On labels, complexity, and the cognitive traps that cost patients the right diagnosis Anthony Pick MD, CDCES, CCD | Multisystem Medicine
Every map is a lie. The useful question is whether it is a productive lie (simplification) — one that gets you somewhere — or a dangerous one that leaves you confidently lost.
Medicine runs on maps. We build taxonomies, diagnostic categories, and disease labels because the human mind cannot function without them. Complexity must be compressed. A clinician seeing thirty patients a day cannot hold every nuance of every pathophysiological pathway in working memory simultaneously. The label — Type 2 diabetes, say — is a cognitive scaffold. It tells you roughly where you are, what to expect, which roads are available.
But the scaffold is not the building. And when we mistake the map for the territory, patients pay.
Few areas of medicine illustrate this more clearly — or more consequentially — than diabetes. What we call “diabetes” is not one disease. It is not two diseases. It is a family of metabolic disorders united by a shared endpoint, elevated blood glucose, but driven by radically different mechanisms, following different trajectories, requiring different treatments, and carrying different implications. Collapsing them into a single label is a bit like diagnosing every chest pain as “heart trouble” — sometimes close enough, often not.
This essay practices three disciplines together, and I want to name them before I begin: deep clinical knowledge of the disease itself, careful reasoning about how clinicians arrive at — or fail to arrive at — the right diagnosis, and honest appraisal of the evidence behind the labels we use. Diabetes is one lens. The disciplines apply everywhere.
“The label is a scaffold. It gets you to the building site. It is not the building.”
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## Type 1 Is Not a Moment — It Is a Trajectory
We teach Type 1 diabetes as an event: the immune system attacks the pancreatic beta cells, insulin production collapses, the patient presents in crisis. In reality, Type 1 is a slow-motion process that begins years — sometimes decades — before a single symptom appears.
TrialNet established a three-stage model, now adopted by the ADA and JDRF, that reframes Type 1 as a process rather than an event. **Stage 1:** two or more islet autoantibodies are present, glucose is normal, the patient is asymptomatic — but the immune war has already begun. **Stage 2:** autoantibodies persist and dysglycemia emerges. **Stage 3:** clinical diabetes, the point at which most patients are first diagnosed and at which most clinicians first look.
Staging changes management. A Stage 1 or Stage 2 patient is now eligible for teplizumab, the first FDA-approved therapy to delay progression to Stage 3 — by a median of two to three years in the landmark TrialNet trial. That window is not trivial. It is time for patient education, psychological preparation, and metabolic optimization before the crisis arrives.
The cognitive trap is anchoring: if we only look for Type 1 when the patient collapses into DKA, we have already missed the chance to intervene upstream. The multisystem lens asks not only where the patient is but where they are headed.
Ref: Insel RA et al. Diabetes Care. 2015;38(10):1964–1974. | Herold KC et al. NEJM. 2019;381:603–613.
↗ Coming in this series: Type 1 as Trajectory: Staging, Teplizumab, and the Window Before the Crisis.
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## Type 2 Is Also a Trajectory — and Prediabetes Is Where It Begins
This is the claim that tends to provoke the most pushback, so I want to make it carefully.
Type 2 diabetes affects over 400 million people worldwide. It is real in the same way that *anemia* is real — as a final common pathway, a phenotypic endpoint reached by multiple distinct mechanisms over a long arc of time. Just as we no longer treat all anemia with iron, we should not treat all Type 2 diabetes as a single biological entity, and we should not treat its earlier stages as a separate disease.
The term *prediabetes* implies proximity to a threshold. The biology suggests something different. Microvascular damage begins in the prediabetes range. Cardiovascular risk is elevated. Small fiber neuropathy can precede a formal diabetes diagnosis by years. Prediabetes is not the anteroom to disease. It is the disease, at an earlier stage, when intervention is most effective. Reading prediabetes as Stage 1 of Type 2 — and the diabetes diagnosis itself as a much later inflection point on a continuous trajectory — changes both who gets treated and when.
The trajectory is also not uniform. In 2018, Ahlqvist and colleagues published a landmark cluster analysis using six variables — GAD antibodies, age at diagnosis, BMI, HbA1c, beta cell function, and insulin resistance — and identified five distinct subgroups within what had been labeled Type 2 diabetes. Severe insulin-resistant diabetes carried the highest risk for fatty liver disease and chronic kidney disease. Severe insulin-deficient diabetes (non-autoimmune) carried the highest risk for retinopathy. Mild age-related diabetes followed a more benign course. These are not minor nuances. They predict which organs will fail first, and they should shape which therapies are reached for first.
Biologically, the distinction between **insulin resistance-predominant** and **beta cell failure-predominant** diabetes is fundamental. Insulin resistance — driven by visceral adiposity, ectopic fat, and chronic inflammation — dominates in many patients early in the trajectory. Progressive beta cell exhaustion, driven by glucotoxicity, lipotoxicity, and polygenic predisposition, dominates in others, including many leaner patients of East and South Asian ancestry where Type 2 at normal BMI is common.
Treating these as the same disease with the same first-line algorithm is not precision medicine. It is pattern-matching with a blunt instrument.
”Type 2 diabetes” is a final common pathway, not a single disease. Treating it as one is like treating all anemia with iron.
Ref: Ahlqvist E et al. Lancet Diabetes Endocrinol. 2018;6(5):361–369.*
↗ Coming in this series: Type 2 as Trajectory: Why Prediabetes Is the Disease, Just Earlier. | The Five Faces of Type 2: Phenotyping for Precision in Cardiometabolic Medicine.
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## The Diagnoses That Don’t Fit Either Trajectory
If Type 1 and Type 2 are two trajectories, a meaningful set of patients are on neither — and these are the patients most likely to be misclassified, mistreated, and sent down the wrong therapeutic road. Four categories deserve naming, even briefly.
LADA — Latent Autoimmune Diabetes in Adults.** Shares the autoimmune mechanism of Type 1 but follows a slower trajectory, typically presenting in adults and progressing to insulin dependence over months to years. Accounts for roughly 5 to 10 percent of adults diagnosed with Type 2. The diagnostic test — GAD65 antibody — is rarely ordered at the time of initial diagnosis. The clinical cost is real: these patients are commonly placed on sulfonylureas, which accelerate beta cell exhaustion in the setting of ongoing autoimmune destruction. They fail predictably. ↗ Coming: LADA: When Type 1 Hides Inside Type 2.
Type 3c — Pancreatic Diabetes. This arises from structural or functional disease of the exocrine pancreas: chronic pancreatitis, cystic fibrosis, hemochromatosis, surgical resection, and — critically — pancreatic cancer. Roughly 5 to 10 percent of all diabetes in Western populations, and almost universally misclassified as Type 2. Two clinical points cannot be overstated. First, combined insulin and glucagon deficiency makes these patients exquisitely sensitive to hypoglycemia and poorly suited to aggressive sulfonylurea regimens. Second, **new-onset diabetes in a patient over 50 with weight loss and no metabolic risk factors should raise immediate suspicion for pancreatic malignancy. Pancreatic cancer can present as diabetes before it presents as anything else. ↗ Coming: Type 3c: The Diabetes That Gets Blamed on Something Else.
Type 5 — Malnutrition-Related Diabetes. Recognized by the International Diabetes Federation in 2025 [verify date] after decades of marginalization in Western-dominated literature. Affects primarily young, lean individuals with histories of chronic malnutrition, particularly in early life. Insulin-deficient, autoantibody-negative, ketosis-resistant. Reminds us that the metabolic phenotype is shaped by the entire life history of the organism — genetics, epigenetics, early environment, nutrition. As patient populations diversify globally, the category matters clinically. ↗ Coming: Type 5: The Diabetes the Textbooks Forgot.
Monogenic diabetes (MODY). Roughly 1 to 5 percent of all diabetes, fourteen-plus subtypes described, and dramatically misclassified. MODY 2 (GCK mutations) causes mild, stable fasting hyperglycemia requiring no pharmacological treatment — patients diagnosed as Type 2 and started on metformin or insulin are being overtreated. MODY 3 (HNF1A mutations) is exquisitely sensitive to low-dose sulfonylureas — patients misdiagnosed as Type 1 and placed on insulin can often be transitioned to an oral agent with dramatically better outcomes. Flags that should prompt genetic testing: diagnosis before age 35, strong multigenerational family history, absence of obesity, absence of islet autoantibodies, stable mild fasting hyperglycemia without progression. ↗ Coming: When the Gene Is the Answer: A Clinical Guide to Monogenic Diabetes, MODY and monogenic obesity.
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## When Cortisol Is the Hidden Driver: MACS
There is a category of diabetes-adjacent metabolic dysfunction that sits outside the standard taxonomy entirely — and is almost never considered at the time of diagnosis.
Mild autonomous cortisol secretion (MACS) — previously called subclinical Cushing’s syndrome — refers to low-grade, unsuppressed cortisol excess from adrenal incidentalomas, found in 20 to 50 percent of patients who undergo adrenal imaging for any reason. These patients lack the classic stigmata of overt Cushing’s: no moon face, no purple striae, no proximal myopathy. What they do have, with striking regularity, is a cardiometabolic phenotype that resists conventional management — hypertension, visceral adiposity, dyslipidemia, insulin resistance, impaired glucose tolerance, and accelerated bone loss.
Two recent trials sharpened the picture considerably. The CATALYST trial demonstrated that even modest cortisol excess — defined by failure to suppress below 1.8 mcg/dL on overnight dexamethasone suppression —was present in 23.8% of patients with difficult to control “type 2 diabetes”. The MOMENTUM trial presented at ACC 2026 showed a surprisingly high incidence of cortisol autonomy in resistant hypertension (27.3%).
The clinical implication: a patient labeled as “difficult-to-control Type 2 diabetes” with resistant hypertension and central obesity may have an adrenal incidentaloma driving the phenotype. Without looking upstream at the hormonal architecture, the label sticks, the medications accumulate, and the underlying driver goes untreated.
↗ Coming in this series: The Cortisol You’re Missing: Adrenal Incidentalomas, MACS, and the Cardiometabolic Consequences Nobody Is Treating. | Reading CATALYST and Momentum: A Worked Example in Critical Appraisal.
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## Why These Errors Are Predictable
A pattern runs beneath every misclassification above, and it is not a pattern of insufficient knowledge. It is a pattern of how clinicians think under load.
Anchoring. The first diagnosis sticks. Once the chart reads “Type 2 diabetes”, subsequent clinicians read through that frame. Disconfirming evidence — brittle control, unexpected weight loss, absence of metabolic risk factors — is processed as noise rather than signal. I have tragically seen this anchoring lead to a fatal and potentially avoidable outcome (see upcoming essay on type 3c diabetes).
Availability. Common diagnoses are mentally available; rarer ones require deliberate effort to access. LADA, Type 3c, MODY, and MACS are all common enough to matter clinically but rare enough to fall outside automatic pattern-matching.
Premature closure. The diagnosis is made and the search stops. The patient has diabetes. Which diabetes — and driven by which mechanism — is never asked.
The antidote is not more protocols. Protocols can encode the same cognitive errors at scale. The antidote is a disciplined practice of differential diagnosis applied not just to symptoms but to mechanism — asking not only what the patient has, but why they have it, and whether the label they carry is actually earning its place in their chart.
↗ Coming as a parallel series: **How Doctors Think (and Where They Go Wrong): A Field Guide to Cognitive Bias, Diagnostic Error, Translation of Guidelines and Clinical Decision Support.
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## What This Series Is For
I want to be direct about why I am writing this — and why the diabetes taxonomy is not an academic exercise.
The way medicine is currently organized — by organ, by specialty, by billing code — produces predictable blind spots. The endocrinologist sees the glucose. The cardiologist sees the coronary artery. The gastroenterologist sees the pancreas. No one is structurally required to see the whole system. And so the patient with LADA misclassified as Type 2, failing sulfonylurea after sulfonylurea, cycles through the system without anyone asking the right question. Further diabetes is much more than is reflected in a “glucocentric” view of the disease syndromes. This deeper understanding of the multiple pathophysiology pathways of diabetes is another thread of essays to look out for.
Multisystem Medicine is my name for the discipline that closes that gap. It is not a new specialty in the bureaucratic sense. It is a way of thinking — one that takes seriously the biological reality that human systems are integrated, that metabolism is a network, and that the presenting complaint is rarely the whole story. This essay practices three of the disciplines that constitute it: clinical depth, careful reasoning, and honest appraisal of evidence. There are others. A future essay will name them all and show how they are woven together.
The success criterion is not knowledge, and not guidelines. Guidelines are inert until implemented. A diagnosis is a hypothesis until it changes a treatment. The practice I am building treats translation — the conversion of knowledge into outcomes for the patient in front of you — as the only criterion that matters. Everything else is preamble.
The diabetes taxonomy is the first illustration. The same logic applies across every domain where a reductionist label is doing incomplete work: bone and muscle, hormonal architecture, women’s health, longevity, cardiometabolic medicine. Weaving complexity into clarity — one system at a time, one essay at a time.
“The endocrine system is the operating system of human metabolism. I am trained to read it whole.”
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If this essay resonated, stay tuned for Multisystem Medicine for essays at the intersection of endocrinology, cardiometabolic medicine, and systems thinking.
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Key References
1. Insel RA et al. Staging presymptomatic type 1 diabetes. Diabetes Care. 2015;38(10):1964–1974.
2. Herold KC et al. Teplizumab in relatives at risk for type 1 diabetes. NEJM. 2019;381:603–613.
3. Ahlqvist E et al. Novel subgroups of adult-onset diabetes. *Lancet Diabetes Endocrinol.* 2018;6(5):361–369.
4. Laugesen E et al. Latent autoimmune diabetes of the adult. Diabetic Medicine 2015; 32 (7), 843-852
5. Hart PA et al. Type 3c diabetes mellitus. Lancet Gastroenterol Hepatol. 2016;1(3):226–237.
6. Misra S et al. Malnutrition-related diabetes. Lancet Diabetes Endocrinol. 2022;10(9):675–685.
7. Hattersley AT, Patel KA. Precision diabetes: learning from monogenic diabetes. Diabetologia. 2017;60(5):769–777.
8. CATALYST trial — A phase 4 study of hypercortisolism in patients with difficult-to-control diabetes. American Heart Journal. Vol 267, January 2024, 134-135
9. MOMENMTUM trial — presented at ACC 2026 showing 27.3% prevalence of hypercortisolism in resistant hypertension.