Blood Chemistry · Functional Ranges · Glucose Regulation
The NHS HbA1c threshold of 48 mmol/mol was designed to diagnose diabetes, not to protect you from getting there. Below that line, you're told everything is fine. But a decade of metabolic dysfunction can unfold before a single conventional marker moves out of range — and five completely different clinical pictures look identical on a basic glucose panel.
In March 2024 I ran my own Randox Signature blood panel. My HbA1c came back at 30.53 mmol/mol. By any measure — NHS, functional, or otherwise — that's optimal. No flags, no concern, no follow-up needed.
But alongside it: fasting glucose of 5.64 mmol/L.
The Randox reference range flags anything from 5.60 mmol/L as pre-diabetic. On that single marker, in isolation, I was technically in the pre-diabetic zone. My HbA1c — which measures three-month average glucose — was at the low end of optimal. My fasting glucose — a snapshot from a single morning — was borderline by one conventional threshold.
Both numbers came from the same blood draw. One said fine. One said watch it. Without context, you'd have no way to know which one to believe — or whether either reading reflected anything clinically meaningful.
HbA1c measures the proportion of haemoglobin that has been glycated — sugar-coated — over the lifespan of a red blood cell, approximately 90–120 days. It is a three-month rolling average of blood glucose exposure. A single fasting glucose reading captures a moment. HbA1c captures a season.
That makes it a better marker than fasting glucose alone. But it has two important limitations that are rarely explained at the point of testing.
The first is that HbA1c is an average. Significant glucose variability — high post-meal spikes followed by reactive lows — can average out to a perfectly normal HbA1c. The person with extreme glucose swings and the person with stable, steady-state glucose can produce identical HbA1c values. The physiological experience underneath is completely different.
The second limitation is the threshold. The NHS uses 48 mmol/mol (6.5%) as the diagnostic threshold for diabetes, and 42–47 mmol/mol (6.0–6.4%) as pre-diabetes. Below 42 mmol/mol, you're normal. But the relationship between HbA1c and health risk is continuous — it doesn't suddenly start at 42. Risk increases progressively from values well below the conventional threshold.
The EPIC-Norfolk prospective study (4,662 men and women, 4 years follow-up) found that cardiovascular mortality increased progressively across the full HbA1c range, including in people with values well below the pre-diabetes threshold. There was no safe lower bound below which HbA1c had no relationship with risk. The conventional threshold is a diagnostic convenience, not a biological cliff edge.
Functional blood chemistry interpretation uses tighter, health-optimisation ranges rather than disease-diagnosis thresholds. The distinction is important: conventional ranges are set at the outer boundaries of the population, calibrated to detect pathology. Functional ranges are set within the population, calibrated to reflect optimal physiology.
| Marker | NHS / Lab range | Functional optimal | Clinical note |
|---|---|---|---|
| HbA1c | Normal <42 mmol/mol | Optimal <35 mmol/mol Review 35–42 |
Values 35–42 warrant investigation of fasting insulin and HOMA-IR even if "normal" on standard criteria |
| Fasting Glucose | Normal 4.0–5.9 mmol/L | Optimal 4.0–5.0 mmol/L Review 5.0–5.6 |
Above 5.0 mmol/L with any elevation in fasting insulin warrants HOMA-IR calculation regardless of NHS threshold |
| Fasting Insulin | Normal 17.8–173 pmol/L | Optimal <60 pmol/L (8.6 µIU/mL) Review 60–100 |
The NHS range is set so wide it includes early-to-mid insulin resistance. Fasting insulin above 60 pmol/L is worth investigating even with normal glucose |
| Triglycerides | Desirable <2.3 mmol/L | Optimal <1.1 mmol/L Review 1.1–1.7 |
Fasting triglycerides above 1.1 mmol/L are an early signal of impaired glucose metabolism and hepatic lipid handling, even within the "desirable" NHS range |
| TG:HDL Ratio | Not routinely calculated | Optimal <1.0 (mmol/L) Concern >1.5 |
One of the most sensitive surrogate markers for insulin resistance. Calculated from standard lipid panel — requires no additional testing |
| HOMA-IR | Rarely calculated on NHS | Optimal <1.0 Concern >1.5 |
Requires fasting glucose and fasting insulin. Calculated, not directly measured. See the HOMA-IR post for the full explanation. |
Even with functional ranges applied, interpreting metabolic markers individually misses the clinical picture. The University of Oxford developed HOMA2 — an updated computational model that generates three values from a single fasting blood draw: HOMA2-IR (insulin resistance), HOMA2-%B (beta-cell secretory output), and HOMA2-%S (peripheral insulin sensitivity).
Individually, none of the three metrics provides meaningful data. Elevated HOMA2-%B, for example, could mean a healthy beta-cell reserve compensating for early insulin resistance — or it could mean diminished beta-cell capacity producing apparently high output against a low glucose input. Without the other two values, you cannot distinguish between these clinical realities.
Evaluated together, they differentiate five distinct glucose dysregulation patterns that look identical on a standard glucose panel.
Each pattern requires a different clinical approach. Treating them identically — as "blood sugar problem, reduce carbohydrates" — will help some, do nothing for others, and potentially worsen a third.
Type 2 diabetes is hyperinsulinaemic — too much insulin, too little effect. Type 3c is insulin-insufficient — not enough insulin being produced at all. Both can present with elevated fasting glucose. Both can appear similar on a basic panel. But the intervention strategies are opposite: increasing insulin sensitivity is appropriate in Type 2 but can be harmful in Type 3c where the primary problem is production failure. Treating Type 3c as Type 2 is clinically dangerous. The HOMA2 matrix is currently one of the most underutilised tools in metabolic assessment.
The HOMA2 model can use either fasting insulin or C-peptide as the input. C-peptide — co-secreted with insulin at equimolar concentrations — is actually the more reliable marker for assessing pancreatic secretion. Unlike insulin, C-peptide is not affected by exogenous insulin administration, it has a longer half-life, and it is not subject to first-pass hepatic clearance.
Many clinicians who use the HOMA2 model recommend C-peptide as the preferred input — particularly in patients receiving insulin, or in any case where insulin dynamics are unpredictable. The Randox Signature panel includes both fasting insulin and C-peptide. Most NHS panels include neither routinely.
"Serial increases in fasting insulin levels in patients whose glucose levels remain within normal limits are a good indication that further testing with the full HOMA2 matrix would be beneficial rather than waiting until their glucose or A1c moves out of range."
Dr Brad Rachman — Optimal DX Podcast, Episode 5Back to my March 2024 results. Fasting glucose 5.64, insulin 104 pmol/L (7.5 µIU/mL), C-peptide 2.06 ng/mL, triglycerides 0.78 mmol/L.
The fasting insulin at 7.5 µIU/mL is comfortably within the functional optimal range — below 8.6 µIU/mL. Triglycerides at 0.78 mmol/L are in the optimal range. TG:HDL ratio of 0.58 is well within optimal. C-peptide at 2.06 ng/mL is mid-range.
The fasting glucose at 5.64 mmol/L is borderline on the Randox lab range, but read against the full metabolic picture — optimal insulin, optimal TG, optimal TG:HDL, good C-peptide, and HbA1c at the low end of optimal — the pattern is not consistent with insulin resistance at any stage. If anything, the matrix looks closest to Pattern 1 (reactive hypoglycaemia direction) but without the symptom pattern that would accompany it.
The more likely explanation for a single slightly elevated fasting glucose reading after a 14-hour 54-minute fast is the dawn phenomenon — cortisol-driven hepatic glucose release in the early morning hours, which produces a transient elevation in fasting glucose that normalises once the cortisol pulse passes. One number, one morning, one explanation.
Without the matrix, that single flagged glucose would have been the story. With the matrix, it is a contextualised data point in a picture that is largely reassuring.
If your HbA1c is below 42 mmol/mol and your GP has told you everything is normal, that may well be true. But it is worth knowing what "normal" actually means in this context — it means you have not yet crossed a diagnostic threshold. It does not mean your metabolic system is operating optimally, or that there is no process underway that will eventually move you across that threshold.
The questions worth asking after any metabolic blood test are not just "is this number in range?" but: what is fasting insulin doing relative to fasting glucose? What is the TG:HDL ratio? Is there a pattern across the matrix that tells a coherent story?
And crucially: is fasting insulin being measured at all? In most NHS metabolic screens, it is not. You can have significant early insulin resistance — detectable, addressable, reversible — with perfectly normal glucose and HbA1c, for a decade or more, without anyone running the test that would show it.
Early insulin resistance — Pattern 2 in the HOMA2 matrix — is highly reversible. Late insulin resistance is reversible with significant intervention. Once beta-cell exhaustion begins and glucose rises consistently, the window narrows but recovery is still possible with the right approach. The argument for early testing is not to create anxiety — it is to identify when the window is widest and intervention requires the least effort.
The Randox Signature blood panel — the test I ran in March 2024 — includes fasting glucose, fasting insulin, HbA1c, C-peptide, triglycerides, HDL cholesterol, adiponectin, leptin, and resistin. This gives enough data to calculate HOMA-IR and TG:HDL, assess the full metabolic syndrome marker set, and begin constructing the HOMA2 matrix with C-peptide as the preferred input.
It also includes LDH (lactate dehydrogenase) — a marker the HOMA2 framework uses as an additional differentiating variable, particularly in the reactive hypoglycaemia and Type 3c patterns where it shows a significantly decreased pattern distinct from the insulin resistance patterns.
The additional context from 130–180 markers across all systems means metabolic findings are never interpreted in isolation. An elevated fasting glucose in someone with elevated hsCRP and low albumin tells a different story from the same glucose in someone with optimal inflammatory markers and good protein status. The blood chemistry is read as a picture, not a list.
Fasting glucose and HbA1c alone are not enough. The Randox Signature blood panel gives you the full marker set — including fasting insulin, C-peptide, and LDH — to construct the metabolic matrix that distinguishes five distinct clinical patterns from a single fasting blood draw.
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