Effects of Chewing Gum on Glycaemic Control in Women With Gestational Diabetes
Condition: Gestational Diabetes Mellitus in Pregnancy
MeSH terms: Diabetes, Gestational; Pregnancy in Diabetics; Diabetes Mellitus
Study type: Interventional

Summary: 
      This study aims to assess the impact of enhanced chewing on glycaemic control in females with
      newly diagnosed GDM. It is hypothesised, that a fixed amount of gum chewed for 20 minutes
      before starting each meal could improve hyperglycaemia. The impact of chewing on postprandial
      capillary blood glucose (measured at one hour after breakfast, lunch and dinner) is
      determined as the primary outcome of this study.

      Differences in fasting glucose and longitudinal changes over the study period should be
      additionally examined.
    

Detailed description: 
      Study design and participants This study is designed as an open-label, mono-centre randomized
      controlled trial with two parallel groups including a total of 74 female patients with recent
      diagnosis of GDM. Diagnosis of GDM is made in accordance with the IADPSG criteria between
      24+0 and 27+6 weeks of gestation [IADPSG 2010]. All pregnant females (aged

      between 18 and 45 years) will be recruited consecutively among women visiting our pregnancy
      outpatient department (Department of Obstetrics and Gynecology, Division of Obstetrics and
      fetomaternal Medicine, Medical University of Vienna).

      Exclusion criteria

        -  Preconceptional overt diabetes (such as type 1 or type 2 diabetes)

        -  History of bariatric surgery or surgeries that induce malabsorption

        -  HIV- or hepatitis infection

        -  Decreased liver or kidney function (before pregnancy)

        -  history of malignant disorders

        -  Abuse of toxic substances

        -  Use of systemic steroids

        -  Multiple pregnancy

      Treatment and Interventions Eligible patients are randomized to receive either routine care
      (control group) or routine care in addition to a chewing gum intervention for five days
      (beginning with the second study day, i.e. the day after baseline examination): sugar-free,
      fruit or mint flavoured gum chewed three times daily for 20 minutes before each meal. Routine
      care includes standard dietary and lifestyle advice for 30 minutes following our local
      recommendations as well as an advice on capillary blood glucose measurement

      (fasting as well as 1h after starting each meal). Capillary blood glucose profiles are re-
      evaluated seven days after starting the blood glucose monitoring.

      Study visits will be scheduled at screening (visit 1, where eligible patients were
      randomized) as well as seven days later (visit 2).

      Randomisation Participants will be randomized to either treatment (chewing gum) or control
      group (routine care) in a 1:1 ratio. The minimisation method [Pocock 1975] will be used to
      minimize the imbalance between the groups according to the preconceptional overweight/obesity
      status with three strata: i. normal weight (i.e. BMI below 25 kg/m2); ii. overweight (BMI 26
      - 30 kg/m2); iii. obesity (BMI and above 30 kg/m2).

      Medical history and baseline examination A broad risk evaluation will be performed in
      participating females at the initial contact (between 24+0 and 32+0 weeks of gestation)
      including: evaluation of maternal age, parity, history of GDM, detailed family history,
      ethnicity, preconceptional diseases, use of ovulation drugs, obstetric history. Moreover, an
      evaluation of preconceptional weight and BMI as well as measurement of blood pressure will be
      performed.

      Assessment of dietary patterns Dietary patterns will be assessed at baseline (visit 1) by
      using a published and validated Food-Frequency-Questionnaire (FFQ) proposed by the German
      Robert Koch Institute [Haftenberg 2010]. It was also previously used for the German DEGS
      project (www.degs-studie.de). Information from the FFQ will be analyzed quantitatively or
      summarized by eating scores proposed in the literature (such as the Healthy Eating Index 2010
      or Alternate Healthy Eating Index 2010) reflecting diet quality based on actual guidelines
      [Guenther 2013, Chiuve 2012]. In addition all patients will be advised to conduct a
      nutritional protocol for seven days. D. End Points

      The three primary end points of this study are the averages (arithmetic mean values) of five
      days 1h postprandial capillary blood glucose measurements: after breakfast (primary end point
      1), lunch (primary end point 2) and dinner (primary end point 3).

      Secondary end points are fasting glucose concentrations and longitudinal changes (i.e.

      assessment of group by time interactions in fasting and postprandial glucose trajectories) as
      well as changes in dietary patterns.

      E. Statistical Analysis

      Sample size With a sample size of n=35 subjects per group we are able to detect a mean
      difference of 8 mg/dl in postprandial glucose levels with a power of 81% and a type 1 error
      of α=0.016 for a two-sided unpaired student's t-test, providing a standard deviation of 10
      mg/dl in accordance with [Landon 2009]. In order to achieve a 95% coverage probability, the
      Bonferroni correction will be used to adjust for multiple testing (three primary outcomes).
      Considering a drop-out rate of 5% n=74 cases are required for this study. A sample size
      review and adaptation is planned after 50% of the subjects have been investigated.

      Analysis Plan Categorical variables will be summarized by counts and percentages; continuous
      variables data are summarized by means and standard deviations (SD) or by median and
      interquartile range in the case of strong deviations from the normal distribution.

      Statistical comparison of continuous parameters (e.g. postprandial or fasting glucose
      concentrations) will be performed by the two-sample t-test or nonparametric

      approaches (e.g. the Brunner-Munzel test), respectively. An adjustment for demographic
      variables (such as age) will be performed in case of significant group differences using
      analysis of covariance (ANCOVA) or by the proportional odds model, if the normality
      assumption is violated. Linear mixed effects models will be used to assess longitudinal
      changes of parameters of interest (i.e. fasting and postprandial glucose). Interaction terms
      are included in the longitudinal models to assess group differences and variable
      transformations (e.g. logarithmic or square root transformation) are used if necessary. A
      two-sided p-value ≤0.05 is considered statistically significant. Using the Bonferroni
      correction for multiple statistical testing (three hypotheses) this results in a 98.33%
      confidence interval to achieve a 95% simultaneous coverage probability. All analyses will be
      performed by using the statistic software R and contributing packages [R Core Team 2016].
    

Intervention name(s): Chewing
Intervention type(s): Other
Intervention description(s): Eligible patients are randomized to receive either routine care (control group) or routine care in addition to a chewing gum intervention for five days (beginning with the second study day, i.e. the day after baseline examination): sugar-free, fruit or mint flavoured gum chewed three times daily for 20 minutes before each meal. Routine care includes standard dietary and lifestyle advice for 30 minutes following our local recommendations as well as an advice on capillary blood glucose measurement (fasting as well as 1h after starting each meal). Capillary blood glucose profiles are reevaluated seven days after starting the blood glucose monitoring. Study visits will be scheduled at screening (visit 1, where eligible patients were randomized) as well as seven days later (visit 2).
Other intervention name(s): chewing, gum, blood glucose
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Screening