Becky McCall

September 20, 2017

LISBON, PORTUGAL — Habitual consumption of artificial sweeteners commonly found in diet drinks alters the gut's response to glucose — affecting absorption, glycemic response, and response of gut glucagonlike peptide 1 (GLP-1) — results of a small, first-in-human study in healthy volunteers indicate.

The findings were presented here at the European Association for the Study of Diabetes (EASD) 2017 Annual Meeting

High levels of artificial-sweetener consumption could therefore predispose people to development of type 2 diabetes, lead researcher Richard Young, MD, from the Adelaide Medical School, University of Adelaide, Australia, hypothesized.

"Two-week diet supplementation with artificial sweeteners augments glucose absorption, glycemic response to glucose, and attenuates the GLP-1 response," said Dr Young, reporting the main results of the study.

"This means that, according to the findings from this trial…artificial sweeteners [may] limit the amount of glucose that can access more distal portions of the gut and reduce glucose exposure to distal cells that release GLP-1."

Artificial Sweeteners Compared With Placebo in Healthy Subjects

"The relationship between sugar-sweetened beverages and type 2 diabetes has prompted policy changes, including the introduction of taxes on these beverages to try to reduce intake," Dr Young pointed out.

As an alternative, artificial sweeteners are used in so-called "diet" sodas and some foodstuffs, but there is ongoing controversy over whether these cause more harm than good.

Previous work by Dr Young's group has shown that switching from sugar to noncaloric-artificial-sweetened (NAS) beverages does not predict a lower risk of type 2 diabetes.

In fact, the association between NAS beverages and type 2 diabetes risk is similar to that seen with sugar-sweetened beverages, even after adjustment for adiposity and energy intake (often those with prediabetes reach for NAS as an alternative to sugar), he said.

Until this study, it was unknown whether NAS alters glucose absorption in humans, and if so, whether this adversely affects postprandial glycemic control.

Healthy volunteers were recruited and the researchers assessed the effects of diet supplementation with combined NAS (such as sucralose and acesulfame-K, often found in diet beverages) for 2 weeks in a double-blind, randomized parallel-group clinical study.

Initially, 60 subjects were screened and those who were high habitual consumers of sweeteners were excluded. Participants had a mean age of 27 years, a body mass index of 24 kg/m2, and 14 were men. After an overnight fast, participants underwent an endoscopy incorporating a 30-minute intraduodenal glucose infusion (30 g/150 mL, 3 kcal/min, including 3 g of the glucose analogue 3-omethyl glucose [3-OMG]) and biopsy collection before and immediately after the intervention.

The scientists assessed the effects on glucose absorption, glycemic responses to intraduodenal glucose infusion, insulin production, and gut hormones, including glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 and GLP-2.

Taken in the form of capsules, three times daily before meals, blinded participants received either the combined NAS (n = 17), equivalent to drinking 1.2 to 1.5 L of diet beverage per day or an inactive placebo (n = 16).

Assessments were performed after participants had taken the NAS capsules or placebo for 2 weeks. At this time, subjects had their response to glucose tested, examining glucose absorption, plasma glucose, and levels of insulin and gut peptides.

Glucose Absorption and Glycemic Response Increased With Sweeteners

With respect to glucose absorption, the two groups showed similar absorption patterns at study start in response to enteral glucose.

But "after 2 weeks of NAS supplementation, there was increased glucose absorption that was significant at 90 to 120 minutes [after start of glucose consumption]. We showed that sweeteners do augment the uptake of glucose," reported Dr Young. There was a 20% difference between glucose absorption in the placebo and NAS-supplemented group (≤ .05).

The two groups had similar prestudy glycemic responses to enteral glucose, but NAS supplementation increased plasma glucose levels by 24% compared with placebo (< .05).

For GLP-1, which acts to limit the rise in blood glucose after meals, the two groups were once again well-matched in response to enteral glucose prior to NAS supplementation.

But after the 2 weeks of supplementation, "the subjects who consumed sweeteners had a lower risk of GLP-1 response to enteral glucose," reported Dr Young. "Those individuals who received supplementation showed a 34% attenuated GLP-1 response (< .05) compared with placebo.

"This response possibly reflects reduced glucose exposure to more distally located L-cells," he added.

The GLP-2, GIP, and insulin responses to enteral glucose were similar between participants on artificial sweeteners and placebo groups, although GLP-2 and insulin were lower 40 and 60 mins after the glucose challenge, respectively, in the NAS group (37% for both vs baseline, ≤ .05).

Findings Provide Impetus for Larger Studies in This Area

The findings highlight "the potential for these responses in habitual consumers of artificial sweeteners and support the concept that artificial sweeteners could reduce the body's control of blood sugar levels, exaggerating postmeal glucose levels, which could predispose them to developing type 2 diabetes," Dr Young remarked.

He also noted that the results provided an impetus to perform larger studies and look at the mechanisms responsible. "We are doing this by looking at cells collected in this study as well as looking at the microbiome," he said, with a view to the next steps in his work.

Commenting on the results, session attendee Viktor Jörgens, MD, former executive director of EASD, from Dusseldorf, Germany, said it was a "brilliant study."

He remarked, "Because less glucose goes to the L cells, these cells make less GLP-1, and this is the reason these individuals have less insulin and higher glucose. I believe this study has enough power to say that this is indeed the mechanism, and it works this way."

Dr Young has declared no relevant financial relationships.

European Association for the Study of Diabetes (EASD) 2016 Annual Meeting. September 14, 2017, Lisbon, Portugal. Abstract 193

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