4 / The Blood Tests That Tell You What Is Really Happening With Your Metabolism

You have changed your food, you’re moving more, protecting your muscle and taking your sleep seriously. But if your waist keeps increasing, your energy isn’t improving or your weight still seems unusually difficult to manage, it may be time to stop guessing and investigate.

Blood tests can give us valuable information about metabolic health, but only when we know what we’re looking for. Rather than ordering every available marker, I prefer to start with a clear question: is there evidence that glucose regulation, insulin sensitivity, lipid metabolism, liver health or thyroid function could be contributing to what is happening?

The most useful information often comes not from one abnormal result, but from several markers beginning to form a pattern. This is where testing becomes genuinely useful.

Start with fasting glucose

Fasting plasma glucose measures the amount of glucose circulating in your blood after you haven’t eaten for at least eight hours. In people without diabetes, insulin helps keep fasting glucose within a relatively narrow range.

A fasting glucose below 100 mg/dL (5.6 mmol/L) is considered normal. 100–125 mg/dL (5.6–6.9 mmol/L) falls within the prediabetes range, while 126 mg/dL (7.0 mmol/L) or above can meet a diagnostic criterion for diabetes when appropriately confirmed.

Fasting glucose is useful, but it is a snapshot. When insulin sensitivity begins declining, the pancreas can compensate by producing more insulin. Glucose may therefore remain within the normal range for some time despite increasing metabolic strain. This is why fasting glucose is a starting point, not the entire assessment.

HbA1c gives us the longer view

HbA1c measures the proportion of haemoglobin with glucose attached to it and gives us an indication of average glucose exposure over approximately the previous two to three months.

An HbA1c below 5.7% is generally considered normal, 5.7–6.4% falls within the prediabetes range and 6.5% or above can meet a diagnostic criterion for diabetes when appropriately confirmed.

Looking at fasting glucose and HbA1c together already tells us more than either test alone. A fasting glucose may look perfectly normal on the morning of your blood test while HbA1c shows that average glucose exposure has gradually increased.

HbA1c also has limitations. Anaemia, altered red blood cell turnover, some haemoglobin variants, kidney disease and other conditions can affect the result, so it always needs clinical context.

What can fasting insulin tell us?

Imagine two women who both have a fasting glucose of 90 mg/dL, approximately 5.0 mmol/L. One requires relatively little insulin to maintain that glucose concentration, while the other’s pancreas is producing considerably more. Their glucose results look identical, but what is happening underneath may be quite different.

Fasting insulin can therefore sometimes provide additional information when insulin resistance is suspected. Together with fasting glucose, it can also be used to calculate HOMA-IR, an estimate of insulin resistance frequently used in research and sometimes clinically.

There is, however, no universally accepted fasting insulin or HOMA-IR cut-off that diagnoses insulin resistance across all populations and laboratories. I prefer to interpret these values alongside glucose, HbA1c, triglycerides, waist circumference, blood pressure, body composition, family history and other risk factors rather than assigning enormous importance to one supposedly “optimal” insulin number.

Sometimes we need to see what happens after you eat

Fasting tests tell us what is happening when no food is coming in. An oral glucose tolerance test (OGTT) gives us information about how effectively the body handles a defined glucose load.

For a standard two-hour 75 g OGTT, a two-hour glucose below 140 mg/dL (7.8 mmol/L) is considered normal, 140–199 mg/dL (7.8–11.0 mmol/L) indicates impaired glucose tolerance and 200 mg/dL (11.1 mmol/L) or above can meet a diagnostic criterion for diabetes when appropriately confirmed.

An OGTT isn’t necessary for everyone, but it can be useful when diabetes or prediabetes is suspected and fasting glucose or HbA1c does not provide a clear answer. This is a good example of using testing to answer a specific clinical question rather than simply collecting more numbers.

Triglycerides and HDL can reveal another part of the pattern

A standard lipid panel can tell us considerably more than whether cholesterol is simply “high.”

Triglycerides are fats carried in the bloodstream. Elevated levels can have several causes, but they commonly occur alongside insulin resistance, visceral adiposity and metabolic dysfunction. HDL-C measures cholesterol carried in high-density lipoprotein particles, and lower HDL-C can also occur as part of an insulin-resistant metabolic pattern.

This becomes particularly interesting when triglycerides are rising at the same time as HDL-C is falling, waist circumference is increasing, blood pressure is climbing and glucose regulation is deteriorating.

The triglyceride-to-HDL ratio is sometimes used as an additional clue to insulin resistance and cardiometabolic risk. It can be informative in certain populations, but it is not a universally standardised diagnostic test and should not be interpreted in isolation.

ApoB adds information that LDL-C can miss

Most women are familiar with LDL cholesterol. Fewer have heard of Apolipoprotein B, or ApoB.

Cholesterol and triglycerides travel through the bloodstream inside lipoprotein particles. Each major atherogenic particle carries one ApoB molecule, so ApoB provides an estimate of the number of atherogenic particles circulating in the blood. LDL-C, by contrast, tells us how much cholesterol is being carried within LDL particles.

These measurements frequently move together, but not always. A person can have an LDL-C result that appears relatively unremarkable while carrying a higher-than-expected number of atherogenic particles. This discordance can be seen in people with insulin resistance, diabetes or elevated triglycerides.

For this reason, ApoB can add useful information to cardiovascular risk assessment rather than simply repeating what LDL-C has already told us.

Lp(a) is different

Lipoprotein(a), or Lp(a), is an LDL-like lipoprotein whose concentration is largely genetically determined. Elevated Lp(a) is associated with increased risk of atherosclerotic cardiovascular disease and calcific aortic valve disease.

Unlike many of the markers we are discussing, lifestyle generally has relatively little influence on Lp(a). Someone can eat well, exercise regularly, have a healthy body weight and still have an elevated level.

Because Lp(a) is largely inherited and relatively stable, measuring it at least once in adulthood can provide useful information about lifetime cardiovascular risk. It isn’t primarily a weight-loss marker, but it belongs in a broader conversation about metabolic and cardiovascular health.

Your liver gives us metabolic information too

The liver is central to glucose and fat metabolism. In insulin resistance, disturbances in fat metabolism can contribute to fat accumulating within liver cells, potentially leading to metabolic dysfunction-associated steatotic liver disease (MASLD).

MASLD is common and often produces no obvious symptoms. Initial blood tests can include ALT, AST and GGT. Abnormal results may provide clues to liver dysfunction, although normal liver enzymes do not rule out excess liver fat or liver disease.

When metabolic risk is present, clinicians may use additional blood-based scores, imaging or other investigations to assess liver fat and, importantly, the possibility of fibrosis.

Liver markers become particularly informative when considered alongside triglycerides, glucose regulation, abdominal adiposity and other evidence of insulin resistance. Your liver, glucose, waist circumference and triglycerides are not necessarily separate metabolic stories. They can be different parts of the same picture.

What about inflammation?

High-sensitivity C-reactive protein (hs-CRP) measures very low concentrations of CRP, a protein produced predominantly by the liver in response to inflammatory signalling. It can provide additional information in cardiovascular risk assessment.

But CRP is nonspecific. Infection, injury, autoimmune disease and many other conditions can increase it. An elevated hs-CRP therefore tells us that inflammatory activity may be present, but not what is causing it.

This is particularly important in functional medicine, where it can be tempting to give every abnormal biomarker its own diagnosis and supplement. Sometimes a marker is simply telling us that we need to look more closely at the bigger picture.

Two important metabolic measurements require no blood at all

Blood pressure and waist circumference are remarkably easy to overlook once we become interested in laboratory testing.

Blood pressure matters because hypertension commonly clusters with impaired glucose regulation, central adiposity and abnormal lipid metabolism. It also frequently causes no symptoms, making regular measurement important.

Waist circumference gives us a simple estimate of central adiposity. It isn’t a direct measurement of visceral fat, and appropriate thresholds vary according to sex and ethnicity, but it adds useful information to cardiometabolic risk assessment.

A woman can lose relatively little weight while reducing her waist circumference, improving her blood pressure, becoming stronger and improving her glucose and lipid markers. From a metabolic perspective, that can represent substantial progress even if the scales have barely moved.

Could your thyroid be contributing?

Thyroid dysfunction can affect energy expenditure, body weight, temperature regulation, bowel function, heart rate and energy levels, so thyroid disease deserves investigation when symptoms or medical history suggest it.

Initial testing for suspected primary hypothyroidism generally begins with TSH, with free T4 assessed according to the TSH result, symptoms and local testing protocols. Additional testing, including thyroid antibodies, may be appropriate when autoimmune thyroid disease is suspected.

What I would not do is assume that difficulty losing weight automatically means thyroid dysfunction. Weight change is one possible feature of hypothyroidism, but diagnosis requires appropriate biochemical testing and clinical assessment. We don’t want to miss genuine thyroid disease, but neither do we want to blame the thyroid for every kilogram gained after 45.

This is where patterns become useful

Consider a woman whose fasting glucose is still within the normal range. On its own, that result may appear reassuring. But suppose her waist circumference has increased, fasting insulin is elevated, triglycerides are rising, HDL-C has fallen and blood pressure is creeping upwards. Those findings together suggest a very different metabolic picture from fasting glucose alone.

Another woman may have gained weight but have healthy glucose regulation, normal blood pressure, favourable triglycerides and HDL-C, an appropriate ApoB for her cardiovascular risk, good muscle mass and a relatively stable waist circumference. Her weight gain deserves attention if it concerns her, but the metabolic interpretation is quite different.

This is why laboratory results become much more useful when they are interpreted together and over time. Trends can be particularly revealing. A gradual rise in HbA1c from one annual test to the next, for example, may deserve attention before it crosses the diagnostic threshold for prediabetes, particularly if waist circumference, triglycerides or blood pressure are moving in the same direction.

Metabolic syndrome is a cluster, not a single test

Metabolic syndrome describes the clustering of several cardiometabolic risk factors. Common criteria include increased waist circumference, elevated triglycerides, reduced HDL-C, elevated blood pressure and elevated fasting glucose. Having several of these abnormalities together is associated with increased risk of type 2 diabetes and cardiovascular disease.

Notice something important here: body weight itself isn’t one of the criteria.

A person’s metabolic health cannot be determined simply by looking at their size. This is precisely why I want us to understand what is happening underneath the weight rather than treating the number on the scales as the final verdict on your health.

When weight changes deserve further investigation

Not every difficulty losing weight requires medical investigation, but unexplained or rapid changes should not simply be attributed to menopause.

Speak with your healthcare professional if your weight changes significantly without an obvious explanation, particularly if this is accompanied by pronounced fatigue, excessive thirst or urination, significant appetite changes, swelling, persistent digestive symptoms, marked weakness or other new symptoms.

A strong family history of type 2 diabetes or premature cardiovascular disease, previous gestational diabetes, hypertension, abnormal cholesterol, increasing waist circumference or known fatty liver disease also provide good reasons to assess cardiometabolic risk.

Medication should be reviewed as part of this picture too, because some medicines can affect appetite, body weight or glucose metabolism. Medication should never be stopped or changed without discussing it with the prescribing clinician.

Which biomarkers I recommend checking

For a useful initial metabolic overview, I would generally discuss fasting glucose, HbA1c, triglycerides, HDL-C, LDL-C, non-HDL cholesterol, ApoB, ALT, AST and GGT, together with blood pressure and waist circumference.

Depending on your history, symptoms and risk factors, additional investigation may include fasting insulin, Lp(a), hs-CRP, TSH and free T4, an oral glucose tolerance test or further liver assessment.

The purpose is not to order every possible test. It is to choose the tests that answer a clinical question and then interpret them together.

A note about “normal” and “optimal”

Laboratory reference ranges, diagnostic thresholds and individual risk are not quite the same thing.

Disease does not suddenly appear the moment a number crosses a line. Many metabolic risks exist on a continuum, which is why changes over time can be useful. If HbA1c, triglycerides, blood pressure and waist circumference are all gradually increasing, that trajectory deserves attention even if the individual results have not yet reached diagnostic thresholds.

At the same time, we should be careful about assigning disease to every result that falls outside a narrow online “optimal range.” For some markers, particularly fasting insulin and HOMA-IR, universally accepted clinical cut-offs simply do not exist.

The useful middle ground is identifying early and meaningful patterns without turning normal biological variation into pathology.

Where do you go from here?

Once you have your results, the question is no longer simply whether each number has an H or L beside it. Look at the pattern with your healthcare professional, compare it with previous results where possible and decide whether anything needs further investigation.

If glucose regulation is deteriorating, that gives us a direction. If liver markers and metabolic risk suggest possible MASLD, that deserves appropriate assessment. If thyroid results are abnormal, we investigate the thyroid. If the results are reassuring, we return to the foundations and continue working on muscle, food quality, movement, sleep and body composition.

Testing is most useful when it changes what we do next.

You can explore more related articles, free and paid resources, my book and programmes in the Weight & Metabolism section of Feel Good Menopause.

If you arrived here first, I recommend beginning with the previous articles in this series: Why Your Old Weight-Loss Rules May Stop Working After 45, Where to Start When Your Weight and Metabolism Feel Stuck, and How to Improve Your Metabolic Health After 45.