Ketogenic diets are low-carbohydrate, high-fat diets that have been shown to reduce weight. They change metabolism so that energy comes from fat instead of sugar.
When researchers in Switzlerland examined what happened to mice in the early stages of a ketogenic diet, they found that the animals showed a poorer ability to regulate blood sugar compared with similar mice on a high-fat, high-carbohydrate diet.
In a paper on their work now published in the Journal of Physiology, they note that "even though [keto diet]-fed animals appear healthy in the fasted state, they exhibit decreased glucose tolerance to a greater extent than [high-fat diet]-fed animals."
The reason for this, they found, was that the livers of the keto diet-fed mice were not responding as well to insulin. This condition, which is known as insulin resistance, raises the risk of developing type 2 diabetes.
"Diabetes is one of the biggest health issues we face," says study author Christian Wolfrum, who is with the Institute of Food, Nutrition and Health at ETH Zürich in Switzerland.
Insulin is a hormone that helps the body control levels of blood sugar, or glucose. If blood sugar stays above normal for long periods of time, it becomes a condition called hyperglycemia that can lead to serious health problems. This is the hallmark of diabetes.
In type 1 diabetes, hyperglycemia develops because the pancreas does not make enough insulin. In type 2 diabetes, organs and tissues lose their ability to respond to insulin. The pancreas tries to compensate by making more insulin, but eventually this is not enough and leads to hyperglycemia.
There are a number of ways in which insulin helps control blood glucose levels. One is by signaling to the liver to reduce glucose production, and another is by helping muscles and tissues absorb glucose and convert it into energy.
Insulin resistance is a "complex metabolic disorder" with no obvious single cause. The liver becomes insulin resistant when it fails to reduce glucose production in response to insulin.
Cells can also become insulin resistant when they need increasing amounts of the hormone to help them use glucose.
However, the researchers found that the main reason for decreased glucose tolerance in the keto diet-fed mice was due to insulin resistance in the liver "rather than impaired glucose clearance and tissue glucose uptake."
Despite extensive research into the causes of insulin resistance and type 2 diabetes, they are not completely understood.
One thing that scientists do know is that fat-like substances called lipids are "clearly associated with insulin resistance." Even here, however, many questions remain, such as, "Is the link due to circulating fats or to fat buildup in tissue?"
Ketogenic diets and ketosis
The lack of carbohydrates makes the body break down fats into fatty acids and then into ketones.
Keto diets are probably among the "most studied" approaches to weight loss of recent times.
A lot of research now backs the idea that keto diets have a sound "physiological and biochemical basis" and can significantly benefit cardiovascular health.
This is welcome news to many physicians, for whom one of the biggest challenges that they face in their daily practices is treating obesity.
However, while keto diets have a proven track record in tackling obesity, some concerns remain. Many of these likely relate to a "broad lack of knowledge about the physiological mechanisms involved."
Mechanisms of insulin resistance not clear
The new study helps plug some of this knowledge gap. It suggests that insulin resistance in the liver can develop in the early stages of keto diets. This now needs to be confirmed in humans.
Also, the underlying mechanisms that lead to insulin resistance are still unclear, especially in relation to different diets. This also needs to be explored further, say the researchers.
Another area that needs further research is the effect on the brain of the byproducts of fatty acid breakdown. The researchers' theory is that the fatty acid byproducts might have important "signaling roles" in the brain.
"Although ketogenic diets are known to be healthy, our findings indicate that there may be an increased risk of insulin resistance with this type of diet that may lead to type 2 diabetes."