Type 2 Diabetes as a Stuck Program Mode
The cleanest mechanistic case of the nine
[Hello, Reader. This is the the paper under the Umbrella of the Stuck State Series. I’m going to tie 9 different chronic illnesses to one commonality.]
Start here if you want to start at the beginning.
→ Paper A: Candida albicans as a Biochemical Computer
This is the sixth installment in the series walking through the Redacted Science Research Initiative — sixteen peer-citable preprints, plus the Architect Reports, in the order they should be read. Each post is the Summary for the Reader from the Architect — a plain-English entry point — followed by where to find the full paper. Technical terms are unpacked in italic brackets where they appear. The Architect’s asides are in there too. You’ll know them when you see them.
Type 2 diabetes is the first of the nine stuck program modes. It’s also the one with the tightest mechanistic chain — a single sensor on the organism’s membrane, calibrated to a single set point in the host. That set point happens to be your blood sugar. Now read on.
Summary for the Reader from the Architect
Of the nine stuck modes, this is the cleanest mechanistic case.
The standard story for type 2 diabetes is: too much weight, not enough exercise, bad genes — and then progressive insulin resistance, eventually beta cell failure. [Beta cells: the pancreatic cells that make insulin. When they fail, you’re insulin-dependent for life.] That story does not explain why the deterioration keeps going in patients whose insulin production is still adequate. And it really does not explain why bariatric surgery and extreme caloric restriction produce remission in timeframes too short for the structural changes the model invokes. [The math doesn’t work. People improve faster than weight loss alone can account for.]
Here’s the alternative. C. albicans has a membrane glucose sensor called Hgt4, calibrated to roughly 5 mM — which happens to be the approximately normal human blood glucose concentration. [Approximately 90 mg/dL in US units. The setpoint your pancreas is trying to hold.] That’s not a coincidence; that’s a receptor tuned to the host’s operating range. Peroumal et al. (2022) demonstrated that C. albicans colonization measurably alters GLP-1, GIP, and insulin levels. [Those are your incretin hormones — the signals that tell your pancreas when and how much insulin to release. The organism can move them.]
The framework proposes that type 2 diabetes is the organism’s glucose-harvesting phase running without a phase transition. The modern dietary environment — effectively unlimited glucose — never delivers the substrate shift that would signal “we’re done here, move to the next phase.” [In the ancestral environment, food availability changed. Seasons, scarcity, feasts, fasts. The signal was built into the environment. Modern food supply removed the signal.] So the organism keeps running the harvest. Continuous glucose draw. Progressive insulin resistance. Eventually, the pancreas can’t keep up.
The model explains bariatric surgery [it rearranges the habitat the organism lives in] and GLP-1 agonists like semaglutide [Ozempic, Wegovy — they override the sensing channel the organism uses] as two different ways of breaking the stuck state. Five testable predictions are presented, including studies correlating organism density with insulin resistance severity and with differential treatment response.
Type 2 Diabetes as a Stuck Program Mode of the Candida albicans Biochemical Computer Craddock, J. — 14 references DOI: 10.5281/zenodo.19582791
The full preprint, with all five testable predictions and the Hgt4 mechanism detail, is on Zenodo at the link above. CC BY 4.0.
Next in the Series
Obesity as a Stuck Program Mode. If T2D is the cleanest stuck mode, obesity is the most diffuse — and the most important. Over 1 billion people worldwide. 95% weight regain within five years. That isn’t insufficient willpower; that is a defended equilibrium. The standard model says you ate too much and now your body is storing the excess. The stuck-program model says the body is doing exactly what it was told to do — and it was told to do it by the organism.
Subscribe to get the Obesity paper in your inbox.
— #TheArchitect
Redacted Science Compilation