for the accurate analysis of dietary behaviours 
-ActiGraph: Allows for the accurate recording of physical activity  
-Physical Activity Questionnaire: Provides a measure of physical activity levels  
-Food frequency questionnaire: Provides a measure of dietary habits  
-Health survey: Provides a indication of current perceived health status 
-Components of the Personal Diabetes Questionnaire: Provides a indication of an individual’s 
readiness to change their lifestyle behaviours following information regarding their diabetes risk   
 
  
 
 
 
 
 

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16. Clinical Study Assessments (Frequency and Duration)  
Procedure 
Frequency 
Duration 
Researcher  
Venous Blood sample for 
measure of HbA1c (if 
surgery does not have a value 
< 12 months) 
1 
10 minutes 
Performed by a practice nurse or 
GP at a mid-Wales General 
Practise 
Recording height and weight 
3 
5 minutes 
Nicholas Gregory or other 
member of the research team. 
This will take place in the 
Carwyn James Building at 
Aberystwyth University 
Recording waist and hip girth 3 
5 minutes 
Nicholas Gregory or other 
member of the research team. 
This will take place in the 
Carwyn James Building at 
Aberystwyth University 
Recording blood pressure 
3 
15 minutes 
Nicholas Gregory or other 
member of the research team. 
This will take place in the 
Carwyn James Building at 
Aberystwyth University 
 
Venous blood sample 
3 
10 minutes 
Nicholas Gregory or other 
member of the research team. 
This will take place in the 
Carwyn James Building at 
Aberystwyth University 
Body composition analysis  
3 
10 minutes 
Nicholas Gregory or other 
member of the research team. 
This will take place in the 
Carwyn James Building at 
Aberystwyth University 
Provision of urine sample for 
dietary analysis 
27 
5 minutes 
Performed by the participant 3 x 
per week for 3 weeks after each 
WARU visit. Samples collected 
at home. 
Actigraph (if randomised to 
receive) 
3 
7 days  
Performed by the participant. 
Actigraph worn by the subject 
around the waist during waking 
hours. Worn for one week 
(within each 3 week urine 
sampling phase) after each 

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WARU visit 
 
17. Qualitative Assessments (Frequency and Duration)  
Procedure 
Frequency 
Duration 
Researcher  
Providing information prior 
to gaining informed consent 
1 
30 minutes 
Nicholas Gregory or other 
member of the research team. 
This will take place in the 
Carwyn James Building at 
Aberystwyth University 
Administration of the 
International Physical 
Activity Questionnaire Short 
Form 
3 
10 minutes 
Nicholas Gregory or other 
member of the research team. 
This will take place in the 
Carwyn James Building at 
Aberystwyth University 
Administration of the Food 
Frequency Questionnaire 
2 
15 minutes 
Nicholas Gregory or other 
member of the research team. 
This will take place in the 
Carwyn James Building at 
Aberystwyth University 
 
36-Item Short Form Health 
Survey Instrument 
3 
10 minutes 
Nicholas Gregory or other 
member of the research team. 
This will take place in the 
Carwyn James Building at 
Aberystwyth University 
Components of the Personal 
Diabetes Questionnaire 
1 
10 minutes 
Nicholas Gregory or other 
member of the research team. 
This will take place in the 
Carwyn James Building at 
Aberystwyth University 
15 minutes pre-diabetes 
consultation (if randomised 
to receive) 
1 
15 minutes 
Performed by a practice nurse at 
a mid-Wales General Practise 
End of Study Feedback 
questionnaire 
1 
10 minutes 
Nicholas Gregory or other 
member of the research team. 
This will take place in the 
Carwyn James Building at 
Aberystwyth University 
 
 

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18. Withdrawal Criteria  
Participants are free to withdraw from the study at any time without giving prior warning or 
reason for withdrawal. Participants will not be replaced if withdrawn. Recruitment will continue 
for the first 6 months of the study. New participants will receive unique individual participant 
numbers.  
 
19. Storage and Analysis of Clinical Samples  
Blood Treatment:  
A 1 mL aliquot of whole blood will be transferred from the heparinised vacutainer into a 1.5 mL 
Eppendorf. The remaining whole blood will be centrifuged at 1500 g for 10 minutes at 4˚C. The 
separated plasma will be pipetted evenly into two separate eppendorfs and frozen at -80˚C for 
subsequent analysis of metabolic content using FIE-MS and GC-MS. Two 1.5 µL aliquots of 
whole blood will be transferred from the 1.mL aliquot into separate test cartridges and will be 
analysed for HbA1c and lipid profile by an automated point of care blood analyser (Afinion 2, 
Abbot, Cheshire, UK).  
 
Urine Treatment:  
Urine samples will be centrifuged at 1500 g for 10 minutes at 4˚C. 1ml of supernatant will be 
pipetted evenly into two separate eppendorfs and frozen at -80˚C prior to analysis of metabolic 
content using FIE-MS and GC-MS.  
 
20. End of Trial  
The testing stage of this study will be defined as finished when the last participant completes the 
final visit (6 month testing). Additionally, the research will be stopped if there is a lack of 

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recruitment after 6 months or if a clinical or research incident prompts a review.    
 
21. Statistics and Data Analysis 
A computerized statistical package will be used to analyse all data associated with the primary 
and secondary outcomes (SPSS version 17.0, SPSS inc., Chicago, IL). Normally distributed data 
will be presented as mean ± SD. Scores from the questionnaires will be calculated based upon 
their respective scoring protocols. A two factor mixed model ANOVA will be conducted on all 
physiological measures and questionnaire responses to determine any differences between groups 
over time. Significant differences identified by the ANOVA will be further analysed by post hoc 
independent or paired t-tests with Bonferroni correction. Data mining of urine samples using 
methods such as PCA will be employed to determine if foods can be discriminated. Statistical 
significance will be accepted at P < 0.05.   
 
22. Sample Size Calculation  
The sample size was decided based upon potential numbers of eligible patients provided to the 
research team by the participating general practice. Potential numbers are based upon the amount 
of registered patients with a BMI > 25 kg/m2 or an existing HbA1c < 12 months. As this is a 
feasibility study for a future large scale randomised control trial, no formal sample size 
calculation has been employed. 
 
23. Planned Recruitment Rate  
Previous work completed by the research team demonstrated an approximate 50% uptake in 
consultation offers in patients with pre-diabetes (n = 420). Our partnering surgery currently have 
737 patients with a BMI >25 kg/m2. A further 216 patients have an HbA1c (recorded within the 
last year) within the eligible range. Furthermore, Church surgery identifies approximately 6 new 

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‘at risk’ individuals each week. Therefore, we estimate it will take one month to recruit 40 
patients into the study.    
 
24. Data Management  
All electronic data will be stored on a password protected computer housed within the office of 
the chief researcher.  Manual files will be kept locked within a filing cabinet within the office of 
the chief investigator. The office will remain locked when the chief investigator is not present. 
The chief investigator and their supervisor will be the only individuals who have direct access to 
the office where the data is stored.  Data will be published in an anonymous form. All data 
handled during the study will be identified by a numeric code assigned to each participant upon 
entry to the study. Aberystwyth University operates its own confidentiality policy which all staff 
and postgraduate students are trained in. The chief investigator educational supervisor and MRes 
student will have access to participants’ name, contact details, and some additional personal 
information (e.g. age, identifying gender). The chief investigator will be responsible for 
communication between the participant and the research team. Participants will consent to the 
storage of their personal data when signing the informed consent form.    
 
Data will be retained for 7 years following completion of the study. Anonymised data will be 
stored on a password protected computer accessible only to chief investigator and educational 
supervisor. After 7 years, the data will be deleted off of the computer hard drive. Paper based 
materials will be kept within locked filing cabinets within the Carwyn James Building and then 
destroyed via confidential waste processes according to Aberystwyth University's Data 
Protection policy.   
 
 

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25. Monitoring, Audit and Inspection  
The research will be monitored within the Institute of Biological, Environmental and Rural 
Sciences (IBERS). Regular meetings between the chief investigator (Nicholas Gregory), 
educational supervisors (Dr Rhys Thatcher and Dr Simon Payne), MRes student (Sam Chapman) 
and collaborators (Dr Heather Cox and Dr Thomas Wilson) will ensure academic progress and 
rigour. Additional post-graduate monitoring is conducted regularly within Aberystwyth 
University by academic individuals outside of the research team. Health and Safety is overseen in 
IBERS by Health and Safety officers. Furthermore, regular meetings between the chief 
investigator, educational supervisors, MRes student and collaborators will take place every 3 
months and additionally when necessary to discuss any issues that may arise and to monitor 
progress.    
 
26. Ethical and Regulatory Considerations  
The study will be subject to ethical review by Aberystwyth University Research Ethics System 
and by an NHS Research Ethics committee. The study will not commence until approvals have 
been granted.  Data generated by the study will be stored and protected in accordance with the 
Data Protection Act 1998 and the study conducted in accordance with the Declaration of Helsinki 
2013.  
 
27. Dissemination Policy 
Participants will be informed of the results in the form of a summary report at the end of the 
study, upon request, written in a lay person format. Participants will be informed if the research 
progresses to publication. The research team will aim to publish the findings of the research in 
scientific journals and present at relevant conferences. An overview of the results will also be 
published on university and departmental websites.