The Relation of HbA1c and Vitamin D with some Biochemical Variables in the Blood of Type1 Diabetic Patients in Tikrit View PDF

Diabetes is a chronic condition caused by genetic and environmental factors that are characterized by high blood sugar due to the absolute or molecular deficiency of insulin, due to the presence of a specific defect that prevents insulin from showing its desired effect [1], the researchers pointed out that the rise in blood sugar from the normal level leads to unusual changes in the tissues The kidneys, liver, small intestine, pancreas, and brain. These changes include the breakdown of most pancreatic beta cells and hepatic cells, and that the size of the Langer Hans islands expands the expansion of Bowman's space, the size of the renal glomeruli and the rupture of the renal blood particles [2].

Diabetes is mainly classified into two types, the first type (insulin dependent) and the second type (not dependent on insulin). Insulin dependent diabetes (type 1) is called juvenile diabetes because it affects people under the age of forty that is, in childhood and represents (5-10%) approximately, and occurs as a result of the absolute lack of insulin secretion as a result of the destruction of beta pancreatic cells occurs [3]. As a result of the destruction of insulin-producing (B) cells in the islets of Langerhans in the pancreas, leading to complete loss of insulin secreted into the body. Insulin is used by the body to facilitate the transfer of glucose from the bloodstream to the target tissues, such as the muscles, for the purpose of energy production, and therefore the lack of insulin leads to hyperglycemia (the lack of it to reach the target tissues, which causes glucose to remain in the blood and accumulation that leads to the transformation of fats in the body into Keto acids, so coma and loss of consciousness of the patient occur as a result of high blood sugar and urine [4]. Typically, patients of the first type do not respond to sugar-lowering tablets nor benefit in treating them except insulin injections, so the patient must take insulin doses to control the level of glucose in the blood [5].

It is characterized by glucose (sugar) hemoglobin in that it gives an idea of the proportion of blood sugar in a relatively long period without affecting certain external factors such as food and exercise. Hence, it includes intoxicated hemoglobin (A1c, A1c, Hb1c), which is a form of hemoglobin and it is measured primarily to determine the average concentration of glucose in the blood plasma for a long period of time and is also an indication of cardiovascular disease and kidney failure [6].

Vitamin D is one of the unique vitamins, as it is produced in the body during exposure to sunlight, so it is called the sun vitamin, and it is one of the fat-soluble vitamins, and it is available in a high percentage in specific types of foods including: fish, oils, and fish liver, Egg yolk, fortified cereal products, dairy, yeast, shellfish, and salmon [7].

Scientists have estimated the low relationship that links vitamin D to diabetes, as it regulates the level of sugar in the blood, as it enters into the formation of beta cells, which in turn works to produce insulin, so vitamin D deficiency leads to less insulin secretion, and adjusting its levels regulates insulin secretion, beta cells, and it activates insulin receptors. Therefore, the intake of vitamin D is one of the preventive factors for diabetes, as it reduces the risk of diabetes from the first type by 80%, and reduces the incidence of type 2 diabetes by up to 33%, but these rates have not been definitively proven [8].

The study was conducted in Salah Al-Din governorate Tikrit, as it collected 30s blood samples between January 2019 to April 2019 from healthy and diabetic people, the type1 of both sexes, and their ages ranged between (30-60) years.

Blood samples were collected and divided according to the request of the biochemical variable (-20?) until tests were conducted, as the level of (glucose, urea, Creatinine, HbA1c, ALP, bilirubin, AST, ALT, and Vitamin D) was estimated using kits supplied from the German human company.

Statistical analysis

Where appropriate, the data are presented as Means ± SD. The relations between two variables were analyzed by simple regression using SPSS statistical software. The unpaired Student’s t-test was used to ascertain relations between two groups. P<0.5 was considered statistically significant.

Figure 1 shows the concentration of glucose in the serum of patients with type 1 diabetes and healthy people. The results showed a significant increase in patients compared to healthy subjects. This increase in glucose is due to the inability of pancreatic cells to produce insulin [1], or a decrease in tissue sensitivity to it, as people with diabetes suffer from metabolic disorders, which is why blood glucose levels rise, and insulin cannot do its job because of its increased resistance by reducing its receptors on the surface of target cells [9].

Table 1 shows the concentration of glucose in the blood serum of patients with type 1 diabetes and healthy people, by gender, and the results showed a significant increase at the probability level of 0.05 in the concentration of glucose in patients compared with healthy people and the absence of differences between males and females despite the presence of some differences that may be attributed to the sample group or the method of measurement.

Table 1: Concentration of biochemical variables in the blood of patients with type 1 diabetes compared to healthy people by gender.

This rise in glucose is due to the inability of the pancreatic cells to produce insulin or a decrease in tissue sensitivity to it, as people with diabetes suffer from metabolic disorders, so the level of glucose in the blood rises as well, insulin is unable to do its job because of its increased resistance by reducing Receptors on the surface of target cells.

Figure 2 shows the percentage of glycated hemoglobin (HbA1c) in diabetics compared with healthy subjects. The results of the study showed a significant increase at the probability level of 0.05 in the percentage of HbA1c in patients, as the cause is attributed This is the result of glucose adhesion to the hemoglobin molecules in red blood cells, as when glucose adheses with it to Glycohemoglobin, when the level of glucose in the blood increases, the percentage of hemoglobin loaded with glucose (Glycohemoglobin) will increase, and remains so until the end of the life of RBCs, which is almost three months.

It is clear from Table 1 the percentage of HbA1c in the blood of patients with type 1 diabetes and healthy people, by sex, and the results showed a significant increase in the percentage of HbA1c in patients compared to healthy people and the absence of significant differences between males and females.

When blood glucose levels continue to raise, this leads to the entry of glucose into the red blood cells, which leads to the breakdown of proteins inside these cells, which leads to the production of hydrogen peroxide and the presence of binary iron in the heme group that produces free radicals as in the Fenton reaction [10].

Figure 3 indicates the urea level in the blood of patients with type 1 diabetes compared to the healthy people, as the results showed a significant increase in the urea level in patients at the probability level of 0.05 compared to the healthy people, and these results are consistent with several studies, including Al-Zamili, et al. (2017) [10].

Table 1 shows the level of urea in the blood of patients with type 1 diabetes and healthy people, by sex. The results showed a high urea level in patients compared to healthy people, and there were no significant differences between males and females despite a slight increase in females than males in both healthy and patients.

Notice the difference in the level of urea between patients and healthy people, which means there is a lack or lethargy in the kidney function for diabetics, and it may lead to a low level of glomerular filtration. Therefore, controlling the level of sugar in the blood is an important factor in maintaining the urea level within the normal rate.

The reason for the high level of urea in the blood serum of patients with diabetes is due to the fact that urea is one of the nitrogenous compounds that include both creatine, creatinine, uric acid, ammonia, and amino acids. The blood urea nitrogen (BUN) represents about 40% of the compounds Nitrogenic is not proteinuria, and it is one of the wastes that are excreted with the urine through the kidneys and the increase in the level of urea in the blood. Artemisia, which leads to less excretion of urea, so it accumulates in the blood, and its concentration increases [2].

Figure 4 shows the creatinine and bilirubin level in the blood of type1 diabetic patients compared with the healthy people, as the results showed a significant increase at the probability level of 0.05 in the creatinine and bilirubin levels than the normal level in patients compared to healthy controls.

High levels of creatinine in the blood serum are usually accompanied by diseases such as: diabetes, autoimmune diseases, and high blood pressure (Hypertension), in addition to chronic infections of the kidneys, especially when they are linked to Rate Glomerular Filtration (GFR).

High creatinine is associated with diabetes or high blood pressure, as one of the common complications of these diseases is kidney damage [4].

Bilirubin has strong antioxidant properties, as it is oxidized to biliverdin, which is directly reduced by reducing biliverdin to bilirubin.

Bilirubin works to suppress the oxidation of fats and lipoproteins, especially low-density lipoprotein cholesterol (LDLc) compared to water-soluble antioxidants such as glutathione, it has been shown that bilirubin is more effective in protecting fats from oxidation [11], in addition to this it has anti-inflammatory properties A study has found that there is a negative relationship between serum bilirubin concentration and soluble forms of CD40 and P-selectin in people with Gilbert syndrome [12]. Several studies also found a negative relationship between serum bilirubin concentration and C-reactive protein [13-15]. In cardiovascular diseases, many studies have found that there is a negative relationship between the concentration of bilirubin and the risk of both coronary and peripheral atherosclerosis [16] has demonstrated that an increased concentration of bilirubin can reduce the risk of cardiovascular injury [17], and these diseases are considered It is a complication of diabetes, as it affects many parts of the body and is associated with serious complications, such as heart disease, stroke, blindness, renal and liver failure, and lower limb disorders that lead to amputation.

Oxidative stress is a major contributor to the complications of diabetes. A study has shown that the serum concentration of bilirubin is negatively correlated with the level of oxidative stress and positively correlated with antioxidant enzyme levels such as peroxide desmotase, catalase, and glutathione peroxidase [18]. Therefore, bilirubin may protect against complications from diabetes, however, until now, the mechanism of complications of diabetes remains unclear. The possible mechanisms underlying the association between bilirubin and complications of diabetes. High blood sugar leads to excessive production of mitochondrial oxidation in the endothelial cells of both large and small vessels, as there are five main pathways that include a polyol pathway flux, and increased formation of advanced glycation end products (AGEs), high receptor production of AGEs, activation of protein kinase C isoforms, and hexosamine pathway. These five pathways are involved in increasing complications of diabetes.

That bilirubin can not only prevent lipid peroxidation and reduce LDL oxidation, but also reduce levels of reactive oxygen types, as several studies have concluded the relationship between bilirubin concentration and the risk of complications from diabetes [19].

Table (1) refers to the creatinine level in the blood of patients with type1 diabetes and healthy people, by sex, and the results showed a significant increase in creatinine level in patients compared to healthy people and a higher level in male than female patients and healthy subjects, these results are consistent with Bamanikar, et al. (2016) [4].

Men usually have higher Creatinine levels in the blood than women, because they have stronger muscle mass, greater volume, as well as a larger and stronger skeleton than women, and Creatinine levels in the blood of vegetarians who depend on eating vegetarian food in meals are lower. Of other people, therefore creatinine has to do with the size of the muscle mass in the body, so there are higher in males than females, and since the skeletal muscle is the primary target tissue of insulin, and that the small size of skeletal muscle means less sites of insulin, which causes increased insulin resistance, and this leads to development of diabetes. There is a relationship between creatinine and urea with glomerulonephritis in diabetes, as diabetes causes kidney damage and increases with age [10].

Figure 5 shows the rate of effectiveness of AST, ALT and ALP enzyme in the blood in patients with type 1 diabetes compared to healthy subjects. The results showed an increase in the effectiveness of the above enzymes in patients compared to healthy people at the probability level of 0.05, and this is consistent with a number of studies, including Zamili, et al. (2017) [10].

The high levels of ALT, AST activity in patients is due to the fact that the AST stimulates the complete conversion of aspartate and α-ketoglutarate to oxaloacetate and glutamate, since the levels of AST in the blood of healthy people are low, and when a liver or muscle cell injury occurs, it is released via the blood. This makes its test useful in detecting such injuries. As for the ALT, it stimulates the reactions of the transport of the amine group from amino acids to keto acids. The medium that carries amino groups is one of the two effective forms of vitamin B6, namely pyridoxal phosphine and pyridoxamine, and their work as an enzymatic auxiliary and this enzyme is spread in many body tissues and that ALT activity is also found in the liver It turns out that the liver cells have been destroyed and in addition to the destruction of the liver cells, a blockage of the bile duct may occur due to the high level of fat in the blood (Hyperlipidemia) usually associated with diabetes, that is, high levels of These enzymes result of diabetes precipitates fat in the liver as a result of an imbalance in food because of its representation of the top of the cells in response to insulin [4,5].

The increase in the effectiveness of ALP is usually due to many pathological conditions such as liver or bile duct disease or the presence of gallstones. The rise of ALP may indicate bone diseases such as osteopenia or Osteoporous osteoporosis. Blood disorders also cause an increase in ALP in addition to some cases cancer [20].

Diabetes leads to changes and complications on the liver related to its function and shape, as the liver has an important role in diabetes, its importance in metabolizing carbohydrates, as high levels of glucose work to damage the liver and cardiac muscle cells [21], and that the increase in the effectiveness of basal phosphatase in the blood serum in case Diabetes can be the result of an increased energy requirement during the ALP activity rather than glycolysis and the Glucose-6-phosphate oxidation pathway, which is attributed to the degradation and damage of liver cells [22].

ALP is one of the widely used directories for bone metabolism as it provides a good impression of the extent of new bone formation and activity of osteoblast cells [23], as high levels of blood glucose cause numerous bone disorders, particularly osteoporosis, which is a metabolic bone disease causing low bone mass or loss of bone mineral density (BMD) [24].

Table 2 indicates the level of Vitamin D in the blood of patients with type I diabetes and healthy people, the results showed a high level of Vitamin D in patients compared to healthy controls.

Table 2: Vitamin D level in the blood of patients with type 1 diabetes compared to healthy people.  

Diabetics of the type1 is more prone to developing osteoporosis, and diabetics often develop gluten allergy, which reduces the absorption of calcium and vitamin D from the intestine, resulting in fragility, and that osteoporosis is a disease that lowers the level of calcium in the bone, making it weak and fragile.

One of the complications resulting from diabetes is the lack of vitamin D as a result of consuming this vitamin by diabetics from 1 to 4 times the normal person [25].

Table 3 indicates the relationship of HbA1c with Urea Createnine, ALT, AST, ALP bilirubin variables in the blood of patients with type 1 diabetes and healthy people. The results showed a positive relation for ALP, Urea, AST and negative for Createnine, ALT for patients compared to healthy people. As shown in the table.

Table 3: Relation of HbA1c correlation with biochemical variables in the blood of patients with type 1 diabetes compared to healthy subjects.

There are some reasonable explanations for the mechanism linking HbA1c and bilirubin. First, bilirubin is involved in the glycation of hemoglobin. Sugars react non-enzymatically with a wide range of proteins to form early glycation products, and oxidative stress is involved in the glycation reaction [26]. Oxidative stress can facilitate the autoxidation of glucose to dicarbonyl intermediates, which is an early step in the Maillard reaction [27]. In addition, malondialdehyde, which is generated by lipid oxidation, is thought to enhance the process of protein glycation by acting as an anchor between sugar and hemoglobin moieties [28]. Therefore, bilirubin may inhibit the glycation of hemoglobin by reducing oxidative stress.

Second, bilirubin may play an significant role in glycemic control. Increased expression of heme oxygenase-1, the enzyme responsible for the conversion of hemoglobin to bilirubin, is associated with enhanced insulin sensitivity and glucose metabolism [29]. In addition, serum bilirubin is inversely associated with insulin resistance and it increases the expression of glucose transporter-1 and the rate of glucose uptake. However, in the present study, we did not collect data related to insulin resistance. We therefore cannot confirm the association between bilirubin and insulin resistance [30].

Although the mechanism underlying the associations between liver enzymes and incidence of diabetes remains unclear, some possibilities can be considered. One is that increased serum AST and ALT levels reflect an excess deposit of fat in the liver, a condition known as non-alcoholic fatty liver disease [31].

The study aimed to find a relation between vitamin D and biochemical variables in the blood of type 1 diabetics and healthy. The results showed that there is a positive relationship between vitamin D and AST, but it is not significant, when looking at the correlation coefficient through Table 4, the relation are negative between vitamin D and Createnine, ALP, Urea, ALT in diabetics patients, and it has been shown that bilirubin Associated with vitamin D with correlation coefficient of -0.44.

Table 4: Correlation of vitamin D with chemical variables in the blood of patients with type 1 diabetes compared to healthy subjects.

In order to understand the effects of vitamin D level on the biochemical parameters, they associated low serum vitamin D level with hyperbilirubinaemia. Our observation could be as a result of possible impaired hepatic excretory function which could culminate in impaired bile acid formation causing impaired vitamin D absorption [32].

In the present study, no significant relationship was detected between level of vitamin D and HbA1C. However, in the study conducted by Danaei N, et al. (2014), a significant negative relationship has been reported between serum level of vitamin D and HbA1C [33].

According to the current study as well as other studies conducted in this regard, since vitamin D necessary for human body is supplied through receiving foods, vitamin D supplements, and sunshine, and given the high prevalence of vitamin D deficiency in diabetic patients, it is recommended to adopt special measures to compensate the deficiency of this vitamin in diabetic patients.

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