|Year : 2020 | Volume
| Issue : 4 | Page : 306-310
Evaluation of carbohydrate antigen 19-9 levels in subjects with diabetes mellitus in Nnamdi Azikiwe university teaching hospital, Nnewi, Nigeria
PO Manafa1, EC Okoye1, O Ekuma-Okereke1, RN Ukibe1, C Ibe1, CR Chukwuanukwu1, OG Chukwuma1, EK Nwene2, SR Ebugosi3, IV Manafa4, CC Manafa5
1 Department of Medical Laboratory Science, Faculty of Health Sciences and Technology, Nnamdi Azikiwe University, Nnewi Campus, Nnewi, Nigeria
2 Center for Clinical Research in Nigeria, Enugu State, Nigeria
3 Department of Biochemistry, Tansian University, Umunya, Anambra State, Nigeria
4 Department of Pathology, Clinical Biochemistry, East Kent Hospital University, NHS Foundation Trust, Kent
5 Department of Respiratory Medicine, Royal Sussex County Hospital, Brighton, England, UK
|Date of Submission||05-Jun-2019|
|Date of Decision||01-Dec-2019|
|Date of Acceptance||03-Dec-2019|
|Date of Web Publication||20-Jul-2020|
Department of Medical Laboratory Science, Faculty of Health Sciences and Technology, Nnamdi Azikiwe University, Nnewi Campus, Nnewi, Anambra State
Source of Support: None, Conflict of Interest: None
Background of Study: Diabetes mellitus (DM) is a multisystemic disorder characterized by hyperglycemia and damage to vital organs most notably the exocrine tissue and islet cells. Carbohydrate antigen 19-9 (CA 19-9) is a glycolipid antigen produced by the exocrine pancreas. Thus, it could be a useful indicator of the intensity of cellular damage to the exocrine pancreas by disease conditions such as DM. Aim: This was a case–control study aimed at evaluating the serum level of CA 19-9 as a diagnostic tool in patients with DM. Materials and Methods: A total of 90 patients aged 20–70 years were randomly selected in this study. They comprised 50 diabetic individuals as test patients and 40 aged-matched apparently healthy individuals as controls. The fasting plasma glucose (FPG) levels were determined spectrophotometrically using the glucose oxidase method, whereas the serum level of CA 19-9 was estimated photometrically using the sandwich enzyme-linked immunosorbent assay technique. Results: There was a statistically significant elevation of CA 19-9 in patients with DM compared to the nondiabetic individuals (P < 0.05). The correlation coefficient between CA 19–9 levels and age in patients with DM showed a nonsignificant positive relationship (r = 0.265, P = 0.063). A nonsignificant positive correlation was also observed when the mean level of CA 19-9 was correlated with the mean plasma level of FPG in patients with DM (r = 0.021, P = 0.884). Conclusion: The significantly elevated serum level of CA 19-9 along with its positive correlation with FPG indicates the need for a careful evaluation of blood glucose regulation while suggesting that CA 19–9 could be a suitable marker to predict chronic inflammatory complications in patients with DM. Hence, further evaluation with a duration of diabetes and glycemic control using glycated hemoglobin to ascertain the relevance of CA 19–9 in glycemic control in individuals with DM.
Keywords: Carbohydrate antigen 19-9, diabetes mellitus, fasting plasma glucose
|How to cite this article:|
Manafa P O, Okoye E C, Ekuma-Okereke O, Ukibe R N, Ibe C, Chukwuanukwu C R, Chukwuma O G, Nwene E K, Ebugosi S R, Manafa I V, Manafa C C. Evaluation of carbohydrate antigen 19-9 levels in subjects with diabetes mellitus in Nnamdi Azikiwe university teaching hospital, Nnewi, Nigeria. Med J DY Patil Vidyapeeth 2020;13:306-10
|How to cite this URL:|
Manafa P O, Okoye E C, Ekuma-Okereke O, Ukibe R N, Ibe C, Chukwuanukwu C R, Chukwuma O G, Nwene E K, Ebugosi S R, Manafa I V, Manafa C C. Evaluation of carbohydrate antigen 19-9 levels in subjects with diabetes mellitus in Nnamdi Azikiwe university teaching hospital, Nnewi, Nigeria. Med J DY Patil Vidyapeeth [serial online] 2020 [cited 2020 Sep 27];13:306-10. Available from: http://www.mjdrdypv.org/text.asp?2020/13/4/306/290160
| Introduction|| |
Diabetes mellitus (DM), commonly known as diabetes, is a group of metabolic disorders, with common symptoms of hyperglycemia. DM is increasing worldwide along with the increase of obesity. It has become a well-known risk factor for inflammatory diseases, including pancreatic disorders, most notably pancreatic cancer. The incidence of pancreatic cancer is also increasing and has one of the lowest survival rates of all cancers.
Carbohydrate antigen 19-9 (CA 19-9) is a glycolipid antigen that is characterized by the monoclonal antibody binding to CA 19-9, a tumor surface marker of Sialyl Lewis A. CA 19-9, also known as cancer antigen 19-9, is expressed by the exocrine pancreas in vivo. It is a tumor-associated antigen that was originally defined by a monoclonal antibody produced by hybridoma prepared from murine spleen cells immunized with a human colorectal cancer cell line. Although increased serum CA 19-9 level is known to be associated with pancreatic cancer, increased serum levels have been reported in benign cases such as inflammatory conditions of the hepatobiliary system, thyroid disease, acute and chronic pancreatitis, DM, and interstitial pulmonary disease. Therefore, CA 19-9 is used in the diagnosis of pancreatic cancer, but it is also a marker of pancreatic tissue damage that might be caused by diabetes. In addition, CA 19-9 is not expressed in individuals who lack Lewis antigen (a blood type antigen on red blood cells), which is about 10% of the Caucasian population. This is because of the deficiency of a fucosyltransferase enzyme that is needed to produce CA 19-9 as well as Lewis antigen. Several studies have shown a correlation between postoperative decline in CA 19-9 levels and the duration of patient survival. Individuals whose CA 19-9 normalized postoperatively may live longer, whereas rising CA 19-9 levels may correlate with shorter survival times.
DM and CA 19-9 seem to be structurally and functionally related in which DM is a chronic inflammatory disease of the pancreas, whereas CA 19-9 is a marker of pancreatic tissue damage. Therefore, CA 19-9 could be an effective indicator of insulin resistance and glycemic metabolism in patients with DM. The mechanisms of DM, including glucose intolerance, insulin resistance, and destruction of islet beta cells, could be effectively expressed by CA 19-9. This is because CA 19-9 long-term poor glycemic control may lead to pancreatic β-cell dysfunction, thereby affecting the systemic expression of CA 19-9. Thus, CA 19-9 levels could be an effective indicator of insulin resistance and glycemic metabolism in patients with DM, a disorder characterized by pancreatic exocrine deficiency. Hence, the result obtained from this work may be useful in evaluating the functional status of the pancreas in DM. It may also be valuable in the prognostic management of patients with DM. Hence, the aim of this study is to evaluate the serum level of CA 19-9 in patients with DM obtainable through the following objectives:
- By determining the plasma glucose level of patients with DM and nondiabetic individuals
- By evaluating the serum level of CA 19-9 in both diabetic and nondiabetic patients
- By correlating the serum level of CA 19-9 with age and fasting plasma glucose (FPG) in test patients.
Diabetes is increasing all over the world along with the increase of obesity and associated diseases as well as pancreatic cancer. The incidence of pancreatic cancer also increases and has one of the lowest survival rates of all cancers.
Justification of research problem
Ca-19–9 is widely known for its use in the diagnosis of pancreatic cancer, but it is also a marker of pancreatic tissue damage which might be caused by diabetes. The association between diabetes, pancreatic cancer, and elevated levels of CA-19-9 has not been well investigated, hence, the need for this research.
| Materials and Methods|| |
This was a case–control study designed to evaluate the serum level of CA 19-9 in patients with DM in the Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, Anambra State, Nigeria. A total of 90 patients aged 20–70 years were recruited for this study. Fifty participants were patients with DM, whereas 40 were apparently healthy nondiabetic individuals.
Subjects and sampling
Subjects with DM aged 20-70 years and apparently healthy age-matched individuals were recruited for this study as test and control subjects respectively. The participants were recruited whether or not they were on therapy, and the study did not exclude Lewis-negative patients. Patients outside the age range of 20–70 years and patients with known pancreatic and gastrointestinal tract disorders were excluded from the study.
Five milliliters of venous blood was collected aseptically from each of the patients. Two milliliters of the blood was dispensed in a fluoride oxalate container for the determination of FPG levels. The remaining 3 ml of blood was dispensed in a plain bottle and allowed to clot, and the serum obtained after centrifugation was used for the evaluation of CA 19-9 level.
The ethical approval for this research was obtained from the Ethics Committee of NAUTH, Nnewi, Anambra State. Consent was sought for and obtained from the participants before the commencement of the study.
FPG levels were estimated by the glucose oxidase method as described by Carl et al., whereas the level of CA 19-9 was estimated by the sandwich Enzyme-linked immunosorbent assay technique as described by Karen et al.
The statistical analysis was performed using the Mann–Whitney U-test and Pearson correlation coefficient. Values were deemed statistically significant when P < 0.05.
| Results|| |
The mean plasma level of FPG was significantly higher (P < 0.05) in patients with DM compared with the control group [Table 1].
|Table 1: Mean rank of fasting plasma glucose level in patients with diabetes mellitus and the control group|
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The mean serum level of CA 19-9 was statistically significantly higher (P = 0.019) in patients with DM compared with the controls [Table 2].
|Table 2: Mean rank level of carbohydrate antigen 19-9 in patients with diabetes mellitus and the control group|
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A nonsignificant positive correlation was observed between CA 19- 9 levels and age in patients with DM (r = 0.265, P = 0.063) [Figure 1].
|Figure 1: Correlation of carbohydrate antigen 19-9 levels and age in patients with diabetes mellitus. (r = 0.265 and P = 0.063)|
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A nonsignificant positive correlation was observed between CA 19–9 levels and FPG levels in patients with DM (r = 0.021, P = 0.884) [Figure 2].
|Figure 2: Correlation of carbohydrate antigen 19–9 levels and fasting plasma glucose levels in patients with diabetes mellitus (r = 0.021 and P = 0.884)|
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| Discussion|| |
DM is a metabolic disorder characterized by insulin deficiency, cellular resistance to insulin action, or both resulting in hyperglycemia and other related metabolic disturbances. Most of these conditions damage exocrine tissue and islet cells. CA 19-9 is typically used as a screening tool to diagnose pancreatic cancer and as a marker of pancreatic tissue damage.
In this study, it was observed that the mean serum level of CA 19-9 was significantly higher in patients with DM compared with the nondiabetic control group. The significantly elevated mean level of CA19-9 may suggest cellular dysfunction, most notably exocrine dysfunction. This is because most pancreatic exocrine insufficiency is predominantly associated with a considerable percentage of patients with diabetes., As a result, the increase of serum CA19-9 level might parallel the intensity of cellular functional disorders. This is in accordance with the findings provided in literature.,,,,,, Futhermore, Blumenthal et al. also demonstrated the same findings, adding that CA19-9 level in Type 1 diabetes was higher than in Type 2 diabetes. More so, there are no capsules or basement membranes around islets, and there are cell-to-cell contacts between exocrine and endocrine cells. Direct connections also exist between the capillaries of islets and acinar that underlie the regulatory connections between islet hormones and exocrine pancreatic secretion as insulin directly enters the acinar cells. CA 19-9 levels have also been postulated to have interaction between the exocrine and endocrine pancreatic cells., Hyperglycemia may, therefore, have deleterious effects on the exocrine pancreas in addition to the endocrine pancreas as demonstrated by the significant elevation of CA 19-9 in diabetic individuals than nondiabetic individuals.
Furthermore, a nonsignificant positive correlation was observed between the levels of CA 19-9 and age in patients with DM. This finding suggests that age could be a predisposing factor to cellular dysfunction. This could be linked to the fact that glycemic control deteriorates with age in all individuals. The age-related increase with a corresponding elevation of CA 19-9 in DM patients could be as a result of functional decline in pancreatic beta cells. This is because during aging, protein synthesis undergoes decrement changes in many organs and tissues including the pancreas as well as other exocrine glands., However, increasing age is also an important risk factor for metabolic disorders, including obesity, impaired glucose tolerance, and Type 2 diabetes., This finding was similar to the observation of Gulet al. and Jiang et al. and Flack et al.,, suggested that the age-related factors contributing to glucose intolerance, which may be improved include insulin signaling defects, reductions in tumor necrosis factor-α, increase in insulin-like growth factor-1 concentrations, and reductions in total and abdominal visceral fat. It has been reported that the prevalence of Type 2 diabetes increases with age and peaks at 60–74 years.,, Similarly, Wang et al. also reported a positive correlation in CA 19-9 levels with age in male diabetic patients. Conversely, Sisik et al. reported no statistically significant correlation between CA 19-9 levels and mean age. Aging, therefore, causes changes throughout the entire body as well as reduced pancreatic exocrine secretary functions., Thus, with aging, there could be a decrease in insulin secretion following stimulation with glucose as well as the amino acid. Arginine, thereby resulting in cellular damage that predisposes the secretion of CA 19-9 as observed in this current study.
Furthermore, there was a nonsignificant positive correlation between CA 19-9 levels and FPG in patients with DM. Hyperglycemia is an independent risk factor for mortality in individuals due to its associated cellular impairment, including the exocrine organs. Therefore, as an independent mortality risk factor could be the major underlying factor in CA 19-9 secretion. This is because exocrine pancreatic dysfunction is often improved with lowered blood glucose levels., Therefore, with glucose toxicity and aging, there could be elevated serum levels of CA 19-9 in patients with DM. This finding is similar to those reported in literature.,,,,
In light of these findings and from several other studies, we hypothesize that DM may be the underlying condition that causes pancreatic exocrine dysfunctions and may also be the factor that predisposes significant cellular secretion of CA 19-9, thus, could be used as a diagnostic marker for exocrine organs and an age-related disease monitoring biomarker.
| Conclusion|| |
The significantly elevated serum level of CA 19-9 along with its positive correlation with FPG indicates the need for a careful evaluation of blood glucose regulation while suggesting that CA 19-9 could be a suitable predictor of chronic inflammatory complications in patients with DM. Hence, further evaluation with a duration of diabetes and glycemic control using glycated hemoglobin could aid the relevance of CA 19-9 in glycemic control in individuals with DM.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]