The Use of Soluble Fibre for the Prevention of Gestational Diabetes Among High-risk Women. A Pilot Study.
Phase: NA
Conditions: Gestational Diabetes
Sponsor: Imperial College London

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Version 6 – 02/03/18  
IRAS ID: 230813 
  
 
 
 
 
 
PROTOCOL 
 
 
 
 
 
 
EFFECT OF FIBRE SUPPLEMENTS ON GESTATIONAL DIABETES 
 
 
 
 
 
 
The use of soluble fibre for the prevention of gestational diabetes among high-risk women. A pilot 
study. 
 
 
 
 
 
 
 
 

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Main Sponsor   
 
Imperial College London 
Funders 
 
 
Department of Investigative Medicine, Imperial College  
 
Protocol authorised by 
 
 
 
 
 
 
 
Professor Gary Frost, 
Professor of Nutrition and Dietetics, 
Department of Investigative Medicine, 
Hammersmith Hospital Campus, Imperial College, 
6th Floor, Commonwealth Building, 
Du Cane Road, London, 
W12 0NN 
 
 
Professor Anne Dornhorst, 
Professor of Endocrinology and Diabetes, 
Department of Investigative Medicine, 
Hammersmith Hospital Campus, Imperial College, 
6th Floor, Commonwealth Building, 
Du Cane Road, London, 
W12 0NN 
 
 
Dr. Lilian Mendoza Mathison, 
Clinical Research Physician, 
Department of Investigative Medicine, 
Hammersmith Hospital Campus, Imperial College, 
6th Floor, Commonwealth Building, 
Du Cane Road, London, 
W12 0NN 
 

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Effect of Fibre Supplements on Gestational Diabetes 
 
Long title 
The use of soluble fibre for the prevention of gestational diabetes among high-risk women. A pilot 
study 
 
Study Management Group 
 
Chief Investigator 
Professor Gary Frost 
Co-investigators 
Professor Anne Dornhorst, Dr. Lilian Mendoza Mathison   
Study Management 
 
 
Sponsor 
Imperial College is the main research sponsor for this study. For further information regarding the 
sponsorship conditions, please contact the Research Governance Manager at: 
 
Room 215 
Level 2, Medical School Building 
Norfolk Place 
London 
W2 1PG 
http://www.imperial.ac.uk/joint-research-compliance-office/  
Clinical Queries 
 
Clinical queries should be directed to Gary Frost who will direct the query to the appropriate person. 
 
PROBLEMS RELATED TO THIS TRIAL SHOULD BE REFERRED TO PROFESSOR GARY FROST 
g.frost@imperial.ac.uk 
 
 
 

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Table of Contents 
 
1. GLOSSARY OF ABBREVIATIONS 
2. KEYWORDS 
3. STUDY SUMMARY 
4. INTRODUCTION 
5. RANDOMISED CONTROLLED STUDY 
6. ASSESSMENTS AND FOLLOW-UP 
7. PARTICIPANT ENTRY 
PRE-RANDOMISATION EVALUATIONS 
INCLUSION CRITERIA 
EXCLUSION CRITERIA 
WITHDRAWAL CRITERIA 
8. PHARMACOVIGILANCE 
DEFINITIONS 
REPORTING PROCEDURES 
9. STATISTICS AND DATA ANALYSIS 
10. REGULATORY ISSUES 
11. STUDY MANAGEMENT 
12. PUBLICATION POLICY 
13. REFERENCES 
 
 

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1. GLOSSARY OF ABBREVIATIONS 
 
GDM 
Gestational diabetes mellitus 
BMI 
Body mass index 
GI 
Glycaemic index 
T2DM 
Type 2 diabetes mellitus 
OGTT 
Oral glucose tolerance test 
FPG 
Fasting plasma glucose 
IS 
Insulin sensitivity 
UCPCR 
Urinary C-peptide creatinine ratio 
PCOS 
Polycystic ovarian syndrome 
GAD 
Glutamic Acid Decarboxylase 
 
 
2. KEYWORDS 
 
Gestational diabetes mellitus 
Risk factors 
Diet 
Soluble fibre 
Insulin sensitivity 
Insulin secretion 
Insulin treatment 
 
 
 

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1. STUDY SUMMARY 
 
TITLE 
The use of soluble fibre for the prevention of gestational diabetes among high-risk women. A 
pilot study. 
 
AIMS 
The primary aim of this study is to evaluate the effect of a soluble fibre supplement in the 
development of gestational diabetes in women at high-risk. The secondary aim will to evaluate the 
effect of the soluble fibre supplement on glycaemic control in high-risk women who develop 
gestational diabetes in early pregnancy. 
 
DESIGN We plan to conduct a randomised single-blinded controlled study to evaluate the effect of 
the consumption of soluble fibre, from early to mid-pregnancy, on the incidence of gestational 
diabetes, insulin sensitivity, insulin secretion and metabolic control in GDM diagnosed participants. 
 
POPULATION We will be studying women with diagnosis of gestational diabetes in previous 
pregnancies, (considered as high-risk) aged >18 years. 
 
ELIGIBILITY 
Women over 18 years old with a history of gestational diabetes in previous 
pregnancies will be eligible to apply to this study. After first assessment, eligible women will be split 
according to their glycaemic status in women with and without early gestational diabetes. 
 
TREATMENT 
Participants in the treatment arms will be taking 5 gr of Guar gum fibre supplement 
with meals three times a day (total daily 15 g). Participants in the placebo arms will be taking 5 gr of 
Cellulose three times a day (total daily dose 15 g). 
 
 
 
DURATION 
Participants will be involved for 12 weeks.  
 
 
 
OUTCOME MEASURES 
In women with normal glucose tolerance at first assessment: 
Primary outcome: Gestational diabetes (yes/no) at 28 weeks gestation. 
Secondary outcomes: Insulin sensitivity and insulin secretion at 28 weeks gestation. 
In women with early gestational diabetes (diagnosed at first assessment): 
Primary outcome: Glycaemic control assessed the need of insulin treatment (yes/no) 
Secondary outcomes: In women requiring insulin treatment: days-to-insulin and total daily insulin 
dose. 

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INTRODUCTION 
 
GESTATIONAL DIABETES 
Gestational diabetes (GDM), currently define as diabetes diagnosed in the second or third trimester 
of pregnancy that is not clearly overt diabetes (1), has been associated with an increased risk 
macrosomia and other perinatal complications as well as a higher risk for offspring to develop 
obesity and type 2 diabetes later in life (2). As for the mothers, women with GDM have a 
significantly increased risk of developing T2DM in the following years (3). According to the 2015 NICE 
guidelines for diabetes in pregnancy, approximately 5% of the women given birth in the UK each 
year have either pre-existing or gestational diabetes. Gestational diabetes accounts for most of the 
cases of diabetes during pregnancy (87.5%) (4) and its prevalence seems to be on the rise. Previous 
GDM is a well-established risk factor for developing GDM in subsequent pregnancies, with a 
recurrence rate of over 40% (5,6). It has been described that women with a history of GDM within 
the previous 5 years have poorer beta cell compensation and show a faster decline in insulin 
sensitivity compared to their counterparts without GDM (7). In the UK women with previous GDM 
should be offered early testing in new pregnancies, either by continuous glucose monitoring or by an 
oral glucose tolerance test (OGTT) before 16 weeks gestation (4). 
 
GLYCAEMIC INDEX AND HIGH-FIBRE DIET 
Glycaemic index is a measure of the impact of carbohydrate-containing foods on post-prandial 
glycaemic excursions. Both epidemiological and clinical trial evidence supports the beneficial effects 
of low glycaemic index (GI) diets on glucose homeostasis.  Diets that are constructed of low 
glycaemic index foods with a high dietary fibre content may provide additional metabolic benefits 
than low glycaemic index diets with a low fibre content.  Soluble viscous (gel forming) fibres such as 
Guar gum, have shown to improve glycaemic control. The consumption of Guar gum before meals 
has shown to lower postprandial glycaemia in both healthy and diabetic subjects (5-7). As for the 
long term effects, the consumption of Guar gum supplement showed a decreased in fasting plasma 
glucose, HbA1c, fasting plasma insulin and HOMA-IR in subjects with metabolic syndrome after 6 
months (8) and in patients with type 2 diabetes, 15 gr of Guar gum supplement consumed daily for 
48 weeks showed an improvement in postprandial glucose, long-term glycaemic control and C-
peptide response after a test meal (9). 
The beneficial effects of Guar gum on glycaemic control can possibly be explained through various 
mechanisms. Firstly, the impact on glycaemic control over the first two hours after consumption of 
food that possibly relates to the impact of soluble viscous fibres on delaying gastric emptying and 
slowing the digestion of carbohydrate in the small intestine. There is an additional benefit as Guar 
gum is fermented by the colonic microbiota to short-chain fatty acids which are recently been shown 
to have important benefits on beta-cell function presumably by stimulating the production of GLP1 
(10). 
 
THE ROLE OF HIGH-FIBRE DIETS IN THE PREVENTION AND TREATMENT OF GESTATIONAL DIABETES 
In pregnancy, a high dietary fibre intake has been associated with a lower risk of GDM (11), and in 
healthy pregnant women, a low GI diet has been associated with lower birth weight and a lower 

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percentage of large for gestational age newborns (12). As for women who develop GDM, high-fibre 
diets have been associated with an improvement in perinatal outcomes such as macrosomia (12–14) 
and risk of C-section (13). In this group of women, high-fibre diets have also to significantly reduce 
the need to commence insulin treatment (13–15). Despite the documented benefits of a high-fibre 
diet, as women progress through pregnancy there are often changes in food perception and 
acceptability which makes compliance to specific diets often difficult. A dietary supplement that can 
be consumed with meals could be an attractive alternative for complying with the recommended 
dietary fibre requirements.   In pregnancy, Guar gum has shown to reduce postprandial glycaemia 
after an OGTT (16) and in one study, long term consumption of 10 gr a day showed to decrease both 
fasting and postprandial glycaemia (17). Therefore, it could be considered in the treatment of 
women with gestational or who are at high risk of developing the condition. 
 
 

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5.  
RANDOMISED CONTROLLED STUDY  
 
Aim:  To evaluate the effect of a soluble fibre supplement in glucose metabolism in pregnant women 
at high risk of developing gestational diabetes. 
 
Study methodology:  12 week randomised, placebo-controlled, single-blinded study.  
 
Intervention:  Women will first be categorised according to their glycaemic status into two groups: 
GDM and glucose tolerant women. Afterwards, each group will be randomised into two groups and 
given either 
1) Fibre supplement (Guar gum) 
2) Placebo (Cellulose) 
The participants will take the dietary supplement three times a day for 12 weeks. They will receive 
regular antenatal control according to NICE guidelines recommendations. Compliance will be 
addressed by weekly phone calls. 
 
Number of volunteers:  The number of participants will be arbitrarily define as no data of this type 
of intervention exists in this cohort. 40 participants will be recruited. Previous studies, outside 
pregnancy, have observed metabolic effects in samples of 15-40 subjects. 
 
Recruitment: Women will be recruited in the antenatal clinic at Queen Charlotte and Chelsea’s 
Hospital. An information sheet will be provided to eligible women in the first antenatal visit to 
explain the purposes of the study. Women who decide to take part will be asked to sign a consent 
form. 
 
Randomisation: Initially women will be categorised according to glycaemic status in two cohorts: 
Glucose tolerant and Early gestational diabetes (GDM) cohort. Each of the two cohorts will then be 
independently randomised to either intervention or standard care using the sealed envelope 
website. Guar gum (intervention) and cellulose (placebo) will be provided in identical packed 
sachets. 
 
STUDY OUTCOME MEASURES 
 
PRIMARY OUTCOME MEASURES 
 

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• 
Glucose values at 0 and 120 minutes during an OGTT performed at 28 weeks in the 
glucose tolerant group. 
• 
Glycaemic control assessed by need of insulin treatment (yes/no), days to insulin 
treatment and total insulin dose. 
SECONDARY OUTCOME MEASURES 
 
Assessing insulin sensitivity and insulin secretion at 28 weeks of pregnancy in the glucose tolerant 
cohort of women through validated indices using glucose and insulin (or C-peptide) values derived 
from the OGTT. 
• 
Insulin sensitivity will be assessed using the Matsuda formula (18). 
• 
Insulin secretion will be assessed by second-void fasting UCPCR as described by 
McDonald et al (19). 
In the gestational diabetes cohort, where a second OGTT will not be performed, parameters of 
insulin resistance (HOMA_IR index) and secretion could be assessed using urinary C-peptide 
obtained from a fasting second-void urine sample at 28 weeks gestation, as described by Oram (20), 
although these measurements have not been validated in pregnancy.  
 
6. ASSESSMENT AND FOLLOW UP 
Women will be assess by the researchers at four different visits. At the first antenatal visit, the 
general care team will mentioned the study, if the patient consents, she will then be approached by 
the researchers to explain the study protocol. At the second visit, when the OGTT is performed, 
women who decided to take part in the study will sign the consent from. At the next antenatal visit 
where results from the OGTT are explained, women included will be randomised. The last research 
visit will take place at 28 weeks gestation. Additionally, they will be contacted weekly, by telephone 
to assess compliance and confirm willingness to participate in the study. All participating women will 
continue to attend routine follow up by the Obstetrics team at the antenatal clinic. Women 
diagnosed with GDM in early pregnancy will continue their routine care under the Obstetric team at 
Queen Charlotte’s Hospital. We will be collecting information regarding treatment from the notes 
taken at this follow-up visits. 
 
1st visit (≤16 weeks gestation) 
Women with a previous history of GDM will be considered at high risk of recurrence and will be 
referred to the antenatal clinic before 16 weeks of pregnancy. At this first visit, the direct care team 
will inform them about the study and ask them if they are willing to speak with a member of the 
research team. If they agree, a research team member will explain the protocol and invite them to 
participate in the study. An information sheet will be provided and women will have time to consider 
if they are willing to participate and inform the research team at their next antenatal visit. 
 
2nd visit 

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Women who decide to participate will inform the research team when they attend their second 
antenatal visit, when an OGTT is to be performed. In this visit, women willing to participate will be 
asked to sign a consent form. 
As part of the standard pregnancy care, these women will be booked for GDM early screening. The 
following investigations will be performed as part of their usual NHS care: 
• 
Blood tests: full blood count, renal function. GAD antibodies can be requested in women in 
whom type 1 diabetes is suspected. 
• 
Urine sample to test for proteinuria, glycosuria, leucocytes and nitrates.  
• 
Women willing to participate in the study will be additionally requested to provide a second 
urine sample after the 120 min during the OGTT. When bloods are taken will also request 
HbA1c as part of the study’s investigations. 
• 
An OGTT to test for early GDM will be performed as part of routine care. During the OGTT 
blood samples are taken at 0 and 120 minutes. Additionally to glucose, which is normally 
measure during the OGTT, for study purposes we will request serum C-peptide at these time 
points. 
Baseline insulin sensitivity and insulin secretion will be estimated through validated indices using 
serum glucose, insulin (or C-peptide) and urinary C-peptide. 
After the participants have agreed to take part in the study and consent has been signed, data 
regarding anthropometrics, demographics and medical history will be collected. This information will 
be obtained by reviewing the participant’s medical notes. 
Anthropometric measurements will be recorded at the first antenatal routine visit, including: pre-
pregnancy weight, weight at first visit and height. BMI will be calculated with this data.  
Demographics, personal and medical history will be extracted from medical records, including: 
maternal age, ethnicity, education, smoking during pregnancy, medical history (hypertension, PCOS, 
other relevant condition), obstetric history (parity, stillbirth, macrosomia, pre-eclampsia). 
 
 3rd visit (Randomisation) 
After obtaining the results from the OGTT, women will be categorised by their glycaemic status and 
divided into two independent cohorts: 
• 
Women diagnosed with gestational diabetes (according to NICE guidelines 2015 diagnostic 
criteria): early GDM cohort 
• 
Women with normal glucose tolerance or impaired glucose tolerance but not fulfilling GDM 
criteria: Glucose tolerant cohort. 
Women from each cohort will be randomised into two groups after the results of the OGTT are 
obtained: 
• 
Intervention group: Guar gum fibre supplement 
• 
Placebo group: Cellulose supplement 

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Women will the fibre supplement 3 times a day (with each main meal) until the 28th week of 
pregnancy when they will be re-evaluated. 
 
 
 
4rd visit (28th weeks gestation) 
Glycaemic status will be assessed at 28 weeks gestation in the two cohorts of women participating in 
the study: 
• 
Women from the Glucose tolerant cohort will undergo a second OGTT. Blood and urine 
samples will be collected at 0 and 120 minutes. Glycaemic status will then be assessed with 
the endpoint being the diagnosis of GDM (yes/no). Insulin sensitivity and insulin secretion 
will be estimated using the same parameters as in the first visit. As part of the study, women 
will be weight to calculate BMI and gestational weight gain at 28 weeks gestation. The 
research team will have their last face to face visit with the participant to discontinue the 
intervention and answer any potential questions about the study. 
 
• 
In women in the Early GDM cohort, glycaemic control will be assessed by the need of insulin 
treatment (yes/no) and in those requiring insulin the days-to-treatment (insulin) and total 
insulin dose will be recorded. Data will be obtained by reviewing medical records. As part of 
the study, women will be weight to calculate BMI and gestational weight gain at 28 weeks 
gestation. The research team will have their last face to face visit with the participant to 
discontinue the intervention and answer any potential questions about the study. 
 
PROCEDURES 
Women will be advised to fast for 10 hours the night before the oral glucose tolerance test. They will 
also be advised no to restrict carbohydrate ingestion the three days prior to the OGTT. At the 
antenatal clinic, blood samples will be collected at baseline (0 min) and at 120 min after the 
administration of an oral load of 75 g of glucose.  
 
Eligible 
women 
 
 
Guar 
gumsupplement 
 
Placebo 
  
 
Guar 
gumsupplement 
Placebo 
OGTT 
Randomisation 
 
Glucose tolerant 
Early GDM 

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In the baseline sample other parameters will also be determined. Creatinine and HbA1c will measure 
in all participants and GAD antibodies will be requested in women in whom type 1 diabetes is 
suspected.  
Serum insulin and C-peptide will be collected at 0 and 120 min during the OGTT.  
Women will be advised to void their first urine before attending the antenatal clinic. Second-void 
fasting urine sample will be collected at 0 min during the OGTT. A second urine sample will be 
collected at 120 min. Urinary C-peptide will measure in these samples will be transfer to boric acid 
containers, the alliquoted into 1 ml cryotubes ans stored at -80 ºC until analysis. Serum creatinine 
will be collected at baseline (0 min) and measure in the central lab. The urinary C-peptide creatinine 
ratio (UCPCR) will be calculated using these data.  
 
ASSESSMENTS 
 
(i) 
Gestational diabetes 
Gestational diabetes will be diagnosed if fasting plasma glucose >5.6 mmol/L and/or 120 min plasma 
glucose >7.8 mmol/L after the glucose load administered in the OGTT. Women with fasting plasma 
glucose <5.6 mmol/L and 120 min plasma glucose <7.8 mmol/L will be classified as “Glucose 
tolerant”. 
 
(ii) 
Insulin sensitivity 
Insulin sensitivity will be assessed using the Matsuda index as originally described (18) (Equation 1) 
and using two modified Matsuda equations in which insulin is substitute by either serum or urinary 
C-peptide (21,22) (Equations 2 and 3). 
Equation 1. 
ISOGTT= 10,000 / √ {[FPG x fasting insulin] x [mean glucose x mean insulin during OGTT]} 
Equation 2. 
ISOGTTC-pep=500,000/√{[FPGxFsC-pep] x [mean glucose x mean sC-pep during the OGTT]} 
Equation 3. 
ISOGTT-UCPCR=500,000/√{[FPG×FUCPCR pmol/mmol] x [mean glucose x mean UCPCR during the OGTT]} 
 
(iii) 
Insulin secretion 
* FPG= fasting plasma glucose. FsC= fasting serum C-peptide. FUCPCR= fasting urinary C-peptide 
creatinine ratio. 

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Insulin secretion will be estimated by the UCPCR obtained using the fasting second-void urine 
sample, as it is strongly correlated with serum insulin, serum C-peptide (19) and 24-h urinary C-
peptide (20). 
Insulin response will be estimated using the UCPCR calculated with 120 min post-OGTT urine sample, 
as it is strongly correlated with the C-peptide and insulin area under the curve (19). 
 
(iv) 
Need of insulin treatment, Days to insulin treatment and Total insulin dose 
Medical records of women in the Early GDM cohort will be review in order to determine the need of 
insulin treatment (yes/no) at 28 weeks gestation. In women requiring insulin treatment at any time 
during follow up, days-to-insulin treatment, calculated from randomisation day to the day insulin 
treatment is prescribed, and total insulin dose, calculated as the total dose of insulin international 
units (IU) divided by weight in Kg (insulin UI/Kg), will be recorded 
 
 

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Timeline for randomised controlled study 
 
 
 
 
 
 
Visit 1 (<16 weeks gestation) – Eligibility assessment 
•
First approach to explain the study protocol 
•
Check for eligibility 
 
 
 
Visit 4 (28 weeks gestation) - Glucose tolerance/metabolic control assessment 
•
In the Glucose tolerant cohort:  
o
Blood tests 
o
OGTT 
o
Urine samples at 0 and 120 min  
•
In the Early GDM cohort: Medical review to assess: 
o
 Need for insulin treatment, and if yes, 
▪
Days to insulin treatment  
▪
Total insulin dose. 
Visit 3 – Randomisation 
• 
According to glucose tolerance status 2 cohorts will be defined 
o 
Glucose tolerant cohort – Randomisation – Fibre supplement vs placebo group 
o 
Early GDM cohort – Randomisation – Fibre supplement vs placebo group 
Visit 2– OGTT and recruitment 
• 
Consent signing 
• 
Blood tests, samples at 0 and 120 min 
• 
Urine sample at 0 and 120 min 
• 
Anthropometrics, demographics and past medical history will be collected from 
medical notes 

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7.  
PARTICIPANT ENTRY 
 
PRE-RANDOMISATION EVALUATIONS 
Women will be evaluated by the mid-wife at the first visit in the antenatal clinic. An OGTT will be 
book to test for early GDM in women with previous GDM considered at high risk of recurrence. 
Personal and medical history will be recorded. When women attend for the OGTT, blood and urine 
samples will be collected at 0 and 120 minutes. 
 
INCLUSION CRITERIA 
• 
Women with a history of GDM in previous pregnancies  
• 
Age ≥ 18 years 
• 
Singleton pregnancy 
• 
≤ 16 weeks gestation 
 
EXCLUSION CRITERIA  
• 
Women unable or unwilling to give consent 
• 
Pre-gestational diabetes or use of anti-diabetic medication in the first visit 
• 
Significant chronic medical conditions (cardiovascular, liver or kidney disease) 
• 
Women participating in other medical trial  
• 
Women who have undergone bariatric surgery 
• 
Women with milk allergy/intolerance 
• 
Women unable to speak/understand English 
 
 
WITHDRAWAL CRITERIA 
Participants will be free to withdraw at any time and are not required to give a reason. 
 
8.  
ADVERSE EVENTS 
Adverse Event (AE): Any untoward medical occurrence in a patient or clinical study subject. 
 

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Serious Adverse Event (SAE): Any untoward and unexpected medical occurrence that: results in 
death, is life- threatening, requires hospitalisation, results in persistent or significant disability or 
incapacity or a congenital abnormality or birth defect 
 
Medical judgement should be exercised in deciding whether an AE is serious in other situations. 
Important AEs that are not immediately life threatening or do not result in death or hospitalisation 
but may jeopardise the subject or may require intervention to prevent one of the other outcomes 
listed in the definition above, should also be considered serious. 
 
REPORTING PROCEDURES 
All adverse events should be reported. Depending on the nature of the event the reporting 
procedures below should be followed. Any questions concerning adverse event reporting should be 
directed to the Chief Investigator in the first instance. 
 
Non serious AEs 
All such events, whether expected or not, should be recorded. 
 
Serious AEs 
An SAE form should be completed and faxed to the Chief Investigator within 24 hours. However, 
relapse, death and hospitalisations for elective treatment of a pre-existing condition do not need 
reporting as SAEs. All SAEs should be reported to the sponsor.  
All SAEs should be reported to the Bromley Research Ethics Committee where in the opinion of the 
Chief Investigator the event was: 
‘Related’, i.e. resulted from the administration of any of the research procedures; and 
‘Unexpected’, i.e. an event that is not listed in the protocol as an expected occurrence. 
Reports of related and unexpected SAEs should be submitted within 15 days of the Chief Investigator 
becoming aware of the event, using the NRES SAE form for non-IMP studies. 
Local investigators should report any SAEs as required by their Local Research Ethics Committee 
and/ or Research and Development Office. 
 
9.  
STATISTICS AND DATA ANALYSIS 
Data handling and analysis will be carried out by SPSS version 20.0 version. 
No power calculation to decide sample size will be used. The number of participants has been 
arbitrarily defined, as it is a pilot study. We aim to recruit 40 women. 
Before randomisation, women will be categorised according to their glycaemic status in two cohorts: 
Glucose tolerant and GDM. Each of these two cohorts will be randomly allocated into the 

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intervention (soluble fibre supplement) and control (placebo) group. Randomisation will be by 
sealed envelopes. Participants but not researchers will be blinded as to the type of intervention 
prescribed. 
Differences between group en each cohort will be assessed using Student t test or Mann-Whitney U 
test for numeric variables depending on distribution; X2 will be used for categorical variables. 
In the Glucose tolerant women cohort:  
For the primary outcome, GDM (yes/no), logistic regression analysis will be performed. 
For the secondary outcomes, insulin sensitivity and insulin secretion, linear regression analysis will 
be performed.  
In the early GDM cohort: 
For the primary outcome, need for insulin treatment (yes/no), logistic regression analysis will be 
performed. Additionally days-to-treatment analysis will be performed for those participants starting 
insulin therapy during follow up. 
 
 
10.  
REGULATORY ISSUES 
 
ETHICS APPROVAL 
The study has obtained approval from the Bromley Research Ethics Committee (REC) and Health 
Regulator Authority (HRA). The study must also receive confirmation of capacity and capability from 
each participating NHS Trust before accepting participants into the study or any research activity is 
carried out. The study will be conducted in accordance with the recommendations for physicians 
involved in research on human subjects adopted by the 18th World Medical Assembly, Helsinki 1964 
and later revisions. 
CONSENT 
Consent to enter the study must be sought from each participant only after a full explanation has 
been given, an information leaflet offered and time allowed for consideration. Signed participant 
consent should be obtained. The right of the participant to refuse to participate without giving 
reasons must be respected. After the participant has entered the study the clinician remains free to 
give alternative treatment to that specified in the protocol at any stage if he/she feels it is in the 
participant’s best interest, but the reasons for doing so should be recorded. In these cases, the 
participants remain within the study for the purposes of follow-up and data analysis. All participants 
are free to withdraw at any time from the protocol treatment without giving reasons and without 
prejudicing further treatment. 
 
CONFIDENTIALITY 
The Chief Investigator will preserve the confidentiality of participants taking part in the study and is 
registered under the Data Protection Act. After consent is obtained, a letter will be sent to the 

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participant’s GP to inform that she will be taking part in the study. Personal data will only be stored 
in Trust’s files. A specific study code will be used to store anonymised data at Imperial College’s  
Department of Investigative Medicine.  Data and all appropriate documentation will be stored for a 
minimum of 10 years after the completion of the study, including the follow-up period.  Blood 
samples will be handled by NHS Trust regular procedures. Urine samples, collected for research 
purposes will be stored at Imperial College’s Department of Medicine until the study is concluded. 
After analysis, samples will be disposed in accordance with the Human Tissue Authority’s Code of 
Practice. 
 
 
 
INDEMNITY 
Imperial College holds negligent harm and non- negligent harm insurance policies which apply to this 
study. 
 
SPONSOR 
Imperial College London will act as the main sponsor for this study. Delegated responsibilities will be 
assigned to the NHS trusts taking part in this study. 
 
FUNDING 
The Department of Investigative Medicine, Imperial College, will be funding this study. 
 
AUDITS AND INSPECTIONS 
The study may be subject to inspection and audit by Imperial College London under their remit as 
sponsor and other regulatory bodies to ensure adherence to GCP and the NHS Research Governance 
Framework for Health and Social Care (2nd edition). 
 
GUAR GUM FIBRE SOURCING 
Sachets containing 5 gr of partially hydrolised Guar gum fibre will be sourced by Nestle. The product 
will be stored at room temperature at Imperial College’s Department of Medicine.  
 
PLACEBO (CELLULOSE) SOURCING 
Cellulose will be sourced by Nestle. The product will be stored at room temperature at Imperial 
College’s Department of Medicine. 
 
11.  
STUDY MANAGEMENT 

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The day to day management of the study will be co-ordinated through Dr. Lilian Mendoza Mathison. 
 
 
12.  
PUBLICATION POLICY 
The findings of the research will be published in an open-access, peer-reviewed journal. In addition 
we will be collaborating with patient groups and professional groups such as the Society for 
Endocrinology to disseminate the findings via multiple media channels such as patient association 
publications, print and broadcast media.           
 
 

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13.  REFERENCES 
 
1.  
American Diabetes Association. Standards of Medical care in diabetes - 2017. J Clin Appl Res 
Educ. 2017;40(January):1–142.  
2.  
Clausen T, Mathiesesn E, Hansen T, Pedersen O, Jensen D, Launborg D, et al. High Prevalence 
of Type 2 Diabetes and Pre-Diabetes in Adult Offspring of Women With Gestational Diabetes 
The role of intrauterine hyperglycemia. Diabetes Care,. 2008;31(2):340–6.  
3.  
Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational 
diabetes: a systematic review and meta-analysis. Lancet [Internet]. 2009;373(9677):1773–9. 
Available from: 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&
list_uids=19465232 
4.  
NICE. Diabetes in pregnancy: management of diabetes and its complications from 
preconception to the postnatal period. NICE Guidel NG3 [Internet]. 2015;(February):2007–9. 
Available from: http://www.nice.org.uk/guidance/ng3/chapter/1-recommendations 
5.  
McIvor ME, Cummings CC, Mendeloff AI. Long-term ingestion of guar gum is not toxic in 
patients with noninsulin-dependent diabetes mellitus. Am J Clin Nutr. 1985 May;41(5):891-4. 
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