Flashback Friday: What Causes Insulin Resistance and Diabetes?

“What Causes Insulin Resistance and Diabetes?” 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.

00:40 - 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 their 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.

01:23 - Insulin is the key that unlocks the door to let the 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 would 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 into the muscles, and blood sugar rises.

02:15 - 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? The key 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 on our muscle cells preventing insulin from letting sugar in? Fat. What’s called intramyocellular lipid, fat inside our muscle cells.

02:50 - Fat in the bloodstream can build up inside the muscle cell, creating 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.

03:38 - One hit of fat can start causing insulin resistance, inhibiting glucose uptake after just 160 minutes. Same thing happens to adolescents. 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. And then you can do the opposite experiment. Lower the level of fat in people’s blood and the insulin resistance comes right down. Clear the fat out of the blood, and you clear the sugar out of the blood. So that explains this finding.

04:16 - On a high fat diet, the ketogenic diet, insulin doesn’t work as well. Our bodies are insulin resistant. 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 pre-diabetes, the cause of type 2 diabetes, by decreasing saturated fat intake. After about age 20, we may have all the insulin-producing beta cells we’re ever going to have in our pancreas, and so if we lose them, we may lose them for good.

05:04 - Autopsy studies show that by the time type 2 diabetes is diagnosed we may have already killed off half of our beta cells. You can do it right in a Petri dish. Expose human beta cells to fat, they suck it up, and then start dying off. A chronic increase in blood fat levels is harmful as shown by the important effects in pancreatic beta cell lipotoxicity. Fat breakdown products can interfere with the function of these cells and ultimately lead to their death. And not just any fat, saturated fat. The predominant fat in olives, nuts, and avocados gives you a tiny bump in death protein 5, but saturated fat really ramps up this contributor to Beta cell death.

05:49 - Saturated fats are harmful to b-cells, harmful to the insulin- producing cells in our pancreas. Cholesterol, too. The uptake of bad cholesterol, LDL, can cause Beta-cell death as a result of free radical formation. So diets rich in saturated fats not only cause obesity and insulin resistance, but the increase levels of circulating free fats in the blood, called NEFAs, non-esterified fatty acids, causes Beta-cell death and may thus contribute to progressive Beta-cell loss in type 2 diabetes. And this isn’t just based on test tube studies. If you infuse fat into people’s blood stream you can directly impair pancreatic Beta-cell function, and the same when we ingest it.

06:35 - Type 2 diabetes is characterized by defects in both insulin secretion and insulin action, and saturated fat appears to impair both. Researchers showed saturated fat ingestion reduces insulin sensitivity within hours, but these were non-diabetics, so their pancreas should have just been able to boost insulin secretion to match, but insulin secretion failed to compensate for insulin resistance in subjects who ingested the saturated fat. And this implies the saturated fat impaired beta cell function as well, again within just hours after it going into our mouth. So increased consumption of saturated fats has a powerful short- and long-term effect on insulin action, contributing to the dysfunction and death of pancreatic beta cells in diabetes. And saturated fat isn’t just toxic to the pancreas.

07:25 - The fats found predominantly in meat and dairy – chicken and cheese are the two main sources in the American diet – are almost universally toxic, whereas the fats found in olives, nuts, and avocados are not. Saturated fat has been found to be particularly toxic to liver cells in the formation of fatty liver disease. You expose human liver cells to plant fat and nothing happens. Expose liver cells to animal fat and a third of them die. This may explain why higher intakes of saturated fat and cholesterol are associated with nonalcoholic fatty liver disease.

08:01 - By cutting down on saturated fat consumption we may be able to help interrupt this process. Decreasing saturated fat intake may help bring down the need for all that excess insulin. So either being fat or eating saturated fat can both cause that excess insulin in the blood. The effect of reducing dietary saturated fat intake on insulin levels is substantial, regardless of how much belly fat we have. And it’s not just that by eating fat we may be more likely to store it as fat.

08:31 - Saturated fats, independently of any role they have making us fat, may contribute to the development of insulin resistance and all its clinical consequences. After controlling for weight, and alcohol, and smoking, and exercise, and family history, diabetes incidence was significantly associated with the proportion of saturated fat in our blood. So what causes diabetes? The consumption of too many calories rich in saturated fats. Now just like everyone who smokes doesn’t develop lung cancer; everyone that eats a lot of saturated fat doesn’t develop diabetes. There’s a genetic component, but just like smoking can be said to cause lung cancer, high calorie diets rich in saturated fats are currently considered the cause of type 2 diabetes. .