HbA1c (glycated haemoglobin) is one of the most important blood tests used in diagnosing and monitoring type 2 diabetes across the NHS. A common question is: does HbA1c come from the liver? The short answer is no — HbA1c is formed within red blood cells circulating in the bloodstream, not produced by the liver. However, liver disease can indirectly affect HbA1c readings in clinically significant ways. This article explains how HbA1c is formed, what influences its accuracy, how liver conditions can alter results, and how to interpret your reading using current NHS and NICE guidance.

What Is HbA1c and How Is It Formed?

HbA1c is formed when glucose binds to haemoglobin inside red blood cells — not in the liver. It reflects average blood glucose over 90–120 days and is the NHS standard diagnostic marker for type 2 diabetes.

HbA1c — formally known as glycated haemoglobin — is a widely used blood marker that reflects average blood glucose levels over the preceding two to three months. It is a central tool in both the diagnosis and ongoing monitoring of type 2 diabetes, and is recommended by NICE (NG28) as a primary diagnostic test for the condition in most adults.

The term 'glycated' refers to a chemical process called glycation, in which glucose molecules in the bloodstream attach themselves to haemoglobin — the oxygen-carrying protein found inside red blood cells. This binding occurs naturally and continuously, without the involvement of enzymes. Once glucose binds to haemoglobin, it remains attached for the lifetime of the red blood cell, which is typically around 90 to 120 days. This is precisely why HbA1c provides a reliable window into longer-term blood glucose control, rather than simply reflecting a single moment in time.

To directly address a common question: HbA1c does not come from the liver. The liver plays no direct role in the formation of HbA1c itself. Instead, HbA1c is formed within red blood cells circulating in the bloodstream. However, as discussed later, liver disease can indirectly affect HbA1c readings in clinically important ways.

The test is performed using a standard venous blood sample and is reported in millimoles per mole (mmol/mol) — the standard unit used across NHS laboratories in the UK — or as a percentage.

Important: when HbA1c should not be used for diagnosis

In line with NICE NG28 and WHO 2011 guidance, HbA1c is not appropriate as a diagnostic test in the following circumstances:

• Pregnancy (including gestational diabetes assessment)

• Children and young people (under 18 years)

• Suspected type 1 diabetes at any age

• Within two months of an acute illness, significant hyperglycaemia, or major surgery

• Conditions that alter red blood cell lifespan or haemoglobin structure (see below)

In these situations, diagnosis should be based on fasting plasma glucose (FPG) or an oral glucose tolerance test (OGTT), in accordance with NICE and WHO criteria. If you are unsure which test applies to your circumstances, your GP or specialist can advise.

The Role of Red Blood Cells in HbA1c Production

HbA1c accuracy depends on red blood cell lifespan; shortened lifespan (e.g. haemolytic anaemia) causes falsely low results, while iron or B12 deficiency anaemia can cause falsely elevated readings.

Since HbA1c is formed within red blood cells, the accuracy of the test is fundamentally dependent on the health, number, and lifespan of those cells. Red blood cells are produced in the bone marrow and contain haemoglobin — specifically haemoglobin A in most adults. As these cells circulate through the bloodstream, they are continuously exposed to glucose, and a proportion of haemoglobin molecules become glycated in direct proportion to the ambient glucose concentration.

Because glycation accumulates over the lifespan of the red blood cell, any condition that shortens or lengthens that lifespan will affect the HbA1c result — regardless of actual blood glucose levels. This is a critical point for clinical interpretation:

• Conditions that shorten red blood cell lifespan — such as haemolytic anaemia, sickle cell disease, or recent significant blood loss — will produce a falsely low HbA1c, because cells are destroyed before they can accumulate glycation.

• Iron deficiency anaemia and vitamin B12 or folate deficiency anaemias are associated with falsely elevated HbA1c, independent of glycaemia. The precise mechanism is not fully established, but the clinical implication is that results may overestimate true glycaemic exposure in affected individuals.

Haemoglobin variants — such as HbS or HbC — can also interfere with certain laboratory assays used to measure HbA1c. It is worth noting that UK laboratories commonly use assay methods with reduced susceptibility to variant interference and will typically flag results where a known variant may affect reliability, in line with guidance from the Association for Clinical Biochemistry and Laboratory Medicine (ACB) and RCPath. If a haemoglobin variant is identified or suspected, your laboratory or clinician can advise on the most appropriate approach.

Where HbA1c is considered unreliable for diagnosis, NICE recommends using fasting plasma glucose or an OGTT instead. For ongoing monitoring of glycaemic control in people with established diabetes, capillary blood glucose profiles are the preferred alternative; continuous glucose monitoring (CGM) or flash glucose monitoring may be appropriate for some individuals where NICE criteria are met, but these are not universally available for all people with type 2 diabetes.

Healthcare professionals should always interpret HbA1c results in the context of a patient's full clinical picture, including any haematological conditions, recent illness, or changes in medication that might affect red blood cell turnover.

How Liver Conditions Can Influence HbA1c Results

Advanced liver disease — particularly cirrhosis with hypersplenism — can shorten red blood cell lifespan, producing falsely low HbA1c and potentially masking poor glycaemic control in patients with diabetes.

Although HbA1c is not produced by the liver, liver disease can have a meaningful indirect effect on HbA1c measurements, and this is an important consideration in clinical practice. The liver is central to glucose metabolism — it stores glucose as glycogen, releases glucose into the bloodstream during fasting, and plays a key role in insulin signalling. When liver function is significantly impaired, glucose regulation is disrupted, which can in turn affect blood glucose levels and, consequently, HbA1c values.

The more clinically significant concern, however, is the effect of advanced liver disease on red blood cell dynamics. In advanced chronic liver disease — particularly cirrhosis complicated by portal hypertension — hypersplenism (an overactive, enlarged spleen) can accelerate the destruction of red blood cells. This shortened red blood cell lifespan leads to a falsely low HbA1c, potentially masking poor glycaemic control in patients who also have diabetes. This effect is most relevant in advanced disease; in earlier or less severe liver conditions, HbA1c may remain a useful and interpretable marker.

Liver disease can also affect iron metabolism and erythropoiesis (red blood cell production), further complicating the interpretation of HbA1c. In patients with non-alcoholic fatty liver disease (NAFLD) — which frequently coexists with type 2 diabetes and insulin resistance — HbA1c is generally interpretable unless there is significant anaemia or a concurrent haemoglobin variant issue.

There is no evidence that the liver directly produces or secretes HbA1c. Any influence the liver exerts on this marker is indirect, mediated through its effects on glucose homeostasis and red blood cell health.

Practical guidance for patients with liver conditions: If HbA1c results appear discordant with your symptoms or capillary glucose readings, your GP or specialist may recommend corroborating the result with fasting plasma glucose, capillary glucose profiles, or an OGTT. Specialist input is advisable when interpreting glycaemic markers in the context of significant liver disease. Do not adjust your diabetes management based on a single unexpected result without first discussing it with your healthcare team.

Understanding Your HbA1c Results: NHS Guidance

An HbA1c of 48 mmol/mol or above indicates type 2 diabetes; 42–47 mmol/mol signals high risk. A second confirmatory test is required before diagnosis in asymptomatic adults.

In the UK, HbA1c testing is carried out routinely in primary care and is interpreted according to thresholds established by NICE (NG28) and aligned with NHS guidance. Understanding what your result means — and what factors might affect its accuracy — is important for both patients and clinicians.

Standard NHS HbA1c thresholds (in mmol/mol):

• Below 42 mmol/mol (6.0%): Normal range — diabetes is unlikely.

• 42–47 mmol/mol (6.0–6.4%): High risk of type 2 diabetes — lifestyle intervention is recommended. You may be eligible for referral to the NHS Diabetes Prevention Programme.

• 48 mmol/mol (6.5%) or above: Indicative of type 2 diabetes. In adults without symptoms, a second confirmatory test is required before a diagnosis is made.

Monitoring targets for people already diagnosed with type 2 diabetes (NICE NG28):

• 48 mmol/mol (6.5%) is the recommended target for people managed by lifestyle measures alone or with a single glucose-lowering medicine that does not carry a risk of hypoglycaemia.

• 53 mmol/mol (7.0%) is recommended for people treated with insulin, a sulfonylurea, or any other agent that carries a significant risk of hypoglycaemia.

• Targets should always be individualised — your GP or diabetes team will take into account your age, frailty, other health conditions, and personal preferences. Tighter or more relaxed targets may be appropriate in some circumstances.

When HbA1c is not appropriate for diagnosis: As noted above, HbA1c should not be used to diagnose diabetes in pregnancy, in children, in suspected type 1 diabetes, during or shortly after acute illness, or where red blood cell lifespan is altered. In these situations, fasting plasma glucose or an OGTT should be used instead.

If you receive an unexpected HbA1c result — whether higher or lower than anticipated — do not draw conclusions without speaking to your GP. Several factors beyond blood glucose control can influence the result, including anaemia, haemoglobin variants, recent illness, and liver conditions, as discussed in this article.

When to seek medical advice:

• If your HbA1c result has changed significantly without an obvious explanation.

• If you have a known blood disorder or liver condition that may affect the result.

• If you are experiencing symptoms of high or low blood sugar that do not align with your HbA1c reading.

• Urgently (same day): If you or someone else develops symptoms that may suggest type 1 diabetes or a hyperglycaemic emergency — such as excessive thirst, frequent urination, unexplained weight loss, vomiting, or drowsiness — seek same-day medical assessment. Do not wait for an HbA1c result.

Regular monitoring, combined with an understanding of the test's limitations, supports safer and more personalised diabetes management across all care settings.

Frequently Asked Questions