 Studies dating back nearly a century noted a striking finding. If you take young, healthy people and split them up into two groups, half on a fat-rich diet and the other half on a carb-rich diet, within just two days, this is what happens. The glucose intolerance skyrockets in the fatty diet group. In response to the same sugar water challenge, the group that had been shoveling in fat ended up with twice the blood sugar. As the amount of fat in the diet goes up, so does one's blood sugar spikes. It would take scientists nearly seven decades to unravel this mystery, but it would end up holding the key to our current understanding of the cause of type 2 diabetes. When athletes carb-load before a race, they're trying to build up the fuel supply within their muscles. They break down the starch into glucose in our digestive tract. It circulates as blood glucose, blood sugar, and is taken up by our muscles to be stored and burned for energy. Blood sugar, though, is like a vampire. It needs an invitation to come into our cells, and that invitation is insulin. Here's a muscle cell. Here's some blood sugar outside, waiting patiently to come in. Insulin is the key that unlocks the door to let sugar in our blood enter the muscle cell. When insulin attaches to the insulin receptor, it activates an enzyme, which activates another enzyme, which activates two more enzymes, which finally activates glucose transport, which acts as a gateway for glucose to enter the cell. So insulin is the key that unlocks the door into our muscle cells. What if there was no insulin, though? Well, blood sugar will be stuck out in the bloodstream, banging on the door to our muscles, and not be able to get inside. And so with nowhere to go, sugar levels would rise and rise. That's what happens in type 1 diabetes. The cells in the pancreas that make insulin get destroyed, and without insulin, sugar in the blood can't get out of the blood and into the muscles, and blood sugar rises. But there's a second way we could end up with high blood sugar. What if there's enough insulin? But the insulin doesn't work. He is there, but something's gummed up the lock. This is called insulin resistance. Our muscle cells become resistant to the effect of insulin. What's gumming up the door locks in our muscle cells, preventing insulin from letting sugar in? Fat, what's called intramiocellular lipid. Fat inside our muscle cells. Fat in the bloodstream can build up inside the muscle cell, making toxic fatty breakdown products and free radicals that can block the signaling pathway process. So no matter how much insulin we have out in our blood, it's not able to open the glucose gates and blood sugar levels build up in the blood. This mechanism by which fat, specifically saturated fat, induces insulin resistance wasn't known until fancy MRI techniques were developed to see what was happening inside people's muscles as fat was infused into their bloodstream. That's how they found out that elevation of fat levels in the blood causes insulin resistance by inhibition of glucose transport into the muscles. And this can happen within just three hours. One hit of fat can start causing insulin resistance, inhibiting glucose uptake after just 160 minutes. Same thing happens in adolescence. You infuse fat into their bloodstream. It builds up in their muscles and decreases their insulin sensitivity, showing that increased fat in the blood can be an important contributor of insulin resistance. Then you can do the opposite experiment. Lower the fat in people's blood, and the insulin resistance comes right down. Clear the fat out of the blood, and you can clear the sugar out of the blood. So that explains this finding. On a high-fat diet, the ketogenic diet, insulin doesn't work as well. Our bodies are insulin resistance. But as the amount of fat in our diet gets lower and lower, insulin works better and better. This is a clear demonstration that the sugar tolerance of even healthy individuals can be impaired by administering a low-carb, high-fat diet. But we can decrease insulin resistance, the cause of prediabetes, the cause of type 2 diabetes, by decreasing saturated fat intake.