Key cause of type 2 diabetes confirmed: Chemicals produced to break down sugar make the condition worse

For decades, scientists have been baffled as to exactly how high blood sugar causes type 2 diabetes.

But University of Oxford researchers may finally have an answer.

Tests revealed that elevated glucose levels were not directly to blame for the pancreas’s inability to produce insulin.

Instead, they found glucose metabolites — chemicals released when sugar is broken down — rather than glucose itself were behind the drop.

The discovery could lead to new treatments being given to diabetes patients to slow glucose metabolism, preventing the condition from getting worse, they said.

Type 2 diabetes affects approximately 2 million people in the UK and 37 million in the US. It occurs when blood sugar is too high, which can lead to complications including blindness, kidney failure and nerve damage if left unchecked.

Patients are currently encouraged to eat well and exercise to maintain a healthy weight to slow progression.

Medications such as Glucophage to improve insulin function are usually prescribed later if diet and exercise alone are not effective.

However, the latest research could lead to new drugs that could stop the disease from getting to that point in the first place.

Co-author Professor Frances Ashcroft, a physiologist, said: ‘This is a potentially useful way to try to prevent beta-cell decline in diabetes.

‘Since glucose metabolism normally stimulates insulin secretion, it was previously hypothesized that increased glucose metabolism would increase insulin secretion in T2D [type 2 diabetes] and glucokinase activators have been tried, with mixed results.’

She added: ‘Our data suggest that glucokinase activators may have a negative effect and, somewhat counterintuitively, that a glucokinase inhibitor may be a better strategy for the treatment of T2D.

‘Of course, it would be important to reduce glucose flux in T2D to that of non-diabetic people – and no further.

‘But there is a very long way to go before we can say whether this approach would be useful for treating beta-cell decline in T2D.

‘In the meantime, the key message from our study if you have type 2 diabetes is that it’s important to keep your blood glucose levels well under control.’

The study, published in the journal Nature Communicationslooked at the effects of hypoglycemia — high blood sugar — in diabetic mice.

They measured how much insulin the mice released when they were given sugar for those with low blood glucose and those with chronic hypoglycemia.

The mice were given drugs that block glucokinase – an enzyme that helps break down glucose in the blood – for two days to see if it was glucose or the breakdown of glucose that caused the normally lower insulin levels in those with hypoglycemia.

The results showed that the drug had little effect on mice with low blood sugar, but ‘largely prevented the dramatic reduction in GSIS and insulin content caused by chronic hyperglycemia’.

This lower insulin level in those with hypoglycemia is caused by the breakdown of glucose, not the sugar itself, the team said.

When people eat carbohydrates, the food is broken down into blood sugar. This tells the pancreas to release insulin, which allows glucose to enter the body’s cells.

But over time, high blood sugar levels can cause insulin resistance.

Because insulin is not as efficient at breaking down sugar, it causes the body to produce more and more of it.

Eventually, this wears out the pancreas, throwing the system out of whack and causing blood sugar levels to remain high.