The entrance of heavy metals such as lead (Pb), nickel (Ni), cadmium, aluminum, mercury, iron, and arsenic into the human body can have extremely harmful effects. These metals can enter the body through various routes, including dermal contact, inhalation, and primarily through the consumption of contaminated food and drinking water.25 Over the past few years, due to increased industrial development, the contamination of land and groundwater has significantly risen. This increased contact between humans and industrial waste has led to emerging health problems. The hazardous effects of these metals occur when they react with certain molecules in the body, such as oxygen and chloride ions.26 When exposure to these metals is prolonged, they begin to accumulate in the body tissues, disrupting the internal balance. Over time, the body starts utilizing these toxic metals as substitutes for other essential elements required by the body. For example, lead can replace calcium, cadmium can substitute for zinc, and aluminum can replace several other essential elements. The accumulation of these metals results in the destruction of vital metabolic activities, compromising the normal functioning of hormones and enzymes.27
In our study conducted in the district of Sargodha, the concentrations of Pb and Ni were found to be significantly higher than the permissible limits set by WHO. These findings are consistent with several previous studies conducted in different regions of Pakistan, which have also reported elevated levels of heavy metals in groundwater.28 For instance, a study conducted in 2014 on groundwater in the industrial area of Kasur, Pakistan, reported higher levels of various heavy metals including Pb, Ni, Zn, Mn, Cd, Co, Fe, and Cr, exceeding the quality standards of the WHO.29 Similarly, a study conducted in 2009 on groundwater in Sialkot city, Pakistan, found elevated levels of Pb, Ni, Zn, Cu, Mn, Fe, and Cr compared to the WHO permissible limits.30 Another study in 2011 investigated groundwater in 18 districts of Karachi, Pakistan, and reported Pb concentrations that exceeded the WHO permissible limit 31. Furthermore, a study in 2019 on groundwater in Rabwah, Pakistan, revealed high contamination levels of Pb, cadmium, zinc in winter and Ni, chromium in summer.31 The results of our study are consistent with these previous findings, highlighting the serious concern of heavy metal pollution in Pakistan and its potential adverse impacts on human health through various exposure pathways. This issue is not limited to Pakistan alone, as several countries in South Asia, including India, China, and Bangladesh, have also reported heavy metal contamination in their groundwater,32 Pakistan32d and Bangladesh.33 These findings emphasize the urgent need to address and mitigate the contamination of groundwater by heavy metals in order to protect human health. It is essential to implement effective measures to prevent further contamination and ensure the provision of safe drinking water to the population.
Heavy metal contamination of groundwater is not limited to South Asian countries but has been reported in several other countries around the world. These countries include Denmark34 ,Egypt35, Nigeria36, Bolivia37, Russia38, and Myanmar.39 For instance, in a study conducted in Egypt in 2018, higher concentrations of heavy metals such as Pb, Cd, Cr, Fe, Mn, and Ni were found in groundwater samples, exceeding the limits set by the World Health Organization (WHO).40 The concentrations of Pb (240 ug/L), Cd (14 ug/L), Cr (2 ug/L), Fe (5 ug/L), Mn (21 ug/L), and Ni (77 ug/L) were reported to be significantly higher than the WHO limits. These findings highlight the global scale of groundwater contamination by heavy metals and emphasize the need for attention, especially in areas where groundwater is used for drinking purposes. The situation of high heavy metal contents in Pakistan aligns with the global/regional perspective on this issue. It is crucial to address and mitigate this problem worldwide to ensure the provision of safe and clean drinking water for populations.
This cross-sectional investigation is believed to have the largest sample size to date in evaluating the relationship between Pb and Ni exposure and DM, thereby ensuring excellent representativeness and generalizability of our findings in the Pakistani population. This enhances the credibility of our results. We discovered a significant association between Ni and Pb exposure and an increased likelihood of diabetes. One of our study conducted in 2019 revealed the potential of arsenic and cadmium to induce diabetes through impaired hepatic glucose homeostasis, in addition to pancreatic and muscle dysfunction. Liver and kidney dysfunction also contribute to elevated blood glucose levels. These metals promote reactive oxygen species production while inhibiting the antioxidative defense mechanism, thereby disrupting various organs. Our current research provides similar results, linking Ni and Pb exposure to the development of diabetes mellitus.41 Several studies conducted in China have reported a positive association between Ni exposure and elevated levels of biomarkers associated with metabolic disorders and the onset of diabetes mellitus.42 Similarly, a study conducted in the USA in 2021 demonstrated a positive association between Ni exposure and the onset of diabetes by disrupting various metabolic pathways.43 A study in New Caledonia reported urinary Ni levels of 4.7 µg/g creatinine, which are notably higher than the results observed in our study.44 In another study in China conducted in 2015, urinary Ni concentration of 3.63 µg/L was reported in the adult population.42d A study in the USA in 2022 reported a urinary Ni concentration of 1.59 µg/L in the general population.45 In 2013, a study in Germany on urinary Ni concentration in the general population reported a concentration of 1.26 µg/L.46 NHANES conducted a cross-sectional study in 2021, concluding that higher Ni levels are positively associated with the pathogenesis of diabetes43, and our recent research supports this finding in a sizable, nationally representative, and age-diverse Pakistani population.
There is limited research specifically designed to investigate the impact of Pb exposure on the development of diabetes, despite strong epidemiological evidence linking exposure to various environmental chemicals to the onset of chronic metabolic diseases, including diabetes.47 A recent study conducted in China in 2023 demonstrated a positive association between Pb exposure and alterations in lipid profiles, including elevated levels of total cholesterol and LDL in individuals exposed to nickel.48 Similarly, a study conducted in Nigeria in 2019 concluded that lipid profiles were altered in individuals occupationally exposed to Pb49 Another study conducted in China in 2021 showed that even low levels of lead exposure can stimulate hepatic gluconeogenesis and raise fasting blood sugar levels.50 A study conducted in China in 2015 reported that lead may contribute to altered glucose metabolism by inhibiting glucose reabsorption and increasing blood sugar levels. An animal study conducted in 2011 suggested that prolonged exposure to low lead concentrations may increase the risk of obesity and weight gain 42d. Epidemiological studies have highlighted the association between Pb exposure and metabolic disorders, including the parameters associated with these disorders such as dyslipidemia, hyperglycemia, and hypertension. A study in the Korean population investigated the association between higher levels of Pb and the prevalence of metabolic disorders, reporting a positive association.51 A similar study conducted in the Iranian population in 2014 found higher levels of Pb in subjects with metabolic disorders compared to the control group, indicating Pb interference with blood lipid metabolism and the development of dyslipidemia. A similar study conducted in the Iranian population in 2014 found higher levels of Pb in subjects with metabolic disorders compared to the control group, indicating Pb interference with blood lipid metabolism and the development of dyslipidemia 52. A study conducted in Sindh, Pakistan in 2011 reported higher urinary levels of Pb in diabetic patients compared to non-diabetic patients.53 Our current study validates the findings of the aforementioned studies, providing further evidence of the association between Pb exposure and the development of metabolic disorders, including diabetes.