In the present study, AGR was independently positively associated with MH among 273 Japanese patients with UC, and ours is the first such study to show a significant positive association between AGR and MH among patients with UC. AGR is independently positively associated with MH but not partial MH among patients with only low CRP UC.
Albumin and globulin are the two major components of serum proteins, and their levels correlate with systemic inflammation [11–13]. Albumin maintains osmotic pressure and functions . Low serum albumin is associated with not only nutritional status but also chronic inflammation [13, 21]. Low serum albumin could weaken the human immune system, thus increasing susceptibility to infection and resulting in cytokine-induced suppression [22, 23]. On the other hand, globulin consists of all types of proinflammatory proteins. A high level of globulin indicated a systematic inflammatory response . Serum globulin level is thought to reflect the degree of continuous systemic inflammation. AGR is less sensitive and less susceptible to measurement variability such as dehydration or fluid retention since it is a ratio rather than an absolute value .
AGR has been reported to be a prognostic marker in patients with colorectal , lung , and breast cancers . Furthermore, AGR is an independent predictor of mortality in patients with chronic heart failure . AGR is significantly inversely associated with cardiovascular diseases and incidence of stroke [17, 25]. Additionally, an inverse association between AGR and the clinical activity was reported among patients with sarcoidosis . The findings in the present study consistent with these findings regarding the AGR and clinical outcomes.
Colonoscopy findings are essential for assessing mucosal status in patients with UC and determining treatment strategies. FC is useful and reliable marker for MH. However, repeated endoscopy is extremely burdensome for patients. Similarly, repeated fecal examinations may be distressing for the young, women, or patients without symptoms. Additionally, colonoscopy and FC might be not suitable for assessment for early response for medication. AGR is simple, rapid, relatively non-invasive, repeatable, and can be measured at all medical institutions. AGR monitoring might be useful to assessment disease activity, treatment response, and prognosis especially among UC patients with low CRP level. However, further research is needed for assessment AGR as a biomarker for diseases activity among patients with UC.
The underlying mechanism linking AGR and MH remains unclear, but there are several biologically plausible options. Serum albumin is known to decrease during inflammation . In fact, in 43 patients with UC, CRP was significantly inversely associated with serum albumin . Because of intestinal tract inflammation, protein loss from the gut and malnutrition may influence serum albumin levels . AGR was associated with plasma TNF-α levels in community-dwelling Japanese elderly women . Levels of α1 globulins (α1-antitrypsin, thyroid-binding globulin, and transcortin) and α2 globulins (ceruloplasmin, α2-macroglobulin, and haptoglobin) are also increased in acute inflammation . Intestinal tract inflammation might elevate AGR with protein loss and elevated TNF-α.
This study has several limitations. First, this was a cross-sectional analysis; therefore, we cannot conclude that there is a causal association between AGR and MH. Second, in this cohort, the sample size was small. Third, the exclusion rate was high. Fourth, we could not estimate the dietary intake of protein. Fifth, most of the patients have been receiving treatment for UC. The long duration of medication might therefore might affect AGR value. Finally, the current study patients might be an unrepresentative sample of Japanese patients with UC. The use of medication in Japanese study based on claims data were similar to those in the present study . However, since this cohort consist of Japanese patients, the findings in the present study might not be generalized to other cohorts.