Probiotic for Pancreatic ß-Cell Function in Type 2 Diabetes: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

INTRODUCTION: Many clinical studies have proved the effectiveness of probiotics in metabolic disorders associated with insulin resistance. However, the impact of probiotic therapy on pancreatic ß-cell function is ambiguous. The influence of probiotic supplementation vs. placebo on ß-cell function in people with type 2 diabetes (T2D) was assessed in a double-blind, single-center, randomized, placebo-controlled trial (RCT). METHODS: Sixty-eight patients with T2D were selected for participation in the RCT. Patients were randomly allocated to consumption of live multistrain probiotics or a placebo for 8 weeks, administered as a sachet formulation in double-blind treatment. The primary main outcome was the assessment of ß-cell function as change in C-peptide and HOMA-ß (homeostasis model assessment-estimated ß-cell function), which was calculated using the HOMA2 calculator (Diabetes Trials Unit, University of Oxford). Secondary outcomes were the changes in glycemic control-related parameters, anthropomorphic variables, and cytokines levels. Analysis of covariance was used to assess the difference between groups. RESULTS: Supplementation with live multiprobiotic was associated with slight significant improvement of ß-cell function (HOMA-ß increased from 32.48 ± 13.12 to 45.71 ± 25.18; p = 0.003) and reduction of fasting glucose level (13.03 ± 3.46 vs 10.66 ± 2.63 mmol/L and 234.63 ± 62.36 vs 192.07 ± 47.46 mg/dL; p < 0.001) and HbA1c (8.86 ± 1.28 vs 8.48 ± 1.22; p = 0.043) as compared to placebo. Probiotic therapy significantly affects chronic systemic inflammation in people with T2D by reducing pro-inflammatory cytokine levels. CONCLUSIONS: Probiotic therapies modestly improved ß-cell function in patients with T2D. Modulating the gut microbiota represents a new diabetes treatment and should be tested in more extensive studies. TRIAL REGISTRATION: NCT05765292.

Metabolic Benefits of Probiotic Combination with Absorbent Smectite in type 2 Diabetes Patients a Randomised Controlled Trial.

BACKGROUND: Numerous non-drug therapies have emerged in recent years for the prevention and improvement of type 2 diabetes (T2D). However, therapies based on dietary modification and/or microbiota may replace a large part of drug therapies in the coming years. AIM: The aim of the current study was to conduct placebo-controlled randomize clinical trial for the efficiency of a combination of multiprobiotics with smectite absorbent gel (Symbiter-Forte formulation) as an adjunction to the standard anti-diabetic therapy. METHODS: A total of 55 patients met the criteria and were included in double-blind single center RCT, to receive "Symbiter-Smectite" or placebo for 8-weeks administered as a sachet formulation. The primary outcome was the change in HOMA2-IR and insulin sensitivity (% S). Secondary outcomes were glycemic control parameters, ß-cells functional activity, anthropometric parameters and markers of a chronic systemic inflammatory response. RESULTS: Combined use of the probiotic mixture with smectite leads to a significant reduction in HOMA2-IR (3.14±0.97 vs 2.79±0.85; р=0.009) and improvement in % S (34.65±9.92 vs 39.42±12.78; p=0.011) after 8 weeks of the treatment period. Simultaneously, in the secondary outcome analysis lowering of HbA1c, waist circumference but not BMI and pro-inflammatory cytokines IL-1ß (p=0.004), TNF-α (p=0.008), IL-6 (p=0.005) and IL-8 (p=0.042) were detected. In placebo group, changes were insignificant. CONCLUSION: Probiotic with smectite due to its absorbent activity and stabilization mucus layer properties can impact the synergistic enhancement of a single effect, which manifested with a significant reduction in IR, waist circumference, markers of chronic systemic inflammation and improvement of glycemic profile as compared to placebo.

Vitamin D3 deficiency is associated with more severe insulin resistance and metformin use in patients with type 2 diabetes.

BACKGROUND: Vitamin D3 (vit. D3) deficiency is considered as one of the main factors involved in the development of type 2 diabetes (T2D). We assessed insulin resistance (IR), ß-cell functional activity and metabolic profile according to 25(OH) vit. D3 status in patients with T2D. METHODS: The study included 109 patients with T2D, divided in 3 groups: group 1 (N.=11) with normal levels of vit. D3 (>30 ng/mL); group 2 (N.=38) with vit. D3 insufficiency (21-29 ng/mL); and group 3 (N.=60) with vit. D3 deficiency (<20 ng/mL). IR and ß-cell functional activity were assessed as change in C-peptide concentration and homeostasis model assessment-estimated (HOMA) ß-cell function which was calculated using HOMA2 calculator. RESULTS: Patients with vit. D3 deficiency presented significantly higher C-peptide concentration compared to other groups. HOMA2 (3.29±1.89 vs. 2.12±0.71; P=0.049) and hemoglobin (H8b)A1c (9.11±1.63 vs. 7.75±1.06; P=0.016) levels changed significantly only in patients with vit. D3 deficiency compared to diabetics with normal vit. D3 levels. Furthermore, in univariate Pearson's correlation analysis, we observed significant association between vit. D3 levels and C-peptide, insulin sensitivity, HOMA2, triglyceride-glucose index, HbA1c and Body Mass Index, only in the vit. D3 deficiency group. In multivariate logistic regression analysis, poor glycemic control, as defined by HbA1c levels, was independent from metformin use while high density lipoprotein-cholesterol levels were associated with vit. D3 deficiency. CONCLUSIONS: Our study demonstrated that vit. D3 deficiency in patients with T2D was associated with more severe IR, poor glycemic control and obesity compared to normal status or vit. D3 insufficiency.

Beneficial effects of probiotic combination with omega-3 fatty acids in NAFLD: a randomized clinical study.

BACKGROUND: The manipulation of gut microbiota via administration of probiotics has been proposed as a potential strategy for the treatment of non-alcoholic fatty liver disease (NAFLD). Hence, we performed a double-blind single center randomized placebo-controlled trial (RCT) to evaluate the efficacy of coadministration of probiotics with omega-3 vs. placebo in type-2 diabetic patients with NAFLD. METHODS: A total of 48 patients met the criteria for inclusion. They were randomly assigned to receive "Symbiter Omega" combination of probiotic biomass supplemented with flax and wheat germ oil (250 mg of each, concentration of omega-3 fatty acids 1-5%) or placebo for 8-weeks. The primary main outcomes were the change in fatty liver index (FLI) and liver stiffness (LS) measured by Shear Wave Elastography (SWE). Secondary outcomes were the changes in transaminases level, serum lipids and cytokines levels. RESULTS: In probiotic-omega group, FLI significantly decreased from 83.53±2.60 to 76.26±2.96 (P<0.001) while no significant changes were observed in the placebo group (82.86±2.45 to 81.09±2.84; P=0.156). Changes of LS in both groups were insignificant. Analysis of secondary outcomes showed that the coadministration of probiotics with omega-3 lead to significant reduction of serum gamma-glutamyl transpeptidase, triglycerides, and total cholesterol. Chronic systemic inflammatory markers after intervention decrease significantly only in Symbiter Omega group: IL-1ß (P=0.029), TNF-α (P<0.001), IL-8 (P=0.029), IL-6 (P=0.003), and INF-γ (P=0.016). CONCLUSIONS: Coadministration of a live multi-strain probiotic mixture with omega-3 fatty acids once daily for 8 weeks to patients with NAFLD can reduce liver fat, improve serum lipids, metabolic profile, and reduce chronic systemic inflammatory state.