We Named the Disease After a Symptom We Could Taste
On insulin, inertia, and what we've been missing while watching the wrong number
We named the disease after a symptom we could taste. The word mellitus, honey sweet, was added to diabetes by Thomas Willis in 1675 after he rediscovered the sweetness of urine and blood in patients. He wasn't the first. Ancient Ayurvedic physicians called the condition madhumeha, honey urine, and diagnosed it by observing whether ants were attracted to a patient's urine. The first clinical test wasn't developed until 1841, when acid hydrolysis was applied to urine samples to detect sugar. Blood glucose testing didn't arrive until 1913. The A1c not until decades later. The testing instruments became more technologically advanced but with inertia behind glucose we just kept asking “how much sugar.” We never paused to think if we were measuring the right biomarker.
“The testing instruments became more technologically advanced but with inertia behind glucose we just kept asking “how much sugar.” We never paused to think if we were measuring the right biomarker.”
When we talk about metabolic disease, namely Type II diabetes or Diabetes mellitus, we talk about glucose: high sugars, A1c numbers (a measure of how much glucose has been binding to your red blood cells over the past three months), and clear delineations of diagnostic thresholds. Prediabetes at 5.7. Diabetes at 6.5. Clean cutoffs that suggest we know exactly when a person becomes sick. Those numbers describe a population screening tool that medicine gradually adopted as a biological truth.
The biological truth is insulin. Insulin resistance develops and becomes measurable up to a decade before glucose ever moves outside a normal range. Meaning, you could check your blood sugars and A1c for 10 years and they could be in the “normal range” all the while insulin has been on an upward trajectory but never part of our screening protocols. The disease is developing and organs are accumulating damage before glucose ever rises to change the numbers we screen. By the time your glucose starts increasing and your A1c registers as high your body has been accumulating the damage and made significant changes responding to your rising insulin. When glucose finally goes up it means you have become so insulin resistant that even high levels of insulin are no longer controlling your glucose.
So one day your glucose crosses a threshold and that is flagged as the "beginning" of a disease process. If you asked most physicians they’d tell you the line is arbitrary and that disease doesn't announce itself with a number. And yet the framework persists. The screening tool was so useful administratively that it quietly became biological truth. We needed a cutoff for guidelines, for billing, for population studies. And somewhere along the way the cutoff became the diagnosis. The disease didn't appear that day, it just finally made it onto the chart as a diagnosis. For years before that, when the signs may have been more subtle, patients are often told “we’ll keep an eye on it” as if watching is the same as acting.
The question precision medicine asks is what was happening before the number moved. The answer is readily available. It’s not complicated. It’s not expensive. It’s just not what we screen for. Fasting insulin, HOMA-IR (a simple calculation from a fasting insulin and glucose that estimates how resistant your tissues are to insulin), a two-hour insulin response to glucose: none of it is standard of care but it tells a more accurate story than glucose can.
Insulin was discovered in 1921 and first used in a fourteen year old boy with type I diabetes. It was, and remains a discovery that changed the trajectory of a fatal disease. A disease of absence: where the pancreas stops making insulin, you replace it and the patient lives. The problem is what happened when that logic met a different disease process and was extrapolated to Type II diabetes. And with the same inertia, we’ve been carrying forward this framework with increasing sophistication without stopping to ask whether this made sense for a disease that can also cause high sugar but does so in a completely different way. High glucose is the outcome of both but Type I and Type II diabetes arrive there in such fundamentally different mechanisms.
Moreover, Type II diabetes isn’t even one disease though we speak of it as it is. It's a diagnostic category that contains multitudes: different genetics, different fat distribution phenotypes, different rates of beta cell exhaustion, different tissues affected, different inflammatory profiles, different trajectories. A uniform A1c target applied across that heterogeneity isn't precision medicine. This is exactly where we started. A number designed to describe populations is now used to describe individuals. Oncology has refined this approach. We no longer treat “cancer", we treat the specific mutation, the receptor status, the tumor microenvironment. A HER2-positive breast cancer and a triple-negative breast cancer share the name and almost nothing else: one has targeted therapy and the other does not. We accepted that complexity and built our treatment around it. We have not done that with type 2 diabetes. We still treat the category.
The fallacy of chasing the glucose target is we used drugs that lowered glucose but didn’t necessarily improve insulin sensitivity. The same inertia of the honey sweetness, the missing insulin, built a treatment algorithm that didn't save people their limbs, their sight, their kidneys or their lives even though the standardized goals for glucose and A1C had been met. But we pushed on because that was the framework even though the data showed it wasn’t working. When we finally used medications that sensitized tissues to insulin, outcomes changed.
Please don’t misconstrue this argument as glucose is a useless biomarker and dump your insulin at the curb. The argument is not that glucose isn’t a useful biomarker or isn’t a big player in the disease process. Nor is this an argument against taking prescribed insulin: high, uncontrolled glucose absolutely warrants insulin. This is an AND not an OR. Insulin is the canary in the coal mine. If we started listening to the canary we could act before people succumb to the chronic diseases that follow. If we test insulin and act when we see it rise disproportionately by helping patients reclaim their insulin sensitivity through precise exercise, nutrition, stress management and for some pharmaceuticals, we could reverse disease processes and truly treat metabolic diseases and the downstream damage they cause.
When we frame biology in terms of populations we become numb to the consequences of following inertia. When we frame biology in terms of individuals we feel the grief of lost limbs, heart attacks, dialysis, lost sight, lost lives. If we shift our perspective upstream our grief can be saved for the things we truly cannot control.
If you're interested in working with a physician who makes these part of standard practice, I would love to start a conversation with you. To subscribe to this newsletter signup here.
In the meantime, live vividly.
Java Tunson, MD
