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Effect of Probiotic Supplementation on Fecal Microbiota, Nutritional Status, Metabolic and Inflammatory Parameters in Patients With Type 2 Diabetes Mellitus

Not Applicable
Recruiting
Conditions
Type 2 Diabetes Mellitus
Interventions
Dietary Supplement: Placebo
Dietary Supplement: Probiotic
Registration Number
NCT05418179
Lead Sponsor
Universidade Federal de Santa Catarina
Brief Summary

The purpose of this study is to evaluate the effect of probiotic supplementation on fecal microbiota, nutritional status, metabolic and inflammatory parameters in patients with type 2 diabetes mellitus.

Study hypothesis: Supplementation of multispecies probiotic (Bifidobacterium Lactis, B. brebe, B. longum, Lactobacillus gasseri, L. casei, L. rhamnosus) during 12 weeks improves the the fecal microbiota composition and promotes reduction of plasma/serum levels of acute phase proteins, cytokines, metabolic and anthropometric parameters in individuals with type 2 diabetes mellitus.

Detailed Description

The purpose of this study is to evaluate the effect of multispecies probiotic supplementation (specifically designed for the present study) on fecal microbiota, nutritional status, metabolic and inflammatory parameters in patients with type 2 diabetes mellitus (T2DM).

Adult individuals (35 to 75 years old) of both sexes with T2DM (diagnosed at least 1 year ago), body mass index from 25.00 kg/m² to 39.99 kg/m², glycated hemoglobin ≤ 9.0% and using metformin will be invited to participate in this randomized, placebo-controlled, triple-blind study.

The participants will be randomized into two groups: G1 - probiotic group and G2 - control group (placebo).

The study will consist of two experimental time points: M0 - baseline and start of supplementation; M1 - after 12 weeks of the first outpatient visit and start of supplementation.

In the two experimental moments, individual fecal samples will be obtained for analysis of the fecal microbiota; The metabolic parameters will be assessed by determination of circulating levels of SCFA, FFA, insulin, fasting glucose and glycated hemoglobin, HOMA-IR; Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides; the inflammatory response will be assessed by determination of plasma indicadors (LPS, Adiponectina, IL-10, IL-1, IL-6, TNF- α, Leptina, Resistina) ; besides the evaluation of indicators of nutritional status (bone densitometry with body composition and anthropometric measurements).

The primary endpoint will be the fecal microbiota composition, SCFA concentrations and the inflammatory parameters.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
80
Inclusion Criteria
  • Age from 35 to 75 years old;
  • Individuals diagnosed with type 2 diabetes mellitus (at least 1 year ago);
  • Body mass index from 25.00 kg/m² to 39.99 kg/m²;
  • Glycated hemoglobin ≤ 9.0% ;
  • Using metformin, combined or not with other antidiabetic drugs
Exclusion Criteria
  • Previous bowel diseases (inflammatory bowel disease and irritable bowel syndrome); or previous gastrointestinal surgery (eg, colectomy, gastrectomy)
  • Intolerances and ∕ or food allergies with a previous medical diagnosis (eg lactose intolerance or celiac disease);
  • Glomerular filtration rate <30 ml/min/1.73m²; inflammatory diseases and immunodeficiencies;
  • Diagnosis of autonomic neuropathy with gastrointestinal involvement such as: diabetic gastroparesis, diabetic enteropathy (diarrhea) or colonic hypomotility (constipation);
  • Hospital admission and/or use of anti-inflammatory drugs (non-hormonal and corticosteroids) up to 1 month before the study; and ∕or use of antibiotics up to 3 months before the study;
  • Regular use of laxatives, opioid narcotic analgesics or appetite suppressants;
  • Current or previous use (up to 1 month) of prebiotics, probiotics, symbiotics or products enriched with these food supplements;
  • Intolerance to prebiotics, probiotics or symbiotics;
  • Pregnant or breastfeeding;
  • Follow-up of a diet, guided by a nutritionist, for weight loss or gain up to 1 month before the study or current follow-up of unusual diets (eg vegetarian, macrobiotic, paleolithic);
  • Alcohol consumption (> 1 drink/day or 14g of alcohol for women; >2 drinks/day or 28 grams of alcohol for men); use of illicit drugs and smokers;
  • Change of lipid-lowering and/or antidiabetic drugs in the last 3 months

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboMaltodextrin (1 capsule/day)
ProbioticProbioticProbiotic (Bifidobacterium animalis subsp. Lactis, Bifidobacterium breve, Bifidobacterium longum, Lactobacillus gasseri, Lactobacillus casei, Lactobacillus rhamnosus) - 1 capsule/day
Primary Outcome Measures
NameTimeMethod
SCFA12 weeks compared to baseline

Acetate, propionate, isobutyrate, butyrate and isovalerate (μmol/L)

Inflammatory parameters12 weeks compared to baseline

Plasma LPS, adiponectin, leptin, resistin, IL-1, IL-6, IL-8, IL-10 and TNF-alpha concentrations (pg/mL)

Fecal Microbiota12 weeks compared to baseline

analysis method: 16s rRNA sequencing and bioinformatics analysis. Reported measure: taxonomic profiles of the microbial populations (operational taxonomic units / OTUs)

Secondary Outcome Measures
NameTimeMethod
Free Fat Acids12 weeks compared to baseline

µmol/L

HOMA-IR12 weeks compared to baseline

HOMA-IR = \[fasting blood glucose (mmol) x fasting insulin (UI/ml)\] ÷ 22,5

LDL-c12 weeks compared to baseline

(Friedewald equation) LDL-c = total colesterol - HDL-c - Triglicerídeos/5

Reported measure: mg/dL

Bone densitometry12 weeks compared to baseline

Dual X-ray Absorptiometry (DXA). Reported measure: T-score and Z-score

Glycated hemoglobin12 weeks compared to baseline

percentage (%)

Triglycerides12 weeks compared to baseline

mg/dL.

Fasting insulin12 weeks compared to baseline

μUI/mL

fasting blood glucose12 weeks compared to baseline

mg/dL

Body mass index (BMI)12 weeks compared to baseline

In metric units: BMI (kg/m²) = weight (kg) ÷ height² (meters). Reported measure: kg/m².

Total cholesterol12 weeks compared to baseline

mg/dL

HDL-c12 weeks compared to baseline

mg/dL

Total Body Fat Percentage (%BF)12 weeks compared to baseline

Dual X-ray Absorptiometry (DXA). Reported measure: Total Body Fat Percentage (%BF)

Body weight (kg)12 weeks compared to baseline

kilograms

Waist circumference (cm)12 weeks compared to baseline

centimeters (cm)

Fat Mass Index (FMI)12 weeks compared to baseline

Dual X-ray Absorptiometry (DXA) - Fat Mass Index (FMI) - the total amount of fat (in kilograms) relative to the height (in meters²)

Total Body lean mass Percentage (%)12 weeks compared to baseline

Dual X-ray Absorptiometry (DXA) - Total Body lean mass Percentage (%): The percent of the body that is not composed of fat.

Trial Locations

Locations (1)

Polydoro Ernani de São Thiago University Hospital

🇧🇷

Florianópolis, Santa Catarina, Brazil

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