The glucose tolerance test is the standard method for detecting diabetes. But our new study suggests a different test can identify the disease earlier than the glucose tolerance test.
Diabetes kills 3.4 million people worldwide each year, and the figure is expected to continue rising. It kills people through secondary diseases such as heart disease, stroke and kidney failure. And the longer diabetes remains untreated, the greater the risk of developing these diseases, so early detection is vital.
Diabetes is detected when the body can no longer regulate blood sugar levels. Blood sugar is controlled by insulin, a hormone made in the pancreas. This hormone lowers blood glucose by making the body’s cells take it up, where it is stored or used for energy.
There are two major forms of diabetes: type 1 and type 2. Type 1 is an autoimmune disease where the body destroys the cells in the pancreas that produce insulin. Type 2 is a progressive disease where the body first becomes resistant to insulin. Initially, the body makes more insulin to keep blood sugar levels in check, but the pancreas then wears out and blood glucose levels become dangerously high.
Fat as the new marker
In type 2 diabetes, the body’s cells become resistant to the effects of insulin before diabetes develops. This made us wonder whether we could detect earlier stages of the disease, when the body is insulin resistant but before the pancreas has worn out and blood glucose levels have increased. We focused on investigating how the body becomes unresponsive to insulin. To do so, we considered fat, not glucose.
Obesity is now established as the leading cause of type 2 diabetes. One of the main ways obesity is thought to cause diabetes is by body fat – adipose tissue – not working properly.
Healthy adipose tissue takes up the fat we consume and stores it until needed for fuel, such as at night when we sleep. When obese people eat a meal, their adipose tissue does not take up the fat. Instead, the fat is directed into other organs, such as the liver and muscle, where it causes insulin resistance.
Insulin acts as a signal and attaches to a receiver on the outside of cells, called the insulin receptor. The insulin receptor activates lots of other signals inside the muscles or liver that tell them what to do, such as: take up glucose. But when the cell is full of fat it muffles the signals. The fact cells don’t respond to insulin makes them “insulin resistant”. The body tries to get around this by turning up the amount of insulin to make the cells take up the right amount of glucose, overcoming the effects of the fat.
The concept faulty adipose tissue can cause insulin resistance and diabetes is strongly supported by evidence from people with lipodystrophy – a condition where the body lacks adipose tissue. People with this condition have severe insulin resistance and diabetes.
Importantly, the adipose tissue of obese people is also bad at releasing fat when they are asleep, meaning obese people have to use lots of glucose when they are sleeping, to provide energy.
The test doctors use to diagnose diabetes is the glucose tolerance test. It is usually performed in the morning before people have eaten. The person is then given a drink containing glucose – sugar – and blood samples are taken over the next two hours.
People – and mice – are classed as having diabetes if they show high blood glucose levels during the test. But we suspected some obese people would pass the test because their adipose tissue does not release enough fat, and their body is primed to use glucose in fasted states, such as when they are asleep.
Conversely, if we gave obese people a large meal, the fat they should store in adipose tissue would go to organs, such as muscle, and cause insulin resistance, causing them to have high blood glucose.