A small study offers a tantalizing hint that
The 3-month trial did not meet its primary endpoint – change in insulin sensitivity as measured by a glucose tolerance test – but it did hit several secondary goals, all of which were related to the inflammation that accompanies prediabetes, Jack A. Yanovski, MD, and colleagues wrote in Diabetes, Obesity, and Metabolism.
“Colchicine is well-known to have anti-inflammatory properties, although its effect on obesity-associated inflammation has not previously been investigated,” said Dr. Yanovski of the National institutes of Health and his coauthors. “Classically, it has been posited that colchicine blocks inflammation by impeding leukocyte locomotion, diapedesis, and, ultimately, recruitment to sites of inflammation. ... Recently, it has been shown that colchicine also inhibits the formation of the NLRP3 [NOD-like receptor family pyrin domain-containing 3] inflammasome, an important component of the obesity-associated inflammatory cascade.”
The NLRP3 inflammasome has been shown to play an important part in promoting the inflammatory state of obesity, the authors noted. When a cell senses danger, NLRP3 uses microtubules to create an inflammasome that then produces interleukin-1 beta gene and interleukin-18. One of colchicine’s known actions is to inhibit microtubule formation, suggesting that it could put the brakes on this process.
The study comprised 40 patients who had metabolic syndrome, significant insulin resistance, and elevated inflammatory markers. Among the exclusionary criteria were having a significant medical illness, a history of gout, and recent or current use of colchicine.
The patients were randomized to colchicine 0.6 mg or placebo twice daily for 3 months. No dietary advice was given during the study period. Of the 40 randomized patients, 37 completed the 3-month study, though none left because of adverse events.
Although there were no significant between-group differences in levels of fasting insulin, colchicine did significantly decrease inflammatory markers, compared with placebo. C-reactive protein dropped by 2.8 mg/L in the active group but increased slightly in the placebo group. The erythrocyte sedimentation rate also decreased in the colchicine group, compared with placebo (difference, –5.9 mm/hr; P = .07). The active group experienced an improvement in fasting insulin as measured by the homeostasis model assessment–estimated insulin resistance index and in glucose effectiveness, which suggests metabolic improvement.
“Larger trials are needed to investigate whether colchicine has efficacy in improving insulin resistance and/or preventing the onset of diabetes mellitus in at-risk individuals with obesity-associated inflammation,” the authors concluded.
The study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by the National Institutes of Health. None of the authors reported any disclosures or conflicts of interest relating to this study.
SOURCE: Yanovski JA et al. Diabetes Obes Metab. 2019 Mar 14. doi: 10.1111/dom.13702.