|Year : 2020 | Volume
| Issue : 2 | Page : 77-83
Alteration of hemostatic and hemorheological parameters in Nigerian patients with type 2 diabetes mellitus: Does age play a role?
Momodu Imoru1, Jessy Medugu2, Rebecca Gali2
1 Department of Haematology, Aminu Kano Teaching Hospital, Kano, Kano State, Nigeria
2 Department of Medical Laboratory Science, University of Maiduguri, Maiduguri, Borno State, Nigeria
|Date of Submission||17-Dec-2019|
|Date of Decision||05-Mar-2020|
|Date of Acceptance||10-Apr-2020|
|Date of Web Publication||29-Jul-2020|
Department of Haematology, Aminu Kano Teaching Hospital, Kano, Kano State.
Source of Support: None, Conflict of Interest: None
Background: Diabetes mellitus has been associated with coagulation abnormalities characterized by decreased levels of antithrombin, protein C, increased concentrations of fibrinogen and von Willebrand factor, and alteration of hemorheological indices, which have been linked to the increased hyperviscosity state. The aim of this study was to determine the effect of age on hemostatic and hemorheological parameters in patients with type 2 diabetes mellitus. Materials and Methods: Eighty-four patients of 168 participants, aged 30–69 years, were recruited from the Metabolic Clinic of the University of Maiduguri Teaching Hospital, Borno State between January and December 2018, whereas the remaining 84, age- and sex-matched nondiabetic subjects resident in Maiduguri served as controls. Samples for platelet indices, fibrinogen concentration, hematocrit, relative plasma viscosity (RPV), whole blood viscosity (WBV), protein C, antithrombin, and d-dimer were analyzed using standard techniques. Results: The values of platelet indices, prothrombin time (PT), activated partial thromboplastin time (aPTT), protein C, antithrombin, d-dimer, fibrinogen, hematocrit, and RPV in diabetic patients with respect to different age groups showed no significance (P > 0.05). However, significantly lower levels of protein C, antithrombin and hematocrit, and significantly higher values of d-dimer, fibrinogen, and WBV were observed in patients with diabetes irrespective of the age compared to that of nondiabetic subjects (P < 0.05). Conclusion: Age had no influence on the values of platelet count, platelet indices, PT, aPTT, protein C, antithrombin III, d-dimer, fibrinogen, hematocrit, RPV, and WBV in patients with diabetes. However, patients with type 2 diabetes mellitus could be prone to thrombosis and increased fibrinolytic activity irrespective of their age.
Keywords: Age, alteration, diabetes mellitus, hemorheology, hemostasis
|How to cite this article:|
Imoru M, Medugu J, Gali R. Alteration of hemostatic and hemorheological parameters in Nigerian patients with type 2 diabetes mellitus: Does age play a role?. Int J Med Health Dev 2020;25:77-83
|How to cite this URL:|
Imoru M, Medugu J, Gali R. Alteration of hemostatic and hemorheological parameters in Nigerian patients with type 2 diabetes mellitus: Does age play a role?. Int J Med Health Dev [serial online] 2020 [cited 2020 Aug 14];25:77-83. Available from: http://www.ijmhdev.com/text.asp?2020/25/2/77/291062
| Introduction|| |
Diabetes mellitus (DM) is a metabolic disorder of chronic hyperglycemia characterized by disturbances to carbohydrate, protein, and fat metabolism, resulting from defects in insulin secretion, insulin action, or both. The effects of DM include long-term damage dysfunction and failure of various organs.
The World Health Organization diagnostic criteria for diabetes have been associated with fasting plasma glucose ≥ 7.0 mmol/L (126 mg/dL) or 2-h plasma glucose ≥ 11.1 mmol/L (200 mg/dL).
Type 1 diabetes and type 2 diabetes have been found to be most prevalent. Type 1 (juvenile diabetes) is characterized by pancreatic β-cell destruction caused by an autoimmune process, usually leading to absolute insulin deficiency,, whereas type 2 diabetes corresponds to approximately 90% of cases of diabetes worldwide and it is characterized by insulin resistance and /or reduced production of insulin probably due to subnormal functioning of the β-cells.
In Nigeria, studies have shown the prevalence of diabetes of 2%–12% in different parts of the country,,,, and the incidence of type 2 diabetes has been shown to increase with age and most especially from 35 years of age.
The most common microvascular complications resulting from type 2 DM are nephropathy, retinopathy, and neuropathy, whereas that of macrovascular complications include coronary artery disease, strokes, and peripheral arterial disease.,, However, approximately 80% of diabetics die from thrombotic events with 75%–80% of these deaths resulting from cardiovascular events.,
Coagulation abnormalities characterized by decreased levels of antithrombin, protein C, protein S, and elevated clotting factors have been associated with DM in the previous study, whereas hyperglycemia has been linked to the stimulation of plasminogen activator inhibitor type 1 (PAI-1) production which favors the permanence of the fibrin clot, and consequently the development of thrombi.,,
Earlier reports in Caucasians have shown altered rheological properties of blood such as plasma viscosity, plasma protein concentrations, whole blood viscosity (WBV), and hematocrit in diabetes.,,, This alteration in hemorheological indices has been linked to the increased hyperviscosity state that is associated with increased risk of cardiovascular, cerebrovascular, and retinal venous occlusion morbidity.,,
There has been scanty information on the effect of age on the hemostatic and hemorheological parameters in patients with diabetes in Nigeria, and this has therefore necessitated the study on the alterations of the values of the platelet count, platelet indices, prothrombin time (PT), activated partial thromboplastin time (aPTT), protein C, antithrombin, d-dimer, hematocrit, relative plasma viscosity (RPV), and WBV with age in patients with type 2 DM in Maiduguri, Northern Nigeria.
| Subjects and Methods|| |
A total of 168 participants were studied, and of which, 84 patients with uncomplicated DM, aged 30–69 years, were recruited from the diabetic clinic of the University of Maiduguri Teaching Hospital (UMTH), Maiduguri, Borno State between January and December 2018, whereas the remaining 84, age- and sex-matched, nondiabetic subjects resident in Maiduguri served as controls. However, patients with bleeding disorders, pregnancy, and hypertension were excluded from the study.
After the ethical approval from the ethical committee of the University of Maiduguri Teaching Hospital, Maiduguri and informed consent obtained from the patients and control subjects, 8.5mL of the venous sample was collected aseptically from each participant. Of this volume of blood, 4.5mL was mixed with 0.5mL of 3.2% trisodium citrate solution in a container and the mixture centrifuged at 2500 revolutions per minute for 15 min. The plasma was separated into the plain container for the determination of PT, aPTT fibrinogen, protein C, antithrombin, and d-dimer. However, the remaining 4mL of blood was added to the dipotassium ethylene diamine tetraacetic acid (EDTA) bottle to the final concentration of 1.5 mg/mL for the determination of hematocrit, platelet count and platelet indices, RPV, and WBV.
Fibrinogen, PT, and aPTT were determined using Diagen kits manufactured by Diagnostic Reagents Limited, United Kingdom, whereas platelet indices and hematocrit were determined using Humacount 30TS, a 3-part analyzer produced by Gesellschaft fur Biomedica und Diagnostica mbH, Wiesbaden, Germany. Antithrombin III, protein C, and D-dimer levels were estimated using Sunlong Human ELISA kits manufactured by Sunlong Biotech Company Limited, Gongshu District, China. All analyses were carried out according to manufacturers’ instructions.
WBV and RPV were determined using Reid and Ugwu methods.
Data were expressed as mean ± standard deviation. Student’s t test and one-way analysis of variance (ANOVA) with Turkey post hoc test were used to compare the differences in values and P < 0.05 was considered to be significant.
| Results|| |
[Table 1] shows the influence of age on coagulation parameters in patients with diabetes. Diabetic patients with age groups of 30–37, 38–45, 46–53, 54–61, and 62–69 years had platelet count (X109/L) of 363.25 ± 64.72, 328.53 ± 115.85, 309.61 ± 117.62, 279.3 ± 73.69, and 286.92 ± 145.2, respectively; plateletcrit (%) of 0.34 ± 0.08, 0.27 ± 0.09, 0.26 ± 0.10, 0.25 ± 0.08, and 0.24 ± 0.12, respectively; mean platelet volume (MPV[fl]) of 9.0 ± 0.69, 8.48 ± 0.83, 8.49 ± 0.98, 8.81 ± 0.98, and 8.28 ± 0.92, respectively; platelet distribution width (PDW[fl]) of 13.2 ± 1.37, 12.22 ± 2.11, 12.29 ± 2.53, 12.6 ± 1.99, and 11.81 ± 2.24, respectively; preliminary results of platelet larger cell ratio (P-LCR) (%) of 41.17 ± 4.97, 35.71 ± 7.3, 35.72 ± 8.44, 38.34 ± 8.74, and 33.94 ± 1.18, 12.66 ± 1.34, 12.27 ± 1.39, and 12.54 ± 1.18, respectively; aPTT (s) of 35.5 ± 4.23, 35.31 ± 3.73, 33.13 ± 4.48, 32.2 ± 4.45, and 34.4 ± 4.47, respectively, compared to platelet count (X109/L) of 299.0 ± 90.17, plateletcrit (%) of 0.26 ± 0.09, MPV(fl) of 8.66 ± 0.73, PDW(fl) of 12.53 ± 1.69, P-LCR(%) of 37.49 ± 6.53, PT (s) of 12.69 ± 1.15, and aPTT(s) of 33.86 ± 4.63 in nondiabetic control subjects. Different values of platelet count, plateletcrit, MPV, PDW, P-LCR, PT, and aPTT in diabetic patients and control groups were not statistically significant (P > 0.05).
|Table 1: Influence of age on coagulation parameters in diabetic patients|
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[Table 2] shows the levels of natural anticoagulants and fibrinolysis in patients with diabetes in relation to age. Diabetic patients with age groups 30–37 years, 38–45 years, 46–53 years, 54–61 years, and 62–69 years had levels of protein C (ng/mL) of 10.36 ± 3.11, 10.31 ± 4.52, 9.78 ± 5.54, 8.08 ± 2.47, and 10.32 ± 6.15, respectively; antithrombin (mg/dL) of 21.61 ± 7.25, 34.24 ± 25.34, 29.54 ± 32.39, 31.79 ± 26.78, and 25.79 ± 28.52, respectively; D-dimer (ng/mL) of 156.34 ± 4.82, 170.72 ± 126.11, 101.96 ± 50.29, 86.06 ± 49.68, and 137.54 ± 132.05, respectively, compared to protein C of 47.67 ± 22.45 ng/mL, antithrombin of 95.01 ± 66.45 mg/dL, and d-dimer of 88.73 ± 47.03 ng/mL in nondiabetic control group. The fluctuated values of protein C and antithrombin in diabetic patients with age groups 30–37, 38–45, 46–53, 54–61, and 62–69 years were not statistically significant (P > 0.05) but showed statistically significant differences when compared to the control group (P < 0.05). However, d-dimer levels fluctuated significantly with different age groups in patients with diabetes and when compared to the control subjects (P < 0.05).
|Table 2: Levels of natural anticoagulants and fibrinolysis in diabetic patients in relation to age|
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Effect of age on hemorheological parameters in type 2 patients with DM is shown in [Table 3]. Diabetic patients with age groups of 30–37, 38–45, 46–53, 54–62, and 62–69 years had the values of fibrinogen (g/L) of 2.46 ± 0.56, 2.55 ± 0.87, 2.78 ± 0.98, 2.44 ± 0.71, and 2.56 ± 0.93, respectively; hematocrit (%) of 37.5 ± 4.66, 35.12 ± 6.39, 34.86 ± 7.28, 37.3 ± 3.78, and 36.83 ± 6.21, respectively; WBV (mPa.s) of 3.30 ± 0.95, 2.87 ± 0.56, 2.95 ± 0.68, 2.82 ± 0.55, and 3.11 ± 0.38, respectively, compared to levels of fibrinogen of 2.23 ± 0.60 g/L, hematocrit of 42.1 ± 3.95%, and 2.67 ± 0.44 mPa.s in nondiabetic subjects. The different values of fibrinogen, hematocrit, and WBV in diabetic patients with regard to age groups 30–37, 38–45, 46–53, 54–61, and 62–69 years were not statistically significant (P > 0.05) but showed statistically significant difference (P < 0.05) when compared to the values in the control subjects. However, the different values of RPV (mPa.s) of 1.27 ± 0.08, 1.3 ± 0.16, 1.28 ± 0.22, 1.27 ± 0.14, and 1.23 ± 0.14 for diabetic patients with age group 30–37, 38–45, 46–53, 54–61, and 62–69 years, respectively, compared to 1.19 ± 0.18 mPa.s in control subjects showed no significance (P > 0.05).
|Table 3: Effect of age on hemorheological parameters in patients with diabetes mellitus|
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| Discussion|| |
Earlier studies have shown a variety of DM-related abnormalities in hemostasis and thrombosis,, whereas alteration in hemorheological indices in patients with diabetes has been linked to increased hyperviscosity state.,,
Divergent views have been expressed in the platelet count in patients with diabetes. Increased platelet count in patients with diabetes has been reported by some authors,, whereas other researchers documented no statistically significant difference in the platelet count between diabetic and nondiabetic (controls) subjects.,, However, Buch et al. reported a significantly lower platelet count in patients with diabetes compared to the control group. Our study has shown no significant difference in platelet count between the control group and patients with type 2 diabetes irrespective of their age.
The study further revealed no statistically significant differences in the values of MPV, PDW, and plateletcrit in patients with diabetes of all age groups compared to the nondiabetic patients. This observation is in agreement with the previous report, but contrary to the significant differences observed in the values of MPV and PDW by other researchers. However, these conflicting reports on MPV and PDW by the various authors could be due to the lumping together of patients with diabetes irrespective of their associated complications for the researches.
The study supports an earlier report on P-LCR value which showed no significant differences between diabetic patients and the control group but it is in disagreement with the report of Pujani et al. that showed significantly lower P-LCR value in diabetic patients compared to the control group. However, the P-LCR is the determinant of the largest sized fraction in platelets in which its proportion has been closely related to thrombotic events.
The study has shown that the values of PT and aPTT fluctuated insignificantly with age in patients with diabetes and there were no statistically significant differences in PT and aPTT values between diabetic patients and the control groups. These findings are at variance with earlier reports that showed significantly lower PT and aPTT values in patients with diabetes., Discrepancy in the reported values of PT and aPTT could be associated with different sample numbers and analytical techniques.
The insignificant fluctuation of protein C level with age in patients with diabetes in this study is contrary to the reported rise in protein C level in healthy men and women over the age range of 20–59 years but in agreement with other researchers that showed no significant age-related increase in protein C level.,
The study revealed that antithrombin in patients with diabetes showed no statistically significant difference with respect to age but showed significantly lower value compared to the control subjects. These observations are in line with earlier studies which reported no influence of age on antithronbin level.,, However, deficiency of protein C and antithronbin has been well established to be risk factors for venous thromboembolism.,
D-dimer level concentration increased significantly between the age range of 30 and 45 years and decreased between the age range of 46 and 61 years in this study. However, there was a sharp increase in the value of d-dimer from 62 years and above. The study further revealed a significantly higher level of d-dimer in diabetic patients compared to the control subjects, which are in line with the previous reports.,
Hyperglycemia has been linked to increased PAI-1 production that favors the permanence of the fibrin clot, and consequently the development of thrombin.,, However, this increased concentration of d-dimer in patients with diabetes may be associated with hyperfibrinolysis probably due to hypercoagulability linked to the condition.
The fibrinogen levels in patients with diabetes fluctuated insignificantly with respect to age in this study but this observation is contrary to the increasing fibrinogen level with advancing age (from 18 to 85 years of age) in healthy individuals reported.,, However, a significantly higher fibrinogen level in the diabetic patient compared to the control group in this study has supported previous studies.,, Increased fibrinogen level has been associated with an elevated interleukin-6 level in diabetes which stimulates hepatocytes to produce fibrinogen, representing an important link between inflammation and hypercoagulation.
There was no significant change in hematocrit value with age in patients with diabetes in this study; however, the value in this condition was significantly lower than that in the nondiabetic subjects (control group). This report is in conformity with earlier findings., It has been observed by Wright et al. that patients with type 2 DM are twice more likely to be prone to anemia than patients without diabetes. However, the mechanism of anemia in patients with diabetes is not fully understood but it is hypothesized to be likely secondary to direct glucose toxicity to erythrocyte precursors in the bone marrow or from oxidative stress to mature erythrocytes.
Higher level of RPV in diabetic patients compared to control subjects showed no statistically significant difference in this study. The study further showed that there were no statistically significant differences in RPV levels with respect to age. The report is comparable to earlier findings on normotensive patients with diabetes. However, it is further revealed that there was the significantly higher value of WBV in diabetic patients compared to the control group but the changes in WBV values with age in patients with diabetes were not significant. The findings are similar to the earlier report on diabetes with and without retinopathy. Increased blood viscosity in patients with diabetes has been associated with their narrower vessels which tend to result in lower flow rate in some vessels.
In conclusion, this study has shown that patients with DM are associated with significantly lower values of protein C, antithrombin and hematocrit, and significantly higher values of d-dimer concentration, fibrinogen, and WBV. However, there were no statistically significant differences in the values of platelet count, platelet indices, PT, aPTT, RPV, protein C, antithrombin III, d-dimer, fibrinogen, hematocrit, and WBV in diabetic patients with respect to age. This study has shown that the patients with diabetes could be prone to anemia, thrombosis and increased fibrinolytic activity irrespective of their age. Therefore, it is recommended that protein C, antithrombin, d-dimer, fibrinogen, and WBV assays be carried out on regular basis to reduce their thrombotic risk.
We would like to acknowledge the assistance of the physicians and the nurses at the metabolic clinic of the University of Maiduguri Teaching Hospital, Maiduguri in making it possible for us to have access to the patients with diabetes used for this study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]