UNDERSTANDING YOUR METABOLISM — PART TWO
Most people think of insulin resistance as a stepping stone to diabetes. A blood sugar problem. A metabolic issue. Something that shows up on a lab report and gets addressed with diet changes and medication.
That understanding significantly underestimates what insulin resistance actually does in the body.
The research of the past two decades has revealed something far more complex and far more consequential. Insulin resistance doesn’t just affect your blood sugar. It influences your brain, your heart, your hormones, your mental health, your nervous system, and your body’s ability to fight inflammation. It is a systemic condition with systemic consequences — and understanding those consequences may change the way you think about your own health.
In Part One of this series, we covered what insulin resistance is and how it develops. Here, we explore where it leads.
We’ll start with the familiar territory before moving into the more surprising connections.
Type 2 Diabetes. The most well-known downstream consequence of insulin resistance. When the pancreas can no longer compensate for cellular insensitivity by producing more insulin, blood sugar begins to rise persistently — and a Type 2 diabetes diagnosis follows. Insulin resistance is not just a precursor to Type 2 diabetes. It is its primary driver.
Pre-Diabetes. An estimated 96 million American adults have pre-diabetes — and more than 80% of them don’t know it. This is the stage where insulin resistance is significant and blood sugar is elevated, but not yet to diabetic levels. It is also the stage where intervention is most effective.
Metabolic Syndrome. A cluster of conditions — elevated blood sugar, high blood pressure, abnormal cholesterol levels, and excess abdominal fat — that occur together and dramatically increase the risk of heart disease, stroke, and Type 2 diabetes. Insulin resistance is the central mechanism driving metabolic syndrome.
Non-Alcoholic Fatty Liver Disease (NAFLD). When glucose can’t be efficiently stored or used, the liver converts the excess into fat. NAFLD — now the most common liver condition in the world — is strongly associated with insulin resistance and affects an estimated 25% of the global population.
Cardiovascular Disease. Chronically elevated insulin levels promote inflammation, damage blood vessel walls, raise triglycerides, and lower HDL cholesterol — all major contributors to heart disease. People with insulin resistance have significantly elevated cardiovascular risk even before a diabetes diagnosis is made.
The brain is not insulated from insulin resistance. In fact, some of the most significant emerging research in neuroscience centers on the relationship between metabolic dysfunction and brain health — and the findings are striking.
Alzheimer’s Disease. Perhaps the most significant connection in this entire article. Researchers have proposed calling Alzheimer’s disease “Type 3 Diabetes” — a term that reflects the growing body of evidence showing that insulin resistance in the brain plays a central role in its development. The brain depends on insulin signaling for glucose uptake, neuron maintenance, and the clearance of amyloid plaques. When that signaling is impaired, cognitive decline follows. Studies have found that people with Type 2 diabetes have a significantly elevated risk of developing Alzheimer’s, and that insulin resistance may be detectable in the brain years before cognitive symptoms emerge.
Parkinson’s Disease. Emerging research has identified links between insulin signaling dysfunction and the dopaminergic neuron loss that characterizes Parkinson’s disease. While the relationship is less established than the Alzheimer’s connection, the evidence is growing and the mechanism is plausible — insulin plays a role in the survival and function of the neurons most vulnerable in Parkinson’s.
Brain Fog and Cognitive Impairment. Long before a formal neurological diagnosis, insulin resistance manifests cognitively as brain fog, difficulty concentrating, memory lapses, and mental fatigue. These symptoms reflect the brain’s impaired ability to efficiently use glucose for energy — a direct consequence of disrupted insulin signaling.
Peripheral Neuropathy. Chronically elevated blood sugar and insulin levels damage the small blood vessels that supply nerves throughout the body. This leads to the numbness, tingling, and pain of peripheral neuropathy — one of the most common and debilitating complications of long-term metabolic dysfunction.
The relationship between metabolic health and mental health is bidirectional, complex, and significantly underappreciated in mainstream healthcare.
Depression. Multiple studies have found elevated rates of insulin resistance in people with depression, and researchers have proposed that metabolic dysfunction may contribute to depression through several pathways — including chronic inflammation, disrupted neurotransmitter production, and impaired brain energy metabolism. The relationship appears to go both ways: depression worsens insulin resistance, and insulin resistance worsens depression.
Anxiety. Blood sugar dysregulation directly affects the nervous system’s stress response. The roller coaster of glucose spikes and crashes triggers cortisol and adrenaline release, creating a physiological state that mimics and amplifies anxiety. Many people experiencing chronic anxiety are simultaneously experiencing unrecognized blood sugar dysregulation.
Mood Instability. Irritability, emotional reactivity, and rapid mood changes are frequently tied to blood sugar fluctuations. The well-documented phenomenon of being “hangry” — irritable when hungry — is a mild version of what people with significant insulin resistance experience more chronically and more severely.
Polycystic Ovary Syndrome (PCOS). Insulin resistance is now recognized as a central driver of PCOS, the most common hormonal disorder in women of reproductive age. Elevated insulin levels stimulate the ovaries to produce excess androgens, disrupting the hormonal balance that governs ovulation, menstrual regularity, and fertility. Addressing insulin resistance is increasingly central to PCOS management.
Thyroid Function. Insulin resistance and thyroid dysfunction frequently coexist and mutually worsen each other. Impaired thyroid function reduces insulin sensitivity, while insulin resistance can disrupt thyroid hormone conversion and signaling.
Testosterone and Estrogen Balance. Chronically elevated insulin levels disrupt sex hormone production and metabolism in both men and women, contributing to low testosterone in men and estrogen dominance in women — with downstream effects on energy, mood, body composition, and sexual health.
Insulin resistance and chronic inflammation have a deeply intertwined relationship. Each drives the other in a cycle that, once established, is difficult to break without deliberate intervention.
Elevated insulin promotes the production of pro-inflammatory signaling molecules throughout the body. That chronic low-grade inflammation, in turn, directly impairs insulin signaling in cells — worsening resistance and driving the cycle forward.
This inflammatory mechanism connects insulin resistance to conditions as diverse as rheumatoid arthritis, inflammatory bowel disease, chronic kidney disease, and certain cancers. The metabolic and inflammatory systems are not separate — they are deeply interconnected, and disruption of one reliably disrupts the other.
For the Holdfast Nutrition community — many of whom are managing MS or supporting someone who is — the metabolic connection deserves specific attention.
Research has found that people with MS have higher rates of insulin resistance and metabolic syndrome than the general population. This is not coincidental. Chronic neuroinflammation — the hallmark of MS — and the inflammatory pathways driven by insulin resistance share overlapping mechanisms. Each can worsen the other.
Fatigue, one of the most debilitating and common MS symptoms, has multiple contributing factors — and disrupted cellular energy metabolism driven by insulin resistance is increasingly recognized as one of them. Supporting metabolic health in the context of MS is not a separate concern from neurological health. They are part of the same picture.
This is precisely why the Holdfast Protocol begins with a metabolic foundation for everyone — regardless of their primary health concern.
In Part Three of the Understanding Your Metabolism series, we move from understanding the problem to exploring what you can actually do about it — the nutritional strategies, lifestyle approaches, and targeted ingredients that research has shown can meaningfully support healthy insulin sensitivity and metabolic function.
Coming next: “Taking Control: Nutritional Strategies for Supporting Healthy Insulin Sensitivity”
These statements have not been evaluated by the Food and Drug Administration. This content is for informational purposes only and is not intended to diagnose, treat, cure, or prevent any disease. Consult your healthcare provider before starting any new supplement regimen.
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