|Year : 2017 | Volume
| Issue : 4 | Page : 240-244
Serum level of prostate-specific antigen in diabetic patients in Basrah, Iraq
Jasim N Al-Asadi1, Lamia M Al-Naama2, Muhannad M Abdul-Kareem2, Fawzi C Mashkoor3
1 Department of Community Medicine, College of Medicine, Basrah University, Basrah, Iraq
2 Department of Biochemistry, College of Medicine, Basrah University, Basrah, Iraq
3 Department of Biochemistry, College of Pharmacy, Basrah University, Basrah, Iraq
|Date of Web Publication||18-Jan-2018|
Dr. Jasim N Al-Asadi
Department of Community Medicine, College of Medicine, Basrah University, Basrah
Source of Support: None, Conflict of Interest: None
Objectives: The aim of this study was to determine the effect of type 2 diabetes mellitus (DM) on the serum level of prostate-specific antigen (PSA) in men in Basrah, Iraq. Patients and Methods: A case–control study was done including 70 confirmed type 2 diabetic patients and 70 non-diabetic persons. Data about age and family history of diabetes were collected. For diabetic patients, data related to disease history were also enquired about. Weight and height were measured and body mass index (BMI) was calculated. Blood examination was done to estimate fasting plasma glucose and PSA. Results: The mean ages of diabetic and non-diabetic patients were 55.2 ± 10.5 and 55.9 ± 10.9 years, respectively. The mean total serum PSA was significantly lower among diabetic than non-diabetic men (1.97 ± 1.05 ng/ml vs. 2.60 ± 1.22 ng/ml, respectively, P = 0.001). The multivariate linear regression analysis showed that age, DM and BMI were independent predictors of serum PSA variation. Age was significantly related to PSA in non-diabetics, but not in diabetic patients. Conclusion: Serum PSA level is significantly lower and less age dependent in type 2 diabetic patients than in non-diabetics. Therefore, DM should be considered in setting of PSA threshold when screening for prostate cancer.
Keywords: Basrah, body mass index, diabetes mellitus, glycosylated haemoglobin, insulin-like growth factor 1, Iraq, prostate-specific antigen, prostate
|How to cite this article:|
Al-Asadi JN, Al-Naama LM, Abdul-Kareem MM, Mashkoor FC. Serum level of prostate-specific antigen in diabetic patients in Basrah, Iraq. Niger Postgrad Med J 2017;24:240-4
|How to cite this URL:|
Al-Asadi JN, Al-Naama LM, Abdul-Kareem MM, Mashkoor FC. Serum level of prostate-specific antigen in diabetic patients in Basrah, Iraq. Niger Postgrad Med J [serial online] 2017 [cited 2019 Dec 6];24:240-4. Available from: http://www.npmj.org/text.asp?2017/24/4/240/223467
| Introduction|| |
Many studies reported that diabetic patients are at higher risk of developing specific malignancies such as cancers of the pancreas, colon and liver compared to non-diabetics. One possible reason for such increased risk is hyperglycaemia. However, recent studies showed that diabetic men showed a decreased risk of prostate cancer.,
Prostate-specific antigen (PSA), which is a glycoprotein secreted by the prostate gland, is commonly used as a biomarker in screening, diagnosis and prognosis of prostate cancer.
In Iraq, as in other Middle East countries,, the incidence of prostate cancer is low, but the disease is being increasingly reported. The crude incidence rate of prostate cancer in Iraq was reported to be 2.78/100,000 in 2011.
Previous studies have demonstrated an inverse association between serum PSA level and type 2 diabetes mellitus (DM).,, It was suggested that men with long-term diabetes have a lower risk of prostate cancer than non-diabetic men, and recently diagnosed men have a higher risk. Higher concentrations of insulin and insulin-like growth factor 1 (IGF-1) in early diabetes and the lower testosterone and IGF-1 levels and higher oestrogen concentrations in long-term diabetes may explain such association., Understanding the effect of diabetes on PSA serum concentration may help clinical detection of prostate tumours, and positive results may lead to considering diabetes when setting the PSA cut-off value at screening. Further, the lack of studies targeting Iraqi men signifies a research specific to Basrah, Iraq.
The aim of this study was to determine the association between type 2 DM and serum PSA level and to investigate the factors that may affect such association.
| Patients and Methods|| |
This case–control study was conducted in Basrah for the period from January 2016 to August 2016. To remove the potential confounding effects of high PSA values, individuals with evident prostate disease (e.g., prostate cancer, benign prostate hypertrophy and prostatitis), lower urinary tract symptoms, recent prostate manipulation (i.e., rectal examination within 1 week and prostate biopsy, surgery or cystoscopy within 1 month) or those whose serum PSA levels >4 ng/ml were excluded from the study.
One hundred sixty-five individuals (80 cases and 85 controls) were targeted. Of those, 12 individuals (5 cases and 7 controls) refused to participate giving a response rate of 92.7%. According to the exclusion criteria, 13 participants (5 cases and 8 controls) were excluded. The remaining 140 men (70 cases and 70 controls) representing the final sample size were included in the study. The diabetic patients (cases), attending Al-Sadr Teaching Hospital during the study period, were chosen randomly. The control group included healthy non-diabetic men who attended a primary healthcare centre for screening tests, were chosen by a simple random sampling.
DM was defined as the presence of both fasting plasma glucose (FPG) of ≥126 mg/dL and HbA1c of ≥6.5% or a positive medical history.
Sociodemographic information and family history of diabetes were enquired about by interviewing using a special questionnaire designed for the purpose of the study. Only the diabetic patients completed the data related to DM such as duration of the disease and the type of antidiabetic treatment. Body weight and height were measured and body mass index (BMI) was calculated (weight in Kg/height in m2), and it was categorised as underweight (<18.5), normal weight (BMI 18.5–24.9), overweight (BMI 25–29.9) or obese (BMI ≥30). Serum was obtained for analysis of FPG and PSA.
Serum PSA was measured using a sandwich-type enzyme-linked immunosorbent assay technique using immunoassay kit supplied by Human Diagnostics Worldwide (HUMAN.de Germany) with an analytical sensitivity of 0.05 ng/mL. The principle of the method is as mentioned by Nilsson et al.
This study was conducted in accordance with the ethical principles stated in the declaration of Helsinki and approved by the Ethical Committee of the College of Medicine, University of Basrah (2016-02). Informed consent was obtained from all participants.
Statistical analyses were done using Statistical Package for the Social Sciences (SPSS), Version 20 (IBM Corp., Chicago, Illinois, USA). The results were presented in Tables. Frequencies and percentages were calculated for the categorical variables, while continuous variables were expressed as means and standard deviations. Differences were assessed using Chi-square, t-test or ANOVA where applicable. Correlations between serum PSA level and various variables were examined by Pearson's correlation analyses. P < 0.05 was considered statistically significant.
| Results|| |
The mean age of the studied population was 55.6 ± 10.6 years (55.2 ± 10.5 for cases and 55.9 ± 10.9 for controls without a significant difference). No significant difference was noticed between cases and controls regarding smoking status and presence of co-morbid conditions. BMI was significantly higher among diabetic than non-diabetic men.
The PSA level was significantly lower among diabetic than non-diabetic men (1.97 ± 1.05 ng/ml vs. 2.60 ± 1.22 ng/ml, respectively, P = 0.001) [Table 1].
To examine the independent effect of certain variables on serum PSA level, a multiple linear regression analysis was done. It demonstrated that age (β = 0.279, P = 0.001), DM (β = −0.181, P = 0.026) and BMI (β = −0.175, P = 0.034) were significant independent determinants of serum PSA level [Table 2].
|Table 2: Multiple regression analysis to examine the predictors of serum level of prostate-specific antigen|
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In non-diabetic men, PSA level increased significantly with age (correlation r = 0.463; P < 0.001), while in diabetic patients, it increased with age until the age of 60 years and then it decreased. No significant association was found between serum PSA level and age in diabetic patients (correlation r = 0.141; P = 0.242) [Figure 1].
|Figure 1: Mean serum prostate-specific antigen level among diabetics compared to non-diabetics according to age|
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In diabetic patients, age and family history of diabetes showed no significant association with serum PSA level. However, BMI, HbA1c, insulin treatment and duration of diabetes showed significant association with serum PSA level (P< 0.05) [Table 3].
|Table 3: Serum prostate-specific antigen level (ng/ml) in diabetic patients according to age and clinical characteristics (n=70)|
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| Discussion|| |
This study showed that the mean level of PSA was significantly lower among diabetics in comparison with non-diabetic men, a result which has been found in several previous studies., Since PSA is androgen regulated, such association may be partly explained by lower serum testosterone concentration among diabetic patients. However, other studies rebutted such association between serum testosterone concentration and serum PSA level., It was postulated that the intraprostatic androgen status seems to be more important than the circulating levels in determining the risk of prostate cancer.
IGF-1 was reported to be a prostate cell growth promoter  and is positively related to PSA. The low level of IGF-1 in long-term diabetes  as insulin production drops  may further explain the low level of PSA in diabetic patients.
Impaired kidney functions  as well as antidiabetic medications particularly metformin  or other common medications, which are commonly used by diabetics such as statins, may also lower serum total prostate-specific antigen.
Although the association between BMI and serum PSA is controversial, our study showed an inverse correlation between BMI and serum PSA in both diabetic and non-diabetic men, a result which agrees with that reported by others. The exact mechanism for the inverse association between BMI and PSA is not well elucidated and several pathways had been suggested. However, some researchers attributed their findings to the hormonal hypothesis, which suggests that serum PSA is influenced by steroid hormone levels. Alternatively, other researchers suggested a haemodilution hypothesis, which suggests that obesity increases plasma volume, thus leading to reduction in circulating PSA concentration.
This study showed an inverse association between HbA1c and serum PSA, a result that is consistent with that reported by others.,
Similar to what was reported by Civtković et al. and Ainahi et al., our study showed that serum PSA is less age dependent in diabetic patients than in non-diabetics, particularly in elderly people. In diabetic patients, PSA increased with age until age of 60 years and then decreased without significant association. While in non-diabetic patients, it increased significantly with age. This may be attributed to the diminished capability of prostate to produce PSA or its decreased leakage  due to prostate ischaemia resulting from local microvascular complications associated with DM.
As reported previously, our study showed that serum PSA was inversely associated with duration of diabetes. A plausible explanation is that with advanced duration of diabetes, the action and level of insulin decrease leading to a subsequent decrease in serum PSA level.
In agreement with the results of Müller et al., our study showed that diabetic men on insulin combined with oral treatment had lower serum PSA level than those on oral antidiabetic medications alone. In addition, serum PSA level was significantly lower in patients on treatment (whether oral or combined oral and insulin) than that in non-diabetic men. Use of insulin may be an approximate surrogate of diabetes severity  and an indicator of a later stage of diabetes that is characterised by a lower level of circulating insulin and insulin resistance and consequently low serum PSA concentration.
In line with what was reported by Fukui et al., multivariate linear regression analysis revealed that age, diabetes and BMI were independent determinants of serum PSA. It showed that only 42.2% of variation in serum PSA was related to these factors. It should be noted that serum level of PSA is affected by many other factors such as demographic, lifestyle and health characteristics.
Some limitations have to be considered in this study. The first is that the prostate volume was not measured which may affect the influence of prostate growth on PSA level. The second imitation is the small sample size, which is mainly due to financial constraint. Furthermore, duration of treatment, dosage of medications and level of adherence to treatment were not analysed because of lack of information. Despite these limitations, the results of our study are still in agreement with published findings that serum PSA level is affected by DM.
| Conclusion|| |
This study supports the evidence that DM is associated with lower serum level of PSA. Moreover, serum PSA level in diabetic patients was influenced by a number of factors such as BMI, glycaemic control, type of treatment and duration of the disease. Therefore, DM should be considered in setting the PSA threshold when screening for prostate cancer, and special attention should be warranted in evaluation of PSA of elderly diabetic patients with further investigation are needed when prostate cancer is suspected.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Atchison EA, Gridley G, Carreon JD, Leitzmann MF, McGlynn KA. Risk of cancer in a large cohort of U.S. Veterans with diabetes. Int J Cancer 2011;128:635-43.
Giovannucci E, Michaud D. The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. Gastroenterology2007;132:2208-25.
Turner EL, Lane JA, Donovan JL, Davis MJ, Metcalfe C, Neal DE, et al.
Association of diabetes mellitus with prostate cancer: Nested case-control study (Prostate testing for cancer and treatment study). Int J Cancer 2011;128:440-6.
Xu H, Jiang HW, Ding GX, Zhang H, Zhang LM, Mao SH, et al.
Diabetes mellitus and prostate cancer risk of different grade or stage: A systematic review and meta-analysis. Diabetes Res Clin Pract 2013;99:241-9.
Diamandis EP. Prostate-specific antigen: Its usefulness in clinical medicine. Trends Endocrinol Metab 1998;9:310-6.
Alghamidi IG, Hussain II, Alghamdi MS, El-Sheemy MA. The incidence rate of prostate cancer in Saudi Arabia: An observational descriptive epidemiological analysis of data from the Saudi cancer registry 2001-2008. Hematol Oncol Stem Cell Ther 2014;7:18-26.
Hanash KA, Al-Othaimeen A, Kattan S, Lindstedt E, Al-Zahrani H, Merdad T, et al.
Prostatic carcinoma: A nutritional disease? Conflicting data from the kingdom of Saudi Arabia. J Urol 2000;164:1570-2.
Hilal L, Shahait M, Mukherji D, Charafeddine M, Farhat Z, Temraz S, et al.
Prostate cancer in the Arab world: A View from the inside. Clin Genitourin Cancer 2015;13:505-11.
Müller H, Raum E, Rothenbacher D, Stegmaier C, Brenner H. Association of diabetes and body mass index with levels of prostate-specific antigen: Implications for correction of prostate-specific antigen cutoff values? Cancer Epidemiol Biomarkers Prev 2009;18:1350-6.
Wallner LP, Morgenstern H, McGree ME, Jacobson DJ, St. Sauver JL, Jacobsen SJ, et al.
The effects of type 2 diabetes and hypertension on changes in serum prostate specific antigen levels: Results from the Olmsted county study. Urology 2011;77:137-41.
Fukui M, Tanaka M, Kadono M, Imai S, Hasegawa G, Yoshikawa T, et al.
Serum prostate-specific antigen levels in men with type 2 diabetes. Diabetes Care 2008;31:930-1.
Liu X, Hemminki K, Försti A, Sundquist K, Sundquist J, Ji J, et al.
Cancer risk in patients with type 2 diabetes mellitus and their relatives. Int J Cancer 2015;137:903-10.
Djavan B, Waldert M, Seitz C, Marberger M. Insulin-like growth factors and prostate cancer. World J Urol 2001;19:225-33.
Betancourt-Albrecht M, Cunningham GR. Hypogonadism and diabetes. Int J Impot Res 2003;15 Suppl 4:S14-20.
American Diabetes Association. 2. Classification and diagnosis of diabetes. Diabetes Care 2016;39 Suppl 1:S13-22.
Physical status: The use and interpretation of anthropometry. Report of a WHO expert committee. World Health Organ Tech Rep Ser 1995;854:1-452.
Nilsson O, Peter A, Andersson I, Nilsson K, Grundström B, Karlsson B, et al.
Antigenic determinants of prostate-specific antigen (PSA) and development of assays specific for different forms of PSA. Br J Cancer 1997;75:789-97.
Werny DM, Saraiya M, Gregg EW. Prostate-specific antigen values in diabetic and nondiabetic US men, 2001-2002. Am J Epidemiol 2006;164:978-83.
Balk SP, Ko YJ, Bubley GJ. Biology of prostate-specific antigen. J Clin Oncol 2003;21:383-91.
Mattack N, Devi R, Kutum T, Patgiri D. The evaluation of serum levels of testosterone in type 2 diabetic men and its relation with lipid profile. J Clin Diagn Res 2015;9:BC04-7.
Mustafa M, Horuz R, Celik M, Kucukcan A. Is there an association between serum prostate-specific antigen values and serum testosterone levels in healthy men? Korean J Urol 2014;55:465-8.
Cohen P, Peehl DM, Rosenfeld RG. The IGF axis in the prostate. Horm Metab Res 1994;26:81-4.
Oliver SE, Barrass B, Gunnell DJ, Donovan JL, Peters TJ, Persad RA, et al.
Serum insulin-like growth factor-I is positively associated with serum prostate-specific antigen in middle-aged men without evidence of prostate cancer. Cancer Epidemiol Biomarkers Prev 2004;13:163-5.
Giovannucci E. Nutrition, insulin, insulin-like growth factors and cancer. Horm Metab Res 2003;35:694-704.
Bruun L, Ekberg H, Bjørk T, Lilja H, Høglund P, Christensson A, et al.
Rapid elimination by glomerular filtration of free prostate specific antigen and human kallikrein 2 after renal transplantation. J Urol 2004;171:1432-5.
Jayalath VH, Ireland C, Fleshner NE, Hamilton RJ, Jenkins DJ. The relationship between metformin and serum prostate-specific antigen levels. Prostate 2016;76:1445-53.
Chang SL, Harshman LC, Presti JC Jr. Impact of common medications on serum total prostate-specific antigen levels: Analysis of the national health and nutrition examination survey. J Clin Oncol 2010;28:3951-7.
Bonn SE, Sjölander A, Tillander A, Wiklund F, Grönberg H, Bälter K, et al.
Body mass index in relation to serum prostate-specific antigen levels and prostate cancer risk. Int J Cancer 2016;139:50-7.
Skolarus TA, Wolin KY, Grubb RL 3rd
. The effect of body mass index on PSA levels and the development, screening and treatment of prostate cancer. Nat Clin Pract Urol 2007;4:605-14.
Kubota Y, Seike K, Maeda S, Shinohara Y, Iwata M, Sugimoto N, et al.
Relationship between prostate-specific antigen and obesity in prostate cancer screening: Analysis of a large cohort in Japan. Int J Urol 2011;18:72-5.
Fowke JH, Matthews CM, Buchowski MS, Signorello LB, Chang SS, Cookson MS, et al.
Association between prostate-specific antigen and leptin, adiponectin, hbA1c or C-peptide among African-American and Caucasian men. Prostate Cancer Prostatic Dis 2008;11:264-9.
Civtković L, Sokolić L, Plvić-Renar I, Ročić B. Prostate specific antigen and type 2 diabetes: A preliminary report. Diabetol Croat 2001;30:121-4.
Ainahi A, Barakat A, Wakrim L, Mohammadi H, ElMdaghri N, Ezzikouri S, et al.
Prostate-specific antigen levels in Moroccan diabetic males: A cross-sectional study. Curr Diabetes Rev 2017;13: [Epub ahead of print Jan 17]. DOI: 10.2174/1573399813666170117113519.
Zhang W, Hu R. Why does diabetes offer protective effects against prostate cancer? The possible role of its microvascular complications. Med Hypotheses 2010;74:242-3.
Parekh N, Lin Y, Marcella S, Kant AK, Lu-Yao G. Associations of lifestyle and physiologic factors with prostate-specific antigen concentrations: Evidence from the national health and nutrition examination survey (2001-2004). Cancer Epidemiol Biomarkers Prev 2008;17:2467-72.
[Table 1], [Table 2], [Table 3]