Sugar and metabolism
Pro-insuline
The precursor of insulin; a small amount normally enters the blood, more when the pancreas is overworked.
Everything about this testWhat it measures
The beta cells of the pancreas first make proinsulin, which enzymes cut into insulin and C-peptide. Normally only a small part enters the blood as uncut proinsulin. If the pancreas has to make a lot of insulin, for example with insulin resistance or early type 2 diabetes, or if the beta cells work less well, relatively more proinsulin is released. Proinsulin itself has only a weak blood sugar-lowering effect.
- Overload of the insulin-producing cells with insulin resistance or early type 2 diabetes
- The cause of unexplained low blood sugar, together with insulin, C-peptide and glucose
- Rarely: an insulin-producing tumor of the pancreas (insulinoma)
High
A raised proinsulin with a normal or high glucose fits a pancreas that has to work hard, for example with overweight, insulin resistance or early type 2 diabetes. Not fasting, reduced kidney function and sulfonylurea tablets also raise the value. A high proinsulin with low blood sugar may point to an insulinoma; this is rare and is investigated further in hospital. A raised value does not cause symptoms itself.
Low
A low value is normal and fits good insulin sensitivity. In type 1 diabetes or longer-standing type 2 diabetes, the value is low because the pancreas makes little insulin; C-peptide is then also low and glucose high. Fasting lowers the value. A low value on its own says little.
Preparation
- Do not eat anything for 12 hours before the sample is taken and drink only water.
If your result is abnormal
The GP assesses a raised proinsulin together with glucose, HbA1c, weight and kidney function; a raised value with normal blood sugar usually does not lead to further tests. With repeated unexplained low blood sugars, referral to an internist (specialist in internal medicine) follows.
Reliability
Proinsulin has limited predictive value as a single measurement. There are no agreed cut-off values for 'too much' proinsulin in people without symptoms, and the measurement is not standardized between laboratories. According to the Dutch GP guideline (NHG) on type 2 diabetes mellitus, fasting glucose and HbA1c say more for detecting diabetes. The result is most meaningful when investigating unexplained low blood sugar, where proinsulin measured during a low glucose is assessed together with insulin and C-peptide.
Limitations
- Nutritional state: a fasting blood draw makes the result comparable; after a meal the value is higher.
- Proinsulin can only be interpreted together with the glucose at the same moment.
- Measurement methods differ: some insulin assays also react to proinsulin, and results from different laboratories are hard to compare.
- Reduced kidney function and sulfonylurea tablets raise the value.
How common is this
In 2024, more than 1.1 million people with type 2 diabetes were known to their GP. How often a raised proinsulin occurs has not been recorded. An insulinoma is very rare.
Who is this useful for
The result is most meaningful when investigating unexplained low blood sugar, together with insulin, C-peptide and glucose. With overweight or suspected diabetes, fasting glucose and HbA1c say more, and a proinsulin value does not change the advice. In people without symptoms, a single value says little.
Downsides and risks
- Without an agreed cut-off value, a 'raised' proinsulin can cause unnecessary worry, while the advice is no different from that for overweight.
- A non-fasting blood draw or reduced kidney function can give a falsely high result.
Sources
Always discuss an abnormal result with your GP. If a result is strongly abnormal, we try to reach you as soon as possible. Read your result yourself as well and contact your GP if in doubt. A test does not make a diagnosis. Read more about risks and results