A possible reason for increased risk of infection of obese people and those with Type 2 diabetes

Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitus
Original source: International Journal of Obesity (2008) Vol. 32, pp. 1407–1414
Authors: G R C Zilverschoon, C J Tack, L A B Joosten, B J Kullberg, J W M van der Meer and M G Netea (corresponding author)
Publication date: published online 22 July 2008
DOI (digital document ID): doi:10.1038/ijo.2008.109
Requires subscription? Not for this article
Publicly-available abstract: Yes

Synopsis:
Interleukin-18 (IL-18) is a signalling chemical (similar to hormones) that has a strong effect on stimulating interferon (IFN) release. It is produced by a number of different white blood cells and central nervous system cells. Interferon is an important chemical in fighting infections.

Higher levels of IL-18 have been shown to decrease abnormally large appetite and to improve insulin sensitivity. Interestingly, several studies have shown high levels of IL-18 in obese people with insulin resistance, and a recent study has demonstrated that a common version of the genes producing IL-18 is associated with a higher body mass index (weight) in people with type 2 diabetes or coronary heart disease. In addition, weight loss after bariatric surgery (such as gastric bypass or lapband) results in lowered blood concentrations of IL-18.

The investigators suspect that the cells of obese people and those with insulin resistant diabetes may have high levels of IL-18 because they do not respond as well to IL-18 as those of people of normal weight and who are not diabetic. To test this theory, they tested white blood cells of obese and Type 2 diabetes patients and compared them to those of lean, non-diabetic people, and measured their IFN production in relation to their IL-18 levels. They found that in the obese and the diabetic subjects, these cells respond poorly to IL-18 and produce less interferon. They also show impaired release of IFN after exposure to disease-carrying bacteria and fungi.

They conclude that the reduced response to IL-18 may be responsible for the increased susceptibility to infection among those who are obese or who have Type 2 diabetes.

Reliability:
The study was conducted with a small number of subjects: seventeen control subjects, eleven obese non-diabetic subjects, and fourteen subjects with Type 2/insulin-resistant diabetes. (The possibility of LADA or other autoimmune diseases was ruled out at the start of the study.) The smaller the number of subjects, the greater the possibility for skewed or atypical results. The research was published in a peer-reviewed journal, and the investigators are all associated with the a University Medical Center in the Netherlands. Based on the small number of subjects, the results should be considered to point in the direction of larger studies to confirm the investigators' results, as well as further research into why these cells have an impaired reaction to IL-18.

Practical Applications:
A confirmed pathway and reason for increased risk of infection among obese people and people with Type 2 diabetes could lead to therapy to reduce that risk and to better fight those infections that do occur. If insulin resistance and excessive appetite are also directly related to impaired IL-18 response, then improving that response could conceivably result in weight loss and improved insulin sensitivity as well.


This synopsis was based on the entire article.