Clinical Trial: Probiotics in Metformin Intolerant Patients with Type 2 Diabetes (ProGasMet).

BACKGROUND: For decades, metformin has been the drug of first choice in the management of type 2 diabetes. However, approximately 2-13% of patients do not tolerate metformin due to gastrointestinal (GI) side effects. Since metformin influences the gut microbiota, we hypothesized that a multi-strain probiotics supplementation would mitigate the gastrointestinal symptoms associated with metformin usage. METHODS AND ANALYSIS: This randomized, double-blind, placebo-controlled, single-center, cross-over trial (ProGasMet study) assessed the efficacy of a multi-strain probiotic in 37 patients with metformin intolerance. Patients were randomly allocated (1:1) to receive probiotic (PRO-PLA) or placebo (PLA-PRO) at baseline and, after 12 weeks (period 1), they crossed-over to the other treatment arm (period 2). The primary outcome was the reduction of GI adverse events of metformin. RESULTS: 37 out of 82 eligible patients were enrolled in the final analysis of whom 35 completed the 32 weeks study period and 2 patients resigned at visit 5. Regardless of the treatment arm allocation, while on probiotic supplementation, there was a significant reduction of incidence (for the probiotic period in PRO-PLA/PLA-PRO: P = 0.017/P = 0.054), quantity and severity of nausea (P = 0.016/P = 0.024), frequency (P = 0.009/P = 0.015) and severity (P = 0.019/P = 0.005) of abdominal bloating/pain as well as significant improvement in self-assessed tolerability of metformin (P < 0.01/P = 0.005). Moreover, there was significant reduction of incidence of diarrhea while on probiotic supplementation in PRO-PLA treatment arm (P = 0.036). CONCLUSION: A multi-strain probiotic diminishes the incidence of gastrointestinal adverse effects in patients with type 2 diabetes and metformin intolerance.

The interplay between bicarbonate kinetics and gastrointestinal upset on ergogenic potential after sodium bicarbonate intake: a randomized double-blind placebo-controlled trial.

This double-blind placebo-controlled cross-over study utilized comprehensive monitoring of blood bicarbonate (HCO3¯) kinetics and evaluation of gastrointestinal (GI) upset to determine their impact on an ergogenic potential of sodium bicarbonate (SB) co-ingested with carbohydrate (CHO). Nineteen CrossFit athletes performed 6 bouts of 15 s Wingate Anaerobic Test (WAnT) 90 min post-ingestion of 0.4 g·kg-1 body mass (BM) of SB (SB + CHO treatment) or PLA (PLA + CHO treatment) with 15 g CHO. Blood HCO3¯ concentration was evaluated at baseline, 30-, 60-, 75- and 90 min post-ingestion, in between WAnT bouts, and 3 and 45 min post-exercise, while GI upset at 120 min after protocol started. Control (no supplementation; CTRL) procedures were also performed. An effective elevation of extra-cellular buffering capacity was observed 60-90 min post-ingestion of SB + CHO. At mean peak blood HCO3¯, or at start of exercise an increase > 6 mmol·L-1 in HCO3¯ was noted in 84% and 52.6% participants, respectively. SB + CHO did not prevent performance decrements in WAnT bouts. There were no significant relationships between changes in blood HCO3¯ and WAnTs' performance. Total GI was significantly higher in SB + CHO compared to CTRL, and stomach problems in SB + CHO compared to CTRL and PLA + CHO. There were inverse associations between peak- (p = 0.031; r = - 0.495), average- (p = 0.002; r = - 0.674) and minimum power (p = 0.008; r = - 0.585) and total GI upset, as well as average power and severe GI distress (p = 0.042; r = - 0.471) at SB + CHO. The implemented dose of SB + CHO was effective in improving buffering capacity, but did not prevent decrements in WAnTs' performance. GI side effects were crucial in affecting the ergogenic potential of SB and thus must be insightfully monitored in future studies.

"Dr. Google, I am in Pain"-Global Internet Searches Associated with Pain: A Retrospective Analysis of Google Trends Data.

We aimed to rank the most common locations of pain among Google users globally and locally and analyze secular and seasonal trends in pain-related searches in the years 2004-2019. We used data generated by Google Trends (GT) to identify and analyze global interest in topics (n = 24) related to locations of pain and how these progressed over time. We analyzed secular trends and time series decomposition to identify seasonal variations. We also calculated the interest in all topics with reference to the relative search volume (RSV) of "Abdominal pain". Google users were most commonly interested in "Headache" (1.30 [times more frequently than "Abdominal pain"]), "Abdominal pain" (1.00), and "Back pain" (0.84). "Headache" was the most frequent search term in n = 41 countries, while "Abdominal pain" was the most frequent term in n = 27 countries. The interest in all pain-related topics except "Dyspareunia" increased over time. The sharpest increase was observed for "Abdominal pain" (5.67 RSV/year), and "Toothache" (5.52 RSV/year). Most of the topics revealed seasonal variations. Among pain-related topics, "Headache," "Abdominal pain," and "Back pain" interested most Google users. GT is a novel tool that allows retrospective investigation of complaints among Internet users.