|Year : 2013 | Volume
| Issue : 2 | Page : 72-76
A study of hemorrhological parameters as risk factors for cardiovascular diseases in Nigerian type 2 diabetes mellitus patients
Olatunde Odusan1, Hussean T Raimi2, Oluranti B Familoni3, O Olayemi4, Jacob O Adenuga4
1 Department of Medicine, Endocrinology Unit, Obafemi Awolowo College of Health Sciences, Olabisi Onabanjo University and Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State, Nigeria
2 Endocrinology Unit, Ekiti State University and EKSUTH, Ado-Ekiti, Ekiti State, Nigeria
3 Cardiology Unit, Obafemi Awolowo College of Health Sciences, Olabisi Onabanjo University and Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State, Nigeria
4 Department of Haematology, Olabisi Onabanjo University and Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State, Nigeria
|Date of Web Publication||13-Feb-2014|
Department of Medicine, Endocrinology Unit, Obafemi Awolowo College of Health Sciences, Olabisi Onabanjo University and Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State
Source of Support: None, Conflict of Interest: None
Background: Diabetes mellitus is a syndrome with multiple aetiology characterized by chronic hyperglycaemia consequent on defects of insulin secretion, insulin action or both. Long term complications of chronic hyperglycaemia arise from underlying microvascular and macrovascular diseases.
Objective: Diabetes mellitus is a major independent risk factor for cardiovascular diseases with diabetic subjects known to be at increased risk of cardiovascular diseases when compared with non-diabetic counterparts. Haemorheological parameters were thus evaluated in type 2 diabetics as possible risk factors for cardiovascular diseases.
Method: One hundred patients with type 2 diabetes mellitus (78 normotensive, 22 hypertensives) were evaluated along with fifty apparently healthy age matched non-diabetic people serving as controls. Fasting blood glucose (FBG), Fibrinogen level (Fib), platelet count (PC), packed cell volume (PCV), plasma viscosity (PV), whole blood viscosity (WBV), white blood cells (WBC), and erythrocyte sedimentation rate (ESR) were determined using conventional methods.
Results: FBG, ESR and Fib were significantly higher in the hypertensive diabetics (126.9±22.3mg/dl, 37.15±22.01mm/hr, and 3.75±1.09g respectively) compared with healthy non-diabetic controls, (83.9±11.5mg/dl, 8.50±4.75mmhr and 2.09±0.286g respectively (P<0.05). There were no significant differences in other measured parameters of normotensive and hypertensive diabetics though plasma viscosity (PV), showed slight but non-significant increase in diabetics with hypertension when compared with non-diabetic controls.
Conclusion: We conclude that elevated blood glucose level results in increased level of fibrinogen and ESR in hypertensive T2DM with possible increased risk of other cardiovascular diseases.
Diabetes mellitus, haemorheological parameters, hypertension, Nigeria
|How to cite this article:|
Odusan O, Raimi HT, Familoni OB, Olayemi O, Adenuga JO. A study of hemorrhological parameters as risk factors for cardiovascular diseases in Nigerian type 2 diabetes mellitus patients. Nig J Cardiol 2013;10:72-6
|How to cite this URL:|
Odusan O, Raimi HT, Familoni OB, Olayemi O, Adenuga JO. A study of hemorrhological parameters as risk factors for cardiovascular diseases in Nigerian type 2 diabetes mellitus patients. Nig J Cardiol [serial online] 2013 [cited 2020 Dec 1];10:72-6. Available from: https://www.nigjcardiol.org/text.asp?2013/10/2/72/127004
| Introduction|| |
Diabetes mellitus (DM) is a heterogeneous group of metabolic disorders characterized by chronic hyperglycemia with disturbances of carbohydrates, fat and protein metabolism resulting from defects in insulin secretion, insulin action or both.  Long-term effects of the chronic hyperglycemia are damage, dysfunction and failure of various organs and tissues particularly eyes, heart, kidneys and blood vessels. It is a major independent risk factor for cardiovascular diseases (CVD). 
DM is the most common endocrine disorder with an estimated global prevalence of 135 million in 1995 (5.4% of the world population) and is projected to increase to 299 million by 2025 (6.3% of the world population). Most of this increase is expected in the developing and emerging economies where there is increasing obesity.  The national prevalence of DM in Nigeria (1992) was 2.2%  with later studies reporting wide variation from 0.6% in rural Mangu of Plateau state to 7.2% in urban Lagos.  Ogunkolo and Amballi in a study of newly admitted students of Olabisi Onabanjo University (Ago-Iwoye) undergoing pre-admission medical examination reported prevalence of 3.3% of newly diagnosed DM. 
DM is a major independent risk factor for CVD, arising mainly from microvascular and macrovascular diseases including and atherosclerosis and thrombosis. , These complications make diabetes the 4 th major cause of death, highest in health expenditure (in the USA) and leading cause of adult blindness, end stage renal disease and non-traumatic lower limb amputation among other complications.  Metabolic dysfunction commonly found in diabetes is reportedly not always sufficient to induce or accelerate the atherosclerosis. ,,
Epidemiological and clinical studies have identified a combination of factors associated with increased incidence of CVD in DM. They are grouped as (i) metabolic; hyperglycemia, hypertrygliceridemia and reduced high-density lipoprotein cholesterol, (ii) coagulation (and inflammatory); increased fibrinogen (Fib), platelet activation, factor VII and tissue factor and (iii) vascular related; hypertension, increased arterial calcification with decreased compliance. ,,
There is increased risk for CVD in response to arterial injury and vascular abnormality like atherosclerosis due to increased deposition of fibrin, cellular proliferation and fibrous scar formation. , These are followed by decreased fibrinolytic activity, increased plasminogen activator inhibitor-1 activity (PAI-1) and decreased thrombus dissolution, which culminate in a pro-thrombotic state.  Hyperglycemia and insulin resistance, both components of the metabolic syndrome (MS) enhances this state. However, the PAI-1 activity does decrease with insulin treatment. ,
In DM, clustering of CVD risk factors coexists. Clustering of at least two cardiovascular risk factors was reported in the Botnia study, which highlighted obesity, hypertension and or dyslipydemia as occurring in about 10% of non-diabetic individuals, nearly 50% of those with impaired fasting glucose and 80% of Type 2 diabetes mellitus (T2DM) patients.  As these risk factors may predate the onset of diabetes, it is possible that pathogenesis begins long before the diagnosis of DM. ,
Hypertension, a major CVD risk factor often coexists with diabetes. The United Kingdom Prospective Diabetes Study (UKPDS), reported a substantially reduced risk of macro-vascular events in T2DM patients with tight blood pressure (BP) control. ,
Hemorheological variations in plasma components lead to hyperviscocity that induces micro-vascular damage and facilitates occlusive events via erythrocyte roellaux formation and platelet aggregation. , Previous studies in Nigerian diabetic subjects reported hyper-fibrinogenemia, increased platelet count (PC), increased platelet factor 3 availability and decreased fibrinolytic activity. , These may suggest increased spontaneous coagulation and fibrinolytic complications in the group.  Impaired micro-vascular flow form the basis of several clinical disorders in T2DM. , There are few reports on the study of hemorheological parameters as risk factors for CVD in Nigerian-African diabetics and there has been no such report from our center at the Olabisi Onabanjo University Teaching Hospital, Sagamu (OOUTH). This study sought to explore the role of hyperviscosity in T2DM subjects as risk factors for CVD. We therefore evaluated fasting plasma glucose (FPG), packed cell volume (PCV), erythrocyte sedimentation rate (ESR), PC, whole blood viscosity (WBV), plasma viscosity (PV) and Fib levels in type 2 diabetic patients with and without hypertension and compared with non-diabetic/non-hypertensive apparently healthy people serving as control.
| Materials and Methods|| |
A total of 100 adult T2DM patients aged 35-70 years attending the Endocrinology clinic of OOUTH and managed by diet and maximum of two oral hypoglycemic agents were recruited for the study. They had no major CVD event (cerebrovascular accident, myocardial infarction) within the previous 12 months.
DM was defined as history of DM or FPG >126 mg/dl while hypertension was defined as history of hypertension, use of BP lowering drugs or systolic blood pressure (SBP) >140 mmHg and or diastolic blood pressure (DBP) >90 mmHg respectively. ,
Fifty normotensive, age-matched, non-diabetic apparently healthy subjects were recruited as controls.
Demographic data of age, sex, height, weight, with SBP and DBP were recorded according to the standard procedure with the body mass index (BMI) calculated from the formula BMI = Weight (kg)/Height (m) 2 .
10 ml of whole blood was collected from the ante-cubital vein using a volume of 10 ml plastic syringe with 22G hypodermic needle under aseptic technique, applying a tourniquet lightly over the upper arm till blood flows freely. Efforts were made to avoid stasis during the blood collection. A total volume of 4.5 ml aliquot of the sample was transferred onto a plastic tube containing 0.5 ml of 3.8% Citrate as an anticoagulant. The two were then mixed gently, but thoroughly and the mixture centrifuged at 3000 rpm for 5 min. The supernatant plasma was separated for immediate laboratory analysis for Fib by the clot weight method of Ingram. 
A volume of 2 ml blood was added into fluoride oxalate bottle for FPG assay by the enzymatic oxidation method of Barham and Trinder.  Another 3 ml of blood was added to ethylenediaminetetraacetic acid container for determination of whole blood and plasma viscosity, as well as, FBC, ESR and platelets count using the method of Dacie and Lewis. ,
Data was entered and analyzed using the Statistical Package for Social Sciences Version 17.0. Categorical variables described as mean ± standard deviation (SD), proportions expressed as frequency (%). Student's t-test was used to compare means between two groups while multiple groups were compared with one-way analysis of variance and level of significance set at P < 0.05.
| Results|| |
The BMI, SBP and DBP of hypertensive diabetic subjects were significantly higher than those of the normotensive diabetics and healthy controls [Table 1]. Similarly, FPG and creatinine levels were significantly higher in the diabetic groups (normotensive and hypertensive) than those of healthy controls (P < 0.05) though there were no statistically significant differences in the BMI, SBP and DBP of normotensive diabetics and healthy controls (P > 0.05).
|Table 1: Clinical and laboratory parameters of the various study groups: Diabetics (with and without hypertension) and healthy control|
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The hemorheological parameters (mean ± SD) of the diabetic subjects and healthy controls are shown in [Table 2]. Though ESR, PV, WBV and Fib levels were significantly higher in diabetics than in the healthy controls (P < 0.05), the PCV and platelets count were significantly lower in diabetics than controls (P < 0.05).
|Table 2: Comparison of study parameters in diabetic and non‑diabetic control group|
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The mean (± SD) of hemorheological variables in the 3 study groups - normotensive, hypertensive diabetic groups and healthy controls are shown in [Table 3]. The ESR, WBV and Fib levels were significantly higher in the diabetic group than the healthy controls (P < 0.05). There were no significant differences between PCV, ESR, white blood cell count (WBC), PV and WBV for normotensive and hypertensive diabetics. However, PC and Fib level were higher in normotensive than hypertensive diabetics and controls. PCV and PC values were lower in normotensive and hypertensive diabetics compared with the control group, though the difference was not significant (P > 0.05).
|Table 3: Hemorheological parameters in the diabetic (normotensive/hypertensive) and control groups|
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| Discussion|| |
Increased blood viscosity is a function of increased hematocrit (PCV) leading to intravascular stasis with consequent thrombosis.  In this study, increased blood viscosity reported among the diabetics (normotensive and hypertensive) was significantly higher compared with non-diabetic healthy control group suggesting that diabetics may be readily prone to thrombotic complications. In addition, high WBC coupled with PCV in diabetics suggests that poor glycemia may have an effect on red cell deformability, agreeability and hence increase blood viscosity  similar to finding in this study and an earlier report in T2DM Nigerian subjects with sickle cell trait. ,
Diabetics are known to be prone to recurrent infections, have increased WBC and ESR levels resulting from increased inflammatory process, but with decreased PCV level.  Furthermore, decreased PCV in diabetics may also result from organ failure particularly nephropathy with decreased renal function, renal perfusion and erythropoietin secretion. Anemia is a known risk factor for CVD.  Consequently, in diabetic subjects, presence of anemia increases risk for CVD. A lower PCV level was found in the hypertensive diabetics than in the normotensive diabetic group. This may be attributable to the processes of the pro-thrombosis resulting from endothelial damage, hyperglycemia and increased red cell adhesiveness.  Reid and Oli, in an earlier study on Nigerian diabetes reported increased PCV with improved glycemic control. 
This study found a significantly lower PC in the diabetic group than healthy controls an observation that is consistent with the earlier report of Famodu et al., Earlier studies also reported an increase in FPG, endothelial cell damage, platelet adhesiveness and endothelial lesion all resulting in increased level of PAI-1. , However, our study showed no correlation between the PC and FPG. It is therefore possible that the low PC maybe mediated through the same mechanism of insulin resistance. 
The use of diuretic agents to control BP in diabetics via a reduction in plasma volume and hence total blood volume may account for their increased PCV, creatinine and pro-coagulants like Fib. This study found a significantly higher Fib level in diabetic groups than the healthy control. This could be because Fib, an acute phase reactant is increased in atherosclerosis more so since glycosylated Fib is less susceptible to plasma degradation. In addition, relative insulin deficiency in diabetic patients result in differential protein synthesis-29% decrease in Albumin synthesis and 50% increase in Fib synthesis. This has been attributed to a further increase in fractional Fib synthesis  with an earlier report showing increased Fib level as a marker of CVD in Africans. 
Obesity is not only a component of MS, it worsens other major components of the syndrome such as hyperglycemia, hypertension, increased cardiovascular and hypertension mortality as well as insulin resistance.  Our study found a significantly higher level of overweight and obesity (BMI) in the diabetic group compared with the healthy controls.
Several studies had reported a positive association between obesity and increased Fib level in T2DM. , Hence weight reduction and control play a very significant role in the management and control of hypertension and blood glucose in diabetic patients.
Though the results of UKPDS and the diabetes control and complications trial showed that intensive glycemic and hypertension control in diabetes can reduce CVD complications, current treatment methods do not eradicate its negative impact on the cardiovascular system. , Diabetes with CVD may arise from the combination of genetic, metabolic and inflammatory antecedents. In addition, they may cause a combination of systemic and intravascular abnormalities that are pro-atherogenic and thrombotic.  Optimal use of therapies will therefore have to begin before the onset of clinical symptoms of CVD while strategies to preserve cardiovascular health in individuals with DM and CVD risk factors need to begin in the early decades of life. 
| Conclusion|| |
Findings from this study reveal that hemorheological parameters of PCV, ESR, Fib and PC may accelerate atherosclerosis through the mechanism of pro-thrombosis and insulin resistance particularly in T2DM Nigerians, thus contributing to increased prevalence of CVD. However, further investigation in a larger population of T2DM subjects that will detect nephropathy and degree of long-term diabetes control using micro-albumin and HbA1c assay respectively is needed.
| References|| |
|1.||World Health Organisation. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications: Report of WHO Consultation Part 1, Diagnosis and Classification of DM. Geneva: WHO; 1999. (WHO/NCD/NCS.99.2). |
|2.||Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, et al. Diabetes and cardiovascular disease: A statement for healthcare professionals from the American Heart Association. Circulation 1999;100:1134-46. |
|3.||Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047-53. |
|4.||National Expert Committee on Non-communicable Diseases in Nigeria. Report of a National Survey. Lagos, Nigeria: Federal Ministry of Health; 1997. p. 64-90. |
|5.||Nyenwe EA, Odia OJ, Ihekwaba AE, Ojule A, Babatunde S. Type 2 diabetes in adult Nigerians: A study of its prevalence and risk factors in Port Harcourt, Nigeria. Diabetes Res Clin Pract 2003;62:177-85. |
|6.||Ogunkolo OF, Amballi AA. Prevalence of diabetes mellitus in newly admitted undergraduates of Olabisi Onabanjo University. Nigeria. Niger Med Pract 2005;47:26-8. |
|7.||Schneil O, Stendl E. Impaired glucose tolerance, diabetes and cardiovascular diseases. Endocr Pract 2006;26:398-408. |
|8.||Feener EP, King GL. Vascular dysfunction in diabetes mellitus. Lancet 1997;350:S19-113. |
|9.||Complications of Diabetes: National Diabetes Statistics, 2011 National Diabetes Information Clearinghouse, (NDIC NIH). available at www.diabetes.niddk.nih.gov. |
|10.||Haffner SM. Impaired glucose tolerance, insulin resistance and cardiovascular disease. Diabet Med 1997;14 Suppl 3:S12-8. |
|11.||Isomaa B, Almgren P, Tuomi T, Forsén B, Lahti K, Nissén M, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001;24:683-9. |
|12.||Thorand B, Baumert J, Chambless L, Meisinger C, Kolb H, Döring A, et al. MONICA/KORA Study Group. Arterioscler Thromb Vasc Biol. 2006;26:398-405. |
|13.||Festa A, D′Agostino R Jr, Mykkänen L, Tracy RP, Zaccaro DJ, Hales CN, et al. Relative contribution of insulin and its precursors to fibrinogen and PAI-1 in a large population with different states of glucose tolerance. The Insulin Resistance Atherosclerosis Study (IRAS). Arterioscler Thromb Vasc Biol 1999;19:562-8. |
|14.||Haffner SM, Mykkänen L, Festa A, Burke JP, Stern MP. Insulin-resistant prediabetic subjects have more atherogenic risk factors than insulin-sensitive prediabetic subjects: Implications for preventing coronary heart disease during the prediabetic state. Circulation 2000;101:975-80. |
|15.||Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998;317:703-13. |
|16.||Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. Am J Cardiol 1995;75:894-903. |
|17.||Danesh J, Collins R, Peto R, Lowe GD. Haematocrit, viscosity, erythrocyte sedimentation rate: Meta-analyses of prospective studies of coronary heart disease. Eur Heart J 2000;21:515-20. |
|18.||Famodu AA, Izaah GO. Platelet count, plasma factor-3 (PF-3) availability and blood pressure in non-insulin dependent diabetes mellitus (NIDDM) Nigerians with sickle cell trait. High Blood Press 1990;7:117-20. |
|19.||Ajayi IO, Famodu AA, Oviasu I. Fibrinogen concentration: A marker of cardiovascular diseases in Nigerians. Turk J Haematol 2007;24:118-22. |
|20.||Gruden G, Cavallo-Perin P, Bazzan M, Stella S, Vuolo A, Pagano G. PAI-1 and factor VII activity are higher in IDDM patients with microalbuminuria. Diabetes 1994;43:426-9. |
|21.||Jain A, Gupta HL, Narayan S. Hyperfibrinogenemia in patients of diabetes mellitus in relation to glycemic control and urinary albumin excretion rate. J Assoc Physicians India 2001;49:227-30. |
|22.||Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: The JNC 7 report. JAMA 2003;289:2560-72. |
|23.||Ingram GI. A suggested schedule for the rapid investigation of acute haemostatic failure. J Clin Pathol 1961;14:356-60. |
|24.||Barham D, Trinder P. An improved colour reagent for the determination of blood glucose by the oxidase system. Analyst 1972;97:142-5. |
|25.||Reid H, Ugwu AC. A simple technique for rapid determination of plasma viscosity. Niger J Physiol Sci 1987;3:45-8. |
|26.||Dacie JV, Lewis SM. Practical Haematology. 7 th ed. Edinburgh, London: Churchill Livingstone; 1994. |
|27.||Ernest E, Koening W, Platral A, Keil U. Plasma viscosity and haemoglobin in the presence of cardiovascular risk factors. Clin Haemorheol 1988;8:507-15. |
|28.||Reid HL, Oli SM. The possible significance of abnormal blood rheology in diabetics with sickle cell trait (HbAS). West Afr J Med 1986;5:249-56. |
|29.||Nordt TK, Klassen KJ, Schneider DJ, Sobel BE. Augmentation of synthesis of plasminogen activator inhibitor type-1 in arterial endothelial cells by glucose and its implications for local fibrinolysis. Arterioscler Thromb 1993;13:1822-8. |
|30.||Juhan-Vague I, Thompson SG, Jespersen J. Involvement of the hemostatic system in the insulin resistance syndrome. A study of 1500 patients with angina pectoris. The ECAT Angina Pectoris Study Group. Arterioscler Thromb 1993;13:1865-73. |
[Table 1], [Table 2], [Table 3]