|
 
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| ORIGINAL ARTICLE |
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| Year : 2021 | Volume
: 5
| Issue : 4 | Page : 398-404 |
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Inflammatory response in relationship with the degree of hyperglycemia and expression of viral immune products in diabetes mellitus patients
Mathew Folaranmi Olaniyan, Tolulope Busayo Ojediran
Department of Medical Laboratory Science, Edo State University Uzairue, Edo State, Nigeria
| Date of Submission | 01-May-2021 |
| Date of Acceptance | 14-Jun-2021 |
| Date of Web Publication | 14-Dec-2021 |
Correspondence Address:
Mathew Folaranmi Olaniyan
Department of Medical Laboratory Science, Edo State University Uzairue, Edo State
Nigeria
 Source of Support: None, Conflict of Interest: None  | 2 |
DOI: 10.4103/bbrj.bbrj_68_21
Background: Diabetes mellitus (DM) is characterized by hyperglycemia which may cause dysfunction in immune response, which may affect the control of infectious agents. The objective of this study is therefore to determine inflammatory response in relationship with the degree of hyperglycemia and the expression of viral immune products in DM patients. Methods: The study population therefore included 151 DM patients (female 71; male 80; aged 43–76 years) and 100 (female 50; male 50; aged 40–76 years) apparently healthy nondiabetes control subjects. All subjects were negative to Giemsa thick blood film staining and Ziehl–Neelsen staining for acid fast bacilli. HIVP24 antigen antibody (Ag Ab), anti hepatitis C virus (HCV), and hepatitis B envelope antigen (HBeAg) were determined in the subjects by ELISA, while blood glucose was measured spectrophotometrically. Results: The frequency of 1.3% (2) HIVP24 Ag Ab, 4.6% (7) anti HCV, and 15.9% (24) HBeAg obtained in DM patients while a frequency 1% (1) HIVP24 Ag Ab. 6% (6) anti HCV, and 6% (6) HBeAg was obtained in non DM control subjects. There was an association between the expression of HIVP24 Ag Ab and DM considering the odds ratio (OR) of 1.329. There was no association between the expression of anti HCV and DM considering the OR of 0.7616 (OR 0.05). However, there was a significant association between the expression of HBeAg and DM considering the OR of 2.961 (OR >1.0; P< 0.05). Overall, 21.9% (33) of the DM expressed viral immune products; HBeAg was the most prevalent immune product in DM patients. There was a significantly higher plasma tumor necrosis factor alpha (TNFα) in DM patients with viral immune products than the results obtained in non DM without viral immune products(P < 0.05). There was a significantly higher difference in the value of TNFα in the degree of hyperglycemia of fasting blood glucose of 251–300 mg/dl compared with 201–250 mg/dl; 301–350 mg/dl compared with 201–250 mg/dl; 351–400 mg/dl compared with 201–250 mg/dl; 351–400 mg/dl compared with 251–300 mg/dl; 251–300 mg/dl compared with nondiabetic control; 301–350 mg/dl compared with nondiabetic control; and 351–400 mg/dl compared with nondiabetic control (P < 0.05). There was a significantly higher difference in the value of fasting blood glucose in the degree of hyperglycemia of fasting blood glucose of 301–350 mg/dl compared with 201–250 mg/dl; 351–400 mg/dl compared with 201–250 mg/dl; 201–250 mg/dl compared with nondiabetic control; 251–300 mg/dl compared with nondiabetic control; 301–350 mg/dl compared with nondiabetic control; and 351–400 mg/dl compared with nondiabetic control (P < 0.05). Conclusions: There was a significant increase in TNFα in diabetes patients, which increases as the degree of hyperglycemia increases and higher in diabetes patients who expressed viral immune product as there was a significant association between the expression of viral immune products, especially HBeAg and DM; hence, there was a significant relationship between inflammatory response, the degree of hyperglycemia, and the expression of viral immune products in DM patients.
Keywords: Inflammatory response, anti-hepatitis C virus, diabetes mellitus, hepatitis B envelope antigen, HIVp24 antigen-antibody, immune products, tumor necrosis factor-alpha
How to cite this article:
Olaniyan MF, Ojediran TB. Inflammatory response in relationship with the degree of hyperglycemia and expression of viral immune products in diabetes mellitus patients. Biomed Biotechnol Res J 2021;5:398-404 |
How to cite this URL:
Olaniyan MF, Ojediran TB. Inflammatory response in relationship with the degree of hyperglycemia and expression of viral immune products in diabetes mellitus patients. Biomed Biotechnol Res J [serial online] 2021 [cited 2023 Mar 23];5:398-404. Available from: https://www.bmbtrj.org/text.asp?2021/5/4/398/332464 |
| Introduction | |  |
Immune products are the substances or proteins that appear or shed into the serum following the invasion of viral agents in the body. Production of these proteins or substances is triggered by the presence of pathogenic virus which may be a natural response to the presence of foreign bodies.[1],[2],[3] The products that are normally proteins could be antigen in case of hepatitis B virus (HBV), hepatitis B surface antigen, and hepatitis B envelope antigen (HBeAg) shed into the blood or antibodies released in response to the infection of pathogenic organisms such as antibody to hepatitis C virus (anti-HCV) in HCV infection, antibody to human immunodeficiency virus (anti-HIV), and HIVp24 antigen-antibody (Ag-Ab) in the case of HIV infection and anti-HBe as antibody to HBeAg which are detectable through immunoassay techniques.[1],[2],[3]
Viral infections indicate the presence of viral agents such as HIV, HCV, and HBV in the body, which may be there as a commensal or pathogen, though most are pathogenic.[4],[5] A pathogenic virus is a virus that when it enters the body can release toxin to destroy tissue, multiply and resist the immunity of the host.[4],[5]
Diabetes mellitus (DM) is characterized by hyperglycemia over a period of time. DM is commonly treated by insulin. Insulin is a hypoglycemic hormone that stimulates the utilization of glucose by the body for the generation of energy through glycolysis in the form of ATP for body activities. Insulin aids the uptake of glucose by the cells. Insulin absolute or relative deficiency or resistance of the body to the action of insulin are the causes of DM.[6],[7],[8],[9] DM can occur when a pregnant woman without a previous history of diabetes develops hyperglycemia. DM patients are susceptible to infection, and infectious agents like virus can be a primary cause of DM, for example, HCV infection can make individuals develop type 2 diabetes and insulin resistance. Adequate understanding of how immune dysfunctions occur during hyperglycemia can reveal novel treatments and preventions for infectious diseases.[10],[11],[12] Insulin resistance can also be caused by an acute or chronic inflammation which can be indicated by elevated tumor necrosis factor-alpha (TNFα).[6],[7],[8],[9]
TNFα is an inflammatory cytokine that may also contribute to insulin resistance by promoting lipolysis, disrupting insulin signaling, and reducing the expression of GLUT4. On infection, macrophages release TNFα to alert other immune system cells as part of an inflammatory response. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homologous TNF domain.[10],[13],[14]
This work was therefore designed to determine inflammatory response in relationship with the degree of hyperglycemia and the expression of viral immune products in DM patients.
| Materials and Methods | | |
Study area
This work was carried out Owo in Ondo State. It is a local government headquarters of Owo Local Government. The town has primary, secondary, and tertiary health and educational institutions.
Study population
The calculated sample size was 151 using the 11% maximum of a range of 0.3%–11% prevalence of DM reported by Dahiru et al[11] in 2016 in Nigeria. Therefore, 151 (female - 71; male - 80; aged 43–76 years) diabetes patients attending DM Clinic of Federal Medical Centre, Owo, Nigeria, and 100 (female - 50; male - 50; aged 40–76 years) apparently healthy nondiabetes volunteers were studied as test and control subjects, respectively. All subjects were negative to Giemsa thick blood film staining and Ziehl–Neelsen staining for acid-fast bacilli (AFB).
Biological specimens
Fasting venous blood samples were obtained from each of the subjects into fluoride oxalate and lithium heparinized bottles for biochemical and immunochemical assays.
| Methods | | |
Hepatitis B envelope antigen ELISA
HBeAg was determined in the subjects by enzyme immunoassay using the reagent kit of Dia.Pro Diagnostic Bioprobes Srl Via Columella, Milano, Italy. Manufacturer's instructions were strictly followed and applied.
HIVp24 antigen and antibodies ELISA
HIVp24 antigen and antibodies were determined in the subjects using Bio-Rad Genscreen™ ULTRA HIV Ag-Ab qualitative enzyme immunoassay kit. Manufacturer's instructions were strictly followed and applied.
Anti-hepatitis C virus ELISA
Anti-HCV test was determined in the subjects using a third-generation enzyme immunoassay reagent kit of Dia.Pro Diagnostic Bioprobes Srl Via Columella, Milano, Italy. Manufacturer's instructions were strictly followed and applied.
Tumor necrosis factor-alpha ELISA
Plasma TNF-α was determined in the subjects by ELISA using Human ABCAM ELISA Kit. Manufacturer's instructions were strictly followed and applied.
Detection of acid-fast bacilli in sputum and identification of Plasmodium in blood
AFB in the sputum and identification of Plasmodium in the blood were determined in the subjects by the method described by Cheesbrough.[12]
Fasting blood glucose
Blood glucose was measured in the subjects by glucose oxidase method using Randox reagent kit. Manufacturer's instructions were strictly followed and applied.
Ethical consideration
The proposal was reviewed by the Research and Ethics Committee of the Department of Medical Laboratory Science, Achievers University, Owo, Nigeria, and approved before the commencement of the work (MLS/AUO/VI/132). The consent of each subject was also obtained.
Statistical analysis
The result was subjected to statistical analysis using SPSS 20.0 (IBM, New York SPSS ) to determine mean, standard deviation, frequency, odds ratio (OR), “t” test, and probability value at 0.05 level of significance.
| Results | | |
The frequency of 1.3% (2) HIVP24 Ag Ab, 4.6% (7) anti HCV, and 15.9% (24) HBeAg obtained in DM patients while a frequency 1% (1) HIVP24 Ag Ab. 6% (6) anti HCV, and 6% (6) HBeAg was obtained in non DM control subjects. There was an association between the expression of HIVP24 Ag-Ab and DM considering the OR of 1.329. There was no association between the expression of anti-HCV and DM considering the OR of 0.7616 (OR <1.0; P > 0.05). However, there was a significant association between the expression of HBeAg and DM considering the OR of 2.961 (OR >1.0; P < 0.05) [Table 1] and [Figure 1]. Overall, 21.9% (33) of the DM expressed viral immune products [Table 1] and [Figure 1]. HBeAg is the most prevalent immune product in DM patients. | Table 1: Frequency of immune products, odds ratio, and probability value obtained in the subjects
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There was a significantly higher plasma TNFα in DM patients with viral immune products than the results obtained in non-DM without viral immune products [P < 0.05; [Table 2], [Table 3] and [Figure 2]]. There was a significantly higher plasma TNFα in non-DM with viral immune product than in non-DM without viral immune product [P < 0.05; [Table 2] and [Table 3]]. However, there was no significant difference in the value of TNFα in total DM patients versus total non-DM control; DM with viral immune products versus DM without viral immune product; DM with viral immune products versus non-DM with viral immune product; and DM without immune product versus non-DM without immune product [P > 0.05; [Table 2], [Table 3] and [Figure 2]]. | Figure 2: Comparative description of plasma tumor necrosis factor-alpha in relationship with the expression of viral immune products
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 | Table 2: Plasma tumor necrosis factor-alpha in relationship with the expression of viral immune products
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 | Table 3: Results of the comparative analysis of plasma tumor necrosis factor-alpha in relationship with the expression of viral immune products in the subjects
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There was a significantly higher difference in the value of TNFα in the degree of hyperglycemia of fasting blood glucose of 251–300 mg/dl compared with 201–250 mg/dl; 301–350 mg/dl compared with 201–250 mg/dl; 351–400 mg/dl compared with 201–250 mg/dl; 351–400 mg/dl compared with 251–300 mg/dl; 251–300 mg/dl compared with nondiabetic control; 301–350 mg/dl compared with nondiabetic control; and 351–400 mg/dl compared with nondiabetic control [P < 0.05; [Table 4], [Table 5] and [Figure 3]]. | Figure 3: Comparative description of plasma fasting glucose and tumor necrosis factor-alpha in relationship with the degree of hyperglycemia in diabetes mellitus and nondiabetes mellitus subjects who do not expressed any of the immune products
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 | Table 4: Plasma fasting glucose and tumor necrosis factor-alpha in relationship with the degree of hyperglycemia in diabetes mellitus and nondiabetes mellitus subjects who do not expressed any of the immune products
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 | Table 5: Results of the comparative analysis of plasma fasting glucose and tumor necrosis factor-alpha in relationship with the degree of hyperglycemia in diabetes mellitus and nondiabetes mellitus subjects who do not expressed any of the immune products
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There was a significantly higher difference in the value of fasting blood glucose in the degree of hyperglycemia of fasting blood glucose of 301–350 mg/dl compared with 201–250 mg/dl; 351–400 mg/dl compared with 201–250 mg/dl; 201–250 mg/dl compared with nondiabetic control; 251–300 mg/dl compared with nondiabetic control; 301–350 mg/dl compared with nondiabetic control; and 351–400 mg/dl compared with nondiabetic control [P < 0.05; [Table 4], [Table 5] and [Figure 3]].
However, there was no significant difference in the plasma value of plasma TNFα of patients with the degree of hyperglycemia of blood glucose 201–250 mg/dl compared with nondiabetic control; 251–300 mg/dl compared with 301–350 mg/dl; and 301–350 mg/dl compared with 351–400 mg/dl control [P > 0.05; [Table 3], [Table 5] and [Figure 3]]. Furthermore, there was no significant difference in the plasma value of plasma fasting glucose of patients with the degree of hyperglycemia of blood glucose 201–250 mg/dl compared with 251–300 mg/dl; 251–300 mg/dl compared with 301–350 mg/dl; 251–300 mg/dl compared with 351–400 mg/dl; and 301–350 mg/dl compared with 351–400 mg/dl [P > 0.05; [Table 4], [Table 5] and [Figure 3]].
| Discussion | | |
This work has revealed an inflammatory response in relationship with the degree of hyperglycemia and the expression of viral immune products in DM patients as discussed in the following paragraphs.
The frequency of 1.3% (2) HIVP24 Ag Ab, 4.6% (7) anti HCV, and 15.9% (24) HBeAg obtained in DM patients while a frequency 1% (1) HIVP24 Ag Ab. 6% (6) anti HCV, and 6% (6) HBeAg was obtained in non DM control subjects. There was an association between the expression of HIVP24 Ag-Ab and DM. There was no association between the expression of anti-HCV and DM. However, there was a significant association between the expression of HBeAg and DM. Overall, 21.9% (33) of the DM expressed viral immune products, with HBeAg being the most prevalent immune product in DM patients.
Expression of viral immune products in diabetes patients can be associated with the findings that viral infection as an environmental factor can trigger DM and that several viruses have been implicated in diabetes. It has also been reported that DM patients are more prone to infection.[15],[16],[17],[18],[19] Rouabhia et al.[20] also reported that the prevalence of DM was higher in HCV-infected patients compared with HBV-infected patients (39.1% vs. 5%), which also supported the association between DM and viral infections as found in this work. However, the report does not agree with the findings of this work that the most prevalent viral infection was HBV as expressed by HBeAg. Ndako et al.[22] also reported a slightly higher prevalence of hepatitis C infection in diabetic patients attending a tertiary healthcare facility, South-west Nigeria.
In this work, the immune products expressed by the DM patients studied include HIVP24 Ag-Ab which is expressed in the plasma upon HIV infection; anti-HCV which is detectable in the blood following HCV infection; HBeAg is a viral protein expressed due to hepatitis B viral infection which also indicates active HBV replication, and the infected person is highly infectious.[22]
In addition, hyperglycemia in diabetes has been reported to be responsible for the dysfunction of the immune response that made it impossible to control the spread of pathogenic organisms in DM patients making the affected individuals more susceptible to invasion of pathogenic microbes.[22]
In addition, microbes survive more in the environment with high glucose concentration as they also need glucose for energy.[18],[22]
Antibody to HCV (anti-HCV) and HBeAg were the more prevalent immune products in DM patients with insulin resistance and DM patients without insulin resistance but higher in DM patients with insulin resistance. These findings could be associated with hyperglycemia and that the prevalence of HCV and especially HBV was higher than HIV infection.[21],[22]
Further, the most prevalent immune product in DM patients was HBeAg; however, higher frequency was found in DM patients with insulin resistance compared to DM patients who were not resisting the action of insulin. Envelope antigen to HBV (HBeAg) is an indication that the virus is highly active, replicating, and infectious. Diabetes mellitus may activate previous and dormant HBV infection because one of the complications of diabetes is immune dysfunction which may make it difficult for the system to produce antibody required for the clearance of the viral antigen to inactive the organism and stop replication. It may also be due to the susceptibility of diabetic patients to HBV infection as HBeAg may also indicate recent infection.[20],[21]
The frequency of DM patients with insulin resistance among the DM recruited for this study was 27.8% (42 out of 151). This frequency of insulin resistance in this study was higher than the prevalence of 24.1% and 21.1% in HIV-infected participants compared to 8.5% and 4.6% in the HIV-uninfected controls reported by Dadaa et al.,[19] among patients attending the HIV clinic in a Nigerian tertiary hospital.
There was a significantly higher plasma TNFα in DM patients with viral immune products than the results obtained in non-DM without viral immune products. There was a significantly higher plasma TNFα in non-DM with viral immune products than in non-DM without viral immune product. This can be attributed to the fact that infection is a major trigger of TNFα which is an inflammatory cytokine. If macrophages (certain white blood cells) detect an infectious pathogenic agent, they release TNFα to alert other immune system cells as part of an inflammatory response.[10],[13],[14]
Elevated TNFα can also be linked with the inflammation of the liver by HIV as it infects all organs and especially inflammation of the liver by HBV and HCV as they are hepatotoxic viruses to cause viral hepatitis which can lead to the release of TNFα which stimulates acute phase response, leading to an increase in C-reactive protein and a number of other mediators.[10],[13],[14]
Elevated TNFα in this work is consistent with the report that an inflammatory response occurs because of the immune response to hyperglycemia, invasion of viral agents, as well as the presence of inflammatory mediators produced by adipocytes and macrophages in fat tissue.[10],[13],[14]
There was a significantly higher difference in the value of TNFα in the degree of hyperglycemia of fasting blood glucose of 251–300 mg/dl compared with 201–250 mg/dl; 301–350 mg/dl compared with 201–250 mg/dl; 351–400 mg/dl compared with 201–250 mg/dl; 351–400 mg/dl compared with 251–300 mg/dl; 251–300 mg/dl compared with nondiabetic control; 301–350 mg/dl compared with nondiabetic control; and 351–400 mg/dl compared with nondiabetic control.
Hyperglycemia in diabetes has been reported to be responsible for the dysfunction of the immune response in the affected patients[6],[7],[8],[18],[21],[22] and especially inflammatory process causing an increase in plasma TNFα which is consistent with the results obtained in this work that found elevated plasma level TNFα with increase in the degree of hyperglycemia.[6],[7],[8],[18],[21],[22] Another reason for elevated TNFα in hyperglycemia is that hyperglycemia favors the survival of pathogens and malignant cell growth by providing energy to cancer cells that can generate inflammatory process, leading to elevated inflammatory cytokine such as TNFα.[23]
There was a significantly higher difference in the value of fasting blood glucose in the degree of hyperglycemia of fasting blood glucose of 301–350 mg/dl compared with 201–250 mg/dl; 351–400 mg/dl compared with 201–250 mg/dl; 201–250 mg/dl compared with nondiabetic control; 251–300 mg/dl compared with nondiabetic control; 301–350 mg/dl compared with nondiabetic control; and 351–400 mg/dl compared with nondiabetic control. This can be explained with the fact that DM is characterized by hyperglycemia of which the degree and severity vary with increase in blood glucose.[6],[7],[8],[18],[21],[22]
| Conclusion | | |
There was a significant increase in TNFα in diabetes patients which increases as the degree of hyperglycemia increases and higher in diabetes patients who expressed viral immune product as there was a significant association between the expression of viral immune products, especially HBeAg and DM; hence, there was a significant relationship between inflammatory response, the degree of hyperglycemia, and the expression of viral immune products in DM patients.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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