Many individuals are told that managing type 2 diabetes is simply a matter of controlling blood sugar. As long as glucose levels fall within a target range, they are often reassured that everything is under control. In some cases, a prescription is provided without much explanation about the underlying causes of elevated blood sugar.
This approach is common, but it tells only part of the story. Focusing exclusively on blood sugar misses the deeper, more complex mechanisms that may drive the condition.
In 2008, Dr. Ralph DeFronzo, a leading researcher and physician in the field of diabetes, delivered the prestigious Banting Lecture. In that address, he introduced a groundbreaking concept known as the “Ominous Octet.”
His research demonstrated that type 2 diabetes is not limited to a single organ or system. It is a multifaceted condition involving dysfunction in multiple areas of the body, including the pancreas, liver, muscles, fat tissue, gut, kidneys, and brain.
These eight mechanisms, when impaired, contribute collectively to insulin resistance and the progression of type 2 diabetes. Addressing only one aspect, such as elevated blood glucose, does not resolve the systemic dysfunction. True management requires a comprehensive understanding of all eight contributors.
If you are a visual learner, you can watch the YouTube episode associated with this article below. You can also listen to the podcast episode (listening links found here):
Why the “Blood Sugar Only” Approach Doesn’t Work
For decades, type 2 diabetes has been approached primarily as a blood sugar disorder. Most medical visits focus on glucose levels, medications are prescribed to reduce blood sugar, and patients are often taught to track only that one metric. As a result, many people are led to believe that as long as their blood sugar is within range, they are managing their condition effectively.
However, blood sugar is a symptom, not the root cause. It is the visible outcome of deeper dysfunction within the body’s metabolic systems.
Managing diabetes by focusing solely on blood sugar is comparable to mopping up water from a leaking pipe without repairing the source of the leak. While medications may help reduce glucose levels temporarily, they do not resolve the underlying issues that led to the imbalance in the first place.
Dr. DeFronzo’s research made it clear that type 2 diabetes is not simply about insufficient insulin production or excessive sugar consumption. It is a systemic issue involving multiple organs and pathways working out of sync.
Eight key systems contribute to this dysfunction. Each one plays a role in the development of insulin resistance and the progression of type 2 diabetes. Despite this, most treatment plans continue to focus on a single goal: lowering blood glucose.
This limited approach fails to account for what is happening elsewhere in the body. The liver may be overproducing glucose. The muscles may no longer respond to insulin. Gut hormones might be impaired, and the kidneys could be recycling glucose back into the bloodstream. In such a complex system, targeting only one aspect is insufficient.
This is why many people experience worsening symptoms over time, even when they follow conventional medical advice. Hemoglobin A1C may improve, but fatigue persists, weight gain continues, and medication needs often increase.
If you have ever wondered why progress feels out of reach despite doing “everything right,” it may be because the current system remains focused on managing symptoms rather than addressing root causes. By understanding the full picture and the eight distinct contributors to metabolic dysfunction, a more effective and lasting strategy becomes possible.
The Ominous Octet: Eight Drivers of Type 2 Diabetes
Dr. Ralph DeFronzo identified eight distinct physiological defects that contribute to the development and progression of type 2 diabetes. Known as the “Ominous Octet,” these mechanisms each play a role in advancing insulin resistance and disrupting metabolic health.
Understanding these contributors is not just academic. It is essential to addressing the root causes of diabetes and improving long-term outcomes.
1. Impaired Insulin Secretion: Pancreatic Beta Cell Dysfunction
The pancreas is the most widely recognized organ involved in diabetes, particularly the beta cells that produce insulin. Insulin helps transport glucose from the bloodstream into cells, where it can be used as energy.
In the early stages of insulin resistance, the body’s cells become less responsive to insulin. To compensate, the pancreas increases insulin production in an attempt to maintain normal blood sugar levels. This leads to a state of hyperinsulinemia or chronically elevated insulin levels.
Over time, the ongoing demand on the pancreas causes beta cells to become dysfunctional. Some cells may stop working altogether. As insulin secretion declines, blood sugar levels begin to rise, often marking the point when type 2 diabetes is formally diagnosed.
However, this decline in insulin production is not the starting point of the disease. It is the result of years of metabolic stress. There is a critical period before this stage when blood sugar may still be within normal range, but insulin levels are elevated. This is when early intervention can be most effective.
Conventional care often delays treatment until glucose levels are abnormal, by which time pancreatic stress has already taken a toll. Once beta cells are damaged or lost, they are difficult to restore. The priority should be to lower insulin demand as early as possible through nutrition, physical activity, and other lifestyle strategies. These steps may help stabilize blood sugar and protect beta cell function.
Although pancreatic impairment is commonly associated with type 2 diabetes, it may be one of the last issues to develop. Focusing on prevention rather than reaction is critical to managing the disease more effectively.
2. Increased Hepatic Glucose Production: Liver Dysfunction
The liver plays a critical but often overlooked role in blood sugar regulation. It acts as a backup generator by producing glucose during periods of fasting, such as overnight or between meals. This process, known as gluconeogenesis, is normal and necessary for maintaining stable blood sugar levels.
In a healthy body, insulin signals the liver to slow down glucose production when blood sugar is already adequate. In insulin resistance, however, the liver stops responding to that signal. It continues to produce and release glucose, even when it is not needed.
This can lead to elevated blood sugar after meals, not just from the food consumed but also from the liver adding more glucose to the bloodstream. The result is a compounding effect that can make blood sugar management more difficult.
One common example is the dawn phenomenon. During the early morning hours, the body experiences a natural rise in hormones like cortisol. These signals prompt the liver to release glucose. In insulin-resistant individuals, the liver often overreacts and releases too much glucose. Since insulin is no longer effective at shutting this process down, fasting blood sugar can rise even when no food has been eaten.
This is not caused by poor dietary habits or lack of effort. It is a breakdown in the body’s ability to regulate glucose production. The solution lies in improving insulin sensitivity in the liver.
Strategies such as reducing refined carbohydrates, improving sleep quality, managing stress, and using time-restricted eating may help restore proper liver function. These approaches target the underlying issue, not just the symptom.
3. Insulin Resistance in the Muscle: Glucose Uptake Breakdown
Muscle tissue plays a vital role in managing blood sugar. Beyond strength and mobility, muscles are one of the body’s most important tools for glucose regulation.
After eating, especially meals containing carbohydrates, blood glucose naturally rises. In response, the body releases insulin, which acts as a key to unlock cells. This allows glucose to move out of the bloodstream and into muscle cells, where it can be used for energy or stored for later use.
In insulin resistance, this process is disrupted. Muscle cells no longer respond to insulin effectively. The cellular “doors” remain closed, and glucose stays in the bloodstream. This leads to elevated blood sugar, not because too much was eaten, but because the body cannot properly absorb and use what was consumed.
This breakdown is significant because muscle is the largest site for glucose disposal. When muscle tissue becomes resistant to insulin, it creates a major bottleneck in overall metabolic function.
What makes this even more critical is that insulin resistance in muscle often begins long before blood glucose levels become abnormal on standard tests. It may show up as post-meal fatigue, energy crashes, or a sluggish feeling after eating, even when meals appear balanced.
If insulin resistance continues, it creates a cycle of dysfunction. The pancreas responds by releasing more insulin in an attempt to force glucose into the muscles. This raises baseline insulin levels and worsens the resistance, creating a feedback loop that is difficult to interrupt.
One of the most effective ways to address this is through movement. Physical activity, even in small amounts, helps muscles absorb glucose with less reliance on insulin. This can happen even when insulin resistance is already present.
Simple strategies such as walking after meals, lifting weights a few times per week, or breaking up long periods of sitting can all make a difference. Regular muscle use improves glucose handling and helps interrupt the cycle of rising insulin and resistance.
Insulin-resistant muscle tissue is not a dead end. It is a signal that change is needed, and fortunately, it is one of the most responsive systems when given the right support.
4. Increased Lipolysis: Fat Cell Dysregulation
Fat cells, or adipose tissue, are not passive storage units for excess calories. They are metabolically active, releasing hormones, sending signals to other tissues, and playing a critical role in overall metabolic function.
Under normal conditions, when the body requires extra energy between meals or during physical activity, fat cells break down stored fat into free fatty acids. These are then released into the bloodstream in a process called lipolysis. In healthy individuals, this is a regulated and beneficial process.
In people with insulin resistance or type 2 diabetes, however, lipolysis becomes dysregulated. Fat cells begin to release excessive amounts of free fatty acids into the bloodstream, even when the body does not need additional fuel. This leads to an oversupply of energy in the system, which disrupts normal metabolic balance.
The excess fatty acids interfere with insulin signaling, particularly in the liver and muscle tissues. These are the same tissues responsible for managing glucose. When they are overwhelmed by fatty acids, they become less responsive to insulin, and glucose uptake is impaired.
This creates a compounding problem. As insulin resistance worsens, insulin levels rise in an attempt to compensate. Elevated insulin promotes more fat storage, yet the fat cells continue releasing fatty acids into circulation. The system is overloaded on both ends.
This dysfunction is not caused by eating dietary fat. It is the result of hormonal imbalance and fat cell miscommunication. One of the most concerning aspects of this issue is the role of visceral fat, which surrounds internal organs. Visceral fat is highly active and, when dysregulated, contributes to inflammation, worsened insulin resistance, and poor glucose control.
The focus should not be solely on total body fat or weight. The more important factor is what the fat cells are doing. When they become dysregulated, they drive a cycle of metabolic disruption that makes type 2 diabetes harder to manage and reverse.
5. Decreased Incretin Effect: Gut Hormone Disruption
The gut plays a critical role in blood sugar regulation, not just through digestion, but through the hormones it releases in response to food. One of the most important of these is GLP-1, or glucagon-like peptide-1.
In a healthy body, when food enters the digestive tract, the gut releases GLP-1. This hormone signals the pancreas to prepare for insulin release, allowing for a faster and more efficient response to rising blood sugar. GLP-1 also tells the liver to reduce glucose production and sends fullness signals to the brain to help regulate appetite.
In people with type 2 diabetes, this hormonal signaling often becomes impaired. The gut may not release enough GLP-1, or the body may not respond to it properly. As a result, key metabolic processes fall out of sync.
When this signal is weak or absent, insulin is not released promptly, allowing glucose from food to remain in the bloodstream longer than it should. The liver continues to produce glucose even after eating, and the brain may not receive the signal to stop eating, leading to overeating and further glucose imbalance.
This disruption can cause blood sugar spikes even after small or balanced meals. It is not always about the carbohydrate content or meal size. In many cases, the body’s hormonal response to food is delayed or blunted.
Some diabetes medications, such as GLP-1 receptor agonists, are designed to mimic the effects of this hormone. While effective for some, these medications address only part of the issue.
From a lifestyle and nutrition perspective, there is also potential to restore and support this gut signaling naturally. Improving gut health, adjusting meal timing, and reducing inflammation through dietary choices can help reestablish this critical communication system.
When gut hormones begin to function properly again, the coordination between the pancreas, liver, and brain improves, creating a more balanced and responsive metabolic environment.
6. Increased Glucagon Secretion: The Other Pancreatic Imbalance
The pancreas is best known for producing insulin, but it also produces another hormone called glucagon. While insulin works to lower blood sugar by moving glucose into cells, glucagon has the opposite role. It raises blood sugar, primarily during periods of fasting or between meals, by signaling the liver to release stored glucose.
In a healthy metabolic system, insulin and glucagon work in balance. When one increases, the other decreases. This coordination helps maintain stable blood sugar levels throughout the day.
In type 2 diabetes, this balance is disrupted. Glucagon levels can become elevated even when blood sugar is already high. This creates a conflicting situation where the body is attempting to lower blood sugar with insulin while simultaneously raising it with glucagon.
As a result, the liver receives mixed signals. In response to glucagon, it releases even more glucose into the bloodstream, compounding an already elevated blood sugar level. This creates a metabolic tug-of-war that is difficult to control, regardless of dietary efforts or carbohydrate intake.
This inappropriate glucagon response is often overlooked in standard diabetes care, yet it plays a significant role in disease progression. Effective treatment must consider both insulin and glucagon regulation to achieve metabolic balance.
Adding to the complexity, certain gut hormones—such as GLP-1—normally help suppress glucagon after a meal. When the incretin response is impaired, as it often is in type 2 diabetes, this suppression does not occur. As a result, glucagon continues to rise even after eating, further fueling glucose production at the wrong time.
Glucagon itself is not harmful when functioning appropriately. The issue arises when it is released in the wrong context, contributing to metabolic dysfunction rather than helping correct it.
7. Increased Renal Glucose Reabsorption: Kidney Miscommunication
The kidneys are widely recognized for their role in filtering waste and maintaining fluid balance. However, they also contribute to blood sugar regulation, a function that is often overlooked.
In a healthy individual, when blood glucose levels rise too high, the kidneys help by filtering out the excess glucose and excreting it through urine. This serves as a backup system to help prevent dangerously elevated blood sugar levels.
In type 2 diabetes, this process changes. Instead of eliminating the excess glucose, the kidneys begin reabsorbing it and returning it to the bloodstream. This action occurs through a specific transporter protein called SGLT2. Although intended as a protective mechanism, it becomes counterproductive in an already glucose-overloaded system.
As a result, the body’s efforts to lower blood sugar are undermined by the kidneys’ tendency to conserve glucose. This recycling effect can keep blood sugar levels elevated, even when dietary and lifestyle changes are in place.
This mechanism is not minor. It plays a meaningful role in the persistent hyperglycemia experienced by many individuals with type 2 diabetes. Some medications, such as SGLT2 inhibitors, are designed to block this glucose reabsorption, allowing more glucose to be expelled in the urine.
For those relying on nutrition and lifestyle interventions, understanding the kidneys’ involvement is essential. Without this insight, it may be easy to overlook a key factor behind continued blood sugar elevation.
This reinforces the broader point: type 2 diabetes is not simply about carbohydrate intake or calorie balance. It is a complex condition involving multiple systems that each respond differently to glucose and insulin.
8. Brain Insulin Resistance: Impaired Appetite Regulation
The final component of the Ominous Octet involves the brain, which is also often overlooked in discussions about insulin resistance. While insulin’s role in the pancreas, liver, and muscle is widely recognized, it also plays a key role in the brain—especially in regulating hunger, satiety, and overall energy balance.
In a healthy state, insulin signals to the brain that the body has received enough fuel. This helps reduce appetite and allows the body to shift from storing energy to using it. Insulin also influences how the brain manages metabolism, energy expenditure, and cravings.
When the brain becomes insulin resistant, these signals break down. The brain no longer receives accurate feedback that fuel is available. As a result, hunger persists even after eating, cravings increase, and the body conserves energy by slowing metabolism.
In practical terms, this might look like persistent hunger shortly after meals, frequent cravings for high-carbohydrate or sugary foods, and difficulty losing weight despite eating less or exercising more. These symptoms are not caused by a lack of discipline but by disrupted communication between insulin and the brain.
This breakdown creates a cycle that reinforces itself. The body stores energy due to elevated insulin, but the brain fails to recognize that energy is available. Hunger continues, energy levels drop, and additional food intake leads to further fat storage and insulin resistance.
This is why focusing solely on blood glucose management is not enough. Insulin resistance in the brain impacts appetite control and energy regulation. Until this is addressed, efforts to improve metabolic health may fall short.
The positive news is that brain insulin resistance can improve. Lowering overall insulin levels through dietary changes, improved sleep, stress management, and regular movement helps restore proper signaling. When insulin begins to function correctly in the brain, appetite cues become more accurate, cravings decline, and the body starts using stored energy more effectively.
Why Insulin Is the Common Thread in the Ominous Octet
Understanding the eight components of the Ominous Octet highlights one crucial fact: type 2 diabetes is not a single-system issue. Each of the eight defects contributes to the progression of the disease, and most treatments focus only on one: blood sugar.
This is why standard approaches, such as prescribing a single glucose-lowering medication, may fail to produce long-term results. These medications may address one mechanism, but the others remain uncorrected, allowing the underlying dysfunction to continue.
All eight systems—liver, muscle, fat cells, gut, brain, pancreas, and kidneys—are influenced by one central factor: insulin. Chronically elevated insulin, often present for years before blood sugar rises, plays a critical role in driving metabolic imbalance across the entire body.
For example, the liver overproduces glucose because it is no longer responding to insulin’s signal to stop. Muscles fail to absorb glucose because insulin resistance is blocking cellular entry. The pancreas becomes overworked trying to produce more insulin to compensate. Fat cells are instructed to store energy rather than release it. The brain loses its ability to detect fullness. Even the kidneys reabsorb glucose that should be excreted.
In each case, insulin resistance is the unifying problem.
Addressing insulin directly, rather than focusing solely on glucose, can influence all of these systems at once. This is not limited to medications. In fact, lifestyle changes such as reducing refined carbohydrates, improving sleep, managing stress, and engaging in regular movement can be powerful tools for lowering insulin levels and restoring metabolic function.
While the healthcare system may still focus heavily on blood sugar metrics, the science points to insulin as the true driver. Measuring insulin, identifying resistance early, and applying interventions that target this root issue are key to lasting improvement.
This is not a fringe concept. It is well supported in current research and clinical evidence. It simply has not been widely adopted in mainstream care. That is beginning to change. Understanding this information allows you to take an informed, proactive role in your health.
What This Means for You
If learning about the Ominous Octet feels overwhelming, take a moment to pause. You do not need to become an expert in metabolic physiology or memorize every detail. What matters most is recognizing the broader picture of how type 2 diabetes develops and progresses.
Many individuals maintain normal blood sugar levels but continue to feel fatigued, experience stubborn weight gain, or struggle with cravings and poor energy. Others follow all the recommended steps yet see little progress. These frustrations are often rooted in a system that is treating symptoms, not addressing the underlying cause.
Understanding that blood sugar is a symptom, insulin resistance is the cause, and the Ominous Octet is the mechanism allows for a more accurate and empowering approach to metabolic health.
When your strategy shifts from simply lowering blood glucose to lowering insulin, everything begins to change. You stop chasing short-term fixes and start repairing the core systems that influence how your body stores, uses, and responds to energy.
This is not about restriction or discipline. It is about working with your body rather than against it. Supporting insulin sensitivity through targeted lifestyle choices allows your metabolism to stabilize, your energy to improve, and your symptoms to finally begin to resolve.
Long-lasting change is possible, but it starts by focusing on the true driver of dysfunction: insulin resistance. When you support your body at this level, you create conditions for real, sustainable health.
Ominous Octet by Dr. Defronzo:
Defronzo R. A. (2009). Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes, 58(4), 773–795. https://doi.org/10.2337/db09-9028
These statements have not been evaluated by the Food and Drug Administration. The contents of this article, made available via Holistic Fit LLC, are for informational purposes only and do not constitute medical advice. The Content presented here is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of a qualified healthcare provider with any questions you may have regarding a medical condition. If you think you may be suffering from any medical condition, you should seek immediate medical attention. You should never delay seeking medical advice, disregard medical advice, or discontinue medical treatment because of information provided by Holistic Fit LLC. Reliance on any information provided by this article is solely at your own risk. The author is not a licensed medical professional. References to specific products, research, or external websites are for informational purposes only and do not constitute endorsements or recommendations. Individual results may vary. Readers are encouraged to consult updated sources and verify information as scientific knowledge evolves. And, of course, never use a new product, herb or essential oil without first reading the label, doing your research, or checking with a local expert.
Trina Krug is a Holistic Nutritionist, Integrative Health Coach and host of the Carbless Conversations Podcast. With a Master’s Degree in Complementary and Alternative Medicine, her single mission in life is to facilitate self-healing in herself and those around her through awareness, lifestyle shifts and low-carb eating. As a current Doctor of Science student, she continues her studies in functional nutrition.