3.3 Carbohydrate Chemistry, Digestion, and Glycemic Pathways

Carbohydrates represent the primary dietary source of metabolic energy for human physiological processes, supplying approximately 4 kcal/g (16.7 kJ/g) of metabolizable energy. In clinical dietetics and metabolic biochemistry, understanding the molecular configuration of carbohydrates, their luminal hydrolysis, transport kinetics across the intestinal mucosal barrier, and their intrahepatic and peripheral fates is essential for managing diabetes mellitus, critical illness, glycogen storage diseases, and metabolic syndrome.

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Carbohydrate Classification and Chemistry

Carbohydrates are polyhydroxy aldehydes or ketones, or substances that yield these compounds upon hydrolysis. They are categorized based on their degree of polymerization into monosaccharides, disaccharides, oligosaccharides, and polysaccharides.

Monosaccharides

Monosaccharides are the simplest carbohydrate units and cannot be hydrolyzed into smaller carbon chains:

• Hexoses ($C_6H_{12}O_6$): The principal dietary hexoses are D-glucose (an aldohexose), D-galactose (an aldohexose and C-4 epimer of glucose), and D-fructose (a ketohexose). In aqueous solutions, monosaccharides exist predominantly in cyclic hemiacetal or hemiketal ring forms: pyranose (six-membered ring) or furanose (five-membered ring).
• Isomerism and Anomers: The cyclization creates an asymmetric center at the former carbonyl carbon, known as the anomeric carbon (C-1 in aldoses, C-2 in ketoses). Mutarotation establishes an equilibrium between $\alpha$ (hydroxyl oriented downward in Haworth projection) and $\beta$ (hydroxyl oriented upward) anomers.
• Pentoses ($C_5H_{10}O_5$): Ribose and deoxyribose serve as structural backbones for ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and high-energy nucleotides (ATP, NADH, FADH2, NADPH).

Disaccharides

Disaccharides consist of two hexose units joined by a condensation reaction yielding an O-glycosidic bond:

• Maltose: Formed by two $\alpha$-D-glucopyranose units linked by an $\alpha(1\to4)$ glycosidic bond. It is an intermediate product of starch hydrolysis and retains a free anomeric carbon, functioning as a reducing sugar.
• Lactose: The predominant carbohydrate in mammalian milk, composed of $\beta$-D-galactopyranose and $\alpha$-D-glucopyranose joined by a $\beta(1\to4)$ glycosidic bond. It is a reducing sugar.
• Sucrose: Table sugar, composed of $\alpha$-D-glucopyranose and $\beta$-D-fructofuranose linked via an $\alpha(1\to\beta2)$ glycosidic bond. Because the bond links the anomeric carbons of both monosaccharides (C-1 of glucose and C-2 of fructose), sucrose has no free hemiacetal or hemiketal group and is a non-reducing sugar.
• Trehalose: Composed of two $\alpha$-D-glucose units joined by an $\alpha(1\to1)$ glycosidic linkage. Found in mushrooms and yeast, it is also a non-reducing sugar.

Polysaccharides: Starch and Glycogen

Polysaccharides are high-molecular-weight polymers composed of repeating monosaccharide subunits:

• Amylose: A linear, unbranched polymer of D-glucose units linked exclusively by $\alpha(1\to4)$ glycosidic bonds. Amylose adopts a tight three-dimensional helical conformation that limits water access and slows down enzymatic hydrolysis by $\alpha$-amylase. Retrograded amylose forms type 2 and type 3 resistant starch.
• Amylopectin: A branched polymer comprising a linear backbone of $\alpha(1\to4)$ glycosidic bonds with $\alpha(1\to6)$ branch points occurring every 24 to 30 glucose residues. Branching exposes numerous non-reducing ends to amylolytic cleavage, facilitating rapid enzymatic breakdown and eliciting a steeper postprandial glycemic surge than amylose.
• Glycogen: The animal storage polysaccharide, concentrated in the liver (up to 5–6% of wet organ weight, ~100–120 g) and skeletal muscle (1–2% wet weight, ~400–500 g). Glycogen is structurally similar to amylopectin but far more densely branched, with $\alpha(1\to6)$ branch points occurring every 8 to 12 glucose units, ensuring rapid mobilization of glucose during exercise or hypoglycemia.

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Dietary Fiber: Viscous Soluble vs. Insoluble Fractions

Dietary fiber consists of non-digestible carbohydrates and lignin that are intrinsic and intact in plants. Functional fiber consists of isolated, non-digestible carbohydrates that have proven beneficial physiological effects in humans. Total fiber is the sum of dietary fiber and functional fiber.

Soluble, Viscous, and Fermentable Fiber

Soluble fibers dissolve in water to form viscous gels within the gastrointestinal tract:

• Major Types: Pectins (citrus fruits, apples), $\beta$-glucans (oats, barley), plant gums (guar gum, gum arabic), and mucilages (psyllium husk).
• Physiological Mechanisms:
  1. Delayed Gastric Emptying: High viscosity increases chyme transit time through the stomach and upper small intestine, blunting postprandial glucose spikes and prolonging satiety signals.
  2. Interference with Micelle Diffusion: Viscous gels thicken the unstirred water layer along the brush border, impeding lipid and carbohydrate diffusion to mucosal transport sites.
  3. Bile Acid Sequestration: Soluble fibers bind bile acids in the ileum, preventing their enterohepatic reabsorption and forcing the liver to convert endogenous cholesterol into bile salts, which upregulates hepatic LDL receptors and lowers serum LDL-C.
  4. Colonic Fermentation: Anaerobic microflora ferment soluble fibers into short-chain fatty acids (SCFAs): acetate (C2), propionate (C3), and butyrate (C4). Butyrate serves as the primary metabolic fuel for colonocytes; propionate travels to the liver via the portal vein where it inhibits hepatic HMG-CoA reductase and modulates gluconeogenesis; acetate serves as a substrate for peripheral tissues.

Insoluble Non-Viscous Fiber

Insoluble fibers do not dissolve in aqueous solutions and resist colonic bacterial fermentation:

• Major Types: Cellulose (unbranched polymer of $\beta(1\to4)$-linked D-glucose), hemicelluloses (xylans, glucuronoxylans), and lignin (a complex non-carbohydrate polymer of phenylpropane units).
• Physiological Mechanisms: Insoluble fibers add physical bulk to the stool by mechanically irritating the colonic mucosa, stimulating water and mucous secretion, and accelerating colonic transit time. This reduces intraluminal colonic pressure, protecting against constipation, diverticulosis, and hemorrhoids.

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Digestion, Brush Border Hydrolysis, and Monosaccharide Absorption

Carbohydrate digestion is an ordered, multi-compartment process converting dietary starch and disaccharides into absorbable monosaccharides.

Dietary Starches (Amylose, Amylopectin)
       │
       ▼ [Salivary Amylase: mouth]
Short Dextrins, Maltose, Maltotriose
       │
       ▼ [Gastric Phase: acid inactivation of amylase at pH < 3.5]
Acid Chyme entering Duodenum
       │
       ▼ [Pancreatic Alpha-Amylase + Bicarbonate: duodenum]
Maltose, Maltotriose, Alpha-Limit Dextrins
       │
       ▼ [Brush Border Disaccharidases: jejunum]
Glucose, Galactose, Fructose
       │
       ├──────────────────────────────┬──────────────────────────────┐
       ▼ [SGLT-1: Active Symport]    ▼ [SGLT-1: Active Symport]    ▼ [GLUT-5: Facilitated Diffusion]
    Glucose                        Galactose                      Fructose
       │                              │                              │
       └──────────────────────────────┴──────────────────────────────┘
                                      │
                                      ▼ [Basolateral GLUT-2]
                                Portal Blood Flow

Luminal Digestion

1. Oral Cavity: Salivary $\alpha$-amylase (ptyalin) initiates digestion by cleaving internal $\alpha(1\to4)$ bonds of starch. It cannot cleave terminal bonds or $\alpha(1\to6)$ branch linkages. Its optimum pH is 6.8, and it is rapidly inactivated by gastric hydrochloric acid in the stomach.
2. Small Intestinal Lumen: Pancreatic $\alpha$-amylase, secreted into the duodenum in response to cholecystokinin (CCK) and secretin, hydrolyzes starches into maltose (disaccharide), maltotriose (trisaccharide), and $\alpha$-limit dextrins (branched oligosaccharides containing the original $\alpha(1\to6)$ branch points).

Brush Border Disaccharidases

The microvillar membrane of enterocytes expresses specific anchored glycoprotein disaccharidases:

• Maltase-Glucoamylase: Cleaves terminal $\alpha(1\to4)$ bonds of maltose, maltotriose, and linear oligosaccharides, releasing free glucose.
• Sucrase-Isomaltase Complex: A bifunctional enzyme. The isomaltase subunit is the only intestinal enzyme capable of cleaving the $\alpha(1\to6)$ bonds of $\alpha$-limit dextrins; the sucrase subunit cleaves sucrose into D-glucose and D-fructose.
• Lactase (Lactase-Phlorizin Hydrolase): Hydrolyzes the $\beta(1\to4)$ linkage of lactose into D-glucose and D-galactose. In primary lactase deficiency (adult-type hypolactasia), unabsorbed lactose exerts an osmotic draw in the ileum and colon, causing watery diarrhea, while colonic bacterial fermentation produces lactic acid, hydrogen gas ($H_2$), carbon dioxide ($CO_2$), and methane ($CH_4$), resulting in abdominal distention, cramping, and flatulence.

Monosaccharide Transporters

Monosaccharides enter and exit enterocytes through specific carrier proteins:

• SGLT-1 (Sodium-Glucose Cotransporter 1): Located on the apical (luminal) brush border membrane. It transports glucose and galactose into the enterocyte against their steep intracellular concentration gradients via secondary active symport, moving two $Na^+$ ions down their electrochemical gradient for every monosaccharide transported. The required intracellular sodium gradient is actively maintained by the ATP-consuming basolateral $Na^+/K^+$ ATPase pump.
• GLUT-5: Located on the apical membrane, GLUT-5 is a uniporter mediating the facilitated diffusion of fructose. Because it is non-energy-dependent, fructose absorption is concentration-dependent and has a limited saturable capacity, explaining why large oral boluses of free fructose trigger osmotic diarrhea and abdominal distress.
• GLUT-2: Positioned primarily on the basolateral membrane, GLUT-2 exports glucose, galactose, and fructose out of the enterocyte into the interstitial space and portal capillaries via facilitated diffusion. Under high luminal glucose concentrations, GLUT-2 can also transiently translocate to the apical membrane to facilitate rapid bulk glucose clearance.

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Central Carbohydrate Metabolic Pathways

                          Extracellular Glucose
                                   │
                                   ▼ (GLUT-1, 2, 3, 4)
                          Intracellular Glucose
                                   │
       Hexokinase/Glucokinase ────┼────► (Consumes 1 ATP)
                                   ▼
                          Glucose-6-Phosphate (G6P)
                                   │
          ┌────────────────────────┼────────────────────────┐
          ▼                        ▼                        ▼
  [Glycogenesis]           [Glycolysis]             [Pentose Phosphate Pathway]
  Glucose-1-Phosphate      Fructose-6-Phosphate     6-Phosphogluconate
          │                        │                        │
  UDP-Glucose                      ▼ (PFK-1: ATP/AMP)       ▼ (G6PD: generates NADPH)
          │                Fructose-1,6-BP          Ribose-5-Phosphate
          ▼                        │
       Glycogen                    ▼
                                Pyruvate (Yield: 2 ATP, 2 NADH)
                                   │
                         ┌─────────┴─────────┐
                         ▼                   ▼
                     (Anaerobic)         (Aerobic / Mitochondria)
                      Lactate           Acetyl-CoA
                                             │
                                             ▼
                                     Citric Acid Cycle (TCA)
                                             │
                                             ▼ (NADH, FADH2)
                                  Electron Transport Chain
                                             │
                                             ▼
                                    30–32 ATP / Glucose

1. Glycolysis (Embden-Meyerhof Pathway)

Glycolysis is a ten-step cytosolic pathway that converts one molecule of glucose ($C_6$) into two molecules of pyruvate ($C_3$), producing a net yield of 2 ATP (substrate-level phosphorylation) and 2 NADH.

Three irreversible, allosterically regulated enzymatic steps govern glycolytic flux:

1. Step 1: Hexokinase vs. Glucokinase (Glucose $\to$ Glucose-6-Phosphate):
   • Hexokinase (Isozymes I–III): Expressed in extrahepatic tissues. Exhibits a low $K_m$ (high affinity, $\approx 0.05–0.1\text{ mM}$) and a low $V_{max}$, operating at maximum velocity even during fasting. It is allosterically inhibited by its product, glucose-6-phosphate (G6P).
   • Glucokinase (Hexokinase IV): Localized exclusively to hepatocytes and pancreatic $\beta$-cells. Exhibits a high $K_m$ (low affinity, $\approx 10\text{ mM}$) and a high $V_{max}$. It is not inhibited by G6P, allowing the liver to rapidly clear high postprandial glucose loads from the portal vein. In the fasting state, glucokinase is bound and sequestered in the nucleus by glucokinase regulatory protein (GKRP); high cytosolic glucose promotes its nuclear release.
2. Step 3: Phosphofructokinase-1 (PFK-1): The rate-limiting, committed step of glycolysis, converting fructose-6-phosphate to fructose-1,6-bisphosphate while consuming one ATP.
   • Allosteric Activators: Fructose-2,6-bisphosphate (F-2,6-BP) is the most potent physiological activator, overriding high-energy inhibition. AMP and ADP also activate PFK-1.
   • Allosteric Inhibitors: ATP and citrate (signaling abundant energy and TCA cycle intermediate availability).
   • Hormonal Control of F-2,6-BP: Regulated by the bifunctional tandem enzyme PFK-2 / FBPase-2. Insulin stimulates protein phosphatase-1, dephosphorylating the enzyme, activating PFK-2, elevating F-2,6-BP, and driving glycolysis. Glucagon activates cAMP-dependent Protein Kinase A (PKA), phosphorylating the enzyme, which inactivates PFK-2 and activates FBPase-2, depleting F-2,6-BP and halting glycolysis.
3. Step 10: Pyruvate Kinase: Catalyzes the conversion of phosphoenolpyruvate (PEP) to pyruvate, generating ATP.
   • Activators: Fructose-1,6-bisphosphate (feedforward activation).
   • Inhibitors: ATP, acetyl-CoA, and alanine.
   • Hormonal Regulation: Glucagon triggers PKA phosphorylation of hepatic pyruvate kinase, inactivating it to prevent PEP consumption during gluconeogenesis.

2. Aerobic vs. Anaerobic Fates of Pyruvate and the Cori Cycle

• Aerobic Oxidation: In the presence of oxygen, pyruvate enters the mitochondrial matrix via the mitochondrial pyruvate carrier (MPC) and is oxidatively decarboxylated to Acetyl-CoA by the multienzyme Pyruvate Dehydrogenase (PDH) Complex, generating 1 NADH and 1 $CO_2$. The PDH complex requires five coenzymes: thiamine pyrophosphate (TPP from $B_1$), flavin adenine dinucleotide (FAD from $B_2$), nicotinamide adenine dinucleotide ($NAD^+$ from $B_3$), coenzyme A (CoA from $B_5$), and lipoic acid.
• Anaerobic Glycolysis: In tissues lacking mitochondria (mature erythrocytes) or poorly oxygenated tissues (intensely contracting skeletal muscle), pyruvate is reduced to L-lactate by cytosolic lactate dehydrogenase (LDH). This reaction is vital because it oxidizes NADH back to $NAD^+$, replenishing the cellular $NAD^+$ required for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to maintain glycolytic ATP synthesis.
• The Cori Cycle: Lactate produced by anaerobic tissues enters the circulation, travels to the liver, and is re-oxidized to pyruvate by hepatic LDH. Hepatic gluconeogenesis converts pyruvate back into glucose at the expense of 6 ATP equivalents, which is then released back into the blood.

3. Citric Acid Cycle (Krebs / TCA Cycle)

Operating within the mitochondrial matrix, the citric acid cycle completely oxidizes the two-carbon acetyl unit of acetyl-CoA to two molecules of $CO_2$. In each turn of the cycle, condensation of acetyl-CoA with oxaloacetate generates citrate (via citrate synthase). Subsequent oxidations yield:

• 3 NADH (via isocitrate dehydrogenase, $\alpha$-ketoglutarate dehydrogenase, and malate dehydrogenase)
• 1 $FADH_2$ (via succinate dehydrogenase / Complex II)
• 1 GTP or ATP (via succinyl-CoA synthetase)
• Oxidation of these reducing equivalents through the mitochondrial electron transport chain (oxidative phosphorylation) yields $\approx 10\text{ ATP}$ per acetyl-CoA, or $30–32\text{ ATP}$ per mole of fully oxidized glucose.

4. Gluconeogenesis

Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors (lactate, glycerol, and glucogenic amino acids, primarily alanine and glutamine). It occurs primarily in the liver (~90%) and to a lesser extent in the renal cortex (~10%; increasing up to 40% during prolonged starvation or chronic metabolic acidosis). Gluconeogenesis bypasses the three irreversible steps of glycolysis:

1. Pyruvate to Phosphoenolpyruvate (PEP): Requires two steps. Mitochondrial Pyruvate Carboxylase carboxylates pyruvate to oxaloacetate (consuming 1 ATP, requires biotin, allosterically activated by acetyl-CoA). Oxaloacetate is reduced to malate or transaminated to aspartate to exit the mitochondria, then reconverted to oxaloacetate in the cytosol. Cytosolic/mitochondrial PEP Carboxykinase (PEPCK) then converts oxaloacetate to PEP (consuming 1 GTP, induced by glucagon, cortisol, and epinephrine).
2. Fructose-1,6-Bisphosphate to Fructose-6-Phosphate: Catalyzed by Fructose-1,6-Bisphosphatase-1 (FBPase-1). This is the rate-limiting enzyme of gluconeogenesis. It is allosterically inhibited by AMP and F-2,6-BP, and stimulated by ATP and citrate.
3. Glucose-6-Phosphate to Free Glucose: Catalyzed by Glucose-6-Phosphatase, located in the lumen of the endoplasmic reticulum. It is expressed in the liver and kidneys, but absent in skeletal muscle. Consequently, skeletal muscle glycogen cannot directly supply free glucose to the systemic circulation to correct hypoglycemia; muscle glycogen can only be used intracellularly for muscle contraction.

5. Glycogenesis and Glycogenolysis

• Glycogenesis: G6P is converted to G-1-P by phosphoglucomutase, then activated to UDP-glucose by UDP-glucose pyrophosphorylase. Glycogen Synthase (the rate-limiting enzyme) transfers glucosyl residues from UDP-glucose to glycogen chains via $\alpha(1\to4)$ linkages. A glycogen branching enzyme (amylo-$\alpha(1\to4)\to\alpha(1\to6)$-transglucosidase) creates $\alpha(1\to6)$ branch points every 8–12 units. Glycogen synthase is activated by insulin (via protein phosphatase-1 dephosphorylation) and high G6P; it is inactivated by glucagon and epinephrine (via PKA phosphorylation).
• Glycogenolysis: Glycogen Phosphorylase (the rate-limiting enzyme, requiring pyridoxal phosphate [PLP / Vitamin $B_6$]) cleaves $\alpha(1\to4)$ bonds phosphorolytically, releasing glucose-1-phosphate until four glucosyl residues remain before an $\alpha(1\to6)$ branch point (forming a "limit dextrin"). A bifunctional debranching enzyme (4-$\alpha$-D-glucanotransferase + amylo-$\alpha(1\to6)$-glucosidase) transfers three outer glucosyl residues to a nearby chain and hydrolyzes the remaining $\alpha(1\to6)$-linked glucose as free glucose (~10% of glycogen residues). Hepatic glycogen phosphorylase is activated by glucagon and epinephrine via PKA; muscle phosphorylase is allosterically activated by AMP and $Ca^{2+}$-calmodulin.

6. Pentose Phosphate Pathway (Hexose Monophosphate Shunt)

This cytosolic pathway operates in tissues requiring high levels of reductive biosynthesis (adrenal cortex, liver, lactating mammary glands, adipose tissue) and erythrocytes:

• Oxidative Branch (Irreversible): Glucose-6-phosphate is oxidized by Glucose-6-Phosphate Dehydrogenase (G6PD), generating 2 NADPH per G6P and ribulose-5-phosphate. G6PD is rate-limiting and strictly regulated by the $NADP^+/NADPH$ ratio.
• Functions of NADPH:
  1. Drives reductive biosynthetic pathways: fatty acid synthesis, cholesterol synthesis, and steroid hormone production.
  2. Maintains cellular antioxidant defenses: reduces oxidized glutathione ($GSSG$) back to reduced glutathione ($GSH$) via glutathione reductase, enabling glutathione peroxidase to neutralize reactive oxygen species ($H_2O_2$).
  3. Serves as a cofactor for cytochrome P450 monooxygenases and phagocytic NADPH oxidase in neutrophils.
• Non-Oxidative Branch (Reversible): Interconverts pentose phosphates with glycolytic intermediates (fructose-6-phosphate and glyceraldehyde-3-phosphate) via transketolase (requires thiamine pyrophosphate [TPP]) and transaldolase, supplying ribose-5-phosphate for DNA/RNA nucleotide synthesis.
• G6PD Deficiency (Favism): An X-linked recessive disorder and the most common human enzyme defect worldwide. Erythrocytes lack mitochondria and depend exclusively on G6PD for NADPH. When exposed to oxidative triggers (infections, fava beans, primaquine, sulfonamides), depleted GSH causes hydrogen peroxide to oxidize hemoglobin into insoluble Heinz bodies, leading to acute intravascular and extravascular hemolytic anemia.

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Glycemic Index (GI) and Glycemic Load (GL)

In medical nutrition therapy, carbohydrates are evaluated not merely by their chemical mass, but by their physiological impact on postprandial glycemia and insulinemia.

Glycemic Index (GI)

The Glycemic Index measures the relative rise in blood glucose concentration following consumption of a defined quantity of available carbohydrate compared to an identical quantity of a reference carbohydrate (pure D-glucose or white bread, standard index = 100):

$\text{GI} = \left( \frac{\text{iAUC}_{\text{test food}}}{\text{iAUC}_{\text{reference food}}} \right) \times 100$

Where $\text{iAUC}$ represents the incremental area under the 2-hour blood glucose response curve after ingesting 50 grams of available (glycemic) carbohydrate from the test food.

• Low GI: $\le 55$ (e.g., legumes, intact whole oats, barley, apples, lentils)
• Medium GI: $56–69$ (e.g., brown rice, sweet potato, whole wheat bread)
• High GI: $\ge 70$ (e.g., white jasmine rice, white baguette, cornflakes, boiled potatoes, glucose)

Determinants of Glycemic Index

1. Starch Architecture: High amylose starches have a lower GI than high amylopectin starches due to tight helical packing.
2. Particle Size and Physical Entrapment: Intact whole grains retain an outer fibrous bran layer that slows amylolytic enzyme access compared to finely milled flours.
3. Starch Gelatinization and Retrogradation: Cooking hydrates and swells starch granules (gelatinization), increasing enzyme accessibility and elevating GI. Cooling cooked starches (such as chilled cooked rice or potatoes) causes amylose polymers to recrystallize into insoluble retrograded resistant starch (Type 3 RS), lowering the GI.
4. Co-ingestion of Fat, Protein, and Acid: Dietary fats and proteins trigger CCK and enterogastrone release, delaying gastric emptying and flattening postprandial glucose curves. Organic acids (acetic acid in vinegar, lactic acid in fermented sourdough) lower gastric pH and suppress gastric motility.

Glycemic Load (GL)

While GI reflects carbohydrate quality, it fails to account for the typical portion size or carbohydrate density of a standard serving. The Glycemic Load combines both quality and quantity:

$\text{GL} = \frac{\text{GI} \times \text{Available Carbohydrate per serving (g)}}{100}$

• Low GL: $\le 10$
• Medium GL: $11–19$
• High GL: $\ge 20$

Clinical Example & Comparison

Consider fresh watermelon versus boiled white rice:

• Watermelon: A high GI of 72. However, watermelon is 92% water; a standard 120 g slice contains only 6 g of available carbohydrate: $\text{GL} = \frac{72 \times 6}{100} = 4.32 \quad (\text{Low GL})$
• Boiled White Rice: A high GI of 73. A standard cooked serving (1 cup, ~160 g) provides 45 g of available carbohydrate: $\text{GL} = \frac{73 \times 45}{100} = 32.85 \quad (\text{High GL})$

Watermelon produces a brief, modest postprandial glucose excursion despite its high GI because of its minimal carbohydrate density, whereas white rice delivers a massive total glycemic impact. Prescribing low-GL diets improves glycated hemoglobin (HbA1c), reduces postprandial glycemic excursions, and improves lipid profiles in individuals with diabetes mellitus.