The Effect of Single Probiotic on Metabolic Control in Type 2 Diabetes
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional

Summary: 
      Recent studies indicate that dysbiosis of intestinal microbiota and low grade inflammation
      are important pathogenic determinants of type 2 diabetes (T2DM), which has increased in
      epidemic size over the last 20 years. Probiotics have been used in T2DM for the modification
      of IM and anti-inflammatory effects. However, effect of probiotics on metabolic control in
      T2DM are inconsistent.

      Present study will be designed to determine the effects of Lactobacillus GG (LGG) on glycemic
      control, lipid profile, inflammation parameters and expression of certain genes linked to
      T2DM. This study will be conducted at the Istanbul Faculty of Medicine, a tertiary care
      diabetes outpatient clinic and should involve 34 T2DM subjects. Subjects will be randomly
      assign to receive either LGG probiotic drop or a placebo.In this placebo controlled trial,
      effect of single strain probiotic vs. placebo on metabolic control and certain genes linked
      to T2DM will be assessed.
    

Detailed description: 
      Evidence-based data showed that intestinal microbiota (IM) plays a role in the development of
      metabolic diseases. Recent studies have reported that dysbiosis of IM and low-grade
      inflammation is effective in pathogenesis of type 2 diabetes mellitus (T2DM), which has
      increased in epidemic size over the last 20 years. Firmicutes, Bacteroidetes and
      Proteobacteria's ratios in obese and T2DM patients were found to be different than healthy
      subjects. In these cases, there is an association between increasing the proportion of
      gram-negative bacteria in the intestines and subclinical inflammation.

      Probiotics are live microorganisms that are intended to have health benefits by regulating
      mucosal and systemic immunity, when consumed as a nutritional supplement. There are studies
      investigating the effects of probiotic use on insulin sensitivity, glycemic control, lipid
      profile and inflammatory parameters in patients with T2DM. However, several probiotic strains
      were used frequently in these studies, or probiotics and prebiotics were given as cocktails.
      Their effects might be together or even synergistic. Lactobacillus rhamnosus GG (or
      Lactobacillus GG: LGG) is a widely used probiotic microorganism. Studies have shown that LGG
      prevents diarrhea and atopic dermatitis, provides antitumor activity, improves the immune
      system, and lowers serum cholesterol levels. However, there is a limited data about the
      effects of LGG on the glycemic control of diabetic animal models but human studies are
      scarce.

      Therefore, present study is designed to determine the effects of LGG on glycemic control,
      lipid profile, inflammation parameters, and expression of certain genes linked to T2DM.

      Subjects will be randomly assign to receive probiotic "Lactobacillus Rhamnosus GG (ATCC
      53103)" or placebo for 8-weeks administered as a drop formulation. Patients in the
      intervention group receive 10 probiotic drops (1x1010 cfu LGG) once daily with breakfast.
      Subjects will be contacted via telephone every week for an assessment of adverse events and
      probiotic/placebo compliance. Fasting blood samples will be taken at baseline and post
      treatment to measure carbohydrate metabolism (glucose, insulin, fructosamine and HbA1c),
      lipid profile (triglycerides; total, HDL- and LDL-cholesterol) and biomarkers of inflammation
      (hs-CRP and IL-6). TLR2, TLR4, MUC2 and MUC3A genes expressions will be investigated on stool
      samples at baseline and post treatment. Stool samples will be stored at -80°C until RNA
      isolation.The gene expression levels will be determined by Quantitative Real Time PCR method
      using the determined cDNA samples. Dietary intake will be evaluated by the 3-day food record.
      During the 4th and 8th week of the study, a 3 day food consumption records will be taken.
      Diabetics will be given detailed oral and written instructions regarding the completion of
      food record, consisting of 2 midweek days and 1 weekend day. In order to determine the
      amounts of consumed foods correctly, information will be given about measuring cups such as
      water glass, tea glass, teaspoon, tablespoon, serving spoon, bowl. Dietary intake will be
      assessed using a food composition database of BEBIS programme including specific Turkish
      foods. All anthropometric measures will be conducted in a fasting state taken at baseline and
      following an 8-week intervention by experienced examiner (dietitian). Body weight and body
      composition will be assessed by bioelectrical impedance analysis device (Tanita BC-420 MA).
      Body mass index (BMI) will be calculated as weight (kg) divided by height squared (m2). Waist
      circumference (measured midway between lowest rib and iliac crest) will be measured using a
      non-stretchable measuring tape.

      All analysis will be performed using the Statistical Package for Social Sciences (SPSS) 21.0
      package program and significance will defined as p<0.05. Descriptive statistics will be given
      as mean, standard deviation and median (minimum to maximum) for continuous measures.
      Categorical variables will be expressed as case numbers and percentage values. The
      Shapiro-Wilk tests will used to determine whether the distribution of continuous measures are
      normal. Student's t test and Mann-Whitney-U test will used for the two groups comparisons
      according to whether the variables showed normal distribution. Comparisons of changes in
      groups within themselves (before and after probiotic or placebo administration) will made
      using the t-test if the variances is normal, and if the Wilcoxon test is not normal in the
      cohort. The web-based RT2 Profiler PCR Array Data Analysis program will used to determine the
      change of ΔCt values obtained from the Real Time-PCR gene expression study (before and after
      probiotic and placebo administration). p<0.05 will be considered statistically significant.
    

Intervention name(s): Lactobacillus rhamnosus GG (ATCC 53103); Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): One probiotic drop contained a formulation of 1x109 Cfu Lactobacillus rhamnosus GG (LGG; ATCC 53103); Carrier material of probiotic product, not containing bacterial strain, similar appearance as the probiotic
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: prospective, single center, interventional
Masking: Single (Participant)
Primary purpose: Supportive Care
Keywords: Diabetes Mellitus, Type 2; Lactobacillus GG; probiotic; gene expression