Salivary N1-Methyl-2-Pyridone-5-Carboxamide, a Biomarker for Uranium Uptake, in Kuwaiti Children Exhibiting Exceptional Weight Gain

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.

Keywords: 2PY; N1-Methyl-2-pyridone-5-carboxamide; adolescent obesity; kuwaiti children; metabolic syndrome; nicotinate metabolism; uranium toxicity.

Figure 1

The design of this study which selected 94 children from a longitudinal study of two visits. The metabolic disease category was selected such that 51 were not obese at the first visit and became obese 2 years later at the second visit (the disease group). The 43 control subjects (the healthy group), were selected for not having obesity at either visit. Mets count is the sum of 4 binary metabolomic syndrome characteristics (obesity by waist circumference + high blood pressure + high salivary glucose + low salivary cholesterol).

Figure 2

(A) Average salivary N1-Methyl-2-pyridone-5-carboxamide (2PY) in Kuwaiti children by mass spectrometry and ²³⁸U activity concentration (4) in soil following remediation completed after the Gulf War. The principal military facility was located at Camp Doha in the Al Asimah governorate (capital) where both 2PY and ²³⁸U soil radioactivity were greatest. (B) Average BMI of children in each Kuwaiti governorate for V1 (n = 8,317) and V2 (n = 6,317). (C) Relative position of each governorate to Camp Doha. Graphic whiskers in (A,B) represent the standard error of the mean for each governorate.

Figure 3

Prevalence of adult (20–79 years old) diabetes in Kuwait and the United States of America from 2000 to 2017. (Data from the International Diabetes Federation, https://www.idf.org/).