Abstract

In a longitudinal study of 6,158 Kuwaiti children, we selected 94 for salivary metabolomic analysis who were neither obese (by waist circumference) nor metabolic syndrome (MetS) positive (<3 diagnostic features). Half (43) remained healthy for 2 years. The other half (51) were selected because they became obese and MetS positive 2 years later. In the half becoming obese, metabolomic analysis revealed that the level of salivary N1-Methyl-2-pyridone-5-carboxamide (2PY) had the highest positive association with obesity (p = 0.0003, AUC = 0.72) of 441 salivary biochemicals detected. 2PY is a recognized uremic toxin. Also, 2PY has been identified as a biomarker for uranium uptake. Considering that a relatively recent military conflict with documented uranium contamination of the area suggests that this weight gain could be a toxicological effect of long-time, low-level uranium ingestion. Comparison of salivary 2PY in samples from the USA and Kuwait found that only Kuwait samples were significantly related to obesity. Also, the geographic distribution of both reported soil radioactivity from 238U and measured salivary 2PY was highest in the area where military activity was highest. The prevalence pattern of adult diabetes in Kuwait suggests that a transient diabetogenic factor has been introduced into the Kuwaiti population. Although we did not measure uranium in our study, the presence of a salivary biomarker for uranium consumption suggests potential toxicity related to obesity in children.

Highlights

  • Kuwait is a small country (4.1 million) that lies at the northern end of the Persian Gulf between Iraq and Saudi Arabia

  • Each was tested for their probability of identifying obese children by non-parametric analysis (p) and the area under the receiver operating curve predicting obesity (AUC)

  • N1methyl-2-pyridone-5-carboxamide (2PY) was identified as the biochemical increasing with obesity most strongly associated with obese children (Table 2)

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Summary

INTRODUCTION

Kuwait is a small country (4.1 million) that lies at the northern end of the Persian Gulf between Iraq and Saudi Arabia. Height, weight and collected saliva samples from 8,317 children in 2012 and 6,317 again in 2014. Metabolic disease was evaluated by determining four binary characteristics that define MetS These included obesity, high blood pressure, and salivary estimates of high blood glucose and low HDLC [19]. Comparison of salivary biomarkers between diseased and healthy children was computed by the Mann-Whitney U-test using the values from the second visit. We computed differences between the USA and Kuwait mass spectrometric analysis of 2PY for each subject from total ion count values divided by the median scaled data for each biochemical. We included the effect of age, sex, five metabolites, and systolic blood pressure

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