How a new diabetes test could save millions of lives

Milkshake test

To study how fat causes insulin resistance and diabetes, we used mice lacking a gene called PPARy2. Removing the gene prevents adipose tissue from taking up and releasing fat, mimicking what is seen in obese people.

Despite their fat not working properly, we already know mice lacking PPARy2 appear healthy, according to the glucose tolerance test. We wanted to see if we could detect their defective fat using a large-meal test. But there was a problem: how do you get a mouse to eat more food?

We exploited the fact mice are normally fed a very boring diet, similar to rusks. When we switched mice to a tastier diet, high in fat, we realised they ate twice as much as normal for the first 24 hours. We collected blood samples before and after the 24 hour overfeeding period, to see if blood glucose and insulin increased.

We tested normal mice and those lacking PPARy2 with our overfeeding challenge. Normal mice increased their insulin levels twofold and kept blood glucose levels normal. But mice lacking PPARy2 increased their insulin levels tenfold following the overfeeding challenge, and had increased blood glucose levels, indicating they were metabolically impaired.

Importantly, we conducted these tests in young mice, the equivalent of people in their early 20s, and at an age when their glucose tolerance tests were normal. Finally we determined when mice with defective adipose tissue reached middle age, they became metabolically ill, even if they ate a healthy diet.

Our study suggests it may be possible to detect some people with metabolic disease earlier by replacing the glucose in a glucose tolerance test with a calorific milkshake, containing glucose, fat and protein. The next step will be to compare the ability of the glucose tolerance test and the milkshake test to predict future diabetes development in humans.

Samuel Virtue is a senior research associate at the University of Cambridge. This article first appeared on The Conversation (theconversation.com)

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