Environmental Heavy Metals on Diabetes Mellitus Type II

ADVERSE HEALTH EFFECTS OF ENVIRONMENTAL HEAVY METALS ON DIABETES MELLITUS (TYPE II) AMONG TANNERY WORKERS IN VELLORE DISTRICT

1.0. INTRODUCTION

Health is a vital aspect of life, determined by controlled lifestyle activities. These include cleanliness, appropriate nutrition, hygiene, and the overall environment. Disruptions in any of these factors can lead to ill-health. Independent or combined changes in lifestyle, genetic traits, heredity, and environment may result in a life-threatening disorder or metabolic syndrome called diabetes.

Diabetes mellitus has undergone a notable transformation over the past decades.

When the pancreas does not produce the required insulin or cannot efficiently utilize the insulin it produces, it results in a long-term illness known as diabetes. This condition leads to elevated blood glucose levels known as hyperglycemia. Owing to the shift towards modern lifestyles, many people are at risk of diabetes mellitus. Symptoms of diabetes mellitus include fatigue, increased thirst, sudden weight loss, unusual urine excretion, frequent headaches, and an increased food intake. Additional symptoms include diminished vision. Severe diabetes can result in chronic disorders affecting the heart, brain, eyes, kidneys, etc.

1.1 ABOUT VELLORE DISTRICT

Vellore district is one of the 32 districts in the Tamil Nadu state of India. Headquartered in the city of Vellore, the district offers a blend of rich heritage and culture representing the ancient Dravidian civilization. Covering an area of 6,077 km2, Vellore district had a total population of 3.47 million in 2001. Approximately 37.62% of its population is urbanized, with a density of 573 people per km2. Geographically, Vellore district lies between 78°20' to 79°50' east longitudes and 12°15' to 13°15' north latitudes in Tamil Nadu state. The district experiences an average maximum temperature of 39.5° Celsius and an average minimum temperature of 15.6° Celsius, with an average annual rainfall of 795 mm, primarily due to the northeast monsoon (535 mm) and the southwest monsoon (442 mm). Major towns in the district include Vellore, Ambur, Vaniyambadi, Tiruppattur, Arakkonam, Arcot, Gudiyattam, Ranipet, Sholinghur, and Walajapet. The district is a hub for hundreds of tanneries and chemical industries with an estimated worker population of more than one lakh. Vellore district is known to be a leading exporter of finished leather goods in the country.

1.2. LEATHER INDUSTRIES IN VELLORE DISTRICT
The Vellore district lies between 12° 15’ to 13° 15’ of Northern latitude and 78° 20’ to 79° 50’ of Eastern longitude. The land in the Eastern part is flat and slopes from East to West. There are about 230-240 tanneries in and around the Vellore district. The Vellore district is a major leather-processing center in Tamil Nadu, with an estimated 60,000 tannery workers. Vaniyambadi, Ambur, Vellore, Ranipet, and Walajah are municipal towns of the Vellore district. As per the 2001 census, the population of each of these towns is 103,841; 99,855; 41,323; and 36,675, respectively. There are 83 tanneries in Ambur, 138 tanneries in Vaniyambadi, 18 tanneries in Pernambut, and 39 tanneries in Ranipet. However, these numbers do not reflect the exact total as more unorganized tanneries spring up every day. This data is from the French Institute Pondicherry.

Leather production in Tamil Nadu accounts for 44% of the total production in India. Over 66% of this production comes from the Vellore district region. Leather from the Vellore district accounts for more than 37% of the country’s export in leather, and leather-related products like finished leathers, shoes, shoe uppers, garments, and gloves, etc.

Leather processing involves several chemical processes, resulting in tannery effluent that is highly concentrated with heavy metals. These effluents contaminate the groundwater when they seep into it. Groundwater is the major source of irrigation in these areas throughout the year. The concentration of heavy metals in the groundwater and surface water of Ranipet exceeds the permissible limit set by the WHO for drinking water. The human population in this area suffers severely from occupational diseases such as asthma, chromium ulcers, and skin diseases.

The Government of Tamil Nadu offers several investment subsidies and infrastructural support, including setting up industrial estates and common effluent treatment plants. Despite this, many tanning industries in the Vellore district prioritize profit over societal health. Small and large scale industries release polluted water containing toxic heavy metals such as chromium, lead, arsenic, calcium, magnesium, zinc, iron, and organic substances such as fluoride, iodine, sulphate, and nitrates into the land. This leads to environmental pollution and spreads diabetes primarily among the tannery workers and nearby dwellers.

In the meantime, many studies have expanded our understanding of the physiological and molecular mechanisms involved in these issues. We are particularly focused on the areas of the Vellore district housing tanneries, to investigate the degree of water contamination and the resultant diseases, such as diabetes, caused by the water in Vaniyambadi, Ambur, Pernambut, Vellore, and Ranipettai.

However, polluted water can spread disease and cause infections. Microorganisms, including bacteria, viruses, and parasites, can spread in water and cause contagious diseases. Because they can transmit from one person to another via infected water or through vectors, most of the diseases are considered infectious. Therefore, water acts as a carrier for the spread of microorganisms and other environmental health hazards.

• Increased or extreme thirst
• Increased appetite
• Increased fatigue
• Increased or frequent urination
• Unusual weight loss
• Blurred vision
• Fruity odor on breath
• In some cases, there may be no symptoms
• Increased thirst
• Increased appetite
• Fatigue
• Increased urination, especially at night
• Weight loss
• Blurred vision
• Sores that do not heal
• In some cases, there may be no symptoms

1.3.2. Gestational Diabetes
This type of diabetes arises in females during pregnancy. Some women have very high blood sugar levels, with their body unable to produce the necessary insulin to transport all the sugar into their cells, resulting in increasingly high glucose levels. The diagnosis of gestational diabetes is carried out during pregnancy. This condition develops in 2% to 5% of all pregnancies but usually disappears when the pregnancy has concluded.

1.3.3. Prediabetes
The vast majority of patients with type 2 diabetes initially had prediabetes. Their blood glucose levels were higher than normal, though not enough to qualify for a diabetes diagnosis. At this stage, the body's cells are somewhat resistant to insulin. Research suggests that even at the prediabetes stage, some damage to the circulatory system and heart may already occur.

1.3.4. Diabetes as a Metabolic Disorder
Diabetes is classified as a metabolic disorder. Metabolism refers to how our bodies use digested food for energy and growth. Most of what we eat is converted into glucose, a form of sugar in the blood which is the primary source of energy for our bodies. Once our food is digested, glucose enters the bloodstream. Our cells need glucose for energy and growth. However, glucose can't enter our cells without insulin - insulin enables our cells to absorb glucose. Insulin is a hormone produced by the pancreas. After eating, the pancreas automatically releases enough insulin to move the glucose present in our blood into the cells. As glucose enters our cells, the blood sugar level decreases. For someone with diabetes, the amount of glucose in the blood is significantly high (hyperglycemia). This is because the body doesn't produce enough insulin or any at all, or the cells don't adequately respond to the insulin produced by the pancreas. This results in excess glucose build-up in the blood. This excessive blood glucose eventually exits the body through urination. Therefore, despite having large amounts of glucose in the blood, the cells aren't getting it for their essential energy and growth needs.

1.3.5. Morbidity
Individuals with diabetes are more likely to be hospitalized than those without diabetes. The stress of illness often increases blood glucose levels in hospitalized patients. These individuals are often managed using a sliding-scale insulin regimen during hospitalization. Diabetes hospitalizations are predominantly due to other major health problems caused or exacerbated by diabetes, as shown in Figure 3. For example:

• Heart Disease – The probability of deaths due to heart attacks is found to be higher in diabetic people than in non-diabetic people.
• Stroke – Diabetic patients are 2 to 4 times more likely to have a stroke than non-diabetic patients.
• High Blood Pressure – 75% of diabetic patients suffer from hypertension.
• Eye Damage - Adult blindness is often caused by diabetes.
• Kidney Disease – Severe diabetes can lead to kidney failure.
• Nerve Damage - 70% of people with diabetes suffer from nerve damage.
• Amputations - Non-traumatic leg or foot amputations are predominantly found in people with diabetes.
• Dental Disease – Severe periodontal disease can also be caused by diabetes.

After the dawn of civilization, man started using an adequate level of nutrients, especially sugar and sugar-enriched stuff. Moreover, an uncontrolled lifestyle is the root cause of all sorts of miseries and many ill-fated diseases to mankind. Of course, diabetes is one such disease. Diabetes mellitus, a predictable and preventable metabolic disorder, is becoming a global epidemic[2]. It is predicted that the diabetes incidence will double in most nations within 20 years, and 19% of the world's diabetic cases are Indians[3]. Diabetes mellitus is a group of chronic metabolic conditions with elevated blood glucose levels due to the body's inability to produce insulin, resistance to insulin action, or both[4]. The etiology of the disease is multifactorial in nature. Some of the prime risk factors for the onset of diabetes and its associated complications include body mass index (BMI)[5,6], age[7,8], ethnicity[9], family history[9,10], sedentary lifestyle and lack of physical activity[11,12], sex[8,13], multiple genes[14], socioeconomic status[15], waist-hip ratio [16], and systolic blood pressure[17]. Studies on diabetes prevalence show that around 6-12% in urban and 2-3% in rural Indian populations are recorded[18, 19].

Several studies have reported that the imbalance of some essential metals might adversely affect pancreatic islet and cause the development of diabetes[20]. It is also evident that some reactive oxygen species (ROS) are formed during diabetes due to the imbalance of essential metals. This oxidative stress might decrease insulin gene promoter activity and mRNA expression in pancreatic islet cells due to hyperglycemic conditions [21-23].

Diabetes mellitus is one of the most common and alarming diseases for human morphology. The existence of bivalent metal ions, both macro and trace elements, is modified in DM. This condition affects all tissues in our body. The complications of diabetes are significant causes of death. Regrettably, the number of patients with diabetes is increasing. Clinical and experimental studies have explained a large number of factors involved in the origination and development of DM. Concentration inequalities of bivalent metal ions are among these.
Diabetes mellitus is defined by an absolute or relative deficit in insulin secretion and/or insulin action, accompanied by serious hyperglycemia and disruption of carbohydrate, lipid, and protein metabolism. Long-term vascular complexity represents a major cause of morbidity and fatality in patients with diabetes mellitus. Metal ions play an essential part in living systems, both in growth and in metabolism. Defective metabolism of trace elements is found in diabetic patients. It has been recorded that the urinary excretion of calcium, zinc, and magnesium is elevated in both types of diabetes mellitus, causing a decrease in blood levels of these elements in patients [24,25]. Another study reported that the levels of zinc and magnesium were significantly lower while the level of copper was significantly higher in the serum of patients with IDDM [26]. In diabetes mellitus (DM), the disorders of carbohydrates, lipids, and proteins metabolism play a vital role in diabetic complications. Hypercholesterolemia (CHOL) and hypertriglyceridemia (TG) are commonly observed and are related largely to the degree of diabetic control [27]. Serum HDL was reported to be low in diabetic patients of both types of DM [28]. Hyperglycemia may alter lipoproteins to a system that promotes atherogenesis. In diabetic patients, the low-density lipoprotein-cholesterol (LDL) levels are found to be frequently altered.

Diabetes mellitus is a heterogeneous metabolic disorder defined by hyperglycemia resulting from abnormal insulin secretion, resistance to insulin action, or both. The role of trace elements in some of these metabolic malfunctions and their contributions to the development of vascular difficulties is not clear. Therefore, the present study investigates the relationship among diabetes mellitus, trace element status, and lipid profiles in the serum of 500 diabetes mellitus patients and healthy subjects. The serum level of Cu was higher, whereas Zn, Mg, and Ca levels were significantly lower in diabetic patients as compared to the healthy subjects. The levels of total cholesterol (CHOL), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL) were increased in diabetes mellitus in comparison to the non-diabetic subjects. The mean value of high-density lipoprotein cholesterol (HDL) was reduced in diabetic patients (AL-Maroof, 2006). These records may determine the role of abnormal trace element status.

1.4. Heavy Metals Found in Ground Water

Groundwater plays a fundamental role in human life and advancement. Safe potable water is essential for healthy living. Groundwater is a basic and suitable fresh water resource for human utilization in both urban and rural areas. In many places, groundwater is polluted by the inflow of sewage and industrial wastewater (Freeze, 1979). Residents who use contaminated groundwater as drinking water may suffer from health problems in the near future. However, it is very difficult to elucidate or predict the pollution pattern because potential sources, which include land disposal of solid wastes, sewage disposal on land, agricultural activities, petroleum leakages, disposal of radioactive waste, and other sources can influence how pollutants move through groundwater (Fetter, 1994).
The importance of groundwater for the existence of human society cannot be overemphasized (Rizwan and Singh, 2009). The nature of groundwater depends on a variety of individual hydrological, physical, chemical, and biological factors. Typically, a higher proportion of dissolved components are found in groundwater than in surface water due to the greater interaction of groundwater with various geological strata. The water used for drinking must be free from toxic elements, living and non-living organisms, and high amounts of minerals that may be hazardous to health. Some heavy metals are extremely essential for humans but consuming them in large quantities might cause physiological disorders. The contamination of groundwater by heavy metals has assumed significant importance due to their toxicity and accumulative behavior. These elements, contrary to most pollutants, are non-biodegradable and undergo a global ecological cycle in which natural waters are the main pathways. Determining the concentration levels of heavy metals in these waters, as well as understanding the chemical forms in which they appear, is a prime target in environmental research today (CPCB, 2008).

Heavy metals are crucial for the proper functioning of biological systems, but their deficiency or excess can lead to numerous disorders [29]. Industrial effluents discharged from tanning factories contain high amounts of metals, especially chromium, copper, lead, iron, magnesium, manganese, zinc, and nickel. These effluents are released onto the land and dumped into surface water, which ultimately permeates groundwater and leads to contamination due to the accumulation of toxic metallic components. This results in several well-documented problems in living beings as these metals cannot be completely degraded [30]. Consequently, industrial pollutants present a wide range of environmental problems and health hazards, which are becoming increasingly complex and critical not only in developing countries like India but also in developed countries.

1.5. Heavy Metals Found in Soil

Various environmental threats include pollution of soil and water caused by several effluents, posing serious problems. Tannery industries discharge large quantities of common salt during the process of tanning. The deposition of these salts into the soil occurs when the effluent comes into contact with it. Besides chlorides, toxic substances like chromium, sodium sulfide, sodium carbonate, and ammonium sulfate are present in the discharged effluent, magnifying the problem of soil pollution.

Heavy metals are considered one of the main sources of environmental pollution due to their significant effect on ecological quality [31]. The primary sources of heavy metal pollution are human-induced activities, including combustion of fossil fuels, mining activities, wastewater discharges from tanneries, and waste disposal [32]. High levels of heavy metals in sediments and soils may percolate into the aquatic environment, groundwater, and plants through transfer processes, and eventually reach animals and humans. Therefore, the employment of simple and accurate methods of monitoring heavy metals using analytical instruments and techniques is crucial. Significant advancements have been made over the past 30 years to determine metal concentrations in our ecosystem, including the atmosphere, water, soil, and sediments [33]. Highly sensitive spectroscopic techniques such as flame atomic absorption spectroscopy (FAAS, ETAAS) and inductively coupled plasma-optical emission spectrometry, and inductively coupled plasma mass spectrometry (ICP- OES and ICP-MS) are the most commonly used methods to determine heavy metals in environmental samples [31].

For solid samples such as sludges, soils, and sediments, the solid form must be transformed to a liquid phase. This process of digestion is required for the spectroscopic analysis. The basic principle during the extraction process is the release of metals from the solid matrix to the acid solution. Conventional acid leaching procedures and microwave-assisted acid digestion systems are used to prepare the sample for further spectroscopic analysis. The traditional procedures are open systems where the solid material is extracted on a heating source in the presence of acid or acid mixtures. In this procedure, different heating systems may be used such as a sand-bath, heating plate, and aluminum blocks [31]. Microwave-assisted acid digestion procedures and pressure digestion bombs are closed systems, rendering higher temperatures and pressures in closed vessels. The need for rapid and accurate determination of heavy metals in sediments and other solid matrices (soils, sludges, etc.) has led to the development of various microwave procedures which provide efficient dissolution of metals [34]. EPA's Acid Digestion Procedure (EPA 3050B) was used as a typical technique and three different microwave-assisted acid digestion procedures were corrected and applied to the standard reference materials. The approved and obtained values were compared with each other to ascertain the most appropriate procedure for each element.

Currently, it is estimated that more than 50,000 ha of productive agricultural lands have been contaminated with Cr alone due to the disposal of tannery wastes in Tamil Nadu, where more than 60% of Indian tanneries are located in the Vellore district. Estimations of Cr levels in contaminated soils in Vellore district reveal that the soils surrounding tannery industries are severely polluted with Cr. Large amounts of Cr (16731-79865mg/kg) were found in surface and subsurface soils in Vellore districts, where a large number of tanneries exist [35]. The accumulation of Cr in soil is concerning because of its possible phytotoxicity, increased movement of metals into the food chain, and the potential for surface and groundwater contamination. Chromium pollution in soil and water has drastically reduced the crop yields (25% to 40%) over the years and continues to decrease significantly [36].

The reaction of the collagen fibers in the hides with tannins, chromium, alum, or other chemical agents is termed as Tanning. Alums, syntans, formaldehyde, glutaraldehyde, and heavy oils are employed as tanning agents. During the tanning process, about 300kg of chemicals are involved per ton of hides. The tanning processes can result in heavy metal contamination of urban and agricultural soils. Heavy metals also occur naturally but rarely at chronic levels. Potentially contaminated soils may occur at old landfill sites (particularly those that accepted industrial wastes), old orchards that were fed with insecticides containing arsenic as an active ingredient, fields that had past applications of wastewater or sludge, areas in or around mining waste piles and tailings, tannery areas where chemicals may have been dumped on the ground, or in areas downwind from tannery sites.

Excess heavy metal concentrate in soils is toxic to humans and other animals. Exposure to heavy metals is normally serious (exposure over a longer period of time) due to food chain transfer. Intense (immediate) poisoning from heavy metals is rare through ingestion or dermal contact, but it is possible. Serious problems associated with long-term heavy metal exposures are: Lead - mental lapse. Cadmium - affects the kidney, liver, and GI tract.

Arsenic - poisons the skin, affects kidneys, and the central nervous system.

The most typical cationic metals (metallic elements which accumulate in soil are positively charged cations, e.g., Pb2+), are mercury, cadmium, lead, nickel, copper, zinc, chromium, and manganese. The most frequent anionic compounds (elements that accumulate in soil are combined with oxygen and are negatively charged, e.g., MoO42-), are arsenic, molybdenum, selenium, and boron.

1.6. Microbial Contamination

Epidemic diseases caused by pathogenic bacteria, viruses, and parasites are the most common and widespread health risk associated with drinking water. The elimination of all these agents from drinking water must be a high priority. The provision of a safe supply of drinking water depends upon the use of either a protected high-quality groundwater, surface water, or a properly selected and operated series of treatments capable of reducing pathogens and other contaminants to a negligible health risk [37].

1.7. Heavy Metals and Chemical Contamination

The environment and human health are closely interrelated. The wellbeing of the people is the reflection of a healthy environment, but both can be damaged by pollution. Prolonged discharge of industrial effluent, domestic sewage, and solid waste dumps cause the groundwater to become polluted and create health problems. Hence, there is always a need and concern for the protection and management of groundwater quality; it should be protected with great care.

Some essential elements and chemicals present in water are of particular importance with regard to their effect on human health. These include chromium, lead, arsenic, calcium, magnesium, zinc, iron, fluoride, iodine, and nitrates that are a mandatory part of dietary intake to sustain human health. Deficiencies or high concentrations of these elements cause a variety of adverse health effects [37]. The toxicity of heavy metals at higher levels of risk is well known, but a current concern is the possibility that continual exposure to relatively low levels of heavy metals may lead to unfavorable health effects. The potential association between chronic heavy metal exposure and diabetes mellitus has several implications.
Metal ions are known to play an important role in living systems, both in growth and in metabolism. Impaired metabolism of trace elements is observed in diabetic patients [38]. Copper (Cu) is one of the essential trace elements and has a particular role in cytochrome oxidase function at the terminal end of the mitochondrial electron transport chain. The loss of this activity may contribute to the characteristic swelling and distortion of mitochondria which can be found in copper deficiency, particularly in metabolically active tissues such as pancreatic acinar cells, enterocytes, and hepatocytes [39]. Magnesium (Mg), another essential trace element, is a cofactor in both the glucose transporting mechanism of cell membranes and various enzymes important in carbohydrate oxidation. It also plays an important role in the mechanism for energy transfer mediated by phosphate bonds. Previous studies have suggested that magnesium metabolism might be altered in patients with diabetes mellitus. Some authors have found a strong positive association of diabetes with hypomagnesemia, while others have demonstrated that increased urinary loss of magnesium caused by osmotic diuresis might contribute to diabetic hypomagnesemia [40]. Zinc (Zn) is one of the essential trace elements required to maintain the normal physiological function of all forms of life [41]. It is a component of many enzymes, and it plays an important role in the maintenance of several tissue functions including the synthesis, storage, and release of insulin. Zinc deficiency has been recognized to be associated with many serious illnesses. Diabetes mellitus (DM) is one of the diseases that affect zinc homeostasis in different ways [42].

Several studies have proposed a possible role of minerals such as iron in insulin resistance or diabetes. Iron (Fe) is a transitional metal and a potential catalyst in many cellular reactions that produce reactive oxygen species. Such reactions contribute to tissue damage and increase oxidative stress, thereby potentially altering the risk of type 2 diabetes [43, 44]. It is widely recognized that iron has a significant impact on glucose metabolism, even in the absence of significant iron overload. In the general population, body iron stores are positively associated with the development of glucose intolerance and type 2 diabetes [45, 46]. Calcium (Ca) is a versatile intracellular messenger that is used throughout the life cycle of an organism to control diverse biological processes. It has been suggested that diabetes and cardiovascular disease are linked by a common defect in divalent cation metabolism, including calcium [47].
Diabetes mellitus is characterized by absolute or relative deficiencies in insulin secretion and/or insulin action, associated with serious hyperglycemia and disturbances of carbohydrate, lipid, and protein metabolism. Long-term vascular complications present a major cause of morbidity and mortality in patients with diabetes mellitus. Metal ions are known to play an important role in living systems, both in growth and in metabolism. Impaired metabolism of trace elements is found in diabetic patients. It has been reported that the urinary excretion of calcium, zinc, and magnesium is greater in both types of diabetes mellitus, causing a decrement in blood levels of these elements in these patients [48, 49]. Another study reported that the levels of zinc and magnesium were significantly lower, while the level of copper was significantly higher in the serum of patients with IDDM [50]. In diabetes mellitus (DM), disorders of carbohydrate, lipid, and protein metabolism play a vital role in diabetic complications. Hypercholesterolemia (CHOL) and hypertriglyceridemia (TG) are commonly observed and related largely to the degree of diabetic control [51]. Serum HDL was reported to be low in diabetic patients of both types of DM [52]. Hyperglycemia may alter lipoproteins to a pattern that promotes atherogenesis. Low-density lipoprotein-cholesterol (LDL) levels are most often altered in diabetic patients.

1.8. Pancreas and Insulin Production

The pancreas is a small, quiet organ that lies behind the stomach and produces digestive enzymes as well as a couple of hormones called insulin and glucagon. When we consume food, our body breaks it down into materials needed by the organs to function. One of these materials is sugar, in the form of glucose. Our cells utilize glucose for energy, and our brains specifically run on glucose. To get the glucose into the cells, the sugar migrates into the bloodstream and triggers the pancreas to produce insulin. Insulin allows the sugar to move from the blood into the cells. When sugar is converted to energy, it's either used or stored until required. Beta cells are groups of cells located in the pancreas and are designed to produce insulin. Beta cells scattered throughout the pancreas are called the islets of Langerhans. A person is diagnosed with diabetes when their pancreas either doesn't produce any insulin or the insulin they do produce is ineffective.

The primary objective of the present study was to assess the heavy metal contamination and their distribution in groundwater in five taluks, namely: Vaniyambadi, Ambur, Pernambut, Vellore, and Ranipet of Vellore district, where numerous tanneries are located. A persisting challenge of public health in resource-poor settings is scaling-up efficacious technical innovations into programs with high community effectiveness. This challenge involves finding interventions whose targets are linked both socially and etiologically.

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