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Increased risk of cardiovascular disease in newly diagnosed Type 2 diabetic patients in a primary health care center in Trinidad
Diabetes Research and Clinical Practice 50 (2000) 137 – 145 www.elsevier.com/locate/diabres
Increased risk of cardiovascular disease in newly diagnosed Type 2 diabetic patients in a primary health care center in Trinidad C.E. Ezenwaka *, G. Davis Unit of Pathology and Microbiology, Department of Paraclinical Sciences, Faculty of Medical Sciences, Uni6ersity of the West Indies, St. Augustine, Trinidad, West Indies Received 8 September 1999; received in revised form 14 February 2000; accepted 24 April 2000
Abstract The prevalence of cardiovascular diseases (CVD) has increased sharply in the developing countries and because Type 2 diabetic patients are at increased risk for CVD, we assessed CVD risk factors in newly diagnosed Type 2 diabetic patients presenting in a primary health care center in Trinidad. Fasting and 2 h postprandial blood samples were collected from 387 (269 females, 118 males) newly diagnosed Type 2 diabetic patients (mean age: 53.1 9 6.6 years) for the determination of plasma glucose, creatinine, cholesterol (chol), triglyceride (TG) and % glycated hemoglobin (HbA1c) concentrations. Blood pressure and anthropometric indices were also measured. There were high prevalence rates of obesity (37%), overweight (35%), hypertension (21%), hypercholesterolemia (25%) and hypertriglyceridemia (22.3%) among the patients and these were significantly higher in women than men (P B 0.001). Patients of Indian descent had a significantly higher prevalence of diastolic hypertension and hypertriglyceridemia compared with patients of African origin or mixed race (PB0.001). In comparison with males, female diabetic patients were at greater risk of cardiovascular morbidity and mortality. Early detection of CVD risk factors and treatment, particularly in women, may be beneficial management strategy in all local diabetic clinics in Trinidad. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Prevalence; Type 2 diabetes; Cardiovascular disease
1. Introduction Type 2 diabetes (non-insulin-dependent) is a heterogeneous disorder characterized by impaired insulin action and insulin resistance [1,2]. The * Corresponding author. Fax: +1-868-6633797. E-mail address: [email protected] (C.E. Ezenwaka).
underlying causes are poorly understood but both genetic and environmental factors are well-recognized [3,4]. Type 2 diabetes but not Type 1, (insulin dependent diabetes), is commoner in black populations [5]. This condition is usually of insidious onset that many patients have 2–3 times normal plasma glucose concentration on first presentation and about 30% develop a clinical com-
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plication within 10 years of diagnosis [6]. The prevalence of Type 2 diabetes in the developing countries has increased sharply in recent years, approaching the rates in North America and Europe in some places [7]. The consequences of this have been increased prevalence rates of cardiovascular diseases (CVD) in these developing nations [8 – 10]. For instance, recent studies have shown that the worsening cardiovascular health in Puerto Ricans is related to high death rate from diabetes and hypertension [11]. Furthermore, a prospective investigation in Puerto Rican population has shown that age-adjusted rates for coronary heart disease, sudden and stroke death was 19 – 37% higher in urban than rural men [12]. Indeed, Type 2 diabetes is one of the important components of metabolic syndrome X which included insulin resistance, hypertension, dyslipidaemia and impaired glucose tolerance [13]. All these are well-recognized CVD risk factors in developed countries [14] and many have been shown to cluster in apparently healthy elderly African subjects [9]. We believe that any attempt at stemming the tide of increasing incidence of CVD in developing countries should start with critical evaluation of Type 2 diabetic patients who as a result of their diabetes are already at greater risk of progressing to CVD than their non-diabetic counterparts. In this regard, we evaluated the biochemical profile of all newly diagnosed Type 2 diabetic patients presenting in a primary health care clinic in Trinidad. We report here the results of our findings and discuss the implications in the management of Type 2 diabetic patients in a primary health care setting.
2. Patients and method
2.1. Patients These were 387 (269 females, 118 males) untreated patients who were diagnosed with Type 2 diabetes between October 1997 and December 1998. They were all referred to Lifestyle Disease Clinic, Arima Health Facility, after presenting with initial signs and symptoms of diabetes to their general practitioner. On their first visit in
this clinic their medical evaluation included performance of oral glucose tolerance tests and blood HbA1c, measurement to assess plasma glycemia in the preceding 3 months. The Lifestyle Disease Clinic is designated primary care diabetes center covering a large number (up to 40%) of diabetic patients in the Central Regional Health Authority (CRHA) in Trinidad. This clinic offers basic diabetes health education to the patients on weekly basis although there is paucity of qualified health educators. CRA is central and the largest of the five regional health authorities in the country, and Arima Health Facility provides regular diabetes care clinics twice per week. Furthermore, CRA, being in the center of Trinidad, is strategically located that it inhabits peoples of all ethnic groups (African or Indian origin and mixed race). All patients were aware of the protocol and gave informed voluntary consent and our institutional Ethics Committee approved the protocol. All the patients were nationals of Trinidad and Tobago, Trinidad is the larger part of the Twin Island Republic located about 11 km off the northern coast of Venezuela in South America. The study was conducted at the Arima Health Facility.
3. Study protocol The patients came to the primary health care center in the morning (07:00–08:00 h) after a 12–14 h overnight fast. All had hitherto been instructed to be on their usual diet and lifestyle 3 days before the study. An overnight fasting state was ascertained by direct questioning and later confirmed by checking the plasma samples for lipaemic clouding. Details of ethnic origin and age were directly ascertained from the patients while weight (kg) and height (m) were measured while they were wearing light clothing, without shoes in a standard hospital balance. After 10 min rest, systolic (first phase) and diastolic (fifth phase) blood pressures (BP) were taken on the dominant arm in a sitting position, using a standard mercury gauge sphygmomano meter (cuff size 23× 22.5 cm, Accoson, England). Three readings were taken for each subject, and the average of the second and third reading was recorded as the
C.E. Ezenwaka, G. Da6is / Diabetes Research and Clinical Practice 50 (2000) 137–145
blood pressure [15]. A 10 ml venous blood sample was taken from each patient and put into EDTA (for HbA1c), sodium fluoride (plasma glucose) and heparin (plasma lipids) tubes. Subsequently, each patient consumed 75 g of anhydrous glucose dissolved in 250–300 ml of water and had another 10 ml of blood taken 2 h after consuming the oral glucose. Blood samples (except for HbA1c) were separated within 2 h of collection and the plasma stored frozen at −20°C.
4. Definition of dyslipidaemia, hypertension, obesity and poor glycaemic levels Dyslipidaemia was considered as total cholesterol levels \5.2 mmol/l and triglyceride \ 2.26 mmol/l [16]. Hypertension was defined as blood pressure \160/90 mmHg [17] while overweight and obesity were considered as BMI \25 B30 and \30 kg/m2 respectively [18]. Poor plasma glycaemic levels in the proceeding 3 months was considered as HbA1c levels \ 7.0% [19].
5. Biochemical analysis Plasma glucose, total cholesterol (T-chol) and tniglycerides (TG) levels were determined by standard automated enzymatic methods using commercial assay kits (DMA Inc., East Arlington, TX, USA) in RA1000 (Technicon, USA) in our laboratory. Glycosylated hemaglobin (%HbA1c) was measured by an affinity microchromatographic methodology using Helena Glyco-Tek HemeSpec® Plus Spectrophotometer (HemeSpec Plus, Helena Laboratories, USA). The precision of the HbA1c measurement was checked using the normal and abnormal quality control samples contained in the assay kits and the intra- and inter-assay coefficients of variation were 1.5 and 1.8%, respectively.
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software was used in all analyses [20]. Comparison between gender was performed using Students t-tests while ANOVA was employed in the analysis of the differences among the different ethnic groups. Multiple linear regression analysis was used to assess the contributions of age, sex, BMI and race in the CVD risk among the different ethnic groups and between gender while x 2 tests were performed for the non-parametric data. A P-value B 0.05 was considered statistically significant.
7. Results Analyses of the data collected on 387 untreated patients presenting with Type 2 diabetes in this clinic indicated high prevalence rates of obesity, overweight, hypertension, hypercholesterolaemia and hypertriglyceridaemia. The results are presented according to gender and ethnic origin.
7.1. Gender-related differences The majority of the patients were women (269 females, 118 males). The prevalence rates of obesity (37%), overweight (35%), hypertension (21%), hypercholesterolaemia (25%) and hypertriglyceridaemia (22.3%) were high among the patients and women had a significantly higher prevalence rates of these parameters than men (PB0.001). In comparison with men, women also had significantly higher fasting plasma glucose levels (PB 0.001) but the 2 h post-prandial levels were similar (P\ 0.05) (Table 1). Although women had higher fasting plasma glucose concentration, both sexes had similar %HbA1c. The high values of glycated hemoglogbin were indicative of poor glycaemic levels in the preceding 3 months. Men had significantly higher plasma creatinine concentration than women (PB 0.001) although multiple linear regression analysis showed that this difference was not independent of age (Table 2).
6. Data analyses
7.2. Multi-ethnic differences
The results are expressed as mean 9SD. The Statistical Package for the Social Sciences (SPSS)
There were no significant differences in the prevalence rates of hypertension and overweight
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Parameters
All patients (n=387)
Age (year) 54.79 11.9 Bmi (kg/m2) 28.5 96.3 sBP (mmHg) 140 9 21.9 dBP (mmHg) 89 912.0 Fpg (mmol/l) 9.493.6 2hppg (mmol/l) 12.74 94.8 T-Chol (mmol/l) 4.4 9 1.3 TG (mmol/l) 1.79 1.2 HbA1c (%) 13.5 99.7 Creatinine (mmol/l) 93.8940.7
Gender-related difference: male versus female
Ethnicity-related differences: Africa versus India versus mixed race
Male (n =118)
Female (n = 269)
Descents of Africa (n = 134)
Descents of India (n=157)
Mixed race (n= 94)
55.6 912.1 26.6 95.4 139920.4 909 11.9 8.7 9 3.3 12.3 94.8 4.291.3 1.9 9 1.3 13.7 9 2.9 109.2 9 43.5
54.2 911.9 29.3 9 6.5* 141 9 22.7 89 9 12.3 9.793.6* 12.9 94.7 4.5 91.3 1.6 9 1.1 13.5 9 11.1 87.3 9 37.7*
54.5 9 13.3 29.0 9 6.2 139 922.8 88 913.6 9.1 9 3.6 12.3 9 4.8 4.1 9 1.1*I,M 1.3 90.8 14.7 915.7 92.7 9 40.4
53.8 910.8*M 28.0 9 6.4 140 9 22.0 89 9 11.5 9.8 93.4 13.19 4.8 4.59 1.3 2.1 9 1.3*A 13.19 2.0 89.3 934.2
56.5+11.6 28.69 6.3 1429 20.6 919 10.5 9.39 3.8 12.69 4.7 4.79 1.4 1.89 1.3 12.392.5 102.2948.9*I
a * PB0.05, for comparison between men and women and three ethnic groups (A, African descendants; I, Indian descendants; M, mixed race), fpg, fasting plasma glucose, 2hppg 2 h postprandial glucose; tg, triglyceride; t-chol, total cholesterol; bmi, body mass index.
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Table 1 Distribution of some selected biochemical characteristics of the patients according to gender and ethnic groupsa
C.E. Ezenwaka, G. Da6is / Diabetes Research and Clinical Practice 50 (2000) 137–145
among the three ethnic groups (P \0.05). However, patients of Indian origin had a significantly higher prevalence of diastolic hypertension compared with patients from mixed race, again this difference was not independent of BMI on multiple linear regression analysis (Table 2). Whereas patients of mixed race had the lowest prevalence of obesity, patients of African descent had the lowest prevalence of hypercholesterolaemia (P B 0.05). Multiple linear regression analysis showed that the differences in the levels of plasma cholesterol and triglyceride were related to differing BMI among the different ethnic groups (Table 2). The fasting and 2 h postprandial glucose concentrations were similar in all ethnic groups although all had high mean %HbA1c. The mean plasma creatinine levels did not differ between patients of African origin and mixed race although patients of latter race had significantly higher mean value compared with patients of Indian origin (P B 0.05) Table 3.
8. Discussion The analyses of our data showed that a high percentage of the newly diagnosed Type 2 diabetic patients additionally had high blood pressure, hypercholesterolaemia, hypertriglyceridaemia and obesity. The prevalence rates of these cardiovascular (CVD) risk factors differ between male and female patients and among different ethnic
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groups. These observations have significant implications in the management of Type 2 diabetes in a primary health care setting. The present study comes at the heels of a recent report from the same population indicating that there were little changes in indicators of metabolic control (blood pressure and body weight) 5 years after educational intervention [21]. Although some authors [22] have argued that there are ‘no magic bullets’ for improving the quality of health care, educational intervention [21] and risk-assessing studies, such as ours, have the potential to bring about modest improvements in quality of care in primary health care settings. For instance, there is evidence of a modest improvement in quality of health care in Trinidad and Tobago 5 years after the introduction of the recommendations of initial research evaluation [21,23]. This suggests that practical application of the results of research studies, such as the present report, could potentially assist in minimizing the progression of diabetes to cardiovascular disorder in the population. Studies done in a developing African country showed a higher prevalence of CVD risk factors in elderly female non-diabetic subjects [9] contrary to male sex preponderance in Caucasian [24] and Puerto Rican populations [12]. However, in our study of newly diagnosed diabetic patients, we observed a high prevalence of hypertension, obesity and hypercholesterolaemia in patients who are already at increased risk for CVD, and these
Table 2 Multiple linear regression anaivsis showing independent contributions of sex, race, body mass index and age to differences in CVD risk factors in the patient population studieda CVD risk factors
Independent contributing factors
Dependent variables
Sex c
Race c
BMI c
Age c
Systolic blood pressure Distolic blood pressure Creatinine Fasting plasma glucose Total cholesterol Triglyceride HBAlc
0.025 −0.078 −0.285** 0.154** 0.098 −0.104 −0.007
0.019 0.065 0.108 0.044 0.167** 0.191 −0.112
0.091 0.142** 0.061 −0.083 0.150* 0.188* −0.095
0.316 0.035 0.199 −0.072 0.061 0.096 −0.008
a
c , standardised regression coefficients (b); *PB0.05; **PB0.01.
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CVD risk factors
Overweight (BMI\25B30 kg/m2) Obesity (BMI\30 kg/m2) Hypertension Systolic hypertension Diastolic hypertension Hypercholesterolemia Hypertriglyceridemia a
Proportion of patients with additional risk
Gender-related difference: male versus female
Ethnicity-related differences: Africa versus India versus mixed race
Male (%)
Africa (%)
India (%)
Mixed race (%)
39 (30.7)
53 (41.7)
35 (27.6)
54 30 31 79 11 4
53 28 33 93 29 21
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40 (32)
136 81 90 242 61 31
27 23 24 79 16 15
(20) (28) (27) (33) (26) (48)
Female (%) 87 (68)* 109 58 66 163 45 16
(80)* (72)* (73) (67) (74) (52)
(40.0) (38.0) (35.2) (33.1) (18)*I,M (13)
(39)*M (35.4) (37.5) (38.9)*M (47.5) (68)
28 21 24 67 21 6
(21)*A,I (26.6) (27.3) (28.0) (34.4) (19)
*PB0.05, for comparison between men and women and among three ethnic groups (A, African descendants; I = Indian descendants; M, mixed race).
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Table 3 Prevalence of additional CVD risk factors distributed according to gender and ethnic groupsa
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factors were higher in female patients then males. It is not completely clear if the preponderance of CVD risk factors in the female patients was due to the larger number of female diabetic patients seen or the well-known greater risk of postmenopausal women to CVD [25]. Indeed, diabetic women usually do not have the pre-menopausal benefit seen in the general female population [26]. However, increased CVD mortality of diabetic women in comparison with diabetic men [27,28] has been associated with reduced insulin sensitivity in female diabetic patients [29]. Furthermore, differing sex hormone concentrations in the men and women is important in the risk of CVD, in that low levels of dehydroepiandrosterone sulfate (DHEAS) concentrations predicted CVD mortality in elderly men [30] but not in postmenopausal women [31]. We did not, however, assess the insulin sensitivity and DHEAS concentrations in the patients to determine if these observations in developed countries would hold true in a Caribbean population. The higher plasma creatinine concentration observed in male rather than female patients may be related to greater muscle mass in the male patients who had greater total body weight. Additionally, multiple linear regression analysis showed that this difference is not independent of age. Although the risk of diabetes and hypertension to CVD and renal disease is well known [32], we are not aware of gender-related differences in severity of kidney disease in diabetes. Further biochemical investigations such as plasma N-acetylglucoasaminidase measurement, known to reflect cellular damage in the proximal tubule [33], will be required to explain the gender-related observation. This is important in view of the fact that the patients had extremely high values of HbA1c indicative of poor plasma glycemia in the preceding 3 months. Indeed, the high mean values of the HbA1c appear to reflect the insidious nature of Type 2 diabetes. It is a common experience that many patients have 2 – 3 times normal plasma glucose concentration on first presentation [6], and is commoner in developing countries [5]. There were few differences in the prevalence rates of CVD risk factors among the different ethnic groups. Hypertriglyceridemia has previ-
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ously been shown to be an important CVD risk factor [34] and its prevalence was highest among the patients of Indian origin. Generally, patients of Indian descent had the highest cluster of CVD risk factors in comparison with those of African origin or mixed race. This is in agreement with previous studies in this population [35–38]. Further analysis of the data (not shown) of this ethnic group showed that the female patients had significantly higher prevalence rates of hypertension, systolic and diastolic hypertension, hypercholesterolaemia, overweight and obesity similar to the overall observation discussed above. Thus, it appears that patients of Indian descent may be more vulnerable to CVD morbidity and mortality in comparison with the other ethnic groups. This ethnic group would probably require special attention in regular patients’ evaluation and treatment. We recognize that the absence of CVD risk factors such as cigarette smoking, waist-to-hip ratio and LDL-cholesterol level in the present report poses limitations to generalization of our result, though we identified significant CVD risk differences between gender and among the different ethnic groups. Consequently, we have submitted research proposal aimed at exploring the gender/ethnicity differences in a larger population based study. In conclusion, our analyses has shown that there were high prevalence rates of recognized CVD risk factors in Type 2 diabetic patients on first presentation in this clinic. These factors cluster more in women than men. Women may be at greater risk of cardiovascular mortality than men. We suggest that early detection of these risk factors and treatment, particularly in women, should be a standard policy in all primary health care centers in Trinidad and Tobago.
Acknowledgements This study was supported by the Research and Publication Fund Committee, University of the West Indies, St Augustine Campus, Trinidad. We are grateful to the Primary Health Care Manager, Central Regional Health Authority, Trini-
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dad and Tobago for permission to undertake this study in the Region, Mr Henry, Aldrick Sandy and Kethurah Williams for technical assistance. We also thank all the members ofstaff, Lifestyle Disease Clinic, Arima Health Facility, for their cooperation and assistance during the studies.
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[14] R.A. DeFronzo, E. Ferannini, Insulin resistance a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidaemia and atheroscierotic vascular disease, Diab. Care 18 (1991) 173 – 194. [15] Hypertension detection and Follow-up Programme Cooperative Group, Blood pressure studies in 14 communities: a two stage screen for hypertension, JAMA 237 (1977) 2385 – 2391. [16] The Expert Panel, Report of the National Cholesterol Education Programme, Expert Panel on detection, evaluation and treatment of high blood cholesterol in adults, Arch. Intern. Med. 148 (1988) 36 – 69. [17] World Health Organization, Arterial hypertension, Report of a World Health Organization Expert Committee 628 (1978). [18] World Health Organization Working Group, Use and interpretation of anthropometric indicators of nutritional status, Bull. WHO 64 (6) (1986) 929 – 941. [19] United Kingdom Prospective Diabetes Study, Implications for the care of people with Type 2 diabetes, British Diabetic Association Publication, December 1998. [20] SPSS-X User’s guide, second ed., McGraw-Hill, New York, 1998. [21] M.C. Gulliford, D. Mahabir, A 5 year evaluation of intervention in diabetes care in Trinidad and Tobago, Diab. Med. 16 (1999) 939 – 945. [22] A.D. Oxman, M.A. Thomson, D.A. Davis, et al., No magic bullets: a systematic review of 102 trials of intervention to improve professional practice, CMAJ 153 (1995) 1423 – 1431. [23] M.C. Gulliford, C.V. Alert, D. Mahabir, S.M. Ariyanayagam-Baksh, H.S. Fraser, D.I. Picou, Diabetes care in middle-income countries: a Caribbean case study, Diab. Med. 13 (1996) 574 – 581. [24] K.T. Khaw, E. Barrett-Connor, Sex differences, hormones and coronary heart disease, in: M. Marmot, P. Elliot (Eds.), Coronary Heart Disease From Aetiology to Public Health, Oxford Medical Publ. 1992, pp. 274 – 286. [25] P. Ebeling, V.A. Kolvisto, Physiological importance of dehydroepiandrosterone, Lancet 343 (1994) 1479 – 1481. [26] M.I. Uusitupa, L.K. Niskanen, O. Siitonen, et al., Tenyear cardiovascular mortality in relation to risk factors and abnormalities in lipoprotein composition in Type 2 (non-insulin-dependent) diabetic and non-diabetic subjects, Diabetologia 36 (1993) 1175 – 1184. [27] S. Heyden, G. Heiss, A.G. Bartel, et al., Sex differences in coronary mortality among diabetics in Evans County, GA, J. Chronic. Dis. 33 (1980) 265 – 271. [28] R.J. Jarrett, P. McCartney, H. Keen, The Bedford survey: 10-year mortality rates in newly diagnosed diabetics, borderline diabetics and normoglycaemie control and risk indices for coronary heart disease on borderline diabetics, Diabetologia 22 (1982) 79 – 84. [29] T.J. Orchard, D.J. Becker, L.H. Kuller, et al., Age and sex variations in glucose tolerance and insulin responses: parallel with cardiovascular risk, J. Chronic. Dis. 35 (1982) 123 – 137.
C.E. Ezenwaka, G. Da6is / Diabetes Research and Clinical Practice 50 (2000) 137–145 [30] E. Barrett-Connor, K.T. Khaw, S.S.C. Yen, A prospective study of dehydroepiandrosterone sulfate, mortality and cardiovascular disease, N. Engl. J. Med. 315 (1986) 1519– 1524. [31] E. Barrett-Connor, K.T. Khaw, Absence of an inverse relation of dehydroeplandrosterone sulfate with cardiovascular mortality in postmenopausal women, N. Engl. J. Med. 317 (1987) 711. [32] T.V. Perneger, F.L. Brancati, P.X. Whelton, et al., Endstage renal disease attributable to diabetes mellitus, Ann. Intem. Med. 121 (1994) 912–918. [33] UK Prospective Diabetes Study (UKPDS) XI, Biochemical risk factors in Type 2 diabetic patients at diagnosis compared with aged-matched normal subjects, Diab. Med. 11 (1994) 534 – 544. [34] F. Cambien, A. Jacqueson, J.L. Richard, et al., Is the level of serum triglyceride a significant predictor of coronary, death in ‘cholesterolemic’ subjects. The Paris Prospective Study, Am. J. Epidemiol. 124 (1986) 624–632.
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[35] D. Ragoobirsingh, J.B. Davidson, The effect of demographic factors on serum lipids in diabetics of Trinidad and Tobago: possible association with ischaemic heart disease, W. Ind. Med. J. 38 (1989) 99 – 104. [36] G.I. Miller, G.L.A. Beckles, G.H. Maude, et al., High density, lipoprotein cholesterol concentration as a predictor of coronary heart disease in West Indian men, J. Epidemiol. Comm. Health 44 (2) (1990) 136 – 138. [37] G.J. Miller, B.R. Kirkwood, G.L.A. Beckles, et al., Adult male all-cause cardiovascular and cerebrovascular mortality in relation to ethnic group, systolic blood pressure and blood glucose concentration in Trinidad, West Indies, Int. J. Epidemiol. 17 (1988) 62 – 69. [38] G.J. Miller, G.L.A. Beckles, S.D. Alexis, et al., Serum lipoproteins and susceptibility of men of Indian descent to coronary heart disease: The St. James survey, Trinidad, Lancet 2 (1982) 200 – 203.
Increased risk of cardiovascular disease in newly diagnosed Type 2 diabetic patients in a primary health care center in Trinidad C.E. Ezenwaka *, G. Davis Unit of Pathology and Microbiology, Department of Paraclinical Sciences, Faculty of Medical Sciences, Uni6ersity of the West Indies, St. Augustine, Trinidad, West Indies Received 8 September 1999; received in revised form 14 February 2000; accepted 24 April 2000
Abstract The prevalence of cardiovascular diseases (CVD) has increased sharply in the developing countries and because Type 2 diabetic patients are at increased risk for CVD, we assessed CVD risk factors in newly diagnosed Type 2 diabetic patients presenting in a primary health care center in Trinidad. Fasting and 2 h postprandial blood samples were collected from 387 (269 females, 118 males) newly diagnosed Type 2 diabetic patients (mean age: 53.1 9 6.6 years) for the determination of plasma glucose, creatinine, cholesterol (chol), triglyceride (TG) and % glycated hemoglobin (HbA1c) concentrations. Blood pressure and anthropometric indices were also measured. There were high prevalence rates of obesity (37%), overweight (35%), hypertension (21%), hypercholesterolemia (25%) and hypertriglyceridemia (22.3%) among the patients and these were significantly higher in women than men (P B 0.001). Patients of Indian descent had a significantly higher prevalence of diastolic hypertension and hypertriglyceridemia compared with patients of African origin or mixed race (PB0.001). In comparison with males, female diabetic patients were at greater risk of cardiovascular morbidity and mortality. Early detection of CVD risk factors and treatment, particularly in women, may be beneficial management strategy in all local diabetic clinics in Trinidad. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Prevalence; Type 2 diabetes; Cardiovascular disease
1. Introduction Type 2 diabetes (non-insulin-dependent) is a heterogeneous disorder characterized by impaired insulin action and insulin resistance [1,2]. The * Corresponding author. Fax: +1-868-6633797. E-mail address: [email protected] (C.E. Ezenwaka).
underlying causes are poorly understood but both genetic and environmental factors are well-recognized [3,4]. Type 2 diabetes but not Type 1, (insulin dependent diabetes), is commoner in black populations [5]. This condition is usually of insidious onset that many patients have 2–3 times normal plasma glucose concentration on first presentation and about 30% develop a clinical com-
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plication within 10 years of diagnosis [6]. The prevalence of Type 2 diabetes in the developing countries has increased sharply in recent years, approaching the rates in North America and Europe in some places [7]. The consequences of this have been increased prevalence rates of cardiovascular diseases (CVD) in these developing nations [8 – 10]. For instance, recent studies have shown that the worsening cardiovascular health in Puerto Ricans is related to high death rate from diabetes and hypertension [11]. Furthermore, a prospective investigation in Puerto Rican population has shown that age-adjusted rates for coronary heart disease, sudden and stroke death was 19 – 37% higher in urban than rural men [12]. Indeed, Type 2 diabetes is one of the important components of metabolic syndrome X which included insulin resistance, hypertension, dyslipidaemia and impaired glucose tolerance [13]. All these are well-recognized CVD risk factors in developed countries [14] and many have been shown to cluster in apparently healthy elderly African subjects [9]. We believe that any attempt at stemming the tide of increasing incidence of CVD in developing countries should start with critical evaluation of Type 2 diabetic patients who as a result of their diabetes are already at greater risk of progressing to CVD than their non-diabetic counterparts. In this regard, we evaluated the biochemical profile of all newly diagnosed Type 2 diabetic patients presenting in a primary health care clinic in Trinidad. We report here the results of our findings and discuss the implications in the management of Type 2 diabetic patients in a primary health care setting.
2. Patients and method
2.1. Patients These were 387 (269 females, 118 males) untreated patients who were diagnosed with Type 2 diabetes between October 1997 and December 1998. They were all referred to Lifestyle Disease Clinic, Arima Health Facility, after presenting with initial signs and symptoms of diabetes to their general practitioner. On their first visit in
this clinic their medical evaluation included performance of oral glucose tolerance tests and blood HbA1c, measurement to assess plasma glycemia in the preceding 3 months. The Lifestyle Disease Clinic is designated primary care diabetes center covering a large number (up to 40%) of diabetic patients in the Central Regional Health Authority (CRHA) in Trinidad. This clinic offers basic diabetes health education to the patients on weekly basis although there is paucity of qualified health educators. CRA is central and the largest of the five regional health authorities in the country, and Arima Health Facility provides regular diabetes care clinics twice per week. Furthermore, CRA, being in the center of Trinidad, is strategically located that it inhabits peoples of all ethnic groups (African or Indian origin and mixed race). All patients were aware of the protocol and gave informed voluntary consent and our institutional Ethics Committee approved the protocol. All the patients were nationals of Trinidad and Tobago, Trinidad is the larger part of the Twin Island Republic located about 11 km off the northern coast of Venezuela in South America. The study was conducted at the Arima Health Facility.
3. Study protocol The patients came to the primary health care center in the morning (07:00–08:00 h) after a 12–14 h overnight fast. All had hitherto been instructed to be on their usual diet and lifestyle 3 days before the study. An overnight fasting state was ascertained by direct questioning and later confirmed by checking the plasma samples for lipaemic clouding. Details of ethnic origin and age were directly ascertained from the patients while weight (kg) and height (m) were measured while they were wearing light clothing, without shoes in a standard hospital balance. After 10 min rest, systolic (first phase) and diastolic (fifth phase) blood pressures (BP) were taken on the dominant arm in a sitting position, using a standard mercury gauge sphygmomano meter (cuff size 23× 22.5 cm, Accoson, England). Three readings were taken for each subject, and the average of the second and third reading was recorded as the
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blood pressure [15]. A 10 ml venous blood sample was taken from each patient and put into EDTA (for HbA1c), sodium fluoride (plasma glucose) and heparin (plasma lipids) tubes. Subsequently, each patient consumed 75 g of anhydrous glucose dissolved in 250–300 ml of water and had another 10 ml of blood taken 2 h after consuming the oral glucose. Blood samples (except for HbA1c) were separated within 2 h of collection and the plasma stored frozen at −20°C.
4. Definition of dyslipidaemia, hypertension, obesity and poor glycaemic levels Dyslipidaemia was considered as total cholesterol levels \5.2 mmol/l and triglyceride \ 2.26 mmol/l [16]. Hypertension was defined as blood pressure \160/90 mmHg [17] while overweight and obesity were considered as BMI \25 B30 and \30 kg/m2 respectively [18]. Poor plasma glycaemic levels in the proceeding 3 months was considered as HbA1c levels \ 7.0% [19].
5. Biochemical analysis Plasma glucose, total cholesterol (T-chol) and tniglycerides (TG) levels were determined by standard automated enzymatic methods using commercial assay kits (DMA Inc., East Arlington, TX, USA) in RA1000 (Technicon, USA) in our laboratory. Glycosylated hemaglobin (%HbA1c) was measured by an affinity microchromatographic methodology using Helena Glyco-Tek HemeSpec® Plus Spectrophotometer (HemeSpec Plus, Helena Laboratories, USA). The precision of the HbA1c measurement was checked using the normal and abnormal quality control samples contained in the assay kits and the intra- and inter-assay coefficients of variation were 1.5 and 1.8%, respectively.
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software was used in all analyses [20]. Comparison between gender was performed using Students t-tests while ANOVA was employed in the analysis of the differences among the different ethnic groups. Multiple linear regression analysis was used to assess the contributions of age, sex, BMI and race in the CVD risk among the different ethnic groups and between gender while x 2 tests were performed for the non-parametric data. A P-value B 0.05 was considered statistically significant.
7. Results Analyses of the data collected on 387 untreated patients presenting with Type 2 diabetes in this clinic indicated high prevalence rates of obesity, overweight, hypertension, hypercholesterolaemia and hypertriglyceridaemia. The results are presented according to gender and ethnic origin.
7.1. Gender-related differences The majority of the patients were women (269 females, 118 males). The prevalence rates of obesity (37%), overweight (35%), hypertension (21%), hypercholesterolaemia (25%) and hypertriglyceridaemia (22.3%) were high among the patients and women had a significantly higher prevalence rates of these parameters than men (PB0.001). In comparison with men, women also had significantly higher fasting plasma glucose levels (PB 0.001) but the 2 h post-prandial levels were similar (P\ 0.05) (Table 1). Although women had higher fasting plasma glucose concentration, both sexes had similar %HbA1c. The high values of glycated hemoglogbin were indicative of poor glycaemic levels in the preceding 3 months. Men had significantly higher plasma creatinine concentration than women (PB 0.001) although multiple linear regression analysis showed that this difference was not independent of age (Table 2).
6. Data analyses
7.2. Multi-ethnic differences
The results are expressed as mean 9SD. The Statistical Package for the Social Sciences (SPSS)
There were no significant differences in the prevalence rates of hypertension and overweight
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Parameters
All patients (n=387)
Age (year) 54.79 11.9 Bmi (kg/m2) 28.5 96.3 sBP (mmHg) 140 9 21.9 dBP (mmHg) 89 912.0 Fpg (mmol/l) 9.493.6 2hppg (mmol/l) 12.74 94.8 T-Chol (mmol/l) 4.4 9 1.3 TG (mmol/l) 1.79 1.2 HbA1c (%) 13.5 99.7 Creatinine (mmol/l) 93.8940.7
Gender-related difference: male versus female
Ethnicity-related differences: Africa versus India versus mixed race
Male (n =118)
Female (n = 269)
Descents of Africa (n = 134)
Descents of India (n=157)
Mixed race (n= 94)
55.6 912.1 26.6 95.4 139920.4 909 11.9 8.7 9 3.3 12.3 94.8 4.291.3 1.9 9 1.3 13.7 9 2.9 109.2 9 43.5
54.2 911.9 29.3 9 6.5* 141 9 22.7 89 9 12.3 9.793.6* 12.9 94.7 4.5 91.3 1.6 9 1.1 13.5 9 11.1 87.3 9 37.7*
54.5 9 13.3 29.0 9 6.2 139 922.8 88 913.6 9.1 9 3.6 12.3 9 4.8 4.1 9 1.1*I,M 1.3 90.8 14.7 915.7 92.7 9 40.4
53.8 910.8*M 28.0 9 6.4 140 9 22.0 89 9 11.5 9.8 93.4 13.19 4.8 4.59 1.3 2.1 9 1.3*A 13.19 2.0 89.3 934.2
56.5+11.6 28.69 6.3 1429 20.6 919 10.5 9.39 3.8 12.69 4.7 4.79 1.4 1.89 1.3 12.392.5 102.2948.9*I
a * PB0.05, for comparison between men and women and three ethnic groups (A, African descendants; I, Indian descendants; M, mixed race), fpg, fasting plasma glucose, 2hppg 2 h postprandial glucose; tg, triglyceride; t-chol, total cholesterol; bmi, body mass index.
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Table 1 Distribution of some selected biochemical characteristics of the patients according to gender and ethnic groupsa
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among the three ethnic groups (P \0.05). However, patients of Indian origin had a significantly higher prevalence of diastolic hypertension compared with patients from mixed race, again this difference was not independent of BMI on multiple linear regression analysis (Table 2). Whereas patients of mixed race had the lowest prevalence of obesity, patients of African descent had the lowest prevalence of hypercholesterolaemia (P B 0.05). Multiple linear regression analysis showed that the differences in the levels of plasma cholesterol and triglyceride were related to differing BMI among the different ethnic groups (Table 2). The fasting and 2 h postprandial glucose concentrations were similar in all ethnic groups although all had high mean %HbA1c. The mean plasma creatinine levels did not differ between patients of African origin and mixed race although patients of latter race had significantly higher mean value compared with patients of Indian origin (P B 0.05) Table 3.
8. Discussion The analyses of our data showed that a high percentage of the newly diagnosed Type 2 diabetic patients additionally had high blood pressure, hypercholesterolaemia, hypertriglyceridaemia and obesity. The prevalence rates of these cardiovascular (CVD) risk factors differ between male and female patients and among different ethnic
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groups. These observations have significant implications in the management of Type 2 diabetes in a primary health care setting. The present study comes at the heels of a recent report from the same population indicating that there were little changes in indicators of metabolic control (blood pressure and body weight) 5 years after educational intervention [21]. Although some authors [22] have argued that there are ‘no magic bullets’ for improving the quality of health care, educational intervention [21] and risk-assessing studies, such as ours, have the potential to bring about modest improvements in quality of care in primary health care settings. For instance, there is evidence of a modest improvement in quality of health care in Trinidad and Tobago 5 years after the introduction of the recommendations of initial research evaluation [21,23]. This suggests that practical application of the results of research studies, such as the present report, could potentially assist in minimizing the progression of diabetes to cardiovascular disorder in the population. Studies done in a developing African country showed a higher prevalence of CVD risk factors in elderly female non-diabetic subjects [9] contrary to male sex preponderance in Caucasian [24] and Puerto Rican populations [12]. However, in our study of newly diagnosed diabetic patients, we observed a high prevalence of hypertension, obesity and hypercholesterolaemia in patients who are already at increased risk for CVD, and these
Table 2 Multiple linear regression anaivsis showing independent contributions of sex, race, body mass index and age to differences in CVD risk factors in the patient population studieda CVD risk factors
Independent contributing factors
Dependent variables
Sex c
Race c
BMI c
Age c
Systolic blood pressure Distolic blood pressure Creatinine Fasting plasma glucose Total cholesterol Triglyceride HBAlc
0.025 −0.078 −0.285** 0.154** 0.098 −0.104 −0.007
0.019 0.065 0.108 0.044 0.167** 0.191 −0.112
0.091 0.142** 0.061 −0.083 0.150* 0.188* −0.095
0.316 0.035 0.199 −0.072 0.061 0.096 −0.008
a
c , standardised regression coefficients (b); *PB0.05; **PB0.01.
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CVD risk factors
Overweight (BMI\25B30 kg/m2) Obesity (BMI\30 kg/m2) Hypertension Systolic hypertension Diastolic hypertension Hypercholesterolemia Hypertriglyceridemia a
Proportion of patients with additional risk
Gender-related difference: male versus female
Ethnicity-related differences: Africa versus India versus mixed race
Male (%)
Africa (%)
India (%)
Mixed race (%)
39 (30.7)
53 (41.7)
35 (27.6)
54 30 31 79 11 4
53 28 33 93 29 21
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40 (32)
136 81 90 242 61 31
27 23 24 79 16 15
(20) (28) (27) (33) (26) (48)
Female (%) 87 (68)* 109 58 66 163 45 16
(80)* (72)* (73) (67) (74) (52)
(40.0) (38.0) (35.2) (33.1) (18)*I,M (13)
(39)*M (35.4) (37.5) (38.9)*M (47.5) (68)
28 21 24 67 21 6
(21)*A,I (26.6) (27.3) (28.0) (34.4) (19)
*PB0.05, for comparison between men and women and among three ethnic groups (A, African descendants; I = Indian descendants; M, mixed race).
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Table 3 Prevalence of additional CVD risk factors distributed according to gender and ethnic groupsa
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factors were higher in female patients then males. It is not completely clear if the preponderance of CVD risk factors in the female patients was due to the larger number of female diabetic patients seen or the well-known greater risk of postmenopausal women to CVD [25]. Indeed, diabetic women usually do not have the pre-menopausal benefit seen in the general female population [26]. However, increased CVD mortality of diabetic women in comparison with diabetic men [27,28] has been associated with reduced insulin sensitivity in female diabetic patients [29]. Furthermore, differing sex hormone concentrations in the men and women is important in the risk of CVD, in that low levels of dehydroepiandrosterone sulfate (DHEAS) concentrations predicted CVD mortality in elderly men [30] but not in postmenopausal women [31]. We did not, however, assess the insulin sensitivity and DHEAS concentrations in the patients to determine if these observations in developed countries would hold true in a Caribbean population. The higher plasma creatinine concentration observed in male rather than female patients may be related to greater muscle mass in the male patients who had greater total body weight. Additionally, multiple linear regression analysis showed that this difference is not independent of age. Although the risk of diabetes and hypertension to CVD and renal disease is well known [32], we are not aware of gender-related differences in severity of kidney disease in diabetes. Further biochemical investigations such as plasma N-acetylglucoasaminidase measurement, known to reflect cellular damage in the proximal tubule [33], will be required to explain the gender-related observation. This is important in view of the fact that the patients had extremely high values of HbA1c indicative of poor plasma glycemia in the preceding 3 months. Indeed, the high mean values of the HbA1c appear to reflect the insidious nature of Type 2 diabetes. It is a common experience that many patients have 2 – 3 times normal plasma glucose concentration on first presentation [6], and is commoner in developing countries [5]. There were few differences in the prevalence rates of CVD risk factors among the different ethnic groups. Hypertriglyceridemia has previ-
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ously been shown to be an important CVD risk factor [34] and its prevalence was highest among the patients of Indian origin. Generally, patients of Indian descent had the highest cluster of CVD risk factors in comparison with those of African origin or mixed race. This is in agreement with previous studies in this population [35–38]. Further analysis of the data (not shown) of this ethnic group showed that the female patients had significantly higher prevalence rates of hypertension, systolic and diastolic hypertension, hypercholesterolaemia, overweight and obesity similar to the overall observation discussed above. Thus, it appears that patients of Indian descent may be more vulnerable to CVD morbidity and mortality in comparison with the other ethnic groups. This ethnic group would probably require special attention in regular patients’ evaluation and treatment. We recognize that the absence of CVD risk factors such as cigarette smoking, waist-to-hip ratio and LDL-cholesterol level in the present report poses limitations to generalization of our result, though we identified significant CVD risk differences between gender and among the different ethnic groups. Consequently, we have submitted research proposal aimed at exploring the gender/ethnicity differences in a larger population based study. In conclusion, our analyses has shown that there were high prevalence rates of recognized CVD risk factors in Type 2 diabetic patients on first presentation in this clinic. These factors cluster more in women than men. Women may be at greater risk of cardiovascular mortality than men. We suggest that early detection of these risk factors and treatment, particularly in women, should be a standard policy in all primary health care centers in Trinidad and Tobago.
Acknowledgements This study was supported by the Research and Publication Fund Committee, University of the West Indies, St Augustine Campus, Trinidad. We are grateful to the Primary Health Care Manager, Central Regional Health Authority, Trini-
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dad and Tobago for permission to undertake this study in the Region, Mr Henry, Aldrick Sandy and Kethurah Williams for technical assistance. We also thank all the members ofstaff, Lifestyle Disease Clinic, Arima Health Facility, for their cooperation and assistance during the studies.
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