Effect of Premeal Consumption of Protein-enriched, Dietary Fiber-fortified Cereal Bar on Long-term Glycemic Control in Patients With Type 2 Diabetes
Phase: NA
Conditions: Patients With Type 2 Diabetes
Sponsor: Seoul National University Hospital

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Effect of pre-meal consumption of protein-enriched, 
dietary fiber-fortified cereal bar on long-term glycemic 
control in patients with type 2 diabetes 
 
Trial No: NCT03727854 
 
Date: April 16, 2018 
 
 

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Effect of pre-meal consumption of protein-enriched, dietary fiber-fortified cereal bar 
on long-term glycemic control in patients with type 2 diabetes 
 
1. Aim of this study 
The aim of this study is to evaluate the effect of premeal protein-enriched bar in long-term 
glycemic control in patients with type 2 diabetes mellitus. Glucose levels in subjects who 
intake premeal protein-enriched bar with dietary modification will be compared to those in 
subjects who only do the dietary modification. 
 
2. Methods 
1> Inclusion/Exclusion criteria 
1) Inclusion criteria 
• BMI 18.5~35 kg/m2  
• Type 2 diabetes patients  
• Fasting blood glucose ≥ 126 mg/dl or  
• HbA1c ≥ 6.5% or • Subjects who were previously diagnosed with type 2 diabetes and who 
have been treated with lifestyle modification only, oral anti-diabetic drugs or basal insulin. 
 
2) Exclusion criteria 
• HbA1c < 6.5% or > 10%  
• Subjects using insulin other than basal insulin  
• Subjects who have newly started or have changed anti diabetic drugs within 3 months 
• Subjects who are allergic to grains, nuts, legumes and milk  
• Previous history of gastrointestinal surgery (except for hemorrhoid surgery, 
appendectomy surgery and hernia surgery)  
• Subjects with chronic unstable disease 
• Subjects with cognitive inpairment who are not able to follow the study protocol 
• Females who are pregnant or doing breast feeding  
• Subjects with Aspartate aminotransferase (AST) or alanine 
aminotransferase (ALT) levels of higher than 3 times of upper normal ranges 
• Subjects with hemoglobin level of less than 10.0 g/dL  

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• Subjects with alcohol addiction or drug abuse 
 
2> Detail methods 
This study was conducted as a randomized, open-labeled study (Figure 1). The study 
subjects first assessed whether they met the criteria for selection and exclusion on the 0th 
visit day, and then enrolled in the study. They individually received diet education and were 
required to do self-monitoring of blood glucose seven times a day [7-point SMBG] until the 
next visit. Only those who have visited on the first visit day passed the screening test, and 
performed the 7-point SMBG correctly, were registered for the study. Subjects enrolled in 
the study were randomly assigned to pre-meal protein enriched bar with dietary modification 
group or dietary modification only group. After the 12 weeks, the second visit and study-
end exam was conducted. 
 
Figure 1. An overview of the study 
1) Signing the consent to participate in the study and confirming for the inclusion and 
exclusion criteria (Visit 0, screening visit) 
-Those willing to participate in the study visited the Seoul National University Hospital 
Clinical Trial Center with 12 hours of fasting. 
-It was confirmed that the person who signed the agreement satisfies the criteria for 
inclusion and exclusion of study subjects. Blood tests were performed and medical history 
surveys, anthropometric measurements (height, weight, abdominal circumference) were 
done. Blood tests include complete blood count, fasting plasma glucose, hemoglobin A1c, 

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aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine, total 
cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein 
cholesterol, Insulin, and C -peptide. 
-After conducting the above test, the study subjects were individually provided with 
diabetes dietary education. 
-7-point SMBG (before / after each meal, before bedtime) should be conducted for one 
day to evaluate compliance. 
-If the criteria for inclusion and exclusion are satisfied and all 7-point SMBG for one day 
has been performed, the subject is selected as the final study. 
-If 7-point SMBG is not performed, revisit after one week and write 7-point SMBG again. 
2) Study start (1st visit date) 
-The study subjects visited the clinical trial center of the Seoul National University Hospital 
until the appointed time on the first visit day. 
-After randomization, in a pre-meal protein-enriched bar with a dietary modification group, 
the cereal bar is consumed 15 minutes before meals and required to follow the diet 
education. In the control group, they are required to follow diet education without a pre-
meal cereal bar. 
-A single intake of protein-enriched cereal bar is 36 g, and its calories are 97 kcal and 
consists of 16.5 g of carbohydrate (12.2 g of dietary fiber), 12.5 g of protein, and 0.6 g of 
fat. 
-A protein-enriched cereal bar is recommended to consume three times a day (at least 
two times a day is mandatory) 
-It is recommended that both groups maintain physical activity according to their usual 
exercise habits during the study period. 
-In order to maintain compliance, the research nurse calls the research subjects every four 
weeks after the start of the study to check whether they are good at maintaining the diet 
and protein-enriched cereal bar as instructed and encouraging them to increase 
compliance. 
-During the last week (week 11), subject subjects should conduct a 7-point SMBG on a 
day that is possible. 
-Subjects should not change their existing diabetes medications and doses during the 

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study period. 
 
3) Rescue strategy 
- In the SMBG result, if the blood glucose level is more than 270 mg / dL at week 0-6, or 
more than 240 mg / dL at week 7-12 for three consecutive days, subjects were required 
to contact the clinical trial center to determine whether a visit is necessary. For those who 
do not use anti-diabetes drugs, lifestyle modification should be strengthened, or the use 
of oral anti-diabetes medications should be started. For those who were using only oral 
anti-diabetes medications, the drug dose should be increased, or another drug added. For 
those who were using basal insulin, they are required to increase the insulin dose. 
-If the subject experience more than one hypoglycemia (less than 70 mg/dL), they are 
required to contact the clinical trial center to determine if a visit is necessary. Re-evaluation 
of the underlying disease should be performed in the case of subjects who have not 
previously used anti-diabetes medications, and in the case of subjects who have used oral 
anti-diabetes drugs, the existing drugs should be reduced or discontinued. Those who 
have been using basal insulin, the insulin dose should be reduced. 
 
4) Outcome measurement 
-Subjects visited the clinical trial center at 12 weeks ± 1 week of study. At the time of visit, 
fasting blood glucose sampling and body measurements were performed while fasting 
was maintained for 12 hours. 
-As the primary end point, change in HbA1c from baseline was evaluated. 
-Secondary endpoints include fasting blood glucose, body weight, weight circumference, 
blood lipid levels (triglycerides, high-density lipoprotein cholesterol, low-density 
lipoprotein cholesterol), HOMA-IR, HOMA-beta.  
 
5) Statistical analysis 
Descriptive statistics are expressed as mean ± standard deviation (SD) for continuous 
variables, and categorical variables are expressed as number and percentage. For comparison 
of baseline characteristics between the intervention group and the control group, t-test 
(when the normal distribution is satisfied) and Mann-Whitney U test (when the normal 

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distribution is not satisfied) are used for continuous variables and Pearson's chi-square test 
for categorical variables. To evaluate the difference between the 12th week and the baseline 
data, the paired t-test or Wilcoxon's signed-rank test was used for the continuous variables, 
and the McNemar's test was used for the categorical variables. The primary and secondary 
endpoints were evaluated using ANCOVA methods. All statistical analysis was performed 
using SPSS version 18.0 (SPSS Inc., Chicago, IL, USA) and GraphPad Prism 5 (GraphPad 
Software Inc., San Diego, CA, USA). If the P-value is less than 0.05, it is evaluated as 
statistically significant.