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How You Got the Number Matters More Than the Number

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Metabolic Health Biomarkers Longevity
Neo W.
Author
Neo W.
Writing about things that intrigue me.
Table of Contents

How You Got the Number Matters More Than the Number
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A trial of over 10,000 people with type 2 diabetes was stopped early because the group pushed to a near-normal HbA1c was dying at a 22% higher rate. The same number reached through food and movement is protective. Reached with aggressive medication, it can kill you.

“Normal” is a diagnostic line, not a target
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HbA1c thresholds exist to make a diagnosis — normal, prediabetic, diabetic. They were never designed to describe optimal.

Glucose harm doesn’t respect those lines. Risk rises continuously with average level, and it is already climbing inside the range that gets reported back to you as reassuring.

The clearest demonstration is dementia. Crane et al. (2013, New England Journal of Medicine) followed more than 2,000 adults aged 65+ in the Adult Changes in Thought study, using five-year average glucose. Among people without diabetes, an average glucose of 115 mg/dL carried an 18% higher dementia risk than 100 mg/dL — and the authors found no threshold below which risk levelled off. Both of those numbers are “normal.”

It’s observational, so causation isn’t established. But it fits the mechanism: high-normal glucose slowly damages the small vessels supplying the brain.

After 60, the same number does more damage
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Two things shift with age. Muscle and tissue become more insulin resistant, and the pancreas loses beta-cell reserve — so people drift upward into high-normal and prediabetic ranges without noticing anything.

At the same time the tissue being exposed is more vulnerable. Glycation — sugar binding to proteins to form advanced glycation end products — drives inflammation and arterial stiffening, and older vessels tolerate it less well.

A glucose level that is fairly harmless at 30 is doing more harm at 65.

And then the trial that inverts the advice
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This is the part that most coverage gets wrong, and it’s the most important thing here.

ACCORD (2008, NEJM) randomised over 10,000 people with type 2 diabetes at high cardiovascular risk, average age early sixties, to either an intensive target of HbA1c below 6.0% — using whatever combination of drugs it took — or a standard target of 7.0–7.9%.

The expectation was straightforward: lower glucose, fewer events. Instead the intensive arm was halted after a median 3.4 years because all-cause mortality was 22% higher (HR 1.22, 95% CI 1.01–1.46).

The likely mechanism is hypoglycaemia. Driving glucose down with multiple agents produces hypo episodes, and in an older person a hypo means falls, arrhythmias, and head injuries that bleed. The number on the page improved while the person got worse.

This is why guidelines set deliberately easier targets for older people on medication — often 7–8.5% depending on overall health — and why good practice increasingly involves deprescribing the riskiest agents rather than adding more.

So the answer splits in two
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If you are not on glucose-lowering medication, the levers are all behavioural and none of them can drive you too low:

  • The plate. The biggest one. Carbohydrate from whole, intact sources — vegetables, beans, lentils, whole grains — absorbed slowly. Cut refined carbohydrate in ultra-processed food hard.
  • Muscle. Skeletal muscle is the main disposal site for glucose. A short walk after meals blunts the post-meal rise; resistance training expands the tank. This is among the most underrated interventions available after 60.
  • Sleep. A few bad nights measurably increase insulin resistance.
  • Waist. Losing modest visceral fat improves the entire picture.

Reasonable targets in this group: fasting glucose in the low 5s mmol/L (under about 100 mg/dL), and HbA1c comfortably below the prediabetic threshold — under roughly 39–42 mmol/mol (5.7–6.0%). Treat those as a floor to aim at, not a finish line.

If you are on insulin or sulfonylureas, the message inverts completely. Lower is not the goal. Your safe number is the one your doctor set, which is deliberately higher, and chasing a better-looking figure on your own can hospitalise you. Report any shaky, sweaty or confused episodes — those are signs treatment is pushing you too far down. Add the lifestyle levers gradually so that medication can be reduced under supervision rather than fighting against it.

Why the paradox resolves
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Two identical HbA1c values can mean opposite things.

A low number your own physiology maintains is a signal that the system works — insulin sensitivity is intact, muscle is absorbing glucose, the pancreas isn’t straining.

A low number that three drugs are dragging below where your body wants to sit isn’t a sign of health. It’s a sign of pharmacological force, and it comes with hypoglycaemia attached. Same figure on the page, opposite meaning underneath.

Summary
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Diagnostic thresholds describe diagnosis, not optimum, and dementia risk rises with average glucose well inside the normal range — 18% higher at 115 mg/dL than at 100 mg/dL in non-diabetics, with no lower threshold where it flattens. After 60, insulin resistance rises and tissue tolerates glycation less well, so the same number costs more. But ACCORD showed that forcing glucose down pharmacologically in older people at cardiac risk raised mortality by 22% and had to be stopped early. The number matters less than the route to it.

What to actually do:

  1. Find out whether you’re on a glucose-lowering drug that can cause hypos — insulin and sulfonylureas can; metformin essentially doesn’t. That single fact determines which half of this article applies to you.
  2. If not on medication: aim below 39–42 mmol/mol (5.7–6.0%), not merely below the diabetic line.
  3. If on insulin or sulfonylureas: use your doctor’s target and don’t chase lower. Report shaky, sweaty or confused episodes.
  4. Work the plate first — whole-food carbohydrate, minimal ultra-processed.
  5. Walk after meals and lift twice a week. Muscle is the disposal site.
  6. Fix sleep, which shifts insulin resistance within days.
  7. Ask about deprescribing if you’re older and on several agents — fewer, safer drugs plus lifestyle often beats more drugs.

Education, not personal medical advice. Anyone on medication should confirm their own target with their doctor.

Sources & further reading
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  • Crane P.K. et al., Glucose levels and risk of dementia, New England Journal of Medicine (2013) — NEJM / PubMed
  • The Action to Control Cardiovascular Risk in Diabetes Study Group, Effects of intensive glucose lowering in type 2 diabetes, New England Journal of Medicine (2008) — NEJM
  • Effects of intensive glucose lowering in the management of patients with type 2 diabetes mellitus in the ACCORD trial, Circulation — AHA Journals
  • ADVANCE Collaborative Group, Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes, New England Journal of Medicine (2008) — NEJM
  • Kaiser Permanente Washington Health Research Institute, Dementia risk tied to blood sugar level, even with no diabetes — KPWHRI
  • Protective effect of intensive glucose lowering therapy on all-cause mortality, adjusted for treatment switching using G-estimation, the ACCORD trial, Scientific Reports (2023) — Nature

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