Lactate, the early warning signal.

Grace is the GNL evidence engine. She holds the depth on the Brooks shuttle work, the Broskey fasting-lactate findings, the San-Millán metabolic-flexibility protocol, and the cohort-design arguments below. Read about Grace on VN or query her directly at app.theglucoseneverlies.com.

For most of the twentieth century, lactate was taught as muscle waste, the byproduct of incomplete glucose breakdown when oxygen ran short. That picture is wrong.

Brooks 2018 in Cell Metabolism reframed lactate as a central metabolic intermediary. The lactate-shuttle work showed that lactate moves continuously between cells, tissues, and organs, carrying energy and carbon from where it is made to where it is needed. Fast-twitch muscle fibres produce it; slow-twitch fibres consume it. The liver clears some of it back to glucose via the Cori cycle. The brain uses it as preferential fuel under load. The heart runs on it during exercise. Lactate is the body’s metabolic currency, not its rubbish.

That reframe matters for what we are about to ask of a continuous lactate device. A continuous lactate signal is not a continuous reading of metabolic damage; it is a continuous reading of how well the body is shuttling energy between systems. Metabolic flexibility, the capacity to switch fuels and clear lactate cleanly, is the underlying capacity the signal measures.

The canary framing rests on three pillars.

Brooks 2018, the substrate anchor, established lactate as the body’s energy currency. San-Millán and Brooks 2018 in Sports Medicine established lactate threshold and metabolic flexibility as the canonical sports-physiology marker. In athletes the signal is strong, well-validated, and reproducible. The deeper observation, the one that drives the canary framing, is that metabolic flexibility is the same physiological capacity that erodes years before fasting glucose drifts and before HbA1c rises. Broskey 2024 in Diabetes & Metabolic Syndrome extends the lactate signal into the metabolic-health context. Resting lactate, post-load lactate, and lactate kinetics correlate with insulin resistance, fatty-acid handling, and the impaired-fasting-glucose / impaired-postprandial-glucose / pre-type-2-diabetes progression arc.

The mechanistic case is defensible. The lead-time observation is not yet a closed finding. The mechanistic case suggests metabolic-flexibility decline precedes glycaemic decompensation by years. The longitudinal validation against HbA1c progression in cohorts comparable to existing IFG, IPG, and pre-T2D registries is the work that would convert mechanism to evidence. The specific lead-time figure, in months and years, is what that work would quantify. Via Negativa Health does not yet have that figure as a closed finding, and any walkthrough that gives you one is over-claiming.

That is the headline. The crystal ball is mechanistically defensible. The longitudinal evidence is still in front of us.

If a continuous lactate device wants to claim broader-metabolic-health usefulness, it has to prove itself against a comparator everyone trusts. HbA1c is the natural choice. It is the metric every clinician understands, every guideline references, and every patient sees on their summary.

HbA1c also has known discriminatory limitations in defined sub-populations: iron deficiency anaemia, haemoglobinopathies, recent transfusion, erythropoiesis variation, pregnancy. The discriminatory power is eroded in these contexts. That is part of the case for an additional signal that is not red-cell-dependent. But HbA1c remains the benchmark.

The principle is simple. The execution is not. A longitudinal cohort that tracks lactate metrics alongside HbA1c year-over-year, across normoglycaemia, the impaired-fasting-and-postprandial-glucose middle, early T2D, and insulin-dependent T2D, would tell us how predictive the lactate signal actually is. The cohort design, the primary endpoint framing, the secondary endpoints, the sample-size rationale, the ethics framework, the pre-registration approach are work Via Negativa Health designs under engagement with the manufacturer building the device. The specific design is not on this page. The principle is.

Whole-blood and plasma lactate is currently measured in millimoles per litre (mmol/L). Typical resting values sit around 0.5 to 1.5 mmol/L; light exercise lifts to 2 to 3 mmol/L; the lactate threshold in athletes runs around 4 mmol/L; sepsis triggers run above 4 mmol/L. The clinical scale is built around these numbers.

A continuous wearable lactate sensor with the right electrochemistry could in principle report at a much finer resolution. Reporting in nanomoles per litre (nmol/L) would surface variation a thousand-fold smaller than the current clinical scale shows. The question is whether the additional resolution carries signal or carries noise.

The trade-offs sit on three axes. Accuracy. The sensor’s accuracy bar has to be tight enough that the finer resolution carries real biological signal and not electrochemical noise. Clinician fluency. Clinicians, guidelines, and existing literature are built around mmol/L. Reporting in nmol/L means the device speaks a language the rest of the system does not. Behavioural usefulness. Does the user actually need finer resolution to change behaviour, or does the existing clinical scale already carry enough signal for the time-in-normal-range pattern to work.

The answer is not yet locked. The walkthrough surfaces the question because the answer shapes the device, and the device shapes the engagement. Reporting in mmol/L with a tight accuracy bar may turn out to be the right answer; reporting in nmol/L with a clear translation layer back to mmol/L may turn out to be the right answer; reporting in both, switching between them by use-case, may turn out to be the right answer. The engagement work resolves it.

Via Negativa Health is a Via Negativa company. Clarity by subtraction, not coverage by addition. The work that is in scope is in scope because we can defend it; the work that is out of scope is out of scope because we cannot. We say so before the conversation starts.