The Three Questions That Change Diabetes Treatment Before the Blood Work Comes Back
April 8, 2026
We have been taught to fixate on the A1c. It is the report card for diabetes. Get it below seven and you are doing well. Keep it above eight and you need to work harder. It is a clean, simple number.
The problem, as Dr. Fernandez lays out in The Diabetes Network, is that the A1c is a snapshot of only one narrow chemical reaction happening in your blood. It tells you how much sugar has glommed onto the hemoglobin in your red blood cells over the past three months. That is useful information. But it does not tell you what has been happening to the collagen in your artery walls, the basement membrane of your kidneys, or the myelin sheath wrapped around your nerves over the past ten years.
The real driver of diabetic complications is something called the Maillard reaction. It is named after the French chemist who first described it in 1912. It is the same reaction that turns a piece of raw dough into a golden brown crust when you bake it. Heat speeds it up. But even at body temperature, this reaction runs slowly and continuously. Glucose binds to proteins. That bond starts out reversible. But over weeks and months, it rearranges into a permanent, damaging structure called an Advanced Glycation End product, or AGE.
Once an AGE forms on a protein, that protein is changed forever. It becomes stiff. It crosslinks with neighboring proteins. And it binds to a receptor on your cells called RAGE. Activating RAGE flips on a master switch of inflammation called NF kappa B. This inflammation then tells the cell to make even more RAGE receptors. It becomes a self feeding loop. The inflammation sticks around even after you get your blood sugar under control. This explains the phenomenon called metabolic memory. Patients who had high blood sugar ten years ago can still develop eye or kidney damage today even if their current A1c is perfect. The AGEs left behind in their tissues are still causing trouble.
Here is the part that matters most for understanding why the same A1c can mean different things for different people. The rate at which AGEs form is not linear. It scales with the square of the glucose concentration. In plain English, one year at an A1c of eleven percent causes roughly three times as much permanent molecular damage as one year at an A1c of seven percent. If you spent five years undiagnosed with prediabetes, your vascular proteins have accumulated a history of damage that the current A1c cannot reveal.
The Diabetes Network maps out seven interconnected pathways that all feed into this damage network. There is the polyol pathway we talked about with the capers. There is the hexosamine pathway that drives insulin resistance. There is the protein kinase C pathway that damages small blood vessels in the eyes and kidneys. They all talk to each other. They all amplify each other.
The book provides a way to measure how far along this network activation has progressed using routine lab tests you probably already get. Your ALT liver enzyme hints at mitochondrial stress. Your uric acid level hints at antioxidant defense collapse. Your triglyceride to HDL ratio hints at the hexosamine pathway. By looking at these markers together, a physician can stage the disease in a way that goes far beyond the A1c. A patient in Stage 1 with a focal problem might respond beautifully to simple medication. A patient in Stage 4 where the network is self sustaining may see very little A1c improvement from the same drugs, but still needs those drugs for organ protection.
Understanding this network changes the conversation from “What is your number?” to “Where is your damage headed?” It is a more honest, more precise way to think about a disease that does its worst work in silence.
