How the Body Manages Fuel: Insulin Resistance, Glucose, Lactate, and the Gut Microbiome

To fully understand insulin resistance, inflammation, and overall wellness, it helps to begin with the fundamentals of how the body manages fuel. Energy metabolism is not just about burning calories — it determines how the brain functions, how the liver handles sugar, and how inflammation spreads throughout the body. While your body can also use fat and, in certain cases, amino acids from protein as energy sources, this discussion focuses on glucose and lactate — the central players in daily metabolism.

Your body’s primary fuel is glucose, a simple sugar from food that enters the bloodstream and then moves into cells, where it is broken down to make ATP, the “energy currency” that powers every heartbeat, thought, and muscle contraction. When oxygen is available, the body uses aerobic metabolism, an efficient process that produces about 30–32 ATP from a single glucose molecule [1]. Aerobic metabolism is much like a fire: a campfire won’t burn without oxygen, and the more oxygen it has, the brighter and cleaner it burns. In your body, oxygen is delivered to every tissue by hemoglobin in red blood cells, which carry it from your lungs to where it is needed most. When oxygen is present, glucose is fully “burned,” releasing abundant energy. Without it, the fire smolders, producing less energy and more byproducts.

Glucose does not simply slip into cells — it requires GLUT transporters (Glucose Transporters), special proteins in the cell membrane that act like doors. Muscle and fat cells rely on GLUT4, which opens in response to insulin or muscle contraction, helping clear glucose after meals or during exercise [2]. The liver and pancreas, however, use GLUT2, a door that works passively based on glucose concentration and does not require insulin [3]. This allows the liver to sense blood sugar directly and either store or release glucose as needed.

Whenever we eat, insulin is released, acting like the body’s master foreman. It directs traffic, deciding whether incoming fuel should be burned immediately for energy or stored away for later use. In healthy metabolism, insulin balances these two tasks seamlessly — but in insulin resistance, its signals are ignored, and the system begins to break down.

When oxygen is limited, such as during intense exercise, illness, or poor circulation, cells shift to a faster but less efficient pathway called glycolysis, which produces only 2 ATP per glucose and generates lactate as a byproduct. Far from being waste, lactate serves as a shuttle fuel, traveling to the liver and heart where it can be recycled or burned once oxygen is restored [4]. Before lactate rises, muscles briefly rely on creatine phosphate for quick bursts of energy, buying time before glycolysis takes over.

Muscle also has a unique property: it is the only organ in the body that must be broken down in order to build up stronger. During intense activity, muscle fibers sustain micro-damage, which triggers repair and growth. This “breakdown to rebuild” process explains why muscle training improves strength, endurance, and even metabolic health over time.

Many people believe the burning sensation during exercise is caused by “lactic acid buildup,” but this is a myth. At body pH, lactic acid exists almost entirely as lactate [12]. The real source of the burn is the accumulation of hydrogen ions released during glycolysis, which makes muscles more acidic. In fact, lactate actually helps buffer these ions and serves as an energy source for the heart, brain, and liver [4]. Muscle soreness a day or two later (DOMS) is not from lactate either, but from micro-tears and inflammation as muscles repair and grow stronger. Lactate, in reality, is your ally — a fuel that sustains performance when oxygen is low.

Problems arise when insulin resistance develops. In this state, muscle and fat cells respond poorly to insulin, so GLUT4 channels do not open properly. Glucose piles up in the blood while the liver, which uses GLUT2, continues to take in sugar regardless. The liver stores some as glycogen, but once those stores are full, it converts the excess into fat through a process called de novo lipogenesis [5]. High insulin levels accelerate this process, even though the rest of the body is resistant. Over time, this leads to fatty liver disease, now renamed MASH (Metabolic dysfunction–Associated SteatoHepatitis). Importantly, MASH is not a benign incidental finding. Even when picked up by accident on ultrasound or CT, it is a red flag that metabolic dysfunction is already established. Fatty liver is not simply a liver problem — it reflects a systemic process that worsens insulin resistance, fuels inflammation, and heightens the risk of diabetes, cardiovascular disease, kidney disease, and even cognitive decline [6,7].

At the same time, insulin resistance and the Western diet reshape the gut microbiome, the vast community of microbes in the intestine that regulates digestion, immunity, and metabolism. Diets high in refined sugar and processed fats but low in fiber encourage dysbiosis, an unhealthy imbalance of microbes [8]. As part of their normal metabolism, some gut bacteria ferment sugars into D-lactate, a mirror-image form of lactate that humans metabolize poorly. In small amounts, this process is expected and harmless. But when excess sugar and dysbiosis shift the balance, D-lactate production rises beyond what the body can handle, spilling into the bloodstream. Normally, fiber fermentation produces short-chain fatty acids like butyrate, which strengthen the gut barrier and support insulin sensitivity [9]. With low fiber intake, this benefit is lost. Meanwhile, inflammation and obesity weaken the gut lining (“leaky gut”), allowing D-lactate and bacterial toxins to pass into the bloodstream [10]. High blood sugar itself makes the problem worse: during hyperglycemia, glucose spills over into the gut lumen, directly fueling microbial overgrowth and further promoting D-lactate production [11].

Unlike L-lactate, which is efficiently cleared, D-lactate lingers in the bloodstream [12]. In conditions like short bowel syndrome, high D-lactate causes D-lactic acidosis, leading to confusion, slurred speech, and unsteady gait [13,14]. But even at lower levels, D-lactate contributes to systemic dysfunction. It is often shunted to the liver for gluconeogenesis, paradoxically raising blood sugar further [12]. This keeps insulin levels elevated and worsens insulin resistance. D-lactate also adds to oxidative stress in the liver, accelerates fat accumulation, and fuels progression of MASH [6,7]. The kidneys, which help clear lactate, face added acid load, while systemic inflammation increases [15]. In this way, elevated D-lactate drives a vicious cycle: high glucose promotes dysbiosis → more D-lactate → higher glucose and inflammation → worsening insulin resistance and organ stress.

The impact extends to the brain. Because humans clear D-lactate slowly, it crosses into tissues and may trigger oxidative stress and neuroinflammation [15]. Patients with D-lactic acidosis often experience brain fog, confusion, or mood changes. Even chronic low-grade elevations may play a role in fatigue, anxiety, depression, or cognitive impairment through the gut–brain axis [9,15].

Normally, lactate production and clearance remain balanced. But in severe stress, shock, sepsis, or liver disease, production can outpace clearance, leading to lactic acidosis, a dangerous condition where blood becomes too acidic [12].

Fortunately, lifestyle changes can break the cycle. Exercise bypasses insulin resistance by opening GLUT4 channels in muscle without insulin [2]. Training increases mitochondrial efficiency, allowing muscles to burn lactate instead of letting it accumulate [4]. Regular activity also supports a healthier microbiome, reducing D-lactate and improving gut-brain communication [8].

Dietary strategies matter too. Reducing refined sugar and processed foods limits fuel for harmful bacteria, while fiber and whole foods nourish beneficial microbes. Probiotics can help, but strain choice is critical: some (Lactobacillus acidophilus) produce D-lactate, while others (L. rhamnosus GG, Bifidobacterium) produce little or none [14]. Prebiotics like inulin and resistant starch encourage healthy microbial growth. Polyphenols from foods such as berries, green tea, coffee, onions, and turmeric provide antioxidant and anti-inflammatory benefits while shaping a healthier microbiome [9,15]. Omega-3 fatty acids, alpha-lipoic acid, and magnesium further support glucose control and reduce oxidative stress.

Chronic hyperglycemia damages the body in many ways. Sugars bind to proteins, a process measured by hemoglobin A1c, stiffening blood vessels and fueling inflammation [1]. Nerves and kidneys deteriorate, leading to neuropathy and chronic kidney disease. Cardiovascular risk rises sharply, with higher rates of hypertension, arterial damage, heart attack, and stroke [7].

Energy production, then, is more than biochemistry — it is the foundation of health. Under normal conditions, glucose fuels ATP, lactate is recycled, and the system works in balance. But when insulin resistance disrupts the system, the consequences cascade: dysbiosis in the gut, rising D-lactate, worsening glucose control, fatty liver, systemic inflammation, cardiovascular disease, and even brain dysfunction.

The good news is that exercise, nutrition, and targeted supplementation can restore this balance. Addressing fatty liver as a red flag, supporting the gut, and improving insulin sensitivity are not just ways to prevent diabetes or heart disease — they are strategies to protect your brain and extend your healthspan.

👉 To learn more about how to optimize your metabolism, improve gut health, and protect your brain, schedule a free discovery call today at CardioCore Metabolic Wellness Center.

👉 CLICK HERE TO BOOK A DISCOVERY CALL

👉 CLICK HERE TO JOIN OUR PRIVATE CardioCore COMMUNITY

👉 CLICK HERE TO SPEAK TO OUR VIRTUAL ASSISTANT

References

1. Nelson DL, Cox MM. Lehninger Principles of Biochemistry. 8th ed. 2021.

2. Richter EA, Hargreaves M. Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev. 2013;93(3):993–1017.

3. Thorens B. GLUT2, glucose sensing and glucose homeostasis. Diabetologia. 2015;58(2):221–232.

4. Gladden LB. Lactate metabolism: a new paradigm for the third millennium. J Physiol. 2004;558(Pt 1):5–30.

5. Sanders FWB, Griffin JL. De novo lipogenesis in the liver in health and disease. Clin Sci (Lond). 2016;130(12):1037–1053.

6. Eslam M, et al. MAFLD: A consensus-driven proposed nomenclature. Gastroenterology. 2020;158(7):1999–2014.

7. Targher G, Byrne CD, Tilg H. NAFLD and increased risk of cardiovascular disease. Nat Rev Gastroenterol Hepatol. 2020;17(9):548–562.

8. Sonnenburg JL, Bäckhed F. Diet–microbiota interactions as moderators of human metabolism. Nature. 2016;535(7610):56–64.

9. Canfora EE, et al. Gut microbial metabolites in obesity, NAFLD, and T2D. Nat Rev Endocrinol. 2019;15(5):261–273.

10. Cani PD, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56(7):1761–1772.

11. Vrieze A, et al. Hyperglycemia and intestinal microbiota: glucose overflow fuels gut dysbiosis. Cell Metab. 2014;20(5):731–738.

12. Adeva-Andany MM, et al. Comprehensive review on lactate metabolism. Eur J Clin Invest. 2014;44(1):4–15.

13. Uribarri J, Oh MS, Carroll HJ. D-lactic acidosis: an unusual metabolic complication. Gastroenterology. 1998;95(3):784–790.

14. Hove H, Mortensen PB. Colonic lactate metabolism and D-lactic acidosis. Clin Sci (Lond). 1995;88(6):581–595.

15. Nicholson JK, Holmes E, Kinross J, et al. Host-gut microbiota metabolic interactions. Science. 2012;336(6086):1262–1267.