Uranium toxicity might have caused obesity and diabetes in Kuwait, finds new study

According to a new research report, the extremely high prevalence of diabetes and obesity in the Gulf nation of Kuwait might be linked to the very high levels of uranium in these individuals. This in turn could be associated with the large amounts of depleted uranium dumped here in the form of US munitions during the Gulf war of 1990-91.

More than half of the Kuwait population is obese and a quarter are diabetic. Prolonged uranium uptake is already known to be associated with the development of diabetes and impaired kidney function. It causes both radiation-induced and chemical toxicity to the human kidneys, lungs and liver through a variety of mechanisms. Quite low exposures of 50 ppb (parts per billion) to 20 ppm (parts per million) can cause uranium poisoning with impaired renal function.

Kuwait City, Kuwait - circa April 1991 : Burned shell of Kuwait AIrways headquarters in Kuwait City following Operation Desert Storm in Persian Gulf War. Image Credit: Karenfoleyphotography / Shutterstock
Kuwait City, Kuwait - circa April 1991 : Burned shell of Kuwait AIrways headquarters in Kuwait City following Operation Desert Storm in Persian Gulf War. Image Credit: Karenfoleyphotography / Shutterstock

In the present study, the researchers took samples of saliva from 94 healthy 10-year-old children in Kuwait at two time points, once in 2012 and then again in 2014. This was then analyzed for a range of biomarkers, including 2PY. The children were also assessed for blood pressure, height, and weight at each visit.

The results showed that at the second measurement, over 50% of the previously healthy children had become obese and showed signs of the metabolic syndrome. This is characterized by high blood sugar and cholesterol levels, and has an increased risk of cardiovascular disease later in life.

In the obese subgroup of children, researchers observed high salivary levels of a chemical called N1-methyl-2-pyridone-5-carboxamide (2PY). Among all the biomarkers, 2PY was most strongly associated with obesity in these children. While practically everyone has some 2PY in their saliva, high levels were found only in the saliva of children from Kuwait who had become obese. A group of comparably obese children from Maine and Massachusetts whose saliva was also measured, as a control group, failed to show the same rise in 2PY levels. This study is the first to report the association of rising 2PY levels with obesity.

2PY is formed from the vitamin niacin or nicotinamide found in meat, fish, mushrooms and nuts. 2PY inhibits an enzyme called PARP-1 which is required for repairing damaged DNA, and is related to poor renal function in humans. In rats, it is known to be associated with long-term exposure to low-level uranium.

Goodson comments, “The implication is that these children may be suffering from uranium toxicity, which may be contributing to the high rates of obesity and diabetes in Kuwait.” The uranium is probably from the contamination caused by the estimated 300 tons of US weaponry dropped on the country during the Gulf war in 1990-91. The central part of the country, where the munitions were dropped, is also the same area where soil radioactivity from 238U is at a peak and where the military is most active. It has the highest prevalence of obesity and the greatest elevations in salivary 2PY levels, while the border areas have the lowest.

The presumption is that the ingestion of low amounts of uranium over a long time has led to this metabolic disorder. However, confounding factors such as the large-scale adoption of a Westernized diet in the country following the war also must be considered.

The link between salivary 2PY and uranium exposure has so far been demonstrated in rats only, and therefore uranium levels need to be assessed in saliva and in blood before this association is confirmed in humans. Moreover, 2PY is only an indirect biomarker for uranium. Direct uranium measurements in blood and saliva in the Kuwaiti population are necessary to examine the premise that these metabolic conditions are really due to uranium toxicity.

Journal reference:

Goodson Jo Max, Hardt Markus, Hartman Mor-Li, Alqaderi Hend, Green Daniel, Tavares Mary, Mutawa Al-Sabiha, Ariga Jitendra, Soparkar Pramod, Behbehani Jawad, Behbehani Kazem, "Salivary N1-Methyl-2-Pyridone-5-Carboxamide, a Biomarker for Uranium Uptake, in Kuwaiti Children Exhibiting Exceptional Weight Gain", Frontiers in Endocrinology,
DOI:10.3389/fendo.2019.00382, https://www.frontiersin.org/articles/10.3389/fendo.2019.00382/full

Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.

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Comments

  1. Saifuddin Iqbaluodain Saifuddin Iqbaluodain Kuwait says:

    A recent longitudinal study published in Frontiers in Endocrinology has conducted salivary metabolomics analyses in 94 Kuwaiti children, out of which 51 became obese and metabolic syndrome positive after the first 2 years, i.e. 2011-2012 (1). In the second phase of this study (2013-2014), the authors selected Kuwaiti children 10 years of age and probably using the same cohort. The authors have very appropriately stated that lifestyle disorders such as obesity, hypertension, and type 2 diabetes are prevalent in Kuwait. Previously, these disorders were suggested to be linked to diet, lack of physical activity, and sleep behavior (2). Alqaderi et al. (2) developed a linear regression, mixed-effect model with waist circumference as the outcome that showed a significant correlation with bedtime, salivary glucose, systolic blood pressure, and ethnicity with the exception of those children of Persian origin.
    The communication of Goodson et al. (1) has stated: “In the current study, we bring together data suggesting that uranium consumption may have contributed to the development of obesity in Kuwait children”. The authors have reported the presence of N1-Methyl-2-Pyridone-5-Carboxamide (NMPC) in the saliva of all the children they tested both in the USA and Kuwait, probably because NMPC is one of the major metabolites of nicotinamide and nicotinate, two commonly consumed vitamins present in meat, fish, nuts, and mushrooms. The elevated levels reported among the obese Kuwaiti children is most logically linked to their dietary and possibly to their sleep behavior and lack of physical activity as the authors appropriately stated in their previous communication of 2017 (2).
    The recent communication from Goodson et al. (1) highlights the Menke et al. (3) exploratory study associating higher levels of urinary uranium with diabetes but not insulin resistance. However, the comment by Wong et al. (4) very appropriately noted paying “attention to the confounders when interpreting data by relying on urinary metal levels as a proxy for environmental exposure to examine potential association with overt diabetes; specifically, it has previously been shown that subtle changes in renal physiology, as well as change in insulin and glucose levels, result in renal excretion rates of cadmium and other metals”. Goodson et al. (1) have indicated NMPC as a biomarker for uranium uptake in Kuwaiti children, based on the Grison et al. (5) metabolomics study on effects of low-dose (40 mg L-1) chronic exposure of uranium in rats over 9 months, proving the robustness of the metabolomic approach in detecting low level exposures and assessing the minimal dose required to detect a measurable biological effect of uranium contamination. However, Grison et al. (5) were very cautious in suggesting that 11 features identified are not sufficient to build diagnostic tests because this requires identifying and quantifying the metabolites. NPMC urinary concentration increases with contamination and is an indicator of an early renal disorder that might lead to morbidity. These authors also suggested a continuation of the work with additional experimental studies by testing additional biological matrixes thereby validating the non-linear dose-effect response observed in urine, and to examine major confounding factors. They were cautious in implying that their results provide some explanation with regards to the biological mechanisms triggered by low dose uranium exposure and risk to organ function, unlike the paper of Goodson et al (1) that characterized salivary NMPC as a uranium biomarker without any supporting data. It would be prudent at this stage to highlight the fact that toxicity of a metal depends on several factors including sex, age, body mass index (6), and species. Humans are suggested to be the least sensitive mammal to uranium (7) compared to other mammals in the following interspecies order: rabbit > rat > guinea pig > pig > mouse > dog > cat > human (8).
    Goodson et al. (1) articulated their study as bringing “together data suggesting that uranium consumption may have contributed to the development of obesity in Kuwait children” without substantiating this claim with data on natural uranium or depleted uranium in the samples. However, it is completely unreasonable to relate levels of 238U in soil with salivary levels of NPMC without assessing the ingestion and inhalation routes and risks.
    A comprehensive assessment of the uranium level in different environmental matrixes has been carried out by researchers at the Kuwait Institute for Scientific Research. The concentration ranges of 238U and 234U in seawater were 0.047–0.050, and 0.054–0.057 Bq l−1, respectively (9). The average ratio for 234U/238U in all the samples was greater than unity when secular equilibrium is attained. The most recent monitoring of the 234U/238U ratio in 10 large-volume seawater samples from Kuwait Bay (10) was comparable to the previously reported results (1.06 ± 0.17) [9]. The concentration of 238U, 235U, 234U in marine sediment varied between 22.3–30.5, 0.99–1.33, and 25.6–34.8 Bq kg-1 dry, respectively (11), and are well within the ranges which have been reported globally (12). The 238U concentrations in terrestrial soils in 2002 at the contaminated site in Al-Doha varied between 14.6 and 87.0 Bq kg-1 dry (13). However, the concentration from the adjacent area in clean soil was 13.5 ± 0.27 Bq kg-1 dry. Hence, the presumption of the Asimah Governorate having 15 – 20 Bq kg-1 higher 238U activity is unsubstantiated by the environmental data. Considering the reported 238U concentrations in soil in the Asimah Governorate, the dose from ingestion of soil using ICRP 119 (14) parameters would be 1.66 nSv y-1, a value that is several orders of magnitude lower than the UNSCEAR reported values for Public exposure to natural radiation from ingestion (12) average value of 0.29 mSv.
    In addition to the marine samples; the concentration of uranium isotopes in aerosols were below the detection limit (2.5 Bq/m3) at six locations sampled during the year 2018 (15). The annual committed effective dose due to inhalation associated with such low concentrations was calculated for adults and children as 21 and 18 nSv, respectively, which are insignificant compared to the UNSCEAR reported values of Public exposure to natural radiation from (12) total inhalation dose (1.26 mSV).
    The argument and assumption of Goodson et al. (1) that uranium consumption may have contributed to the development of obesity in Kuwaiti children call for reconsideration since the baseline data for uranium does not support an increase in dose contribution via inhalation and/or ingestion pathways. In addition to our observations, the IAEA report (13) cited by Goodson et al. (1) explicitly states that DU does not pose a radiological hazard to the population in Kuwait, and underscores that no remedial measures are necessary at any of the investigated sites, with the exception of DU stored at the Um Al-Kwaty military base. To set the record straight, that site has been remediated and the military base closed in 2005. Hence, associating obesity among Kuwaiti children to a higher uranium dose in the Asimah Governorate remains a counterfactual assumption unsubstantiated with local environmental uranium data.


    References
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    2.  H. Alqaderi, S. Redline, M. Tavares and J. Goodson: Effect of Late Bedtime on Salivary Glucose and Abdominal Obesity in Children.  (2017) doi:10.1007/s41105-017-0105-y
    3.  A. Menke, E. Guallar and C. C. Cowie: Metals in Urine and Diabetes in U.S. Adults. Diabetes, 65(1), 164-171 (2016) doi:10.2337/db15-0316
    4.  W. P. Wong, A. Wallia, J. R. Edwards and M. El Muayed: Comment on Menke et al. Metals in Urine and Diabetes in U.S. Adults. Diabetes 2016;65:164-171. Diabetes, 65(9), e31 (2016) doi:10.2337/db16-0555
    5.  S. Grison, G. Fave, M. Maillot, L. Manens, O. Delissen, E. Blanchardon, I. Dublineau, J. Aigueperse, S. Bohand, J. C. Martin and M. Souidi: Metabolomics reveals dose effects of low-dose chronic exposure to uranium in rats: identification of candidate biomarkers in urine samples. Metabolomics, 12(10), 154-1 - 154-16 (2016) doi:10.1007/s11306-016-1092-8
    6.  P. Kurttio, A. Harmoinen, H. Saha, L. Salonen, Z. Karpas, H. Komulainen and A. Auvinen: Kidney toxicity of ingested uranium from drinking water. Am J Kidney Dis, 47(6), 972-82 (2006) doi:10.1053/j.ajkd.2006.03.002
    7.  R. L. Kathren and R. H. Moore: Acute Accidental Inhalation of U: A 38-year Follow-up. Health Physics, 51(5), 609-619 (1986)
    8.  L. Vicente, Y. Quiros, F. Pérez-Barriocanal, J. Lopez-Novoa, F. López-Hernández and A. Morales: Nephrotoxicity of Uranium: Pathophysiological, Diagnostic and Therapeutic Perspectives.  (2010) doi:10.1093/toxsci/kfq178
    9.  S. Uddin, M. Behbehani, A. Aba and A. N. Al Ghadban: Naturally Occurring Radioactive Material (NORM) in seawater of the northern Arabian Gulf – Baseline measurements. Marine Pollution Bulletin, 123(1), 365-372 (2017) doi:https://doi.org/10.1016/j.marpolbul.2017.09.009
    10.  A. Alboloushi, A. Aba and O. Alboloushi: Cesium and Uranium Radioisotopes Monitoring in Kuwait Bay Seawater. Advances in Sustainable and Environmental Hydrology, Hydrogeology, Hydrochemistry and Water Resources, 219-221 (2019) doi:10.1007/978-3-030-01572-5_53
    11.  S. Uddin and M. Behbehani: Concentrations of selected radionuclides and their spatial distribution in marine sediments from the northwestern Gulf, Kuwait. Marine Pollution Bulletin, 127, 73-81 (2018) doi:https://doi.org/10.1016/j.marpolbul.2017.11.052
    12.  UNSCEAR: Sources and Effects of Ionizing Radiation. United Nations Scientific Committee on the Effects of Atomic Radiation, 1, 654p (2000)
    13.  IAEA: Radiological Conditions in Areas of Kuwait with Residues of Depleted Uranium. Radiological assessment reports series, International Atomic Energy Agency, Vienna, 81p (2003)
    14.  K. Eckerman, J. Harrison, H.-G. Menzel and C. H. Clement: Compendium of Dose Coefficients based on ICRP Publication 60. International Commission on radiological Protection, Publication 119(Annals of the ICRP (Suppliment)) (2012)
    15.  A. Ismaeel, A. Aba, A. Al-Boloushi, H. Al-Shammari, O. Al-Boloushi, M. Malak, A. Al-Dabbous, S. Al-Tamimi and G. Al-Qadeeri: Estimating Internal Radiation Dose due to radioactive Airborne Particles in Kuwait. Kuwait Insitute for Scientific Research, Final Report KISR 15532 (2019)

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