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Year : 2017  |  Volume : 6  |  Issue : 3  |  Page : 145-150

Carotid intima-media thickness and cardiometabolic risk factors in Pakistani type 2 diabetics

Department of Medicine, United Medical and Dental College, Karachi, Pakistan

Date of Web Publication6-Feb-2018

Correspondence Address:
Dr. Farhat Bashir
40-B, 1st East Street, Phase 1, DHA, Karachi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/sjhs.sjhs_66_17

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Context: Carotid intima-media thickness (CIMT) is a surrogate measure of atherosclerosis. In patients with type 2 diabetes mellitus, coexistent cardiometabolic risk factors contribute to atherosclerosis. Aims: The aim of this study is to explore the relationship between known cardiometabolic risk factors and CIMT in patients with type 2 diabetes mellitus. Settings and Design: A cross-sectional comparative study was conducted from June 2015 to May 2016 in a tertiary care center in Pakistan. Subjects and Methods: We recruited 237 participants among whom 119 had type 2 diabetes mellitus while 118 were controls. After complete history and examination, investigations including fasting and random blood glucose, glycated hemoglobin, and fasting lipid profile were obtained. All participants underwent Doppler ultrasound scanning of the carotid arteries for measurement of CIMT. Statistical Analysis Used: The data were analyzed through SPSS version 20.0 using Pearson's correlation coefficient. P < 0.05 was considered significant. Results: The target population constituted 44.3% males and 55.7% females. Among the participating males, 49.6% were diabetic while 50.4% of the female population was diabetic. There was a strong positive correlation of CIMT with duration of diabetes mellitus, systolic blood pressure, and total cholesterol. This correlation was moderately positive with age, diastolic blood pressure, and low-density lipoprotein levels in patients with type 2 diabetes mellitus. Conclusions: Different cardiometabolic risk factors have a varying impact on CIMT in patients with type 2 diabetes mellitus. The major contribution to CIMT is by the blood pressure, cholesterol, and duration of diabetes mellitus.

Keywords: Cardiometabolic risk factors, carotid intima-media thickness, type 2 diabetes mellitus

How to cite this article:
Bashir F, Nageen A, Kidwai SS, Ara J. Carotid intima-media thickness and cardiometabolic risk factors in Pakistani type 2 diabetics. Saudi J Health Sci 2017;6:145-50

How to cite this URL:
Bashir F, Nageen A, Kidwai SS, Ara J. Carotid intima-media thickness and cardiometabolic risk factors in Pakistani type 2 diabetics. Saudi J Health Sci [serial online] 2017 [cited 2019 Jan 19];6:145-50. Available from: http://www.saudijhealthsci.org/text.asp?2017/6/3/145/224750

  Introduction Top

Diabetic patients have a 2–4 times higher mortality due to cardiovascular causes as compared to normal population [1] because they develop premature and severe atherosclerosis. Hyperglycemia, dyslipidemia, obesity, hypertension, nephropathy,[2] and the pro-inflammatory condition generated through insulin deficiency and insulin resistance contribute toward the development of atherosclerosis. Diagnosis and management of the complications of diabetes, especially the macrovascular complications such as coronary artery disease and cerebrovascular disease at the subclinical stage, is an important part of management of diabetes mellitus. Cerebrovascular complications are also common in diabetic patients, with the risk of stroke increasing to around four times in these patients. Peripheral vascular disease is also a feature of diabetes. Thus, severe and diffuse atherosclerosis occurs in diabetic patients and at a younger age.[3] Although coronary and carotid angiography is the gold standard test for diagnosis of atherosclerosis in the respective circulations, the expense, mortality risk, and complications preclude the common use of this modality. Ultrasonographic measurement of carotid arterial wall thickness is a useful noninvasive tool to measure the extent of atherosclerosis. This method corresponds well with histological examination of the carotid arteries.[4]

Measurement at different sites within the carotid circulation such as common carotid artery, carotid bifurcation, internal carotid artery, and combination of these sites has approximately the same capacity to identify the occurrence of coronary artery disease.[5] Measuring only common carotid arteries, IMT, as opposed to a more detailed carotid Doppler study, is a reliable method to detect the severity of atherosclerosis.[6] It is also related to systemic generalized atherosclerosis.[7] Carotid Doppler studies are used to assess intimal-medial thickness, plaque presence, degree of stenosis, and calcification. It is utilized to find the current status of atherosclerosis, to predict future cardiovascular events, and to detect asymptomatic vascular target organ damage. It can also be used to determine the efficacy of interventions which are aimed to reduce the risk of development of cardiovascular events. Carotid intima-media thickness (CIMT) in healthy normal middle-aged adults has been defined as 0.6–0.7 mm and a value of more than 1.2 mm is considered to be a plaque.[8]

CIMT is associated with all atherogenic risk factors such as diabetes mellitus, hypertension, dyslipidemia, and smoking.[9] Some of the studies to assess the effects of these factors on carotid thickness have been conducted in South Asian populations.[10],[11] CIMT increase in participants over a period of 6.5 years was related to male gender, increasing age, body mass index (BMI), smoking, and hypertension while no relationship was observed with dyslipidemia.[12]

The association of increased CIMT with type 2 diabetes mellitus is well documented.[1] However, we need to keep in mind that diabetes mellitus is a syndrome with a cluster of metabolic features. The contribution of these cardiometabolic factors toward atherosclerosis needs to be ascertained. The purpose of the current study was to determine the relationship between different cardiometabolic risk factors and CIMT in Pakistani participants with type 2 diabetes mellitus.

  Subjects and Methods Top

All patients with type 2 diabetes mellitus presenting to the medical department of a tertiary care center in Karachi, Pakistan, from June 2015 to May 2016 were recruited for the study. Controls were age- and gender-matched participants without diabetes mellitus. Cases included patients with diabetes mellitus diagnosed on the basis of oral glucose tolerance test criteria, glycated hemoglobin (HbA1c) levels, increased fasting, or random blood glucose levels or were previously diagnosed cases of diabetes mellitus that were on regular antidiabetic drugs. The participants were labeled as type 2 diabetics if the diagnosis was made after the age of 35 years, irrespective of the type of antidiabetic drugs, or if they had been treated with dietary control measures and oral antidiabetic drugs regardless of the age at the time of diagnosis. The exclusion criteria eliminated the individuals from the study who had any history of cardiovascular diseases, thyroid disorders, hepatic ailments, rheumatologic diseases, and pregnancy.

The approval for the study had been provided by the Ethical Review Committee of the institution. Consent has been obtained from each participant that had been followed by the filling of a detailed survey form for recording the patient's details. Investigations including fasting and random blood glucose, HbA1c, and fasting lipid profile were obtained. The factors affecting cardiovascular health were recorded.

The recruited study participants were further investigated by measuring the CIMT by the use of B-mode carotid Doppler ultrasound. The carotid Doppler was conducted by a single operator with the help of a 7.5 MHz linear transducer probe (Toshiba Nemio 35). The CIMT was taken as the distance between lumen-intima interface and the media-adventitia interface.

Collected data were analyzed through SPSS version 20.0 (IBM Corp., NY). Descriptive variables were reported through mean with standard deviation and proportion. The association of the continuous variables was estimated by Student's t-test while that of the categorical variables was computed through Chi-square test. Pearson's correlation coefficient was used to find the correlation of the cardiovascular risk factors with CIMT. P < 0.05 was considered significant.

  Results Top

The study recruited 237 individuals, according to the inclusion criteria, among whom 50.2% (n = 119) were diabetic patients and 49.8% (n = 118) were nondiabetic individuals. The target population constituted of 44.3% of males and 55.7% of females. Among these participating males, 56% (n = 59) were diabetic while 46% (n = 60) of the female participants had diabetes mellitus [Table 1]. The study of categorical variables in [Table 1] reveals that hypertension is more prevalent in the diabetic patients (52%) while majority of the diabetic population had a poor glycemic control (72.3%) [Table 1].
Table 1: Characteristics of the population

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There was a significant association of body weight, systolic blood pressure, the parameters of glycemic controls, total cholesterol, low-density lipoproteins (LDL), and triglyceride levels with the presence of type 2 diabetes mellitus in the participants [Table 1].

A Pearson's correlation coefficient was assessed for the relationship of the different cardiometabolic risk factors with carotid thickness among the diabetic patients. The factors which show relationship with carotid thickness are age of participant, duration of diabetes, blood pressure values, and the total cholesterol and LDL cholesterol values. While BMI, glycemic indices, fasting and random blood glucose and HbA1c, high-density lipoproteins (HDL), and triglycerides showed no relationship with CIMT [Table 2]. The same relationship was carried out for the nondiabetic population of the recruited sample group. A significant relationship of the CIMT was seen with age, total cholesterol, LDL cholesterol, and triglyceride levels. Except for the triglyceride levels, the factors related with CIMT showed a stronger relationship in the diabetic population than in the nondiabetic population [Table 2].
Table 2: Relationship of cardiometabolic risk factors with carotid intima-media thickness in diabetic and nondiabetic populations

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The study revealed strong linear relationship of CIMT with the duration of diabetes, systolic blood pressure, and total cholesterol. Similarly, parameters including age, diastolic blood pressure, and LDL levels in blood also exhibited a moderate positive association with carotid atherosclerosis in diabetic patients. The parameters of glycemic control, i.e., fasting and random blood glucose levels and HbA1c showed no relationship with the CIMT.

  Discussion Top

Type 2 diabetes mellitus leads to macrovascular complications caused by atherosclerosis. We studied the relationship of various cardiometabolic risk factors, present in diabetes mellitus, on CIMT. The persistent hyperglycemic conditions in diabetes mellitus provide a favorable environment required for plaque formation leading to thickening of the vessel wall. The various interconnected metabolic abnormalities due to diabetes contribute toward atherosclerosis. Atherosclerosis can be measured by CIMT.

Doppler CIMT measurements are comparable to histopathologic finding of carotid thickness.[4] CIMT was found to be greater in diabetic patients with clinical and subclinical coronary artery disease.[9]

The first preliminary limb of the study which dealt with association of the cardiovascular risk factors and type 2 diabetes mellitus showed that there were significant associations of systolic blood pressure, total cholesterol, LDL, cholesterol, and triglycerides along with the measures of glycemic indices in patients with diabetes mellitus. Although most studies show that diabetic patients have a higher BMI compared to nondiabetic populations.[13],[14],[15],[16] Our study did not show a significant difference between the diabetic and nondiabetic participants. Some other regional studies have shown no correlation of BMI with diabetes mellitus.[17],[18] The reason could be that the population under study in the current research was an urban population with unhealthy eating habits and inadequate physical activity. Thus, both cases and controls have a mean BMI that is consistent with overweight category.

CIMT was significantly higher in patients with type 2 diabetes mellitus, and similarly, the presence of carotid plaque was also significantly associated with diabetes. The same association was observed in the diabetic patient in many studies.[9],[19],[20]

The study also evaluated the relationship between CIMT and different cardiometabolic risk factors in the study population. In a Pakistani study conducted on patients with type 2 diabetes mellitus, association was seen with duration of diabetes mellitus, BMI, and HDL cholesterol while hypertension and other lipid fractions showed no association with CIMT.[21] A European study showed that patient age, presence of hypertension, and the total cholesterol were associated with an increased CIMT in newly diagnosed type 2 diabetes mellitus.[22]

Age does contribute to thickening of the arterial wall in all people, but type 2 diabetics develop atherosclerosis at a younger age. The increased capacity for developing the plaque is mainly primed by the high glucose level in the circulating blood. Carotid wall thickness increases approximately 0.005–0.010 mm per year.[23] This process occurs at an accelerated rate in people with diabetes mellitus. The current study reveals a strong relationship of age with CIMT. The measurement of CIMT was seen to increase with age in both the cases and controls with a stronger relationship observed among the diabetic population (r = 0.3 in the diabetic population and r = 0.2 in the nondiabetic population). This is similar to observations in other studies.[20] In a study which evaluated the effect of age on CIMT in diabetic patients, it was seen that CIMT had a higher value in diabetic patients at all ages, but this difference became significant after the participant age of 50 years.[19]

Although male gender is a risk factor for cardiovascular disease, gender was not found to be associated with CIMT in the diabetic or nondiabetic participants in our study. Males were found to have higher CIMT measurements in patients with or without overt coronary artery disease in an Indian study.[9]

A Pakistani study has shown correlation of BMI, duration of diabetes, and HDL levels with CIMT, but this correlation was not very strong.[21] BMI did not show association with CIMT in either cases or controls in our study. However, BMI has been seen shown in several studies to be associated with CIMT. A relationship of CIMT with abdominal obesity has been observed. Visceral fat may cause early subclinical atherosclerosis. Patients with central obesity are at greater risk of developing cardiovascular disease. High BMI, increased systolic blood pressure, and diabetes mellitus or impaired glucose tolerance lead to a higher CIMT in smokers.[24]

The duration of diabetes can directly influence the thickness of the carotid arteries through ongoing atherosclerosis. Chronic hyperglycemia has been found to be an independent risk factor for the carotid thickening. It has also been noted that individuals with type 2 diabetes mellitus are more susceptible to atherosclerosis demonstrated by increasing value of CIMT that is potentially a consequence of alteration in metabolic state of the body in a diabetic condition.[19]

The strong relationship of CIMT with duration of diabetes underlines the fact that the prolonged exposure to the atherogenic factors related to type 2 diabetes mellitus has a deleterious effect on the process of arterial wall thickening. Long-standing uncontrolled or poorly controlled diabetes leads to the emergence of complications. As the control among our diabetic population was unsatisfactory in around 72% of the diabetic population, this would augment the adverse metabolic events of the disease and the development of complications. It is the duration of the metabolic change that affects atherosclerotic process more than the current glucose levels. In our study, neither the levels of fasting and random blood glucose nor the level of HbA1c was related to the CIMT. The relationship of glycemic control with CIMT has been measured in many studies with conflicting results. Independent association between parameters of glycemic control and CIMT has not been observed. The UK Prospective Diabetes Study (UKPDS) also revealed that blood pressure control was more important for all end points, especially cardiovascular complications in diabetic patients as compared to the glycemic control.[25],[26] Chronic hyperglycemic exposure and not the current glycemic control is related to the development of atherosclerosis.

Hypertension showed no significant difference in its prevalence in the diabetic and nondiabetic populations in our study. Around 52% of the patients with diabetes had hypertension. Hypertension has been observed in up to 60% of the diabetic population in other studies.[27] Hypertension is a factor which relates to the progression of macrovascular diseases in type 2 diabetes mellitus.[9],[20] Control of hypertension is an important part of the diabetic management. Our study showed that although the presence of hypertension was not a significant associate of type 2 diabetes mellitus, systolic blood pressure in the diabetic population under study was significantly higher than the nondiabetic population, and also, systolic blood pressure showed a strong relationship with CIMT.

Dyslipidemia is an important part of the diabetic metabolic abnormalities.[28] Different patterns of dyslipidemia have been observed in type 2 diabetes mellitus. The most common abnormalities being high triglycerides, low HDL, and high dense LDL levels.[29] Other studies have shown that the lipid profile abnormalities seen with type 2 diabetes mellitus are increased triglycerides, low HDL, increased total cholesterol, and increased LDL cholesterol, respectively.[19],[30] Still, other studies have demonstrated only deranged LDL and HDL cholesterol in the diabetic patients.[31],[32] In our study, total cholesterol, LDL cholesterol, and triglycerides were all high and HDL levels were low in the diabetic patients. However, when compared with the nondiabetic population, the total cholesterol, LDL cholesterol, and triglyceride levels showed significant differences, while HDL cholesterol was not significantly lower in the diabetic population. Hypertension and dyslipidemia accelerate the processes that lead to plaque formation in the circulation in early stages of diabetes mellitus, and they may further worsen atherosclerosis in the diabetic patient as were supported by the results of our study.[21] The different fractions of lipid profile showed a strong relationship with CIMT, especially in the diabetic patient. This relationship was strongest with total cholesterol while HDL levels showed no relationship with CIMT. The relationship was also observed in nondiabetic patients but was not as strong as that observed in patients with diabetes.

In our study, the Pearson's correlation showed that age, duration of diabetes, both systolic and diastolic blood pressures, and total and LDL cholesterol levels were related to CIMT in the diabetic patient while the glycemic indices did not show any correlation with the CIMT. This observation is supported by the fact, as observed in the Diabetes Control and Complications Trial and UKPDS trials that although glycemic control has a definite role in delaying the occurrence and progression of microvascular complications, its effect on atherosclerosis and macrovascular complications is not well demonstrated. Long-term posttrial follow-up of the patients in the intensive therapy group demonstrated that there was substantial risk reduction for myocardial infarction.[33],[34] The combination of diabetes and hypertension will lead to increased incidence of cardiovascular disease.[35] There is a significant relationship of blood pressure with CIMT in the diabetic patient. In our study, it was observed that both systolic and diastolic blood pressures were related with a greater value of CIMT. The importance of the role of hypertension in the development of macrovascular complications of diabetes is supported by the UKPDS study has shown that tight blood pressure controls lead to a reduction of both microvascular and macrovascular complications of diabetes mellitus. It was observed that there was also a reduction in mortality related to diabetes mellitus in these patients.[24]

  Conclusions Top

Type 2 diabetes mellitus is associated with increased CIMT. Age, blood pressure, different fractions of the lipid profile, and duration of diabetes mellitus play a role in this process. The parameters of glycemic control are not related to CIMT. Prevention of atherosclerosis is an important part of the effort to control the epidemic of cardiovascular disease. Control of obesity, hypertension, and dyslipidemias along with management of type 2 diabetes mellitus should be the long-term health strategies.

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  [Table 1], [Table 2]


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