People with diabetes have more heart attacks and strokes than people without diabetes. The risk of heart disease and stroke is worse if diabetic control is poor. In diabetes, the level of sugar (glucose) in the blood tends to go very high, and is brought back to normal by tablets or injections of insulin. We already know that inadequate control of glucose levels tends to cause inflammation in the blood vessels, which results in furring up of these vessels, and causes strokes and heart attacks. Because of that clear link between poor control of diabetes and heart attacks, we've been focusing treatment on getting ever better control of sugar levels in the blood in our patients. However, we've started to realise that where the sugar level goes too low, this is also harmful. Acute drops in sugar levels are very unpleasant for patients, and are also associated with heart attacks and heart damage. We are beginning to understand that low blood sugar may cause inflammation in a similar way to high blood sugar levels. I want to see if this is true and if I can do things to prevent the harmful effects of low blood sugar. To do this, I'm going to set up an experiment in otherwise healthy people where we deliberately make their blood sugar low, then expose them to material purified from dead bacteria. This will test how low blood sugars affect the inflammatory response, and look at how the immune system handles stress and infection after episodes of low blood sugar. I will also set up models where I can see the exact mechanism of inflammation. I will look in mice that are prone to furring up of the arteries, and see if low blood sugars makes this artery damage worse. I will see whether, as I suspect, the low blood sugars cause the immune system to become overactive. Finally, I will see if I can prevent this low blood sugar-associated damage and help to develop treatments that could be used in humans to reduce heart attack risks. These studies together will work to show why and how low blood sugars are harmful to the heart and circulation. I hope that they will help us understand the very best levels of blood sugar to aim for in people with diabetes, and help us to understand how to minimise any harm that might occur when sugar levels go too low.