In the last post, I described how cellular energy excess causes insulin resistance, and how this is triggered by whole-body energy imbalance. In this post, I'll describe another major cause of insulin resistance: inflammation.
In 1876, a German physician named W Ebstein reported that high doses of sodium salicylate could totally eliminate the signs and symptoms of diabetes in certain patients (Berliner Klinische Wochenschrift. 13:337. 1876). Following up on this work in 1901, the British physician RT Williamson reported that treating diabetic patients with sodium salicylate caused a striking decrease in the amount of glucose contained in the patients' urine, also indicating an apparent improvement in diabetes (2). This effect was essentially forgotten until 1957, when it was rediscovered.
What is sodium salicylate? It is an anti-inflammatory drug very similar to aspirin*. It is important to note that high-dose aspirin is not a good long-term treatment for diabetes due to its side effects.
Modern research has confirmed that high doses of aspirin or related compounds have a striking effect on diabetics, not only lowering blood glucose but also increasing insulin sensitivity (3). In 2001, a landmark paper in the journal Science confirmed that aspirin has this effect due to its inhibition of a specific inflammatory signaling pathway** (4). Since then, it has been shown that blocking inflammation in various other ways prevents the development of insulin resistance (5, 6, 7).
Inflammation and energy excess are tightly interlinked. Flipping the calendar back to 1993, Dr. Gokhan Hotamisligil and colleagues showed in another landmark paper that blocking an inflammatory signal prevents the insulin resistance caused by obesity (8), and similar findings have been reported many times since then (5, 6, 7). This suggests that energy excess causes insulin resistance in part by engaging inflammatory pathways in the body. The concept has received additional support from studies showing that salicylate can block the insulin resistance caused by acute energy excess due to infusing fatty acids into the circulation (9). Since insulin resistance is a protective mechanism against cellular energy excess, suppressing it with anti-inflammatory drugs may not be the greatest idea.
Energy excess causes inflammation, and inflammation causes insulin resistance. However, inflammation can be caused by other factors, and this can also contribute to insulin resistance. For example, inflammatory substances that mimic infection can cause insulin resistance (10). The digestive tract is full of these substances, and normally the gut barrier does a good job of keeping them out of circulation. However, under certain conditions these can enter the circulation in larger amounts, and this is thought to contribute to insulin resistance (11). It's worth emphasizing that the type of inflammation linked with insulin resistance is not the same powerful, acute inflammation that you might get at the site of a physical injury. It is a low-grade, chronic type of inflammation.
The immune system is extremely complex, and "inflammation" is a catch-all term for a number of different related processes in the body. Specific types of inflammatory signaling play an important role in insulin resistance. Others do not, for example, the transient inflammation that follows strenuous exercise. The inflammatory pathways activated by energy excess and poor digestive health seem to contribute to insulin resistance.
* Acts by inhibiting cyclooxygenase-2 and NF-kB.
** NF-kB pathway.