Glycemic Index of three Oral Nutritional Supplements in healthy adults: a single-blind crossover study CURRENT

Background: The main objective of this study was to evaluate the glycemic index (GI) and insulin index (II) of three oral nutritional supplements (ONS) in healthy adults. Methods: A single-blind crossover study was conducted in 12 healthy adults. Fasted subjects consumed one of three treatments at each visit, with a one week wash out period between visits. Every subject received all treatments. Treatments included two newly developed ONS (powder A, powder B) as well as a positive control Nutren ® Diabetes (powder C). Blood glucose and insulin levels at 15, 30, 45, 60, 90, 120, 180 and 240 mins were measured after the volunteers consumed one of the treatments which all of containing 50g carbohydrates per serving. The Wolever method was used to compute the area under the curve (AUC) for blood glucose and insulin, and GI and II of three powders were obtained. Results: Using the GI and II of 50g glucose powder as reference standard, the GI of nutrition powders A, B and C are 44, 54, 29, respectively, and the II of nutrition powders A, B and C are 163, 182, 119, respectively. Conclusions: Among the two newly developed ONS formulas, powder A is more suitable as an ONS for diabetics. registration:


Conclusions:
Among the two newly developed ONS formulas, powder A is more suitable as an ONS for diabetics.

Background
Studies have shown that the risk of diabetes is positively correlated with the glycemic index (GI), which is a measure of relative rise in blood glucose levels after the consumption of carbohydrates [1].
In 2011, the International Diabetes Federation (IDF) updated and released the "guidelines for postprandial blood glucose management" which showed through evidence-based medicine that dietary interventions are the basis of diabetes treatment. It recommended the use of GI to evaluate the ability of carbohydrate rich food to raise blood glucose [2]. GI describes the ability of food to raise blood glucose levels, measuring the effect that food has on postprandial blood glucose [3]. Research shows that food with low GI absorbs slowly and releases energy continuously after entering the body, allowing for the peak value of glucose to be lower and less variation in postprandial blood glucose, helping to maintain blood glucose homeostasis [4]. GI was initially used in the selection of carbohydrate rich food for diabetic patients with the goal of minimizing wide fluctuations in blood glucose. Research has shown that diets with low GI foods have important value in the prevention and treatment of obesity, cardiovascular disease and a multitude of chronic metabolic diseases [5][6].
In this study, we selected one ONS for diabetes called Nutren ® Diabetes as a positive control, and two newly developed ONS. Using the internationally recognized standard AS4694-2007, we comupted the GI [7] and II of these three supplements to provide a reference for the research and development of more oral nutritional supplements for diabetic patients.

Methods Subjects
In this study, a total of 12 healthy subjects (6 men, 6 women) were included. Inclusion criteria were as follows: (1) Age between 18 and 27 years old. (2) Body mass index (BMI) within 18.5-23.9 kg/m2. (3) Inability to fast for longer than 10 hours and therefore unable to complete the experiment. (4) Gastrointestinal disease. (5) Participation in other clinical trials within three months. The Ethics Committee of Shanghai Sixth People's Hospital approved the study protocol (ID: 2016 − 127). The study, along with its risks and benefits were fully explained to all participants. Written informed consent was obtained from all subjects prior to the study.

Study Design
We conducted a single-blind crossover design study (three 1-day study periods scheduled 1 week apart) at Shanghai Jiao Tong University Affiliated Sixth People's Hospital. Every subjects received the same treatments on the same day and had a 1 week washout period between two treatments. All of them were required to receive the three treatments.

Study Procedures
Subjects were recruited through university intern and the clinic volunteer roster. The day before the test day, subjects were asked to avoid excessive exercise, smoking or drinking. Subjects arrived in the morning after a 12-hour overnight fasting for a baseline venous blood draw to measure glucose and insulin concentrations. One of the four powders (3 were ONS, 1 was glucose powder) was made into 250 ml drinks. Subjects were asked to finish the drinks in 10 minutes. Additional venous samples were drawn at 15 30 45 60 90 120 180 240 min and were collected into vacutainer tubes (Becton Dickinson, Franklin Lakes, NJ). During this period, subjects were not allowed to eat other food or medicine, but they can drink 100-200 ml water with a small amount of activity.

Treatments
Three powders were consumed by all subjects (Table 1)   Results were statistically significantly at P 0.05.

Results
All 12 subjects tolerated the study with no adverse events reported. The fasting blood glucose of the 12 subjects was within the normal range, and reached the peak height 30 minutes after taking the test products (Table 2, Fig. 1). The peak blood glucose in powder B was the highest. At 180 and 240 min, glucose levels were significantly higher for powder A, compared with the powder C ( Table 2). At 180 min, glucose levels were significantly lower for powder A, comparing with powder B ( Table 2). The iAUC 0 − 120min and iAUC 0 − 180min of glucose were significantly lower after consumption of powder A and powder C, comparing with the glucose powder (Table 3). There was no significant difference between the iAUC 0 − 120min, iAUC 0 − 180min, iAUC 0 − 240min of glucose after powder B and glucose powder.
The fasting serum insulin of the 12 subjects was within the normal range, reaching peak height 30 minutes after taking the test powder (Table 4, Fig. 2). The peak value of serum insulin in powder B was the highest. There was no significant difference between serum insulin at any time point in powder A and powder C. At 15, 30 and 90 min, insulin levels were significantly higher for powder B, comparing with the powder C (Table 4).
The iAUC 0 − 120min of insulin was significantly higher for powder B, comparing with the powder C (Table 5). There was no significant difference between the iAUC 0 − 120min, iAUC 0 − 180min, iAUC 0 − 240min of glucose after consumption of powder A and glucose powder. The ratio under the iAUC of insulin and glucose often indicates sensitivity of the body to insulin. The results are shown in Table 6. The ratio of insulin / glucose at each time point after the intake of the three powders was higher than that of glucose powder, and the ratio of powder B from 30 min to 180 min was significantly higher, comparing with that of glucose powder. The ratio of powder C from 30 min to 240 min was significantly higher than that of glucose powder. processed and prepared to meet the special needs of people with digestion and absorption disorders, metabolic disorders, limited food intake, or specific disease status for nutrients or meals. Such products must be taken alone or in combination with other foods under the guidance of a doctor or dietitian ". FSMP is mainly divided into three categories, namely, full nutrition formula (which can be used as a single nutrition source to meet the nutrition requirements of the target population), specific full nutrition formula (which can be used as a single nutrition source to meet the nutrition requirements of a target population with specific diseases or medical conditions) and non-full nutrition formula (which meets part of the nutrition requirements of the target population) [9].
The glycemic index (GI) was first proposed by Jenkins [8] in 1981; it represents a kind of food physiological parameter and is an effective index to measure the postprandial blood glucose response of human body after food intake. After food with high GI enters the gastrointestinal tract, glucose enters the blood rapidly due to its high digestibility and absorption rate, resulting in high peaks of blood glucose. The main mechanism of low GI food is to reduce postprandial blood glucose response and insulin response, increase satiety, reduce energy intake, inhibit the generation of free fatty acids, help in the regulation of gastrointestinal hormones, and affect the blood glucose response of the second meal [10]. Insulin index (II) represents the ratio of postprandial insulin response of test food to reference food (glucose powder) [11]. Therefore, the guidelines of many countries suggest that diabetics choose foods with low GI and II.
The powder A and powder B proposed in this study are full nutrition formula under development, and the product types are low GI type and balanced type respectively. As a positive control of this study, powder C is a suitable nutrition preparation for diabetics currently on the market. The result shows that GI of powder C was 29, which was similar to that of official data, indicating that the test results are reliable. The GI of low GI type, powder A is 44, which belongs in the category of products with low GI. The GI of balanced type, powder B is 54. Taking into consideration the possibility of measurement error, powder B is between low and medium GI. Only the area under the 2-hour blood glucose curve of powder A and C was significantly smaller than that of glucose powder. In addition, II of powder A and C were lower than that of powder B. The area under the 2-hour insulin curve of powder B was higher than that of the other two powder, and the difference was statistically significant between powder B and powder C. When choosing the ONS formula for diabetics, we should consider that powder B has a large amount of insulin secretion and a relatively high glycemic index, while these two factors are low in powder A. Powder A is more suitable for diabetics. For those who do not require strict blood glucose control, the other two ONS formula can be used.

Conclusions
In conclusion, the determination of GI and II is an important index to judge whether an ONS formula is suitable for the diabetic population, which can provide reference opinions when giving suggestions to patients. Availability of data and materials The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.