Prediabetes is a pre-diagnosis — a warning rather than a disease in waiting. It is also reversible. The mistake embedded in standard practice is treating the diagnostic threshold as the point at which harm begins.
Damage starts at 5.7, not 6.5
Most physicians wait until HbA1c exceeds 6.5 before intervening. Macrovascular tissue damage is already occurring between 5.7 and 6.5. The increased cardiovascular risk associated with type 2 diabetes does not begin at the diagnostic cutoff — there is a continuum of microvascular and macrovascular risk extending well below it. (Hopper I, Billah B, Skiba M, Krum H. Prevention of diabetes and reduction in major cardiovascular events in studies of subjects with prediabetes: a meta-analysis of randomized controlled trials.)
It is also worth knowing that HbA1c has a significant tendency to miss cases compared with an oral glucose tolerance test. A normal HbA1c is weaker reassurance than most patients are given to believe.
How common, and how silent
In 2015 an estimated 84.1 million American adults had prediabetes — roughly one in three. Most did not know. Diabetes develops gradually, over years, and during the prediabetic phase there may be no symptoms at all.
What people sometimes notice:
- Eating a standard American processed-food diet.
- Being hungrier than usual.
- Losing weight despite eating more, or gaining despite eating less.
- Increased thirst.
- Passing urine more frequently.
- Unusual fatigue.
Glycation, and what HbA1c is measuring
Glycation is a spontaneous chemical reaction — a Maillard reaction — in which a sugar molecule bonds covalently to a protein or lipid without enzymatic control. It is haphazard and it impairs the function of whatever it modifies. Notably, fructose has roughly ten times the glycation activity of glucose, which is why the source of the sugar matters and not only the quantity.
HbA1c measures the fraction of hemoglobin that has been glycated, which is why it reflects an average over the lifespan of the red cell rather than a single moment.
The economics of treating early
Delaying progression to type 2 diabetes is cost-effective even when it requires medication. Generic metformin costs well under five cents per 1,000 mg tablet — roughly six dollars for a thirty-day supply — against the eventual cost of insulin supplementation once beta-cell fatigue sets in.
Metformin also has effects beyond glucose. In the prediabetic range it appears cardioprotective: insulin resistance is implicated in the development of left ventricular hypertrophy, one of the strongest independent predictors of cardiovascular outcome, and dysglycemia is common in patients with coronary artery disease and linked to insulin resistance.
How many carbohydrates do you actually need?
A patient once asked how many carbohydrates she should eat daily, because her dietitian had told her at least 250 grams or she risked brain injury from hypoglycemia. The USDA, the Institute of Medicine and the American Heart Association recommend carbohydrates make up 45 to 65 percent of daily calories — on 2,000 calories, roughly 900 to 1,300 calories from carbohydrate.
The human dietary requirement for carbohydrate is, strictly, zero: the body manufactures the glucose it needs through gluconeogenesis. That is not an argument for eliminating all carbohydrate, but it is a reason to treat the recommended range as a convention rather than a physiological necessity.
Why it is worth reversing before it is diabetes
Obesity, prediabetes and type 2 diabetes are associated with most of the diseases of modern society — cardiovascular and cerebrovascular disease, cancer, Alzheimer’s disease. All are metabolic dysfunctions related to the malnutrition of overconsumption, which produces metabolic inflammation.
Reversing diabetes while it is still prediabetes is safe, cost-effective and disease-modifying. The best way to reverse diabetes is not to develop it, because the risk of heart disease, cancer and death is already elevated in the prediabetic range. Treating the root cause rather than the symptom is the whole of the approach: eliminating refined carbohydrates is where it starts.
