Diabetes: It's NOT as Sweet as You Think it is

Diabetes: Unveiling the Complexity Beyond Sugar

Abstract

Diabetes is a complex condition that extends beyond glucose control, rooted in insulin resistance with far-reaching consequences for cardiovascular health, cancer risk, and cognitive function. The traditional view of diabetes as a disease of sugar is outdated, and it is essential to recognize the role of insulin resistance in driving a cascade of negative effects, including inflammation, atherosclerosis, and tumor growth. A comprehensive approach to prevention, diagnosis, and treatment is necessary, focusing on addressing the underlying drivers of insulin resistance rather than just glucose control. By shifting the focus from glucose-centric to insulin resistance-centric, we can mitigate the devastating consequences of this complex disease and develop more effective prevention and treatment strategies.

Diabetes: It’s not as Sweet as You Might Think
Behind the sweetness lies a complex reality: Diabetes is more than just a sugar coated diagnosis. From ancient civilizations to now, the recognition of sugar as a prominent feature in diabetes mellitus was apparent. It was associated with excessive urination and thirst, originally documented in ancient civilizations around the world (ancient Egyptians- Ebers Papyrus 1550 BC, ancient India- Ayurvedic medical text ‘Charaka Samhita’ 400 BC, Ancient Greece- Aretaeus of Cappadocia 100 AD). The word ‘diabetes’ comes from the Greek meaning ‘siphon’ or ‘pipe’ referring to the excessive thirst & urination. ‘Mellitus’ is derived from Latin meaning ‘honeyed’ or ‘sweet’. It conjures up memories of our grandmothers dipping their urine for sugar and today, pricking the finger or using a Continuous Glucose Monitor (CGM).

Diabetes began as a glucose centric disease and through inertia persists that way today. The expression became the disease. For all intents and purposes diabetes can be split into two main categories: diabetes type 1 in the young and type 2 in the older age groups. Both types express elevated glucose but are vastly different. Type 1 is a disease of insulin deficiency, where the body's immune system attacks and destroys the insulin producing beta cells in the pancreas, rendering the body unable to produce enough insulin. This causes a wasting of energy leaving individuals thin and weak. In contrast, type 2 diabetes is a disease of insulin excess, a condition based on insulin resistance. The cell becomes less responsive to the actions of the hormone insulin due to a variety of factors. This in turn causes the body to store excess energy leading to weight gain and metabolic complications. Both types are completely unrelated except for the fact that glucose is elevated. In this article I will only discuss adult onset type 2 diabetes mellitus and leave the rest for another time. The sugar coated truth about type 2 diabetes it’s not just about sweetness, it’s about resistance.

As you will see sweetness turns sour. At its core, type 2 diabetes is a disease of insulin resistance. As the body's cells become less responsive to insulin it is harder for glucose to enter the cells. Thus the circulating sugars in the blood rise with less availability on a cellular level. This resistance leads to a cascade of events, including increased glucose production in the liver, impaired insulin secretion, and eventually sustained elevations of blood sugar. It's a complex interplay of hormonal and metabolic factors, rather than just a simple matter of consuming too much sugar.

Normally after eating, nutrients are absorbed in the intestine and sent to the liver. Here the dietary nutrients are converted into glucose which the cell needs for energy production. The biggest utilizers of glucose are the muscle cells although in a resting state the heart, brain and kidneys have a much higher metabolic requirement. Excess energy is stored away for a later time in adipose tissue (the fat cells) in the form of triglycerides. Insulin acts as the 'foreman' directing what happens to energy. Without insulin cells don’t know what to do with energy-whether to store energy or release it. Insulin acts as a key, unlocking the cell's door, allowing glucose to enter. Here it can be used for energy production or for energy storage. High insulin levels slow metabolism, storing energy as fat or glycogen. Conversely low insulin allows for the release of energy in the form of free fatty acids from adipose cells to fuel metabolism. The brain has extremely low capacity to store energy and relies on a constant supply of energy availability from the blood. Any reduction in this availability causes a primal response known as hunger.

Here's a simple explanation. Glucose has its own receptor or door to enter the cell, but unfortunately, that door is always locked. In response to elevated blood sugars, whether dietary or due to insulin resistance, the pancreas releases insulin. This has its own receptor on the cell that's always open. Insulin enters the cell and triggers a series of enzymatic processes, specifically phosphorylation pathways, essentially unlocking the door for glucose to enter. However, with insulin resistance, this pathway is blocked, preventing insulin from opening the glucose door. As sugar levels increase, it is sensed by the pancreas, resulting in an increased production of insulin. This overproduction of insulin, a state of high insulin known as hyperinsulinemia occurs for 10-20 years. With time the pancreas becomes exhausted, a phenomenon known as "pancreatic beta-cell burnout." By the time 85% of beta-cell function is lost, blood sugars are in the borderline range, a condition known as prediabetes. At this stage, doctors often advise patients to watch their diet, lose weight, and limit carbohydrates. Nothing is done until further burnout occurs. When 90% of beta-cell function is lost, blood sugars become elevated, and diabetes is diagnosed. Thus, the diagnostic criteria for type 2 diabetes are based on glucose levels, which is a late manifestation of the disease. The elevated sugars attract attention but the sad reality is that it's core driver, namely insulin resistance, has been silently driving the progression of disease for years, often decades before symptoms become apparent.

Insulin resistance is a growing concern in Western societies, affecting an estimated 40% of adults over 18 and over 50% by age 65, often manifesting as prediabetes. This is more in certain ethnic groups. As prediabetes is a late manifestation, the actual incidence of insulin resistance may in fact be much higher. To understand the underlying factors involved in insulin resistance , consider the B-A-D-G-E acronym: Belly fat, Age, Diet or Drugs, Genetics or Gut, and Exercise or lack thereof. Increased waist circumference is a sign of fat accumulation around the internal organs known as visceral fat. This is a sure sign of elevated diabetic risk. The incidence of insulin resistance increases significantly with age. High carbohydrate dietary intake raises insulin levels worsening resistance. Certain medication can also exacerbate it. These drugs include beta blockers and thiazide diuretics used to treat hypertension, steroid use such as prednisone or decadron, psychiatric drugs such as antipsychotics and certain antiviral drugs known as protease inhibitors used in HIV treatment to name a few. Genetic predispositions influence diabetic expression as it is well known to run in families, especially prevalent in certain ethnic populations. As more and more is learned, we recognize the increasing importance of the Gut microbiome, the trillions of micro-organisms inhabiting our large intestine, as influencing our metabolic processes. I'm beginning to feel guilty washing my hands after using the rest room; Am I destroying the good guys? Just kidding. Lastly, exercise and the percent lean body mass is directly related to insulin sensitivity. As more is learned, additional factors such as stress, sleep, socialization, spirituality and environmental factors come into play.

As insulin resistance progresses, things turn sour. Excess insulin triggers a cascade of negative effects. When insulin resistance impedes insulin from reaching the glucose receptor, insulin is diverted to an alternative back pathway in the cell, the MAP 3 kinase pathway. This pathway leads to increased inflammation, atherosclerosis, and a reduced nitric oxide production, which is crucial for blood vessel dilation and anti-inflammatory responses. This process sets the stage for cardiovascular disease, often years before blood sugar levels even become borderline. In fact, since 2013 all the major medical societies (AHA, ADA) consider diabetes as a cardiovascular equivalent meaning that with diabetes, the risk of a subsequent cardiovascular event is the same as someone with preexisting heart disease. High insulin levels also promote fat storage, slows metabolism, and fuels inflammation, while elevated blood pressure and promotes atherosclerosis. Furthermore, excessive insulin can act as a tumor-promoting growth factor, contributing to cancer development. Cancer cells often have 10-50 times more insulin receptors, driving their rapid growth and metastasis. Many of the most common cancers are highly related to insulin resistance and I recommend anyone with those cancers, irrespective of their Hemoglobin A1c levels or fasting blood levels to get a 2 hour glucose tolerance test with a fasting, 1 hour & 2 hour insulin response.

Beyond insulin levels, in established diabetes, there is additional risk associated with the increased sugars. The elevated blood sugar levels, independent of insulin resistance, contribute to microvascular disease, meaning small vessel disease. These include diabetic eye disease called retinopathy, nerve disease called neuropathy, and kidney disease called nephropathy. Elevated blood sugar is not the underlying driver of the most ‘severe’ complications of diabetes, namely the cardiovascular and malignant diseases that kill you. Simply improving blood sugar without addressing underlying insulin resistance does not lead to reduced mortality. The claim that unmanaged blood sugar directly leads to heart attacks and strokes doesn't capture the full picture. For many years researchers were perplexed by the fact that using insulin or drugs that increased insulin, though while normalizing sugars and improving microvascular disease, failed to improve cardiovascular outcomes. Insulin resistance and related metabolic issues significantly contribute to cardiovascular risk, making the relationship between blood sugar control and cardiovascular health more complex. After the rare ApoE genotype, insulin resistance is arguably the most significant risk factor for developing dementia, outweighing the risks associated with hypertension, blood sugar levels, cholesterol, smoking, obesity, and sedentary lifestyle. Most people as well as most physicians don’t know that the diagnostic criteria for diabetes is based solely on the risk of developing diabetic eye disease and not the most severe complications leading to excessive morbidity and mortality, that of insulin resistance. [fasting glucose >126, random glucose with symptoms >200, hemoglobin A1c >6.5 or a 2 hour glucose >200]. A very sad commentary indeed.

Diabetes is far more than just a matter of sugar; it's a complex condition rooted in insulin resistance, with far-reaching consequences for cardiovascular health, cancer risk, and cognitive function. The concept that diabetes is a disease of sugar is archaic. As we've seen, the sweetness of diabetes belies a far more sinister reality, where insulin resistance drives a cascade of negative effects, from inflammation and atherosclerosis to tumor growth and dementia. By recognizing the true nature of diabetes, we can move beyond simplistic solutions, glucose centric, and towards a more comprehensive approach to prevention, diagnosis, and treatment. Only by addressing the underlying drivers of insulin resistance can we hope to mitigate the devastating consequences of this complex disease. Ultimately, it’s time to redefine our understanding of diabetes and shift the focus from mere glucose control to a more nuanced approach that tackles the root causes of insulin resistance, paving the way for more effective prevention and treatment strategies.

As blood sugars approach borderline levels, it is essential to shift our tunnel vision from sugars to cardiovascular disease and the complications driven by the proinflammatory state. I urge all those with even borderline glucose levels to have at the very least a CT coronary calcium score. This is an inexpensive ($100) test that measures the amount of atherosclerotic calcium in the coronary arteries. Not only does it directly check the status of your heart, potentially saving lives, it evaluates the individualized burden of metabolic risk that is expressed by your metabolic dysfunction. I use it to assess the potential opportunities and aggressiveness for future risk management. I would not know how to formulate a sophisticated treatment plan for elevated sugars without knowing the metabolic consequences it has on the body. The cardiac involvement is a window into the entire body's metabolic dysfunction. This proactive assessment and approach will avoid much of the deleterious consequences that occur with this deadly disease. Conversely, the presence of any of the conditions associated with insulin resistance as mentioned above, regardless of ‘sugar or diabetic’ markers in routine testing, should be thoroughly evaluated by a minimum of the 2 hour glucose tolerance test and insulin response. The American Journal of Cardiology in 2013 published an article investigating the amount of "undiagnosed" diabetes in those with coronary artery disease. https://pubmed.ncbi.nlm.nih.gov/23168282/ . In the 'nondiabetics' with coronary artery disease, a simple 2 hr glucose tolerance test revealed that 48% had either prediabetes or diabetes. When this population was followed for 3 years, follow up testing identified a staggering 88% with it. Most experts agree that those with coronary artery disease has diabetes but it's just a matter of time before we identify it. When it comes to cardiac disease prediabetes is to diabetes as being 1 month pregnant is to being 9 months; you either have it or you don't. Yet, I've never seen a cardiologist order a 2 hr glucose tolerance test and only rarely have seen an endocrinologist order a cardiac evaluation in an asymptomatic patient. The cardiologist gets paid to lower cholesterol and the diabetic doctor to lower glucose...and the poor patient is left in the dark waiting for mother nature to take its toll.

Functional metabolic medicine seeks to address chronic disease at its root by identifying and modifying the underlying drivers in a proactive, individualized way. Research consistently shows that early intervention leads to better long-term outcomes, especially when guided by holistic, personalized strategies. While traditional medicine often reacts to symptoms—focusing primarily on glucose levels in the case of diabetes—true prevention and management require a paradigm shift. To effectively combat diabetes, we must move beyond viewing it solely as a sugar disorder and instead recognize insulin resistance as the central issue. This shift calls for a comprehensive approach that integrates lifestyle changes, such as nutrition, physical activity, stress management, and sleep, along with innovative therapies and technologies. Acknowledging the multifactorial nature of diabetes allows for more precise, meaningful interventions. Only by addressing the root causes of insulin resistance can we truly change the trajectory of this condition and offer patients sustainable, science-based solutions.

If you’ve experienced signs of insulin resistance, elevated sugars or diabetes including weight gain, fatigue, sugar cravings, high blood pressure, cardiovascular disease, elevated blood sugar, or difficulty losing weight—don’t wait for a diagnosis to take control of your health. Early action is key. Contact us today to schedule a personalized evaluation and begin a treatment plan tailored to your unique needs. Together, we can address the root causes and guide you toward lasting wellness.