EVALUATION OF THE SERUM LEVELS OF SOME TRACE ELEMENTS AND ANTIOXIDANT LEVELS IN APPARENTLY HEALTHY INDIVIDUALS WITH FAMILY HISTORY OF TYPE 2 DIABETES IN NNEWI, NIGERIA
HTML Full TextEVALUATION OF THE SERUM LEVELS OF SOME TRACE ELEMENTS AND ANTIOXIDANT LEVELS IN APPARENTLY HEALTHY INDIVIDUALS WITH FAMILY HISTORY OF TYPE 2 DIABETES IN NNEWI, NIGERIA
J. E. Okwara 1, C. C. Agudi 2, E. C. Ogbodo * 2, C. M. Njoku 1, R. A. Analike 1, A. K. Amah 3, O. O. Eze 4 and S. C. Meludu 5
Department of Chemical Pathology 1, Faculty of Medicine, Department of Medical Laboratory Science 2, Faculty of Health Sciences and Technology, Department of Human Biochemistry 5, Faculty of Basic Medical Sciences, Nnamdi Azikiwe University, Awka, Nigeria.
Department of Human Physiology 3, College of Medicine, Imo State University, Owerri, Nigeria.
Department of Epidemiology and Medical Statistics 4, Faculty of Public Health, University of Ibadan, Nigeria.
ABSTRACT: There is a paucity of data on studies evaluating trace elements and antioxidant levels and susceptibility of offspring of diabetic parents to type 2 diabetes in Nigerian population. This study evaluated the serum level of some trace elements and antioxidants among apparently healthy individuals with a family history of type2 diabetes mellitus (FH-T2DM). This was a cross-sectional study involving 122 Students (aged between 18-30 years) consisting of 60 apparently healthy subjects with FH-T2DM and 62 apparently healthy subjects without FH-T2DM. Serum levels of Cr, Zn, Se, and Mn and catalase and superoxide dismutase of these subjects were measured using atomic absorption spectrophotometric technique and spectrophotometric technique, respectively. The plasma glucose, body mass index (BMI), waist circumferences, and a waist-to-hip ratio of these subjects were also determined using standard methods. Results from this study showed that mean fasting plasma glucose level was significantly higher (p=0.001); serum levels of Cr was significantly lower (p=0.04) while serum levels of Zn, Mn, Se, SOD and Catalase did not differ significantly (p>0.05) in those with FH-T2DM when compared with those without the FH-T2DM. There were no significant differences in the BMI (P = 0.236), WHR (P=0.794) between FH-T2DM and those without FH-T2DM. However, selenium was significantly higher in male offspring of diabetic mothers compared to female offspring of diabetic fathers (p=0.015), and catalase was significantly lower in males from diabetic mothers compared to males from diabetic fathers (p=0.009). This finding may imply that males from diabetic mothers may be at a greater risk of developing diabetes in the future, considering the respective roles of the trace elements and antioxidants in glucose metabolism.
Keywords: |
Trace elements, Antioxidants, Plasma glucose, Type2 diabetes mellitus, Family history of type2 diabetes mellitus, Body mass index
INTRODUCTION: Family history of specific diseases reflects the consequences of genetic susceptibility, shared environment, and common behaviors 1, 2.
Family history is a non-modifiable risk factor for diabetes mellitus, which, when present, might influence the probability of a suspected diagnosis 3, 4. Family history taking is essential in the practice of preventive medicine to assess disease risk and influence early detection and prevention strategies 5. Professional guidelines for clerking of patients usually include family history to assess health risk, initiate interventions, and motivate behavioral changes 6. It may provide a useful screening tool for detection and prevention of diabetes 5.
In a study among adult Chinese, it was reported that sufficient physical activity and negative family history of diabetes might jointly reduce the risk of developing hyperglycemia and T2DM 7. In the US population, family history of diabetes showed significant, independent, and graded association with the prevalence of diabetes 8. This association points to the possibility of formally adding family history to public health strategies aimed at detecting and preventing the disease 8.
Diabetes mellitus is a metabolic disorder that affects carbohydrate, fat, and protein metabolism, which could result from defects in insulin secretion, insulin action, or both 9. It is a chronic metabolic disease resulting from the diminished or absent secretion of insulin or due to reduced tissue sensitivity to insulin and has a global health burden especially in developing countries like Nigeria 9, 10.
International Diabetes Federation (IDF), in 2017, estimated that 425 million adults were living with diabetes, and further, it is estimated to affect up to 629 million people by the year 2045 11. Diabetes Mellitus has become a major public health problem in Nigeria, accounting for a prevalence of 2.4%, with a total number of mortality amounting to 3028 deaths in 2017 11, with type 2 diabetes making up about 90% of the cases. This indicates a pandemic in full flight, and the greatest increase in rates is expected to occur by the year 2030 12.
Research has shown that an imbalance of some essential metals might adversely affect pancreatic islet and cause the development of diabetes 13. It has also been reported that there is a relationship between diabetes mellitus and trace elements in many with an alteration in the metabolism of these minerals 14. Insulin action has been shown to be influenced by some trace elements like chromium, magnesium, vanadium, zinc, manganese, moly-bdenum and selenium 14. Proposed mechanisms of enhancement of insulin action by trace elements include activation of insulin receptor sites 15, serving as cofactors or components for enzyme systems that are involved in glucose metabolism 16, increasing insulin sensitivity, and acting as antioxidants for preventing tissue peroxidation 17.
Zinc activates β cells for the production of insulin and increases insulin signals in the muscle through activation of phosphatidylinositol 3-kinases (PI3-KAKT) pathway and Glucose transporter4 GLUT4 18. Zinc is essential for insulin synthesis and release, and its deficiency seems to impair release of insulin 19. Growing evidence suggests that chromium supplementation, particularly at higher doses and in the form of Chromium Picolinate, may improve insulin sensitivity and glucose metabolism in patients with glucose intolerance and type 1, type 2, gestational, and steroid-induced diabetes and in some individuals without diabetes 20, 21. Selenium has been known to possess cytoprotective properties as a result of its ability to upregulate antioxidant selenoenzymes. Thus, it was believed that Se supplementation could prevent the onset of metabolic diseases, such as type 2 diabetes (T2D), by counteracting oxidative stress 22, 23. Several studies have revealed selenium to be an insulin-mimetic, because it plays roles in the regulation of enzymes in the insulin signaling cascade, the expression of lipogenic enzymes, and carbohydrate metabolism in the liver 24, 25.
Manganese (Mn) has an important role in the phosphorylation reactions of glucose and its metabolism. Its deficiency has been implicated in insulin resistance, carbohydrate intolerance, dyslipidaemia, and complications of diabetes 26. It is an essential micronutrient required for normal carbohydrate, lipid, and protein metabolism. As a major antioxidant due to its mitochondria matrix localization, MnSOD plays a critical role in protecting mitochondria and islets from elevated reactive oxygen species (ROS), which may serve as an important trigger of insulin resistance and type 2 diabetes 26, 27.
Oxidative stress has been shown in some experimental models to negatively impact insulin secretion, thus increasing insulin resistance. This may play a causal role in the pathogenesis of diabetes 28.
Overweight and obese individuals are at increased risk for many diseases and health conditions, including the following: Hypertension, Dyslipidemia, and Type 2 diabetes. Increased waist circumference is also closely associated with an increased risk of diabetes 29. Therefore, high waist circumference (WC), waist-hip ratio (WHR), body mass index (BMI), and age are risk factors as well as predictors of type 2 diabetes mellitus 30.
The development of type 2 diabetes is caused by a combination of lifestyle and genetic factors 9. Although some of the risk factors of diabetes mellitus, such as diet and obesity, could be modifiable through dietary management and physical activity, others such as increasing age and genetics non-modifiable risk factors. Oxidative stress impacts negatively on insulin secretion resulting in insulin resistance, and may thus play a causal role in the pathogenesis of diabetes 28. The pancreatic islets contain relatively small amounts of the antioxidant enzymes, Copper-Zinc Superoxide Dismutase (CuZn-SOD), Manganese Superoxide Dismutase (Mn-SOD), catalase, and glutathione peroxidase (GPx). This unusual situation sets up the β-cell as an easy target for ROS, whether generated by interactions with cytokines or too much glucose 31. Research has shown that the imbalance of some essential metals might adversely affect pancreatic islet and cause the development of diabetes 32, 33. Therefore, this study was designed to investigate and compare the glucose, trace elements, antioxidant levels, and BMI of those healthy individuals with a family history of DM Type 2 and that of those without a family history. This study will provide information on the way to reduce or ameliorate the conditions that predispose individuals to alterations of mineral elements and oxidants that may lead to the development of diabetes in the future, especially for individuals with a family history of Type 2 diabetes.
MATERIALS AND METHODS:
Study Design: This is a cross-sectional study that was designed to evaluate the serum levels of some trace elements and antioxidant levels in apparently healthy individuals with a family history of type2 diabetes in Nnewi, Nigeria.
Target Subjects: The subjects were students (aged between 18-30 years) consisting of 122 individuals, 60 apparently healthy subjects with a family history of type 2 diabetes (35- fathers and 25- mothers diabetics), and 62 apparently healthy subjects without a family history of type 2 diabetes.
Inclusion Criteria: Inclusion criteria included First degree relatives with a family history of type 2 diabetes, individual between the age of 18-30 years, males and females with one parent or more parents being positive to type 2 diabetes who were healthy and not on any special diets were recruited for the study.
Exclusion Criteria: Exclusion criteria included Individuals- males and females whose parents never had type 2 diabetes at the time of this research and who were below the age of 18 and above 30 years of age were also excluded from the study.
Sampling Technique and Administration of Questionnaire: The subjects were selected by simple random sampling technique with Questionnaire which included questions such as age, sex, family history of diabetes, etc.
Ethical Approval and Consent: Ethical approval letter (dated 19/10/2016) was obtained from the Ethics Committee of the Faculty of Health Sciences Nnamdi Azikiwe University Nnewi campus. The consent of the participants was sought and obtained before the commencement of the study.
Blood Sample Collection and Storage: Seven milliliters (7ml) of venous blood was collected from each of the participants after an overnight fast of 12 hours. Two milliliters (2mls) of the blood was dispensed into fluoride oxalate bottles for glucose estimation. The remaining sample was dispensed into a plain bottle and allowed to clot, retracted and serum separated and stored at -20 °C for two months until analyzed. The stored aliquots were used for trace elements and antioxidants estimations.
Anthropometric Measurements: Height and weight were measured using a calibrated stadiometer and portable weighing machine (SH 2003B), respectively. The height and weight were recorded to the nearest centimeters and kilograms, respectively. Body mass index (BMI) was obtained through a calculation using the formulae:
BMI = Weight (kg) ÷ height2 (m2).
Waist circumference (WC) was also measured using non elastic flexible tape in the standing position. Waist-hip ratio (WHR) was calculated as waist circumference divided by hip circumference.
Quality Control Measures: Quality control sera were run alongside tests in each batch of analysis and their results were compared to the manufacturer’s control range and found to be within the acceptable limit.
Methods of Sample Analysis:
Determination of Plasma Glucose: This was done using the Glucose oxidase method (GOD-POD) RANDOX according to the method described by Stein 34.
Determination of Trace Elements: Trace elements (Manganese, Selenium, Chromium, and Zinc) were assayed by Atomic Absorption Spectro-photometry 35.
Determination of SOD Activity: This was determined using the method as described by Misra and Fredovich 36.
Determination of Catalase Activity: Catalase activity was determined using the method as described by Sinha 37.
Statistical Analysis: Statistical Package for Social Sciences (SPSS) version 20 software was used to analyze the data obtained in this study. The statistical tools used to analyze the data obtained in this study were the Student independent t-test, One Way Anova, and PostHoc. Values were expressed as mean ± SD, and the results obtained were considered significant at p≤0.05.
RESULTS: Table 1 shows the serum levels of Trace elements, Antioxidant levels, and anthropometric characteristics of those with a family history of type 2 diabetes and those without a family history of diabetes. The mean plasma levels of fasting plasma glucose of those subjects with a family history of type2DM and those without a family history of T2DM were (4.5±0.4 and 4.2±0.4) respectively. This result showed that the fasting blood glucose was significantly higher in those with a family history of T2DM (P=0.001) when compared to those without a family history of diabetes type 2. The mean serum levels of Chromium of subjects with a family history of type 2 diabetes and those without family history were (0.16±0.10 mcg/l and 0.25±0.22 µg/L) respectively. This result shows that the mean levels of chromium were significantly lower in subjects with a family history of T2DM (P= 0.004) compared to the control subjects. The mean serum levels of their Zinc were 959.6±94 µg/L and 981.8±95 µg/L, respectively. The result of their zinc levels showed no significant difference when compared (p=0.220). The mean levels of manganese and selenium of the subject with family history of type2DM and the control subjects were (0.8±0.45 µg/L and 0.88±0.52 µg/L) and (109.4±35.7 µg/L and112.8 ±36 µg/L) respectively. The results of their mean levels of Manganese and Selenium showed no significant difference when compared (p=0.768 and p=0.411) respectively. The serum mean levels of Superoxide Dismutase and Catalase of those with family history of T2DM and those without family history are (6.8±1.4 and 6.8±1.5 U/mL) and (27.2±7.2 and 29±10.3) respectively. These results showed no statistical significant difference when compared (p=0.849 and p= 0.270) respectively. The mean values of the BMI of the subjects with family history of diabetes and those without the family history were 25.5±2.5 and 24.9±3.5 respectively. The mean values of WHR of those with family history of diabetes type2 and the control were 0.79±0.04 and0.79± 0.03 respectively. There was no statistically significant difference in the values of the Anthropometrical (BMI AND WHR) assessments between subjects with family history of T2DM compared with those without family history of T2DM (p= 0.236 and 0.794) respectively.
Table 2 shows the serum levels of Trace elements, antioxidants and anthropometric features of the study population of subjects whose fathers have diabetes mellitus type2 and those whose mothers have type2 diabetes mellitus according to history.
The mean plasma levels of glucose in subjects whose mothers have T2DM and those whose fathers have T2DM were (4.5±0.4 and 4.49±0.38) respectively. The result of their mean plasma levels of glucose showed no statistical significance when compared (p=0.936). The mean serum levels of their chromium were 0.15±0.10 and 0.16±0.10) respectively. The result of their chromium levels showed no significance when compared (p=0.732). The mean serum levels of their Zinc were 981±66 µg/L and 983±107 µg/L, respectively. The result of their zinc levels showed no significant difference when compared (p=0.224). The mean levels of manganese and selenium in the subjects whose mothers have T2DM and those whose father have type2 DM are (0.9±0.47 µg/L and 0.7±0.4 µg/L) and (121.6±35 µg/L and 100.8±34 µg/L) respectively. The results of their mean levels of Manganese and Selenium showed no significant difference when compared (p=0.490 and p=0.278) respectively.
The mean serum levels of Superoxide Dismutase and Catalase of those whose mother were positive to T2DM and those whose fathers were positive to T2DM were (6.6±1.1 and 6.9±1.5) and (24.5±5 and 29±27) respectively. These results showed no statistical significant difference when compared (p=0.440 and p= 0.11) respectively.
The mean values of the BMI of the subjects who have positive mother T2DM and those who have positive father T2DM were 25.2±2.6 and 25.8±2.4 and their mean values of WHR were 0.79±0.05 and 0.79± 0.03 respectively. There was no statistically significant difference in the values when compared (p= 0.332 and 0.656).
Table 3 Shows sex distribution of some parameters of the first generation offspring of type 2 diabetic parents.
The mean plasma levels of fasting blood glucose (FPG) of females from diabetic mothers (fm) (4.5±0.5) and males from diabetic mothers(mm) were 4.48±0.3, and mean plasma levels of fasting blood glucose (Fpg) of females from diabetic fathers (ff) and males whose fathers (mf) were positive to type 2 Diabetes mellitus were (4.5±0.37 and 4.47±0.4) respectively. This result showed no statistical significance when compared (p=0.982).
The mean serum levels of chromium of (Fm) (0.13±0.09) males (Mm) whose mothers were positive to type2 Diabetes mellitus (0.18±0.11) and the mean serum levels of chromium of females(Ff) and males (Mf) whose fathers were positive to type 2 Diabetes mellitus were (0.18±0.10 and 0.15±0.10) respectively. The result of their mean serum chromium levels was significantly lower when compared (p=0.536). The mean serum levels of Zinc of Fm and Mm were 987±56 µg/L and 975±80 µg/L respectively, and that of Ff (942±103 µg/L) and Mf (945±113 µg/L) and the result of their zinc levels showed no significance when compared (p=0.448).
The mean serum levels of manganese of Fm (0.9±0.5mcg/l) Mm (0.9±0.40 µg/L) Ff (0.7±0.4 µg/L) and Mf were (0.73±0.40 µg/L) and selenium of Fm (115±29 µg/L), Mm (130±41 µg/L), ff (95.4±29 µg/L) and mf (105±35 µg/L) respectively. The results of their mean levels of Manganese showed no significant difference when compared (p=0.260). However, the mean serum levels of selenium of mm were significantly higher when compared with ff (p=0.015).
The serum mean levels of Superoxide Dismutase of (Ff) and males (Mf) were (7.±1.6 and 6.8±1.4) U/mL, and serum mean levels of Superoxide Dismutase females (FM) and males (Mm) with positive T2DM mothers were (7.1±1.1 and 6.0±0.9) These results showed no statistical difference when compared (p=0.367). The serum mean levels of Catalase of fm and ff were (25.7±6.7 and 28.±6.5U/L), and the serum mean levels of mm and mf were (23±5 and 30±8) U/L, respectively. Furthermore, the mean serum levels of catalase of mm were significantly decreased compared to mf (p=0.009).
TABLE 1: FASTING PLASMA GLUCOSE, SERUM TRACE ELEMENTS, ANTIOXIDANTS LEVELS AND ANTHROPOMETRIC PARAMETERS OF HEALTHY INDIVIDUALS WITH FAMILY HISTORY OF TYPE2 DIABETES MELLITUS AND THOSE WITHOUT FAMILY HISTORY OF TYPE 2 DIABETES (MEAN AND STANDARD DEVIATION)
Parameters | DM History N=60 | CONTROL N=62 | t-test | p-value |
Fasting plamsa glucose (mmol/L) | 4.5±0.4 | 4.2±0.3 | -3.66 | 0.000 |
Chromium (µg/L) | 0.16±0.10 | 0.25±0.22 | 2.969 | 0.004 |
Zinc (µg/L) | 959±94 | 981±94 | 1.234 | 0.220 |
Mn (µg/L) | 0.88±0.46 | 0.87±0.55 | 0.768 | 0.444 |
Selenium (µg/L ) | 109.5±36 | 112±35.5 | 0.411 | 0.682 |
Superoxide Dismutase (U/ml) | 6.8±1.4 | 6.9±1.5 | 0.191 | 0.849 |
Catalase (U/ml) | 27.2±7.2 | 29±10.3 | 1.109 | 0.270 |
BMI kg/m2 | 25.5±2.5 | 24.9±3.5 | -1.109 | 0.236 |
WHR | 0.79±0.04 | 0.79±0.03 | 0.262 | 0.794 |
Significance=≤0.05, Mn=Manganese, BMI=Body Mass Index, Fpg=fasting plasma glucose, mcg/l= Microgram per litre, IU/ml= International unit per millitre
The mean values of the BMI of the Fm and Mm were 25±3 and 25.5±2.4, and the mean of their WHR were 0.8±0.05 and 0.79±0.03 respectively, while that of Ff and Mf were 25.3±3.7 and 25.5±2.9 for BMI and 0.79±0.03 and 0.8±0.03 for their WHR. The result showed no statistical significance when compared (p= 0.585 and 0.893).
TABLE 2: FASTING PLASMA GLUCOSE, SERUM TRACE ELEMENTS, ANTIOXIDANT LEVELS AND ANTHROPOMETRIC PARAMETERS OF HEALTHY INDIVIDUALS WITH FAMILY HISTORY OF TYPE2 DIABETES MELLITUS
Parameters | Type2history due to Mother N=25 | Type2history due to Father
N=35 |
t-test | p-value |
Fasting blood Sugar (mmol/L) | 4.5±0.4 | 4.4.9±0.38 | 0.080 | 0.936 |
Chromium (µg/L l) | 0.15±0.10 | 0.16±0.10 | -0.377 | 0.732 |
Zinc (µg/L) | 981.8±66 | 943±107 | 1.682 | 0.098 |
Mn (µg/L) | 0.9±0.47 | 0.7±0.4 | 2.016 | 0.49 |
Selenium (µg/L) | 121.6±35 | 100.8±34 | 50.8 | 0.278 |
Superoxide Dismutase (U/ml) | 6.6±1.1 | 6.9.±1.5 | -778. | 0.440 |
Catalase (U/ml) | 24.5±5 | 29±7 | 56.418 | 0.110 |
BMI kg/m2 | 23.7±3.5 | 25±3.3 | 48.652 | 0.332 |
WHR | 0.78±0.03 | 0.80±0.03 | 37.035 | 0.6567 |
P≤0.05 is significant
TABLE 3: SEX DISTRIBUTION OF SOME PARAMETERS OF THE FIRST GENERATION OFFSPRING OF TYPE-2 DIABETIC PARENTS
Groups | FPG | Chromium | Zinc | Manganese | Selenium | SOD | CAT | BMI | WHR |
FM n=14 | 4.5±0.5 | 0.13±0.09 | 987±56 | 0.9±0.5 | 115±29 | 7.0±1.1 | 25.7±6.8 | 25±3 | 0.8±0.05 |
MM n= 11 | 4.48±0.3 | 0.18±0.11 | 975±80 | 0.9±0.4 | 130±41 | 6.0±0.9 | 23±5 | 25.5±2.4 | 0.79±0.04 |
FF(n=15) | 4.5±0.4 | 0.18±0.10 | 942±103 | 0.7±0.4 | 95.4±29 | 7.0±1.6 | 28±6.5 | 25.5±2.5 | 0.78±0.03 |
MF(n=20)
FM vs MM FM vs FF FM vs MF MM vs MF FF vs MF FF vs MM F-Value p-value |
4.4±0.4
P=0.846 P= 0.970 P=0.760 P=0.940 P=0.725 P=0. 817 0.56 0.982 |
0.15±0.10
P=0.270 P=0. 215 P=0. 665 P=0. 432 P=0.361 P=0. 966 0.735 0.536 |
945±113
P=0. 751 P=0.207 P=0. 206 P=0. 401 P=0. 934 P=0. 387 0.821 0.488 |
0.7±0.4
P=0. 852 P=0. 144 P=0. 107 P=0. 192 P=0. 955 P=0. 236 1.374 0.260
|
105±35
P=0.287 P=0. 133 P=0. 406 P=0. 058 P=0. 425 P=0. 015 2.353 0.082 |
6.8±1.4
P=0.110 =0.720 P=0.857 P=0.121 P=0. 837 P=0.195 1.076 0.367 |
30±8.0
P=0. 348 P=0. 082 P=0. 076 p=0. 009 p=0. 371 p=0. 082 2.727 0.053 |
25.5±2.9
P=0.549 P=0.571 P=0.173 P=0. 529 P=0. 435 P=0. 938 0.652 0.585 |
0.79±0.04
P=0.613 P=0.447 P=0.641 P=0.912 P=0.723 P=0.841 0.205 0.893 |
Key: FPG; Fasting plasma glucose, SOD: Superoxide dismutase, CAT: Catalase, P≤0.05 is significant, FM: FEMALES FROM DIABETIC MOTHERS, MM; Males from diabetic mothers, FF; Females from diabetic fathers, mf; males from diabetic fathers
DISCUSSION: Family medical history of diabetes is an important factor worthy of consideration in the event to prevent and manage diabetes mellitus. Individuals who have a family history of diabetes tend to have a higher risk of type 2 diabetes (T2DM) compared with individuals with no family history of type 2 diabetes 38-40. Katulanda et al. noted the prevalence of diabetes was 23% higher in patients with a family history of diabetes 41.
Although this study revealed that both subjects with and without a family history of type2 diabetes (T2DM) had normal fasting plasma glucose levels, the plasma means the level of glucose was significantly higher (P=0.0001) in those subjects with a family history of T2Dm (4.5±0.4) when compared with those without a family history (4.2±0.3).
This is in accordance with the work of Marianne et al., who observed that individuals with a family history of diabetes had a significantly higher concentration of glucose than individuals without a family history of diabetes 42.
This increase in plasma glucose level of those with a family history of Type2 diabetes is also in agreement with the work of Allison et al., who demonstrated that non-diabetic offspring of diabetic parents have modest hyperglycemia, even within the normal range, which may contribute to attenuated endothelial function since they have impaired endothelium-dependent vasodilation and lower nitric oxide that lead to cardiovascular risk in advance to the development of overt diabetes 43. The increase in glucose may be due to insulin resistance, according to Akbar et al., who observed a high prevalence of insulin resistance among the young subjects with a positive family history of diabetes during the evaluation of cardiac autonomic function in non-diabetic offspring of type 2 diabetes mellitus patients through assessment of heart rate variability 44. Insulin resistance plays an important role in the pathogenesis of type 2 diabetes; the two principal components of the blood glucose regulation path-way are insulin secretion and insulin sensitivity.
Moreover, a significantly lower mean serum level of chromium was observed in subjects with a family history of type 2 diabetes (0.16±0.10mcg/l) compared with the control (0.25±0.22) (p=0.004). Some researchers have earlier reported chromium to improve insulin receptor /post-receptor signaling 45. Chromium potentiates the actions of insulin, augments the insulin signaling pathway, blunts the negative-regulators of insulin signaling, enhances AMPK activity, up-regulating cellular glucose uptake, and attenuates oxidative stress 46. Reduced chromium levels may contribute to explain why those with family history of T2Dm have higher mean glucose level than those without family history of T2D as observed in this study. This also may be a contributing factor to the pathogenesis of insulin resistance and the development of diabetes mellitus as often observed among the offspring of diabetic parents. However, the mean serum levels of selenium of males from diabetic mothers (mm) (130±41 µg/L) were significantly higher (p=0.015) when compared with mean serum levels of selenium of females from diabetic fathers (ff) (95.4±29 µg/L ).
It has been previously shown that an excessive amount of selenium in the body is associated with the pathogenesis of insulin resistance and the development of diabetes mellitus 23. It is known that selenium at plasma concentrations in the range of 80-120 μg/L 47 acts as an antioxidant and insulin-mimetic nutrient and favors the synthesis and action of insulin. However, at plasma levels above 120 μg/L, selenium may loss its function as an antioxidant as a result of dysregulation of the redox state which can compromise the chemical interactions involved in the insulin signaling cascade. This outcome may elucidate that male offspring from diabetic mothers may have impaired glucose metabolism and increased risk of T2D due to selenium supporting the hypothesis that the risk of T2D is higher in the offspring if the mother rather than the father has type 2 diabetes 48.
The serum mean levels of serum superoxide dismutase and catalase of those with a family history of T2DM and those without family history were (6.8±1.4 and 6.9±1.4) and (27.2±7.2 and 29±10) respectively. These results showed no significant difference when compared (p=0.849 and p= 0.270), respectively. However, the mean serum levels of catalase of males from diabetic mothers were significantly decreased compared to males from diabetic fathers (p=0.009). This further suggests that pancreatic islets of male offspring of diabetic mothers contain a relatively smaller amount of catalase which could further predispose their β-cell as an easy target for reactive oxygen species that may increase insulin resistance and impair pancreatic β-cell function 49. Given this existing data, it is reasonable to hypothesize that a significant low level of catalase in male offspring of diabetic mothers with type 2 Dm may predispose males more to insulin resistance, glucose intolerance, and subsequent to Diabetics than the females from diabetic mothers.
Demographic and anthropometric characteristics of the study group and the control group without a family history of DM showed that there were no significant differences in any of demographic or anthropometric characteristics between the 2 groups. This is in agreement with the work of Akbar et al., who documented similar results in their study 44.
Obesity is a predisposing factor of importance in diabetes mellitus affecting the population of all age groups and socio-economic levels in both developed and developing countries. It is known to be a contributory risk factor for several disease states, including diabetes mellitus 50. The mean levels of the anthropometric parameters such as BMI and WHR of the studied population showed no significant difference when compared with the control group, and this may be as a result of the fact that means values showed the individuals were not obese.
CONCLUSION: The trace elements assayed in this study revealed significantly lower chromium levels in subjects with a family history of T2D compared to non-diabetic history subjects. Male offspring of diabetic mothers showed significantly lower serum levels of catalase and lower serum levels of selenium compared to females from diabetic fathers and males from diabetic fathers, respectively. Males from diabetic mothers may be at a greater risk of developing insulin resistance, glucose intolerance, and subsequently diabetes in the future, considering the respective roles of the trace elements and antioxidants in glucose metabolism.
RECOMMENDATION: Having observed the slight alteration in the levels of glucose and chromium in the subjects with a family history of T2DM and significant changes in serum levels of selenium and catalase of male offspring of diabetic mothers. Maternal diabetic history may be a serious risk factor of diabetes mellitus, and we recommend that more work should be done on male subjects whose mothers are diabetic with a wider and larger population may however, be necessary to collaborate these findings.
ACKNOWLEDGEMENT: The authors wish to acknowledge the sincere efforts, willingness and dedication shown by the participants of this study which was instrumental to the success of this study.
FUNDING: No funding sources
CONFLICTS OF INTEREST: None declared
REFERENCES:
- Kiani F, Naz MSG, Sayehmiri F, Sayehmiri K and Zali HJD: The risk factors of gestational diabetes mellitus: a systematic review and meta-analysis study. Diabetes 2017; 10: 17.
- Alharithy MK, Alobaylan MM, Alsugair ZO and Alswat K: AJEP: Impact of Family History of Diabetes on Diabetes Control and Complications. Endocrine Practice 2018; 24(9): 773-79.
- Khan IA, Jahan P, Hasan Q and Rao PJD: Genetic confirmation of T2dm meta-analysis variants studied in gestational diabetes mellitus in an indian population. Diabetes and Metabolic Syndrome: Clinical Research and Reviews 2019; 13(1): 688-94.
- Rodrigues MRK, Lima SAM, Da Silvia MGMF, Calderon IMP, Magalhães CG, Ferraz GAR, Molina AC, De Araújo Costa RA, Nogueira VDSN and Rudge MVCJPO: Efficacy of Vitamin D supplementation in gestational diabetes mellitus: systematic review and meta-analysis of randomized trials. PLoS One 2019; 14(3): e0213006.
- Ginsburg SG, Wu RR and Orlando LA: Family health history: underused for actionable risk assessment. Lancet 2019: 394(10198): 596-603.
- Valdez R, Yoon PW, Qureshi N, Green RF and Khoury MJ: Family history in public health practice: A genomic tool for disease prevention and health promotion. Annual Revision of Public Health 2010; 31: 69-87.
- Xu F, Wang Y, Ware RS, Tse LA, Dunstan DW and Liang Y: Physical activity, family history of diabetes and risk of developing hyperglycaemia and diabetes among adults in mainland China. Diabetes Medicine 2011; 21(12): 65-77.
- Valdez R, Yoon PW, Liu T and Khoury MJ: Family history and prevalence of diabetes in the U. S. population: The 6-year results from the National Health and Nutrition Examination Survey (1999-2004). Diabetes Care 2007; 30: 2517-22.
- Ogbodo EC, Okafor CC, Ogah HGO, Ezeugwunne IP, Igwebuobi CF, Okezie AO, Agada UN, Amah AK and Odumodu IO: Thyroid hormone profiling and enzymatic antioxidant status in diagnosis and management of Type-II-diabetes mellitus: a review of literature. World Journal of Pharmaceutical and Life Sciences 2019; 5(12): 06-21.
- American Diabetes Association: Standards of Medical Care in Diabetes - 2016. Diabetes Care 2016; 39 (Supplement1): S1-S112.
- International Diabetes Federation: IDF Diabetes Atlas; 8th Belgium: International Diabetes Federation 2017.
- Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, Colagiuri S, Guariguata L, Motala AA, Ogurtsova K, Shaw JE, Bright D and Williams R: On behalf of the IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Research and Clinical practice 2019; 157: 107843.
- Maret W: Zinc in Pancreatic Islet Biology, Insulin Sensitivity, and Diabetes. Preventive Nutrition and Food Science 2017; 22(1): 1-8
- Dubey P, Thakur V and Chattopadhyay M: Role of Minerals and Trace Elements in Diabetes and Insulin Resistance. Nutrients 2020, 12: 1864.
- Vincent JB: Quest for the molecular mechanisms of chromium action and its relationship to diabetes. Nutritional Revision 2000; 58: 67-72.
- Waltr-Monika K, Zimmermann MB, Spinas GA and Hurrell RF: Low plasma magnesium in type 2 diabetes. Swiss Medical Weekly 2003; 133: 289-92.
- Kruse-Jarres JD and Rukguaer M: Trace Elements in Diabetes Mellitus; Peculiarities and Clinical Validity of determinations of red blood cells. Journal of Trace Elements in Medical Biology 2000; 14: 21-27.
- Norouzi S, Adulcikas J, Sohal SS and Myers S: Zinc stimulates glucose oxidation and glycemic control by modulating the insulin signaling pathway in human and mouse skeletal muscle cell lines. PLoS ONE 2018; 13(1): e0191727.
- Poudel RR, Bhusal Y, Tharu B and Kafle NK: Role of zinc in insulin regulation and diabetes. Journal of Social Health and Diabetes 2017; 5: 83-87.
- San Mauro MI, Ruiz LAM, Camina MMA, Garicano VE, Collado-Yurrita L, de Mateo-Silleras B and Redondo del Rio MP: Chromium supplementation in patients with type 2 diabetes and high risk of type 2 diabetes: A meta-analysis of randomized controlled trials. Nutricion Hospitalaria 2016; 33: 156-61.
- Huang H, Chen G, Dong Y, Zhu Y and Chen H: Chromium supplementation for adjuvant treatment of type 2 diabetes mellitus: Results from a pooled analysis. Molecular Nutrition and Food Research 2018; 62(1). doi: 10.1002/mnfr.201700438.
- Ogawa-Wong AN, Berry MJ and Seale LA: Selenium and Metabolic Disorders: An Emphasis on Type 2 Diabetes Risk. Nutrients 2016; 8: 80.
- Fontenelle CL, FeitosaMM, Silva Morais JB, SeveroSJ, Coelho de Freitas ET, Beserra BJ, Henriques SG and Dilina do Nascimento Marreiro: The role of selenium in insulin resistance. Brazilian Journal of Pharmaceutical Science 2018; 54(1): e00139.
- Chen H, Qiu Q, Zou C, Dou L and Liang J: Regulation of hepatic carbohydrate metabolism by selenium during diabetes. Chemico-Biological Interactions 2015; 232: 1-6.
- Zou C, Qiu Q, Chen H, Dou L and Liang J: Hepato-protective effects of selenium during diabetes in rats. Hum andan Experimental Toxicology 2016; 35(2): 114-23.
- Ekpenyong CE: Micronutrient deficiency, a novel nutritional risk factor for insulin resistance and Syndrom X. Archive of Food and Nutritional Sci 2018; 2: 016-030.
- Wang X, Zhang M, Lui G, Chang H, Zhang M, Liu W, Li Z, Liu Y and Huang G: Associations of Serum Manganese Levels with Prediabetes and Diabetes among _60-Year-Old Chinese Adults: A Population-Based Cross-Sectional Analysis. Nutrients 2016; 8: 497.
- Newsholme P, Keane NK, Carlessi R and Cruzat V: Oxidative stress pathways in pancreatic β-cells and insulin-sensitive cells and tissues: importance to cell metabolism, function, and dysfunction. American Journal of Physiology- Cell Physiology 2019; 317: C420-C433.
- Haghighatdoost F, Amini M, Feizi A and Iraj B: Are body mass index and waist circumference significant predictors of diabetes and prediabetes risk: Results from a population based cohort study. World Journal of Diabetes 2017; 8(7): 365-73.
- Tran NTT, Blizzard CL, Luong KN, Truong NLV, Tran BQ and Otahal P: The importance of waist circumference and body mass index in cross-sectional relationships with risk of cardiovascular disease in Vietnam. PLoS ONE 2018; 13(5): e0198202.
- Jezˇek P, Jabu° rek M and Plecita´-Hlavata L: Contribution of Oxidative Stress and Impaired Biogenesis of Pancreatic b-Cells to Type 2 Diabetes. Antioxidants and Redox Signaling 2019; 31(10): 722-51.
- Asif M: Role of heavy metals in human health and particularly in respect to diabetic patients. Tang 2017; 7(1): e1
- Tongzhang Z, Simin L, Yana B, Ning C and Stephone B: Current Understanding of the Relationship between Metal Exposures and Risk of Type 2 Diabetes. Current Research in Diabetes and Obesity Journal 2018; 7(2): 555710.
- Stein, MW: Methods of Enzymatic Analysis. Bergmeyer, H.K., ed. Academic prep. New York 1974; 1196-1201.
- Michael LB, Edward PF and Larry ES: Clinical Chemistry: Principle, Procedures, Correlations. 5th Philadelphia: Lippincott Williams and Wilkins 2005; 153-56.
- Misra HP and Fridovich I: The Role of Superoxide Anion in the Autoxidation of Epinephrine and a Simple Assay for Superoxide Dismutase. Journal of Biological Chemistry 1972; 247: 1972-3170.
- Sinha AK: Colorimetric assay of catalase. Analytical Biochemistry 1972; 47: 389-94.
- Chernausek SD, Arslanian S, Caprio S, Copeland KC, Kelsey MM, Koontz MB and Wilfley D: Relationship between parental diabetes and presentation of metabolic and glycemic function in youth with type 2 diabetes: baseline findings from the TODAY trial. Diabetes care 2016, 39(1): 110-17.
- Raghavan S, Pachucki MC, Chang Y, Porneala B, Fox CS, Dupuis J and Meigs JB: Incident Type 2 Diabetes Risk is influenced by Obesity and Diabetes in Social Contacts: a Social Network Analysis. Journal of General Internal Medicine 2016; 1-7. doi:10.1007/s11606-016-3723-1
- Vornanen M, Konttinen H, Kaariainen H, Mannisto S, Salomaa V, Perola M and Haukkala A: Family history and perceived risk of diabetes, cardiovascular disease, cancer, and depression. Preventive Medicine 2016; 90: 177-83.
- Katulanda P, Ranasinghe P, Jayawardena R, Sheriff R and Matthews DR: The influence of family history of diabetes on disease prevalence and associated metabolic risk factors among Sri Lankan adults. Diabetic Medicine 2016; 32(3): 314-23.
- Marianne AB, Gijs EL, Paul JM, Winston AS, Sana M, Ousman A and Keith PWJ: Family history: An opportunity for early interventions and improved control of hypertension, obesity and diabetes. Bulletin of the World Health Organization 2001; 79: 321-28.
- Allison B, Joshua A, Rebecca A and Mark Creeger A: Family History is a major determinant of endothelial function. Journal of the American College of Cardiology 2006; 47(12); 2456-2461.
- Akbar DH, Hegazi MA, Al Kudi HA and Ahmad MM: A Possible Early Alteration of Autonomic Activity Assessed By Heart Rate Variability: In Saudi Offspring of Type 2 Diabetic Patients. Saudi Journal of Internal Medicine 2011; 1(2): 17-23.
- Wiernsperger N and Rapin JR: Trace elements in glucometabolic disorders: an update. Diabetology and Metabolic Syndrome 2010; 2: 70.
- Hua Y, Clark S, Ren J and Sreejayan N: Molecular Mechanisms of Chromium in Alleviating Insulin Resistance. Journal of Nutritional Biochemistry 2012; 23(4): 313-19.
- Rayman MP: Selenium and human health. Lancet 2012; 379(9822): 1256-68.
- Valeriya L, Leif G and Rashmi BP9: Genetics of type2diabetes: It matters from which parents we inherit the risk. Review of Diabetic Studies 2015; 12(3-4): 233-42.
- Evans JL, Maddux BA and Goldfine ID: The molecular basis for oxidativestress-induced insulin resistance. Antioxidant and Redox Signalling 2005; 7: 1040-52.
- Al-Saleh E, Nandakumaran M, Al-Harmi J, Sadan T and Al-Enezi H: Maternal-fetal status of copper, iron, molybdenum, selenium, and zinc in obese pregnant women in late gestation. Biological Trace Element Research 2006; 113: 113-23.
How to cite this article:
Okwara JE, Agudi CC, Ogbodo EC, Njoku CM, Analike RA, Amah AK, Eze OO and Meludu SC: Evaluation of the serum levels of some trace elements and antioxidant levels in apparently healthy individuals with family history of type 2 diabetes in Nnewi, Nigeria. Int J Pharm Sci & Res 2021; 12(4): 2108-16. doi: 10.13040/IJPSR.0975-8232.12(4).2108-16.
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Article Information
15
2108-2116
620
631
English
IJPSR
J. E. Okwara, C. C. Agudi, E. C. Ogbodo *, C. M. Njoku, R. A. Analike, A. K. Amah, O. O. Eze and S. C. Meludu
Department of Medical Laboratory Science, Faculty of Health Sciences and Technology, Nnamdi Azikiwe University, Awka, Nigeria.
augustinee442@gmail.com
03 April 2020
09 October 2020
11 October 2020
10.13040/IJPSR.0975-8232.12(4).2108-16
01 April 2021