Elevated blood sugar doesn’t just affect your energy—it sparks chronic inflammation that can harm your metabolism, gut, and overall health. In this blog, Dr. Mindy explains the science behind hyperglycemia-induced inflammation and shares actionable strategies, like prebiotic fiber and antioxidant-rich foods, to help you take control naturally.
High blood glucose (or hyperglycemia), occurs when blood glucose levels rise above normal. It is diagnosed by a fasting glucose exceeds 100 mg/dL. The underlying causes may be:
· Too little insulin, which helps glucose get into the cells and out of the bloodstream.
· Insulin resistance where cells fail to recognize insulin, resulting in persistently elevated glucose levels. This also triggers the liver and kidneys to produce more glucose, further worsening hyperglycemia.
If left untreated, hyperglycemia can damage blood vessels, nerves, tissues, and even organs. A major culprit of this damage is chronic inflammation.
Culprit 1 – Advanced-Glycation End Products (AGEs) (1)
AGEs are formed when glucose interacts with the nitrogen found in proteins, lipids, and even the nucleic acids in our DNA. No enzymes are involved, so once the AGE is formed, it cannot be reversed. Although AGEs take a few weeks to build they can impact long-lived compounds in connective tissue, collagen, myelin, and fibrinogen. Increased stiffness of the protein matrix can impede function of such tissues. AGEs can also trap cholesterol on vessel walls leading to atherosclerosis.
Even more harmful than AGEs are the intermediate compounds, like fructose-3-phospate, which is produced when AGEs are being formed. Fructose-3-phosphate, among other intermediates, lead to hyperglycemia-induced damage like oxidative stress and cellular death.
Interestingly, glycated hemoglobin, or A1c, is also a type of AGE. Glucose attaches irreversibly to an amino acid in hemoglobin to form A1c. Higher blood glucose leads to higher glycation and corresponds to elevated A1c. Once A1c is formed, it circulates in the blood until the red blood cell dies, which takes about 2-3 months. This test is used to assess hyperglycemia over a period of time.
AGEs can also form from tobacco use and by heating protein-rich foods with sugar (known as the Maillard reaction). Dietary AGEs can be challenging to quantify as they are not differentiated from AGEs formed internally.
Culprit 2 – Pro-Inflammatory Cytokines (1)
AGEs can bind to receptors found on smooth muscle cells, macrophages, and endothelial cells. Binding AGEs to their receptors sparks a cascade of reactions inside the cell. First, free radicals and oxidative stress are induced that activates NF-kB and its genes. Second, NF-kB forms pro-inflammatory cytokines (IL-6 and TNF-α), as well as proteins involved in coagulation, vasoconstriction, and adhesion molecules (Figure 1). TNF-α inhibits insulin and beta-cell function further causing metabolic dysfunction.
Figure 1. Singh R et al., 2001 Diabetalogia
AGE receptors are, unfortunately, increased in prediabetes and diabetes. Aside from controlling blood glucose within a tight range, adequate antioxidant intake can neutralize free radicals and oxidative stress.
Examples of Antioxidants:
- Vitamin C: Protects cells from damage
- Vitamin E: Neutralizes free radicals in cell membranes and DNA
- Selenium: A cofactor for antioxidant defense
- Glutathione: Made from 3 amino acids (glutamate, cysteine, and glycine) in our body, it maintains the active form of other antioxidants
One study (2) found that individuals with impaired glucose tolerance had higher fasting blood levels of IL-6 and TNF-α which remained longer in the blood than control subjects after receiving 3 IV pulses of glucose over 3 hours. Oxidative stress from these elevated cytokines promoted low-grade systemic inflammation in these subjects. Interestingly, adding glutathione eradicated the cytokine elevation from IV glucose.
Culprit 3 – Gut Microbiome Dysbiosis
Dysbiosis is a condition in which pathogenic and toxic bacteria outnumber beneficial in our gut, mostly the large intestine. Gram-negative bacteria release lipopolysaccharide, or LPS, into the gut lumen. Tight junctions between the intestinal cells keep invaders in the gut lumen; however, high-fat diets low in fiber increase LPS formation that cause tight junctions to break down and increase permeability. Thus, LPS cross into circulation to cause endotoxemia causing a pro-inflammatory state (2; Figure 2).
Figure 2. Dysbiosis leads to chronic inflammation and aberrations in insulin function. Salazar J et al., 2020 Nutrients
LPS in circulation binds to proteins on immune and adipose cells to release TINF-α, IL-1, and IL-6 that creates low-grade, chronic inflammation that also impairs insulin’s actions. Ultimately, LPS causes pancreatic beta-cell dysfunction to reduce insulin production leading to insulin resistance.
Good news – one study administered 30 g of resistant starch from potatoes (the same resistant starch found in Renutrin®) reduced insulin, glucose, and insulin resistant measures after 12 weeks in older adults (3; Figure 3). Improvements in glucose regulation are likely due increased Bifidobacteria and correcting Proteobacteria dysbiosis. Adding a prebiotic, fuel for the beneficial bacteria, reversed dysbiosis and improved glucose regulation. Although inflammation was not measured in this study, changes in bacteria that produce LPS will ultimately lessen chronic inflammation.
Figure 3. Blood glucose levels over time in older adults (white bars) consuming resistant potato starch (30 g/d for 12 weeks) and control (black bars).
Alfa MJ et al., 2018, Front Med
Conclusion
Chronic hyperglycemia is a biochemical trigger for widespread inflammation that affects nearly every system in the body. Through the formation of AGEs, activation of inflammatory pathways, and disruption of the gut microbiome, elevated blood glucose creates a pro-inflammatory state that contributes to insulin resistance, tissue damage, and long-term disease risk.
The good news is that diet plays a powerful role in breaking this cycle. Increasing dietary fiber, especially prebiotic fibers like resistant starch, can help restore microbial balance, reduce the formation of inflammatory molecules, and improve metabolic health. When combined with dietary antioxidants and lifestyle changes, these strategies offer a science-backed way to address inflammation at its root and support long-term blood glucose regulation.
Making small but consistent changes in your daily routine, like eating more whole plant foods with natural antioxidants, and adding a prebiotic supplement, can have a lasting impact on your gut, metabolism, and overall health.
References:
(1) Singh R et al., 2001 Diabetalogia
(2) Salazar J et al., 2020 Nutrients
(3) Alfa MJ et al., 2018 Front Med