Associations of 13C-Sucrose Breath Test Dynamics with Anthropometry and Demographics: A Comparison of Studies in the United Kingdom and Zambia

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Background The 13 C-sucrose breath test ( 13 C-SBT) is a noninvasive diagnostic test that has been used to assess intestinal sucrase-isomaltase activity, which may be altered in gut function disorders such as environmental enteric dysfunction (EED), a syndrome characterized by chronic inflammation and histologic changes in the small intestine and thought to be ubiquitous among people living without access to improved water and sanitation. However, characterizing associations between 13 C-SBT breath curves and gut function status requires disaggregating associations with sucrase-isomaltase activity from associations with other aspects of sucrose metabolism. Objectives This analysis aimed to identify anthropometric and demographic patterns in 13 C-SBT breath curves. Methods We investigated the associations between anthropometry (height, weight, body mass index) or demographics (sex, age) and each of 3 mechanistic pharmacokinetic model parameters estimated from 13 C-SBT breath curves, comparing adult populations in United Kingdom and Zambia, who have different risk of EED. Results Zambian participants had higher values of the parameter associated with intestinal sucrase-isomaltase activity and liver metabolism [ρ: 2.4 (United Kingdom) compared with 3.5 (Zambia), P = 0.005] and higher fractions of tracer recovery [κ: 0.69 (United Kingdom) compared with 0.93 (Zambia), P <0.001]. The rate-limiting parameter, speculated to be associated with pulmonary excretion of plasma bicarbonate as CO 2 , was lower among Zambian participants [πρ: 0.30 (United Kingdom) compared with 0.22 (Zambia), P = 0.009]. We found a similar association between the rate-limiting parameter (πρ) and weight in both cohorts, with higher weight associated with slower tracer recovery. We did not find significant associations between anthropometry and the parameter associated with sucrase-isomaltase activity (ρ), helping to alleviate concerns about potential confounding by anthropometry when using ρ as a model-based 13 C-SBT diagnostic of intestinal sucrase-isomaltase activity. Conclusions The associations we identified between weight and the rate-limiting parameter (πρ) should be further investigated and better understood mechanistically. These anthropometric associations identified for adults should be further confirmed in infants and children.

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