Mechanisms for Reducing the Glycemic Response

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1		Eliana Bistriche Giuntini	--	1752	2022-12-16 16:12:18	\|
2	layout	Camila Xu	+ 331 word(s)	2083	2022-12-19 03:20:08	\|

This entry is adapted from the peer-reviewed paper 10.3390/foods11233934

Dietary fiber (DF), especially viscous DF, can contribute to a reduction in the glycemic response resulting from the consumption of carbohydrate-rich foods.

glycemia postprandial insulin response glycemic control

1. Introduction

According to the Codex Alimentarius Commission (CAC), ‘‘Dietary fiber means carbohydrate polymers with ten or more monomeric units, which are not hydrolyzed by the endogenous enzymes in the small intestine of humans”. This fraction includes carbohydrates polymers that occur naturally in food or are obtained from food raw materials or even synthetic polymers as long as the beneficial health effects have been proven. This definition, published in 2009, which remains in the official CAC labeling guide update ^[1], considers the physiological effects as well as the chemical nature due to the interdependence between definition and analytical methods that quantify all components of the DF ^[2]. Although non-plant sources, such as chitin and chitosan, are present in fungi, insects, and invertebrates ^[3], the most significant sources of DF are of plant origin. Different sources of DF have highly variable compositions and cell wall structures, which include the properties of polysaccharides cell wall matrix such as porosity, cell separation or rupture, and viscosity. These properties affect nutrient bioaccessibility, gastric emptying rate, gastrointestinal transit rate, and the extent of macronutrient digestion and absorption. Fiber plays a role in nutrient encapsulation, where cell walls may remain intact even after mastication and other phases of the digestion process ^[4]. This is an identified mechanism by which structurally intact plant tissues tend to be digested at a slower rate and, to a lesser extent, attenuates the postprandial increase in glycemia ^[5]. Some fiber-rich foods, such as those shown in Table 1, can influence gastric function, which includes gastrointestinal transit time and chyme viscosity, thus affecting the flow and behavior of the mixture. The ratio of liquids to solids in a meal influences the time it takes to digest; larger, denser, and/or harder food particles delay gastric emptying, while liquids and small particles move faster through the stomach (during digestive motility). In contrast, larger and heavier particles are collected in the pyloric antrum, with free lipids forming a floating layer on the surface of the bolus ^[6].

Diabetes care and management evidence analysis provide updated data on the importance of postprandial glycemic targets to delay the onset of clinical complications. The use of modern continuous glucose monitoring devices contributes more robust evidence to this field ^[7]. Results from a meta-analysis that included 11 randomized clinical trials, with volunteers mainly healthy, mean age ≥19 years, comparing low-GI (≤55) breakfast intervention (s) with high-GI (≥70) breakfast control (s) and evaluated postprandial blood glucose and/or insulin concentrations at 60, 90, and 120 min, showed that low-GI breakfasts significantly reduced postprandial blood glucose concentrations at all time points. This calls attention to the benefits of lowering the breakfast meal GI to provide clinically relevant reductions in acute glucose response ^[8].

Some factors affect the glycemic response to carbohydrate-rich food, which is the case for soluble dietary fiber (SDF), particularly viscous fibers (that promote the reduction of the gastric emptying rate and/or glucose absorption through the intestinal mucosa) and organic acids and fatty acids (that make the structure more compact by reinforcing the interactions between starch and protein, and by reducing the rate of gastric emptying). Another factor is limiting the accessibility of α-amylase to the starch molecule, which can be obtained during food production by using cereal varieties with high amylose content, whose linear structure has a lower hydrolysis rate than the branched form of amylopectin. Another option is incorporating cereal grains into products because these food particles in the gastrointestinal tract are preserved and emptied more slowly from the stomach, reducing the glycemic response ^[9].

Table 1. Examples of soluble dietary fiber (SDF), characteristics, and sources.

SDF	Main Polymer	Main Monomers	Linkage	Viscosity	Source	Reference
	Alginate	Mannuronic acid and guluronic acid	β-(1,4) D-mannuronic acid or α-(1,4) L-guluronic acid	Viscous	Cell walls from brown seaweed (Phaeophyceae)	Garcia-Cruz et al., 2008 ^[10]
	Arabinoxylan	Arabinose and xylose	β-D-(1,4) xylose	Viscous	Cereal grains	Elleuch et al., 2011 ^[11]
Psyllium	Arabinoxylan	Arabinose and xylose	β-(1,4) linked D-xylopyranosyl residues (Polymer of arabinoxylans with 1,4 and 1,3 linkages)	Viscous	Plantago ovata (seeds)	Fischer et al., 2004 ^[12]
	β-glucan	Glucose	β-(1,4) and β-(1,3) glucose	Viscous	Oat, barley, yeast, algae	Elleuch et al., 2011 ^[11]
	Galactomannan	Mannose and galactose	β-(1,4) mannopyranose, β-(1,6) D-galactopyranosyl	Viscous	Seed gums from leguminous plants and microbial sources (yeast and fungi)	Srivastava; Kapoor, 2005 ^[13]
Guar gum	Galactomannan	Mannose and galactose	β-(1,4) linked D-mannopyranosyl units with α-(1,6)-linked D-galactopyranosyl residues as side chains	Viscous	Cyamopsis tetragonolobus shrub	Mudgill et al., 2018 ^[14]
	Inulin	Fructose, glucose	β-(2,1) D fructosyl-fructose	Non-viscous	Chicory (root), onion, garlic	Elleuch et al., 2011 ^[11]
Konjak gum	Glucomannan	Glucose e mannose	β-(1,4) D-glucose and D-mannose, β-(1,6)-glucosyl	Viscous	Amorphophallus konja (tubérculo)	Chua et al., 2010 ^[15]
	Pectin	Galacturonic acid and rhamnose,	α-(1,4) linked D-galacturonic acid, (1,2) linked L-rhamnose	Viscous	Citrus peel, apple pomace, sugar beet pulp	Voragen et al., 2009 ^[16]
	Pullulan	Glucose	three α-1,4-linked glucose polymerized by α-1,6 linkages on the terminal glucose, resulting in a stair-step structure	Low viscosity	Secreted by the fungus Aureobasidium pullulans	Wolf et al., 2003 ^[17]
	Resistant maltodextrin (RD)	Dextrose	α-(1,4) D-glucose, α-(1,6) D-glucose	Low viscosity	Heat and enzymatic treatment of starch	Elleuch et al., 2011 ^[11]
Soluble corn fiber	RD	Dextrose, fructose	α-(1,4) glucose α-(1,6) D-glucose	Low viscosity	Product from enzymatic hydrolysis of cornstarch	Harrison; Hoffman, 2007 ^[18]
Nutriose	RD	Dextrose	α-(1,4) glucose α-(1,6) D-glucose and α-1,6 and (or) β-1,6; a-1,2 and (or) β-1,2; α-1,3 and (or) β-1,3; and β-1,4	Non-viscous	RD obtained from wheat, maize, or other edible starch	Hobden et al., 2021 ^[19] Li et al., 2010 ^[20]
Polydextrose		Glucose	α- and β-(1,2) (1,3) (1,4) (1,6) D-glucose, with a predominance of α and β (1.6)	Viscous	PDX is a highly branched, randomly bonded synthetic glucose polymer	do Carmo et al., 2016 ^[21]
Xanthan gum		Glucose, mannose, glucuronic acid	β-(1–4) D-glucose	Viscous	Fermentation by Xanthomonas campestris	Bhat et al., 2022 ^[22]

In recent decades, several studies have demonstrated that extracts rich in polyphenols are also effective α-amylase inhibitors that reduce postprandial blood glucose ^[23]^[24]^[25]. Produced by the pancreas and salivary glands, α-amylase catalyzes the hydrolysis of α-(1,4)-D-glucan linkages from starch and other glucose polymers. Many flavonoids have already been tested for the inhibitory activities of α-amylase, and according to Mahmood (2014) ^[23], luteolin, luteolin 7-O-glycoside, and daidzein appear to be the most efficient inhibitors. Consumption of native Brazilian fruit juices (300 mL), which are rich in flavonoids, reduced the glycemic response of bread (50 g) from 11% to 64% after consumption by 23 healthy volunteers in a short-term trial ^[24]. Polyphenols are compounds associated with DF, and the association of these two components could contribute to reducing the glycemic response of foods. However, the processing and structural alteration of food sources of DF is a critical factor that can alter intestinal digestion and the bioavailability of intracellular nutrients, which can undergo oxidation, for example ^[25].

A systematic review study with a meta-analysis of RCT analyzed the effect of dietary fiber (DF) intake on glycemic control in patients with type 2 diabetes (T2DM), using glycated hemoglobin (HbA1c) and fasting plasma glucose as parameters, evaluated at the beginning and end of the study. Data from 11 studies with a duration range of 8−24 weeks, n = 605 patients, were used. Diets rich in DF, which include fiber-rich foods (up to 42.5 g/day; four studies) or supplements containing SDF (up to 15.0 g/day; nine studies) reduced HbA1c values by ~5%, which was considered clinically relevant as it is similar to the proportion obtained by some medications for T2DM. The 9.97 mg/dL reduction in fasting plasma glucose led the authors to consider SDF as an adjuvant tool in the treatment of patients with T2DM ^[26].

Adding DF to solid and liquid foods rich in carbohydrates can promote significant reductions in postprandial glucose absorption. However, palatability issues at the concentrations needed to see the beneficial effect may limit its applications as a functional food ingredient. At the same time, food processing can cause changes in the physicochemical properties of DF and negatively impact the viscosity of soluble fractions, reducing their effectiveness ^[27].

Oat β-glucan was extruded under different conditions, thus resulting in a range of molecular weight fractions and distinct viscosities. Microscopic examination showed that more severe extrusion conditions cause depolymerization, where the integrity of the cell walls was lost, and β-glucan dispersed throughout the cereal. Differences in the hardness and density of the extruded cereals were also evident as the molecular weight decreased ^[28].

An interesting study using several imaging techniques (X-ray diffraction, micro-X-ray microtomography, and electronic microscopy) evaluated four food products produced with different processing technologies (extruded products, rusks, soft-baked cakes, and rotary-molded biscuits). It was possible to observe that the rotary-molded process preserved the higher content of slowly digestible starch and its crystalline structure, thus resulting in a lower glycemic and insulinemic response ^[29].

2. Mechanisms for Reducing the Glycemic Response

According to McRorie Jr. and McKeown (2017) ^[30], the efficacy of soluble dietary fiber (SDF) in glucose and insulin metabolism seems to be proportional to the viscosity of hydrated fiber, which has been observed in short-term studies ^[31]. Several clinical studies lasting a few months found that consumption of a viscous, soluble fiber supplement (for example, gel-forming fibers such as psyllium and guar gum) given with meals can improve glycemic control ^[12]^[30]^[32]^[33]^[34]. This involves reducing fasting plasma levels of glucose, insulin, and HbA1c, which are observed in individuals at risk of developing T2DM and patients being treated for T2DM. A mechanism to improve glycemic control with an SDF supplement is to significantly increase the viscosity of the chyme in a dose-dependent manner ^[35]. Viscosity can delay gastric emptying, and the absorption of glucose in the small intestine slows down; in addition, there are increases in the viscosity of the unstirred layer ^[31]. The effect of viscosity on glucose release was studied in a well-controlled in vitro model (TIM-1-system). Three different conditions (∼1 mPa·s, ∼15 mPa·s, and ∼100 mPa·s) were tested, and when the bolus viscosity increased from ∼1 mPa·s to ∼15 mPa·s, the maltodextrin to glucose conversion was reduced by 35%, but no effect was present in the remaining increment ^[36].

The increasing viscosity slows the interaction between digestive enzymes and nutrients and, consequently, the breakdown of nutrients into components that will be absorbed in the brush border, including glucose ^[37]. A more viscous chyme, due to the presence of SDF, slows digestion and absorption; hence, nutrients that would usually be absorbed at the beginning of the small intestine can reach the distal ileum, where they are usually minimally present ^[38]. Nutrients administered to the distal ileum can stimulate mucosal L cells to release glucagon-like peptide (GLP-1) into the bloodstream. GLP-1 has a short half-life (~2 min) associated with reduced appetite, stimulating the growth of pancreatic beta cells (insulin-producing cells), improving insulin production and sensitivity, and decreasing glucagon secretion (the peptide that stimulates glucose production in the liver) ^[37]. The presence of macronutrients in the distal ileum can also stimulate the phenomenon of the ileal brake, a mechanism mediated by the ileal hormone peptide YY and GLP-1, in a combination of effects that influence the digestive process and food consumption ^[38]. The ileal brake phenomenon can effectively delay gastric emptying and small bowel transit, attenuating nutrient loss to the large intestine ^[37]^[38]. It is important to note that viscous fiber can only delay but not reduce total nutrient absorption ^[39], which can occur throughout the entire small intestine.

The mechanism related to the viscosity of SDF is well-documented ^[6]^[31]^[36]^[39]. Still, the presence of fermentable soluble fibers may also be responsible for the reduction in blood glucose and postprandial insulin levels ^[40], and the decrease in blood glucose and insulin peaks after the first and second meals ^[41]. This effect may be due to the reduced digestibility of soluble fiber, such as soluble corn fiber ^[40], and short-chain fatty acids (SCFAs) production during colonic fermentation. SCFAs act on intestinal endocrine cells and/or in neurons of the enteric nervous system to alter gastrointestinal motility and secretion ^[42].

SCFAs also act as signaling molecules, activating G protein-coupled receptors (GPCRs), especially GPR41 and GPR43 on the brush border membrane. They stimulate the release of GLP-1 and peptide YY by enteroendocrine cells ^[43], which are hormones also stimulated by macronutrients in the ileum, with the effects described above. The Na⁺ glucose cotransporter SGLT1 facilitates intestinal absorption of glucose and galactose. In contrast, fructose uptake is facilitated by GLUT5, transporters expressed on the apical surface of enterocytes from the small intestine ^[44]. If an SDF delays the arrival of sugars in the intestinal lumen, it limits their accessibility to their respective enterocyte receptors. In that case, the absorption of these sugars and the postprandial glucose response will be delayed. In addition, SGLT1 stimulation can be reduced by releasing GLP-1 and peptide YY due to the presence of glucose in the most distal region of the intestine, with a higher prevalence of L cells.

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Eliana Bistriche Giuntini

Fabiana Andrea Hoffmann Sardá

Elizabete Wenzel de Menezes

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1. Introduction

2. Mechanisms for Reducing the Glycemic Response

References