Published: 10:00, November 14, 2022 | Updated: 11:10, November 14, 2022
For decades, scientists have puzzled over exactly how high blood sugar causes type 2 diabetes. But Oxford University researchers may finally have the answer. The tests revealed that it was not the elevated glucose levels that were directly responsible for the pancreas being deprived of its ability to produce insulin. Instead, they found glucose metabolites — the chemicals released when sugar breaks down — and not glucose itself are behind the decline. The discovery could lead to diabetes patients receiving new treatments to slow glucose metabolism, preventing the condition from worsening, they said. Type 2 diabetes affects around 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 such as blindness, kidney failure and nerve damage if left unchecked. Currently, patients are encouraged to eat well and exercise to maintain a healthy weight to slow its progression. Medicines 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. Oxford University researchers have found that glucose metabolites – the chemicals released when sugar is broken down – and not glucose itself are behind the development of type 2 diabetes
WHAT IS TYPE 2 DIABETES?
Type 2 diabetes is a condition that causes a person’s blood sugar to be too high. More than 4 million people in the UK are thought to have some form of diabetes. Type 2 diabetes is associated with being overweight, and you may be more likely to develop it if it runs in the family. The condition means that the body does not respond properly to insulin – the hormone that controls the absorption of sugar into the blood – and cannot properly regulate blood sugar glucose levels. Excess fat in the liver increases the risk of developing type 2 diabetes, as the accumulation makes it harder to control glucose levels and also makes the body more resistant to insulin. Losing weight is key to reducing fatty liver and controlling symptoms. Symptoms include fatigue, feeling thirsty and frequent urination. It can lead to more serious nerve, vision and heart problems. Treatment usually involves changing your diet and lifestyle, but more severe cases may require medication. Source: NHS Choices; Diabetes.co.uk Co-author Professor Francis Ashcroft, a physiologist, said: “This is potentially a useful way to try to prevent beta-cell decline in diabetes. “Because glucose metabolism normally stimulates insulin secretion, it was previously hypothesized that increased glucose metabolism would enhance insulin secretion in T2D [type 2 diabetes] and glucokinase activators were tested, with mixed results.’ He added: “Our data suggest that glucokinase activators could have negative effects and, somewhat conversely, 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 people without diabetes — and no further. “But there is a long way to go before we can say whether this approach would be useful for treating beta cell depletion 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 well controlled.” The study, published in the journal Nature Communications, looked at the effects of hypoglycemia – high blood sugar – in diabetic mice. They measured how much insulin the mice released when given sugar for those with low blood glucose and for those with chronic hypoglycemia. 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 lower-than-normal insulin levels in people with hypoglycemia. The results showed that the drug had little effect on the mice with low blood sugar levels, but “largely prevented the dramatic reduction in GSIS and insulin content produced by chronic hyperglycemia.” These lower insulin levels in people with hypoglycemia were 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 effective at breaking down sugars, it causes the body to produce more and more of it. Eventually, this leads to the pancreas wearing out, blocking the system and causing blood sugar levels to remain high.
