Much like obesity, while it's unclear how much of a problem insulin resistance is in and of itself, the condition clearly is associated with a number of diseases. It is also "a key component of diabetes," Scott Summers told BioWorld Today.

In the March 2007 issue of Cell Metabolism, senior author Summers and his colleagues from the University of Utah, Lilly Research Laboratories, Lexicon Genetics and the University of Pennsylvania describe a way to prevent insulin resistance resulting from both saturated fat and glucocorticoids - though not from unsaturated fats: by interfering with ceramide synthesis.

Glucocorticoids are among the most frequently prescribed medicines; while they are not used to treat diabetes per se, diabetics are prone to infection and thus have a good chance of being prescribed glucorticoids sooner or later. From the point of view of blood sugar control, though, glucocorticoids tend to make a bad situation worse. The glucocorticoids exacerbate the pre-existing insulin resistance of diabetics.

"It becomes impossible to monitor or maintain blood glucose," said Summers, who noted that a family member of his once totalled a car after his blood sugar went out of control. "He's fine, but I think this happens more often that we care to contemplate."

In their paper, Summers, an assistant professor at the University of Utah, and his colleagues showed that both the glucocorticoid dexamethasone and saturated fats (which the rats in the studies mainlined) led to increased synthesis of ceramides and insulin resistance, while preventing the synthesis of ceramides improved glucose tolerance in both cases.

Unsaturated fats appear to cause insulin resistance via a different intermediate. The effects of lard oil infusions on glucose metabolism could be prevented by blocking ceramide synthesis, while those of soy oil infuations could not.

Many questions remain about whether the research can be harnessed therapeutically. For one thing, the paper shows clearly that insulin resistant caused by unsaturated fat is totally unaffected by tinkering with ceramide synthesis. Since most obese people probably eat too much unsaturated fat as well as too much saturated fat, it is possible that trying to prevent insulin resistance by interfering with ceramide synthesis will lead to nothing more than patients with unsaturated fat-induced insulin resistance. But Summer pointed out that "all the dietary data" point to saturated fats as bigger culprits than unsaturated ones in insulin resistance, as well as other health problems caused by high-fat diets.

Another point worth noting is that, as the authors stated in their paper, "ceramide is the precursor of most active sphingolipids," a group of fats whose roles, when they are at reasonable levels, are critical to health. In the paper, Summers and his colleagues showed that knockout mice that cannot synthesize sphingolipids are sickly and only live for a few months.

Summers acknowledged,"The question is, could one titrate [the ceramide level] down to bring it back down to baseline levels without overshooting." He added that "this is the big issue for all the drug companies I've spoken with."

Summers said the problem clearly needs to be addressed empirically. But he is an optimist. Asked if it will be possible to dial down ceramide synthesis without overshooting the mark, he said, "I believe we can, yes."