Janet A. Vogt

Inulin increases short-term markers for colonic fermentation similarly in healthy and hyperinsulinaemic humans.

Background/Objectives:Colonic fermentation of dietary fibre produces short-chain fatty acids (SCFAs), acetate, propionate and butyrate, which may protect against type 2 diabetes by reducing serum free-fatty acids (FFAs). Since hyperinsulinaemia is associated with insulin resistance and increased diabetes risk, the main objective was to compare markers of colonic fermentation after acute inulin ingestion in subjects with normal (<40 pmol/l, NI) and high (⩾40 pmol/l, HI) plasma insulin.Subjects/Methods:Overnight fasted NI (n=9) and HI (n=9) subjects were studied for 4 h on two separate days after consuming 300 ml drinks containing 75 g glucose (Glucose) or 75 g glucose plus 24 g inulin (Inulin) using a randomized, single-blind, crossover design.Results:Inulin elicited a higher breath hydrogen and methane areas under the curve (AUC), but the increases in SCFA responses were not statistically significant. Mean serum-acetate concentration over the 4-h study period was higher in NI than in HI subjects (44.3±6.9 vs 22.5±3.7 μmol/l, P=0.001). The rate of rebound of FFA was reduced by Inulin, with FFA at 4 h being less after Inulin than Glucose, regardless of insulin status (0.310±0.028 vs 0.432±0.042 mEq/l, P=0.008).Conclusions:This suggests that inulin increases short-term markers for colonic fermentation, but a longer study period may be necessary to observe differences in SCFA production. The reason for the lower serum acetate in HI is unclear but may be due to reduced absorption, increased clearance or decreased endogenous production. This suggests the need to compare acetate kinetics in normal and hyperinsulinaemic subjects.

Intravenous acetate elicits a greater free fatty acid rebound in normal than hyperinsulinaemic humans.

Background/objectives:Colonic fermentation of dietary fiber may improve insulin sensitivity by the metabolic effects of short chain fatty acids (SCFA) in reducing free fatty acids (FFA). The main objectives of this study were to compare peripheral uptake of acetate (AC) in participants with normal (<40 pmol/l, NI) and high (⩾40 pmol/l, HI) plasma insulin, and the ability of AC to reduce FFA in both the groups.Subjects/methods:Overnight fasted NI (n=9) and HI (n=9) participants were given an intravenous (IV) infusion of 140 mmol/l sodium acetate at three different rates over 90 min. The total amount of AC infused was 51.85 mmols.Results:AC clearance in NI participants was not significantly different than that in HI participants (2.11±0.23 vs 2.09±0.24 ml/min). FFA fell in both the groups, but rebounded to a greater extent in NI than HI participants (time × group interaction, P=0.001). Significant correlations between insulin resistance (IR) indices (homeostasis model assessment of insulin resistance (HOMA-IR), Matsuda and insulinogenic index) vs FFA rebound during IV AC infusion were also observed.Conclusions:These findings suggest that AC uptake is similar in both the groups. Participants with lower plasma insulin and lower IR indices had a greater FFA rebound. These results support the hypothesis that increasing AC concentrations in the systemic circulation may reduce lipolysis and plasma FFA concentrations and thus improve insulin sensitivity. More in-depth studies are needed to look at the effects of SCFA on FFA metabolism in insulin-resistant participants.

Kinetic model of acetate metabolism in healthy and hyperinsulinaemic humans

Background/objectives:The short chain fatty acid acetate (AC), may have a role in increasing insulin sensitivity, thus lowering risk for obesity and type 2 diabetes mellitus. It is unclear if AC kinetics is similar in normal (NI) and hyperinsulinaemic (HI) participants. Therefore, we studied AC absorption from the distal colon in participants with normal (<40 pmol/l) and high (⩾40 pmol/l) plasma insulin. This work was a part of a series of studies conceived to compute a kinetic model for AC. Kinetic parameters such as estimates of rate of entry into peripheral blood, hepatic uptake and endogenous/exogenous production were compared in the groups.Subjects/methods:Overnight fasted NI (n=9) and HI (n=8) participants were given rectal infusions containing sodium AC (90 mmol/l). The solutions were retained for 40 min, then voided for AC measurement. Total amount of AC infused was 27 mmols.Results:AC absorption from the distal colon (279±103 vs 322±91 μmol/min, P=0.76) and hepatic uptake of AC (155±101 vs 146±85 μmol/min, P=0.94) were similar in the groups. Endogenous and exogenous AC production was significantly higher in NI than HI participants. Plasma AC was inversely proportional to plasma insulin concentrations in the entire cohort (y=k/x, where k=1813).Conclusions:There was low power to detect differences in AC absorption rate and hepatic AC uptake in NI vs HI. The rate of entry of AC into peripheral blood was similar in NI and HI participants. However, hyperinsulinaemia may alter endogenous and exogenous AC metabolism.