Diabetes mellitus and its definition
A group of metabolic disorders that can be noted by Hyperglycemia, which decreases the secretion of insulin or insulin action in a body (Adler 2004, pp. 2095-2106). The period of the damage as long as it is affected by chronic hyperglycemia of diabetes, dysfunctions, and later failure of various organs in the human body. Therefore, various pathological processes are involved in developing a cure for diabetes. The range of the effect varies from autoimmune ?-cells of parts of the pancreas with the rise in subsequent insulin deficiency to abnormal behavior, which later impacts the resistance to insulin action.
- Diabetes results in the absolute cause are deficiency of insulin secretion.
- The cause of diabetes, a much more common category, consists of insulin resistance and a compensatory secretory response of insulin.
Type 1 diabetes is also known as child diabetes or an “insulin-dependent” disorder of diabetes, and is chronic in which the pancreas secrete little or no insulin on their own. Having the access to cheap medication of diabetes, such as insulin, is critical for individuals with the disorder. By the year 2025, an agreement has been made worldwide to halt obesity rise and diabetes However, type 2 diabetes prevalence has enhanced drastically in most of the countries (Alqurashi, Aljabri and Bokhari 2011, 19-23).
Diabetes has an impact on nearly 422 million people globally, the majority of whom live in low as well as middle-income countries, where diabetes is responsible for 1.5 million deaths per year. In the last few decades, the number of cases and the prevalence of diabetes have increased considerably. However, according to the World Health Organization (WHO), Saudi Arabia possesses the second-higest rate of the disorder in the Middle East and ranks globally seventh. Therefore, about 7 million people are diabetic, and about 3 million contain pre-diabetes, as per estimates. The current enhancement in diabetes cases reported in Saudi Arabia is highly concerning.
Hyperglycemia containing ketoacidosis as well as non-ketotic hyperosmolar syndrome is an acute, threatening complexity of untreated diabetes. Long-term complications of diabetes include retinopathy, causing vision loss and “peripheral neuropathy”, leading to foot ulcers, Charcot’s joints, amputations, and autonomic neuropathy can cause gastrointestinal, cardiovascular and genitourinary symptoms, and sexual dysfunction. Diabetes patients can develop diseases like cardiovascular, atherosclerotic, peripheral arterial, and cerebrovascular disorder, and nephropathy, leading to complete renal failure. (Qi et al. 2018, 373-381). The disturbance of the oxidative balance could be one explanation for the subsequent consequences of diabetes mellitus. As a result, an increase in reactive oxygen species (ROS) production may damage cells by damaging membrane lipids or proteins or generating nucleotide changes (1,3,4). More solid information about the involvement of micronutrients in diabetes mellitus has been obtained by the recent advancements in trace element methods.
Diabetic nephropathy (DN) is a renowned cause for the failure of kidneys. (ESRD). 1.2. There is a large enhancement of DN and diabetes rate, which later signifies a medical disaster in various dialysis units, causing more consumption of economic resources. 3,4. In Saudi Arabia, nearly 11 000 people contain ESRD, with diabetes accounting for 20% of the cases(Swaminathan et al. 2007, 1926-1933). In Saudi Arabia, the cost of dialysis care is US$14 000 per patient every year, with a complete economic burden of US$540 million.6. Almost all DN patients unfortunately fall short of the levels of target which have been indicated by worldwide guidelines. 7. Recently shown studies have reflected the rate of complication for type 2 diabetes that was 32% for renal issues and around 23% for cardiovascular problems. (8, 9).
Types of diabetes mellitus
Diabetes nephropathy, affecting around 40% of type 1 and 2 diabetic patients, appears to be the main cause of kidney damage in patients who commence treatment of renal replacement. In the absence of other renal disorders, (DN) increases “urine albumin excretion” (UAE). Macroalbuminuria and Microalbuminuria are two stages of diabetic nephropathy. The major risk factors for the development of “diabetic nephropathy” include high BP, hyperglycemia, and genetic susceptibility. Elevated blood lipids, smoking, and the kind of dietary proteins appearing in the diet are concerning factors as well.
The course of diabetic nephropathy is influenced by age, socioeconomic factors, gender, diet, obesity, and higher hypertension prevalence. Age, low initial glomerular filtration rates (GFR), initial–hospital-visit fasting glucose plasma, and the development of retinopathy have all been found as relevant risk factors for (GFR) reduction in several studies.
Proteinuria is a key factor of risk for (DN) development in and of itself. These factors of risks for the evolution of “chronic kidney disease” (CKD) in individuals with “type 2 diabetes” are still unknown.
Markers play a significant role in the first DN detection. The indicators can be used to track the progression of renal involvement during (MAU) or microalbuminuria, as well as the development of norm albuminuria before (MAU).
Diabetic nephropathy is known to be a severe microvascular diabetes consequence that is the largest reason of end-stage renal disorder and causes mortality and morbidity in type 1 and type 2 diabetics. A progressive enhancement in urine albumin excretion and a drop-in glomerular filtration rate (GFR), which occurs in conjunction with a rise in blood pressure, is the result of the clinical markers of diabetic nephropathy. These renal changes develop for structural abnormalities, like enlargement of the glomerular basement membrane, thickening of mesangial expansions along with accumulation of the extracellular matrix, alteration in glomerular epithelial cells (podocytes),like a reduction in number or density, podocytes foot process effacement and broadening, tubulointerstitial fibrosis, glomerulosclerosis, finally leading to end-stage renal disorder after failure.
However, inorganic elements such as Cr, Zn, Cu, Fe, and Ni are rapidly being recognized for their function in the improvement of poor glucose tolerance and their indirect impact on the management of diabetes mellitus.
Treatment of hypertension (130/80 mmHg or “125/75 mmHg if proteinuria” should be more than 1.0 g/24 h and enhanced serum creatinine), utilizing drugs that block the renin-angiotensin-aldosterone systems, and treat dyslipidemia (“LDL cholesterol 100 mg/dl”) are efficient strategies for prevention of developing microalbuminuria, thereby delaying the progress of disorder to advanced phases of nephropathy, and enabling in the reduction of cardiac mortality in patients having type 1 and 2 diabetes. GFR decreases at a varied rate, while ranging from “2 to 20 mL/min/year”. While glycemic management has been shown to slow the course of nephropathy, “angiotensin blockers of receptors” and “angiotensin-converting enzyme inhibitors” have been discovered to have a renoprotective impact.
To ensure the solution in the future there are a few steps that must be followed:
The first step is to diagnose diabetes nephropathy early by examining microalbuminuria and macroalbuminuria and looking for indicators that can assist detect the early stages of diabetic nephropathy in patients.
The occurrence of Diabetes Mellitus
Secondly, look for various ways to slow and decrease the advancement of diabetic nephropathy. Therefore, given the increased prevalence of both (DM) and (DN), early identification of (DN) is critical for providing appropriate medication that avoids or slows progression to (ESRD). However, some pathologists believe that a disruption in the trace element levels in the human body can cause kidney function to worsen (Giacco and Brownlee 2010, pp, c317-c323).
And thirdly, it is believed by some experts that the degradation of kidney function permits nephrotoxic substances to accumulate in the body. Trace elements and minerals are significant micronutrients for the body’s normal functioning. These elements are very advantageous for physiological functioning. These substances in the body are required for numerous metabolic reactions, which then act as stabilizers in enzymes and proteins, and serve as cofactors for a variety of enzymes. Specific trace elements have governed crucial biological processes by attachment to the receptor sites of cell membranes or modifying the shapes of the receptor to prevent particular molecules from cell entry. (Barnett and Cummings 2018, pp.379-380). Micronutrients play a dual role, as they keep cellular structures stable at appropriate levels, but their deficiency leads to other routes, which can lead to illness. These vital micronutrients have a significant physiological significance which has been determinedand linked to diabetes mellitus. Diabetes mellitus can disrupt trace element homeostasis. Changes in the status of trace element status and enhanced oxidative diabetic stress, on the other hand, may lead to insulin resistance, consequently leading to diabetic complications.
Markers play a significant role in the first detection of (DN). The signs cover a period of normal albuminuria before (MAU), as well as the onset of renal involvement during MAU or macroalbuminuria (10).
Although scientists have begun to study and unravel the mysteries of the intimate relationship between (IR), some blood and urine indicators with trace elements, and their physiological consequences, there is still more to learn.
- Cobalt
- Fumarate
- Selenious Acid
- Selenic Acid
- Nickel
- Molybdenum
- Iodine
- ferrous
- cupric oxide
- Vanadium
- Tin
- ferrous citrate
- Copper
- Chromium
- Iron
- Silicon
- Selenium
- Zinc
- Sodium Selenite
A trace element (also known as a minor element) is a chemical element with a very low concentration (or another unit of measurement) of a “trace amount”. These elements are then divided into two categories, which are necessary and non-essential. Many physiological and metabolic processes in plants and animals require essential trace elements. Trace elements not only play a part in biological processes, but they also act as an important role in catalysts in oxidation and reduction reactions.
The four main basic organic elements: C, N, O, H
- “Quantity elements” – Mg, Ca, K, Na, S, CI, P
- “Important trace elements”: Fe, Mn, Zn, Ni, Co, Se, Mo, I.
- Suggested functions from active human handlings, no functions are specified for biochemical identifications – As, Si, F, Cr, B, V, Li.
Zinc (Zn); is considered to be an absolute abundant living organism by the most scientist. It helps with brain development, nucleic acid metabolism, and signal transmission, which have been categorized among other biological processes. It is then, involved in immunological functions, synthesis of the DNA and proteins, as well as cell division, also studied among other biological activities. Zinc aids normal development and growth during pregnancy, childhood, and adolescence. It also contains antioxidants and is necessary for a healthy sense of taste and smell. Zinc is found in a variety of tissues throughout the body, but it is not kept in any one location. Zinc insufficiency can arise in anabolic conditions when zinc requirements exceed intake or when absorption is low.
Diabetes Mellitus and its complications
The elements like Anemia which causes short stature, hypogonadism leads to decreased wound healing, and geophagia are all symptoms of this metal deficiency. Zinc is a vital micronutrient that aids in the performance of numerous enzymes and serves as an effective antioxidant.Whereas, storage of insulin synthesis and secretion induced by pancreatic islet cells are affected by zinc. The scenario has been long recognized and studies and indicates, that the diabetic pancreas has a lower (Zn) concentration than the normal pancreas, and that (Zn) plays a large role in the signalling of insulin. (Zn) may raise the content of pancreatic insulin and improve the test of glucose tolerance by stimulating energy which can lead to the consumption in skeletal muscle and the formation of the brown adipose tissue.
Chromium is a significant trace element required for optimal glucose metabolism. It comes in a variety of chemical forms and the trivalent form indicates it to be useful and the hexavalent form indicates it to be poisonous. However, as an antioxidant, chromium provides several advantages. The use of these elements has been extensively researched in metabolic illnesses. Chromium has been discovered to aid in the improvement of insulin action, and as a result, it can be utilized to manage type 2 diabetes. (Cr) helps to increase insulin receptor-mediated which then allows signalling and hence potentiates the impact of insulin in patients which enhances the poor glucose tolerance (Lin et al., 2018. Pp. 330-336). Supplementing with chromium tends to enhance glycemic control in type 2 diabetics, which later appears to be related to an increase in insulin reactionrather than insulin secretion stimulation. (Cr) enhances insulin receptor responsiveness which later forms a compound with chromomodulin, an intracellular peptide. (Cr) the shortage that has been recommended by experts as a possible risk for diabetes and its development. (Cr) the administration has been shown to improve glucose control in diabetic patients. When food is consumed with enough chromium, It will have a lower need for insulin and a better blood lipid profile.
Selenium is a trace mineral that can be found in soil, water, and some external foods. It plays a key role in a variety of bodily functions. Selenium boosts the body’s antioxidant defences. Selenium is often used to treat selenium deficiency as well as it enables lower the risk of high blood pressure during pregnancy. It is also claimed to treat prostate cancer, statin pill side effects, high cholesterol, cataracts, and a variety of other causing ailments, but most of these claims aren’t backed up by scientific research. However, no advice on (Se) supplementation or restriction for diabetes prevention was given. Treatment of (Se) µmol/µL non-obese diabetic mice who drank the water for three weeks had lower serum glucose levels and had improved lipid metabolism. Selenium is required for the activity of the glutathione peroxidase (GPx) enzyme. Due to the formation of such reactive oxygen species, the oxidative burden of diabetes increased (ROS). (GPx) is termed to be a crucial component of the cell’s defence against all free radicals of the human body system.
Diabetes nephropathy
The element copper is known to be a popular element in biology, with current chemical properties in the substance, which are distinct in each of its two states of oxidation +I and + II. Therefore, copper is an important component of cells because it can accept or give electrons and participate in a variety of reactions. Excessive copper ions in cells can cause oxidative stress by generating free radicals.
Copper homeostasis should be maintained in organisms as both deficiency or excess of copper ions are harmful (Giacco and Brownlee, 2010, pp. 1058-1070). A copper deficiency, on the other hand, can cause various issues, as it plays a role in the appearance function of cytochrome oxidase at the mitochondrial electron transport chain. Moreover, the lack of this function could play a role in the enlargement and distortion of mitochondria which can be seen in copper shortage, especially metabolically with active organs including pancreatic acinar cells, enterocytes, and hepatocytes.
Iron is an important haemoglobin component, a RBC or erythrocyte (red blood cell) protein transferring oxygen to the tissues from the lungs. Thus, a myoglobin component, another protein providing oxygen, iron helps in supporting musclemetabolism and leads to healthy connective tissue. As iron is considered to be an important part of neurological development, physical growth, cellular functioning, and hormones synthesis, that requires the assistance of haemoglobin, an erythrocyte (red blood cell) protein, that later, transports oxygen and is followed by the need of functional iron. Iron helps in the metabolism of the muscles and health of connective tissues as a myoglobin component, therefore, leads to become an oxygen-carrying protein. However, Iron is essential for muscular and functions of brain development, cellular functions, and the development of synthesis of hormones. Whereas, the fact that diabetes is more common in those with classic hereditary hemochromatosis was the first piece of evidence indicating systemic iron, which had an excess amount and could play a role in aberrant glucose metabolism (HH). However, with the recognition of genetic diseases in addition to iron metabolism, it is clear that excess iron causes an increase in the risks of type 2 diabetes, regardless of the cause of the gene implicated. The following evidence suggests that iron has a role in the pathological of diabetes
- A risk that has increased from type 2 diabetes, as a result of several forms of iron excess, and
- reduction in the iron load achieved through therapy or phlebotomy of iron chelation to improve or reverse diabetes (glycemic control). The improved sensitivity of insulin and the secretion of inducing blood donation frequently and low iron storage suggests a causal relationship with iron overload.
Free (Fe) is an extremely pro-oxidant chemical that can produce reactive oxygen species (ROS). As a result, large levels of free Fe may be detrimental, and maintaining its homeostasis is crucial.
Magnesium is an important ion that plays several roles in glucose control. Magnesium and glucose metabolism have a complicated relationship. Both (IDDM and NIDDM) patients have been reported to have hypomagnesaemia. ”10 mg is critical for the activity of several enzymes involved in glucose oxidation, and it may also have a role in insulin release.” Magnesium, a cofactor required for glucose transport into the cells and carbohydrate metabolism. It has a role to play in the cellular function of insulin. Therefore, diabetes is linked to a low magnesium intake. (Mg) deficiency impairs cellular defences against oxidation damage, resulting in reduced resistance to the oxidative stress induced by diabetes, hastening the onset of diabetes-related diseases. However, as a result, hypomagnesemia may aggravate (T2DM), although studies have shown that increasing magnesium intake reduces the risk of (T2DM) and metabolic syndrome by reducing insulin resistance. In diabetic mice, dietary (Mg) (50 mg/mL in drinking water) for 6 weeks reduced blood glucose levels, enhanced mitochondrial activity, and reduced oxidative stress, according to animal studies.
The possible cause of Nephropathy diabetes
Although some elements, such as mercury, arsenic, cadmium, and lead, can cause nephrotoxicity, which is also defined as the harmful effect of chemicals on renal function. Humans can be exposed to harmful elements by drinking polluted water, breathing contaminated air, or eating contaminated food. Chronic renal illness is known to be caused by various environmental content of contaminant’s lead,arsenic and cadmium, as well as the various molecular mechanisms of harmful events that are investigated. The process of “Urinary elimination” is a main excretion route for heavy metals, and concerned “proximal tubules” are specifically vulnerable due to their enhanced activity of re-absorption. The chemical metal form, the acute dose amount, and whether the exposures are chronic or acute, all have an impact on pathological effects of metals on kidneys in a human body. These pathological effects may be altered due to unknown interactions of these metals within the kidney, therefore, according to the isolated studies of metal exposures that remain combined. Increased formation of reactive species of oxygen, reduction of anti-oxidative type of scavengers, while binding to the resident proteins indiscriminately, all contribute to toxic element-induced oxidative stress, which disrupts normal tissue physiochemistry.
(Cd) poisoning is caused by eating Cd-contaminated rice and causes a variety of health problems, involving severe kidney damage.5 The levels of Cd in liver and kidney tissue samples were the highest among the participants of this study from central Jamaica, where the exposure of Cd was similarly on the higher side for environmental and dietary factors.6 Naturally present Cadmium has measured high as 409 mg/kg in soil.7 The studies conducted on animals in the same area has given a confirmation of a ten-fold rise of (Cd) in the kidney, in comparison to samples from various non-pollution based areas.
Various studies have linked high levels of occupational lead exposure to cellular alterations, increased creatinine levels, and kidney damage in study participants.9 Epidemiological research on mercury exposure and CKD has yielded mixed results. Silica (SiO2), Aluminium (Al), and strontium (Sr) are all harmful substances that the kidneys remove from the body. Some of them are nephrotoxic, where a malfunctioning kidney enhances the retention of heavy metals, continuing levels of damage. 10 Hazardous metals are reabsorbed actively following glomerular filtration through metal transporters, utilizing methods that are still poorly understood, in addition to their tendency to accumulate within the kidney. Some speculate that a disruption in the normal reabsorption of important micronutrients from urine is caused by these mechanisms.
Diabetic nephropathy (DN) is the most common cause of kidney failure (ESRD). 1,2. The incidence of diabetes and (DN) is on the rise, suggesting a medical disaster in dialysis units and the growing use of financial resources (Alwakeel et al. 2011, 236-242). Approximately 11 000 people in Saudi Arabia have (ESRD), with diabetes accounting for 20% of the cases. In Saudi Arabia, the cost of dialysis care is US$14 000 per patient per year, with a complete economic burden of more than US$540 million. Given the factors, determining the concentrations of these TEs in patients having diabetes is critical. The objective of the study is to be comparing serum Cu, Zn, Se, Cr, Mg, and Fe concentrations in patients with diabetes and diabetes patients with nephropathy to nondiabetic control people.
- The first step of the theory is to study all the possible disturbances of trace elements in the human body.
- Followed by the step to study further the accumulation of nephrotoxic elements in a body.
- Studying both the theories simultaneously, otherwise.
- There hasn’t been a study that combines these two notions yet.
Nephropathy diabetes and its mechanisms
The goal of our research was to look at the variations and patterns in GFR over time, as well as the potential factors of risk linked to increased renala functional loss and all-cause mortality in Saudis with nephropathy and diabetes.
- Analyzing the study of all the trace elements (Se, Cr, Fe, Zn, Cu and Mg) contained in a serum.
- To analyze and study all the nephrotoxic elements such as (Pb, As and Cd)
- To see if there’s a link between the renal function test and the amounts of trace elements in the blood.
The current research will be conducted in a cross-sectional manner. The subject of the study will all be Saudi Arabian residents. Univariate analysis of baseline demography and clinical laboratory findings are also available. Standard data analysis techniques such as Pearson correlation and (SPSS) would be employed. For categorical data comparison, methods such as the unpaired t-test and the chi-square test will be employed. Patients from King Faisal University’s polyclinic were randomly be selected and placed into four groups for this study. Twenty-five per cent of these patients had diabetes without nephropathy problems, while twenty-five per cent had kidney disease but were not diabetic. The diabetic patient with nephropathy will be the third group, and the normal control group will be the fourth. To document nephropathy, patients will undergo clinical and biochemical testing. A 24-hour urine protein excretion of more than 500 mg was categorized as nephropathy.
- The percentage of people suffering from type 2 diabetes should be 50%.
- The treatment for such cases should not involve supplements like minerals and vitamins.
- There should not be any records of illness or clinic visits within the period.
- Evidence that suggests any symptoms of liver endocrine disease
After a 10-hour overnight fast, blood and urine samples (10 mL) were all collected into tubes. A portion of the blood samples was utilized to determine the level of contamination of HbA1C. The remaining samples of serum were stored at -70 °C until they were required to determine such trace elements. Other portions of blood samples were centrifuged to obtain serum for tests in clinical laboratories; where the remaining serum samples were stored at -70 °C until they could be required for the determination of the trace elements. Atomic absorption spectroscopy will be utilized for determining the amount of trace elements in the serum (Johnson et al. pp.96-116).
References
Adler, S. (2004). Diabetic nephropathy: Linking histology, cell biology, and genetics. Kidney International, 66(5), 2095-2106
Alqurashi, K. A., Aljabri, K. S., & Bokhari, S. A. (2011). Prevalence of diabetes mellitus in a Saudi community. Annals of Saudi Medicine, 31(1), 19-23
Alwakeel, J. S., Isnani, A. C., Alsuwaida, A., AlHarbi, A., Shaikh, S. A., AlMohaya, S., & Al Ghonaim, M. (2011). Factors affecting the progression of diabetic nephropathy and its complications: a single-center experience in Saudi Arabia. Annals of Saudi Medicine, 31(3), 236-242
Farag, Y. M., & Al Wakeel, J. S. (2011). Diabetic nephropathy in the Arab Gulf countries. Nephron clinical practice, 119(4), c317-c323
Giacco, F., & Brownlee, M. (2010). Oxidative stress and diabetic complications. Circulation Research, 107(9), 1058-1070
Johnson, R. J., Perez-Pozo, S. E., Sautin, Y. Y., Manitius, J., Sanchez-Lozada, L. G., Feig, D. I., … & Nakagawa, T. (2009). Hypothesis: could excessive fructose intake and uric acid cause type 2 diabetes?. Endocrine Reviews, 30(1), 96-116
Lin, C. C., Shih, C. T., Lee, C. H., & Huang, Y. L. (2018). Changes in trace elements during early stages of chronic kidney disease in type 2 diabetic patients. Biological trace element research, 186(2), 330-336
Qi, W., Li, Q., Gordin, D., & King, G. L. (2018). Preservation of renal function in chronic diabetes by enhancing glomerular glucose metabolism. Journal of Molecular Medicine, 96(5), 373-381
[1]S. Swaminathan, V. Fonseca, M. Alam and S. Shah, “The Role of Iron in Diabetes and Its Complications”, Diabetes Care, vol. 30, no. 7, pp. 1926-1933, 2007. Available: 10.2337/dc06-2625.https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/
[3]L. Barnett and B. Cummings, “Nephrotoxicity and Renal Pathophysiology: A Contemporary Perspective”, Toxicological Sciences, vol. 164, no. 2, pp. 379-390, 2018. Available: 10.1093/toxsci/kfy159.
Madden, E. and Fowler, B., 2000.
Mechanisms Of Nephrotoxicity From Metal Combinations: A Review
. Drug and Chemical Toxicology, 23(1), pp.1-12.
Role of Toxic Elements in Chronic Kidney Disease Adwalia Fevrier-Paul; Adedamola K Soyibo; Sylvia Mitchell; Mitko VoutchkovJournal of Health and Pollution (2018) 8 (20): 181202.
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