bstract - Basic and Clinical Science
Topic	Diabetes management

Abstract title :Effect of probiotic use on glycemic control in type1 diabetes : A randomized, double-blind, placebo controlled trial

Co-authors
	N. Pandey1, S. Ramkumar1, P. Kaur1, A. Gupta 1, R. Goswami1, N. Tandon1.
         All India Institute of Medical Sciences, Department of Endocrinology, New delhi, India.!

Abstract body	

Background
There has been recent evidence to suggest that major shifts in the intestinal mucosal inflammatory and immune responses consequent to alteration of the gut microbiome may play a role in the pathogenesis of many forms of autoimmune and metabolic diseases, including type 1 diabetes mellitus (T1DM)

We designed this study to see whether probiotics by virtue of their anti-inflammatory action, can improve glycemia in patients with type 1 diabetes of recent onset (<5 years) 

Aim
To assess the effect of a probiotic preparation, VSL#3 on glycemic control in patients with type-1 diabetes mellitus. Primary objective was to see change in glycosylated haemoglobin (HbA1c), secondary objectives included the improvement in glycemic indices (percentage of time spent in hypo-/hyper-/euglycemia), measured using continuous glucose monitoring system (CGMS) before and after 16 weeks of intervention

Method
In this single-centre, prospective, double blind, placebo controlled, randomised pilot study; 50 adult (≥ 18yrs) patients with T1 DM without pancreatic calcification, with duration of diabetes < 5 years were enrolled. Written informed consent was taken after obtaining approval from the institutional ethics committee (Clinical Trials Registry India - CTRI/2012/11/003125; registered on 20/11/2012).
Eligible patients were randomized (using permuted blocks of four) to either the probiotic (n=25; mean age=24±5y) or the placebo (n=25; mean age=23±4y) arm; one group received the probiotic (2 caps thrice daily; 675 billion CFU/day) and the other group received placebo (2 caps thrice daily;) preparation, for 16 weeks. HbA1c estimation and CGM study was conducted at the start and end of the study. All patients received standard medical therapy and dietary counselling for better glycemic control. Compliance was monitored by counting the used strips returned by the patients on every 4 weekly visit .

Results
Out of 25 patients in the probiotic group, 2 did not complete the study ; owing to pregnancy and antibiotic use respectively, but were included in analysis under intention to treat. CGMS data was available for only 35 patients (eighteen in probiotic group and seventeen patients in placebo group). HbA1c levels were comparable between groups before and after treatment (p=0.252 and p=0.764 respectively), but the probiotic group showed a statistically significant decline in HbA1c levels after treatment as compared to baseline (10.1±1.6 vs 9.24±2.0; p=0.047).
There was no significant difference in the CGMS parameters (percentage time spent in hypo-/hyper-/euglycemia) after 16 week therapy between the study groups or within the study groups, however an improvement was seen in the percentage time spent in hyperglycemia (>140 mg/dl) in the probiotic group (81 (range 5-100) vs 72 (range 7-100); p=0.191).
GLP-1 levels were comparable and there were no changes in cytokine (IFN-γ, TNF-α and IL-1β) levels after intervention, in either group; while IL-10 levels decreased significantly in both groups.

Discussion
In view of significant improvement in HbA1c and glycemic variability parameters with intervention in the VSL#3 group (though statistically insignificant in comparison to placebo ), we believe probiotics might play a permissive role in improving glycemia in patients with T1DM probably due to their impact on gut environment and food assimilation.
Probiotic use is found to affect glycemia in type 2 diabetes by modulation of anti-inflammatory response and insulin resistance, which are potentially modifiable factors even in patients with type1 diabetes. Further, probiotic supplementation may facilitate in preserving residual beta cells in recent onset type1 DM from further autoimmune insult (as seen in other autoimmune diseases -ulcerative colitis).

To the best of our knowledge, this is the first RCT evaluating the impact of probiotics in glycemic control and variability in patients with T1DM. .

Our data suggest that administration of probiotic preparation, led to no significant impact of VSL#3 on the glycemic control in patients with type 1 diabetes mellitus.
 However, there was a trend towards improvement in key variables of glycemic variability with VSL#3 administration. Larger studies are needed to understand their specific role in prevention and treatment of type 1 diabetes.

Effect of probiotic use on glycemic control in type1 diabetes: a randomized, double-blind, placebo controlled trial