Prediabetes: Impaired fasting glucose increases the risk of gastrointestinal carcinomas

In their nationwide cohort study (DOI:10.1002/cncr.35197), the researchers included almost 1.5 million people aged 40 and over who had neither diabetes nor cancer to date. They had taken part in four consecutive national health examinations. An IFG exposure score ranging from 0 (no elevated values in all check-ups) to 4 (persistently elevated values in each of the 4 check-ups) was determined on the basis of the blood glucose values determined during the check-ups. In addition, baseline blood glucose levels at the time of the index date were categorised into 5 categories (from 80 mg/dL to 110-125 mg/dL).

How much did impaired fasting glucose increase the risk of cancer?

More than half of all participants had elevated blood glucose levels at least once, 5 per cent even in all 4 examinations. In only about 44 per cent were glucose levels consistently within the normal range. People with high IFG exposure tended to be older, male, overweight and drink too much alcohol.

After an average follow-up period of 6.4 years, some 23,000 people (1.6 per cent) had been diagnosed with gastrointestinal carcinomas, including mainly bowel and stomach cancer. The risk increased continuously with increasing glucose load. Compared to those with persistently normal blood glucose (IFG exposure score 0), people with a score of 1, 2, 3 and 4 had a 5%, 8%, 9% and 12% increased risk of gastrointestinal cancer. In addition, the higher the baseline blood glucose level, the greater the risk. With fasting values between 100 and 109 mg/dl, the risk was increased by 6 per cent compared to the reference group with < 80 mg/dl; with values between 110 and 125 mg/dl, the risk increased to 14 per cent.

How can the link between blood sugar and gastrointestinal cancer be explained?

The researchers put forward several hypotheses for their findings:

1. Increased insulin resistance with compensatory hyperinsulinaemia also increases levels of insulin-like growth factor 1, which in turn is associated with tumour cell proliferation.
2. A hyperglycaemic environment induces chronic oxidative stress and inflammation, which can lead to DNA damage.
3. A genetic predisposition could favour both diabetes and bowel cancer.

Whatever the cause, elevated blood glucose levels for years, even below the diagnostic threshold for diabetes mellitus, appear to be a risk factor for numerous diseases, including gastrointestinal cancer. The good news is that hyperglycaemia and prediabetes can be prevented by recognising them early and correcting them with lifestyle interventions. According to the researchers, it is advisable to regularly measure blood glucose levels.

Therapy adjustment is necessary

Impaired fasting glucose is associated with an increased risk of gastrointestinal carcinomas, which rises steadily with the level of blood glucose and cumulative exposure over the years. People at risk should be recognised early and subjected to strict blood sugar control. This would presumably prevent numerous cancer diagnoses.