doi:10.1038/nindia.2013.175 Published online 26 December 2013
Increased circulatory levels of lipopolysaccharide (LPS), a bacterial component, could be the underlying trigger that links inflammation and insulin resistance in patients with type 2 diabetes, new research suggests .
Although chronic inflammation is one of the causative factors of insulin resistance and type 2 diabetes, the clinically relevant triggers of inflammation are not clearly understood. Recent studies have linked LPS to inflammation through changes in gut bacteria (or gut microbiota) and the accompanying loss of gut integrity. While the gut integrity is maintained by tight junction proteins such as Zonulin, animal studies report that intestinal loss of Zonulin might drive translocation of LPS and other bacteria-associated fragments into the circulation and thereby promote inflammation.
Researchers now report a clinically relevant explanation to the above cascade. "Our results of increased circulatory levels of LPS, Zonulin and proinflammatory markers (TNFα & IL6) in patients with type 2 diabetes appear to expand our understanding of the emerging role of gut bacteria in the pathogenesis of diabetes," says one of the authors of the study Muthuswamy Balasubramanyam.
While high density lipoprotein (HDL) is the main factor involved in the detoxification/neutralization of LPS, this study showed a negative relationship between circulatory levels of LPS and HDL. "Since the Asian Indian phenotype is characterized by low HDL levels, it appears that LPS may get redistributed in circulation and start 'SMSing' inflammatory reactions on various peripheral tissues related to the etiology of type 2 diabetes," Balasubramanyam says.
The study implies a biomarker role for LPS in inflammation, insulin resistance and diabetes. The researchers say circulatory levels of LPS can be limited by appropriate diet and structured exercise most likely through beneficial alteration of gut bacteria.