To Compare the Effects of Non-nutritive Sweeteners Intake in Subjects With T2DM
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional

Summary: 
      ABSTRACT

      Introduction: There is no current data about the effects of non-nutritive sweeteners (NNS)
      about important factors, such as the energy intake, appetite and its relationship in people
      with diabetes when tasting sweet. It is highly relevant to compare the effects of NNS intake,
      such as, stevia (steviol glycosides) and sucralose, previous to a mixed food on glycemic
      response, insulin and plasmatic concentrations of Glucagon-like peptide type 1 (GLP-1) and
      ghrelin in subjects with type 2 diabetes mellitus (T2DM).

      Objective: To compare the effects of non-nutritive sweeteners intake: stevia (steviol
      glyco-sides) and sucralose previous to mixed food on appetite, glycemia, insulin,
      ghrelin,incretin plasmatic concentrations GLP-1 in people with T2DM.

      Methods: Seventeen subjects with T2DM were studied in 3 different moments and they received 3
      treatments: pre-load of water or sucralose or stevia and then offered to consume mixed food
      as a test, which provided 332 Kcal and 75 grams of available carbohydrates. Blood samples
      were obtained to measure the dependent variables, glycemic and insulin at times -10, 0, 30,
      60, 90, 120, 150 and 180 minutes and GLP-1 with ghrelin, at times -10, 0, 30, 90, and 180
      minutes. The analogue visual scale questionnaires (VAS) was conducted every 30 minutes in
      order to obtain the results of the depend variables: appetite and wish of specific type of
      food in a subjective way; appetite, satiety, relax, wish to eat any food, craving for
      something sweet, craving for something salty, something tasty, something fatty. Through food
      provided ad libi-tum (objective appetite), were obtained the results of: energy,
      carbohydrates, proteins and lipid intakes. The statistical analysis applied included the
      Shapiro-Wilk's Normality test, repeated measures ANOVA to assess differences among
      treatments, Friedman's test followed by Wilcoxon test corrected by Bonferroni as needed. The
      degree of association between variables was conducted using the Pearson's or Spearman's
      correlation coefficient tests, as requested. A probability value p <0.05 was considered
      significant.
    

Detailed description: 
      Protocol The experimental design was developed 3 times. Each intervention was performed
      separately for a minimum period of 7 days out and a maximum of 14 days, depending on the
      availability of the experimental subjects. Cross treatment design (crossover) each subject
      serves as its own control The first intervention corresponded to the control group, in order
      to maintain the ignorance of the type of sweetener they were receiving, between day 7 or
      maximum 14 days post-intervention the order of the test of the NNS was reversed. Therefore,
      during the second or third intervention they were given to drink water with sucralose or
      stevia respectively. For each intervention a check list was followed.

      Subjects were asked to maintain their normal diet between study days and abstain from
      strenuous exercise and alcohol intake for 24 hours before each evaluation. The subjects
      attended with an 8-hour fast, without having ingested metformin or other medication, to the
      sampling room of the Department of Nutrition (Faculty of Medicine, University of Chile). The
      study was only begun if they had a capillary glycemia <140%, measured through a glucometer.

      Then, they were asked to answer the analogue visual scale (VAS) questionnaire and an
      intravenous catheter was installed in the antecubital vein to take the blood samples at "time
      -10". Immediately, they were given to drink 60 ml of water or 60 ml of water with 48 mg of
      sucralose or an equivalent volume with 96 mg of stevia (steviol glycosides), which they had
      to consume in less than 2 minutes, and then answer to a question about the "sensation" that
      came with drinking this preparation, to make an estimate of your predisposition to the taste
      of the sweetener: sweet, bitter, metallic or other flavor.

      After 10 minutes, at "time 0" immediately after the second blood sample, the individuals
      consumed a mixed test meal consisting of a cup of tea with three teaspoons of sugar, plus 126
      grams of a homemade bread. , without fat, using the bread maker, brand; program 3,
      traditional bread.

      The following blood samples were taken at times 30, 60, 90, 120, 150 and 180 minutes after
      "time 0". In total, 42 ml of blood was extracted, in each time the glycemia and insulin were
      determined (4 ml was taken at a time). Furthermore, only at time -10, 0, 30, 90 and 180
      minutes, the value of GLP-1 and ghrelin was determined (at this time, 2 ml extra was
      extracted at a time).

      In addition, VAS questionnaires were applied every 30 minutes, from "time -10" to 180 minutes
      for appetite determinations.

      After completing the extraction of blood samples at 180 minutes and removing the intravenous
      catheter, the subjects were offered a meal for 30 minutes, which consisted of a variety of
      foods of high acceptability, previously weighed and fractionated.

      Statistic analysis The normal distribution of the variables was determined by the
      Shapiro-Wilk test. The natural logarithm was applied to the parameters without normal
      distribution. The variables were expressed as mean ± standard deviation or median plus
      interquartile interval (Q1-Q3). The statistical significance between the differences in
      plasma glucose concentrations, area under the curve (AUC) of glycaemia, energy intake and
      macronutrients by treatment (preload water, sucralose and stevia), was evaluated through
      Anova of repeated samples . To analyze the differences between plasma concentrations and AUC
      of insulin and GLP-1 per treatment (preload water, sucralose and stevia), Friedman's test was
      used, followed by Wilcoxon and adjusted by Bonferroni.

      To identify differences between the perception of sweet, bitter, and metallic taste by
      treatment (preload water, sucralose and stevia) Friedman test was used, followed by Wilcoxon
      and adjusted by Bonferroni.

      To identify the relationships between glycemic responses and intake of food at will (energy
      intake and macronutrients by treatment, preload water, sucralose and stevia), the Pearson
      correlation factor was used, in contrast to insulinemic response, incretin GLP-1 and the
      visual analogue scale (VAS) and food intake at will per treatment Spearman's correlation
      factor was used.

      The statistical analysis was performed with the SPSS 20.0 computer program (SPSS Inc.,
      Chicago Illinois). A p <0.05 was considered statistically significant for all the analyzes.
    

Intervention name(s): Intervention ingest a 48 mg of sucralose; Intervention ingest a 96 mg of stevia
Intervention type(s): Other; Other
Intervention description(s): Intervention: Subjects with type 2 diabetes who ingest a 48 mg of sucralose. Sucralose is a non-caloric sweetener derived from sucrose and is 600 times more sweet than sucrose. Your allowable daily intake is 15 mg / kg of body weight per day. 85% is not absorbed and is excreted unchanged in the stool; the rest that is absorbed is excreted unchanged by the urine; Intervention: Subjects with type 2 diabetes who ingest a 96 mg of stevia (steviol glycosides). The word "stevia" refers to the whole plant of Stevia rebaudiana Bertoni (SRB), only some of the components of the stevia leaf are sweet. Steviol glycosides are up to 300 times sweeter than sucrose, do not provide calories and can be used as a substitute for sucrose or as a non-nutritive sweetener alternative. Your allowable daily intake is 4 mg / kg / body weight (expressed as steviol)
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: The experimental design was developed 3 times. Each intervention was performed separately for a minimum period of 7 days out and a maximum of 14 days, depending on the availability of the experimental subjects. Cross treatment design (crossover) each subject serves as its own control The first intervention corresponded to the control group, in order to maintain the ignorance of the type of sweetener they were receiving, between day 7 or maximum 14 days post-intervention the order of the test of the ENN was reversed. Therefore, during the second or third intervention they were given to drink water with sucralose or stevia respectively
Masking: Single (Participant)
Primary purpose: Screening
Keywords: High-Intensity Sweeteners; insulin; ghrelin; Glucagon-Like Peptide 1; Non-Nutritive Sweeteners; Stevia rebaudiana