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 Table of Contents  
Year : 2018  |  Volume : 15  |  Issue : 1  |  Page : 1-8

Clinical and echocardiographic determinants of heart disease in uncomplicated type II Nigerian diabetic patients

1 Department of Internal Medicine, Division of Cardiology, University of Uyo Teaching Hospital, Uyo, Akwa-Ibom State, Nigeria
2 Department of Internal Medicine, Division of Nephrology, University of Uyo Teaching Hospital, Uyo, Akwa-Ibom State, Nigeria
3 Department of Internal Medicine, Division of Endocrinology, University of Uyo Teaching Hospital, Uyo, Akwa-Ibom State, Nigeria

Date of Web Publication7-May-2018

Correspondence Address:
Dr. Taiwo Tolulope Shogade
Department of Internal Medicine, University of Uyo Teaching Hospital, PMB 1136, Uyo, Akwa-Ibom State
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/njc.njc_27_17

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Background: Recent epidemiological studies indicate an increasing prevalence of type 2 diabetes mellitus (T2DM) in the world. T2DM is now widely accepted as a major predisposing factor to ischemic heart disease, stroke, dilated cardiomyopathy, and congestive heart failure (HF). Significant subclinical myocardial dysfunction before overt HF can easily be detected by Echocardiography.
Aims: The aim is to detect the prevalence and types of abnormal left ventricular (LV) functions and geometry in uncomplicated, normoalbuminuric normotensive T2DM in Nigeria, before the onset of overt heart disease.
Subjects and Methods: This was a cross-sectional study conducted at the diabetic and Cardiology clinics of University Teaching Hospital State, Nigeria, from January 2013 to March 2014. Diabetic patients positive for albuminuria were excluded and echo-derived indices of LV functions and geometry were compared between the two groups.
Results: Fifty normotensive T2DM patients who had no albuminuria were selected with 59 age- and sex-matched normal controls for the study. LV diastolic dysfunction (LVDD) was significantly more in normoalbuminuric T2DM compared to healthy controls (54% vs. 36%) P = 0.007. LV systolic dysfunction was rare in T2DM and in controls. Abnormal geometric patterns were higher in patients than controls, 70% versus 36% (P = 0.002). Age (odds ratio [OR] =1.05, 95% confidence interval (CI) of 1.01–1.11, P = 0.0273) and presence of diabetes mellitus (DM) (OR = 2.70, 95% CI of 1.12–6.53, P = 0.0273) were the independent predictor of LVDD in the participants.
Conclusions: LV diastolic function and geometry are altered in Nigerian normotensive normoalbuminuric T2DM; therefore, its prognostic importance and effectiveness of intervention need to be further elucidated.

Keywords: Diabetes mellitus, diastolic dysfunction, geometry, left ventricle, normoalbuminuria, normotensive

How to cite this article:
Shogade TT, Essien IO, Ekrikpo UE, Umoh IO, Utin CT, Unadike BC, Andy JJ. Clinical and echocardiographic determinants of heart disease in uncomplicated type II Nigerian diabetic patients. Nig J Cardiol 2018;15:1-8

How to cite this URL:
Shogade TT, Essien IO, Ekrikpo UE, Umoh IO, Utin CT, Unadike BC, Andy JJ. Clinical and echocardiographic determinants of heart disease in uncomplicated type II Nigerian diabetic patients. Nig J Cardiol [serial online] 2018 [cited 2023 Jun 10];15:1-8. Available from: https://www.nigjcardiol.org/text.asp?2018/15/1/1/231970

  Introduction Top

Diabetes mellitus (DM) is usually complicated with diverse cardiovascular conditions such as hypertension, myocardial infarction, heart failure (HF), stroke, and diabetic cardiomyopathy (DMCMP) which are the leading causes of diabetes-related morbidity and mortality.[1],[2] The previous studies elsewhere and in Nigeria have demonstrated left ventricular diastolic dysfunction (LVDD)[3],[4],[5] and geometric remodeling [6],[7] in normotensive patients with diabetes independent of albuminuria status, supporting the existence of a DMCMP.

The Framingham Heart Study showed that the frequency of HF is two times more in diabetic men and five times more in diabetic women compared with age-matched controls and that this increased incidence of HF-persisted despite correction for age, hypertension, obesity, hypercholesterolemia, and coronary artery disease (CAD).[8] An increased risk for developing HF in prospective analyses after correction for confounding variables have also been reported in other studies.[9] Therefore, screening for the presence of DMCMP at the earliest stage is appropriate for early detection and prevention of HF. The most sensitive noninvasive test for the detection of LV dysfunction and geometry remodeling is a two-dimensional echocardiogram with pulsed-wave Doppler.[10]

It is suggested here that LVDD and geometric remodeling may still be present in normotensive type 2 DM (T2DM) without microvascular complications induced by microalbuminuria.

This study was designed to determine the prevalence LV dysfunction and geometric remodeling in Nigerian T2DM after excluding hypertension and albuminuria (Uncomplicated Nigerian T2DM).

  Subjects and Methods Top

The study was done in accordance with the Declaration of Helsinki and the protocol was approved by the University of Teaching Hospital, Institutional Health Research Ethical Committee reference number XXXX/AD/S/96/VOL. XII/38. This study was conducted in the diabetic and cardiology clinics of XXX between January 2013 and March 2014. One hundred and ninety-three participants were recruited, 50 consecutive diabetic patients diagnosed according to the American Diabetes Association diagnosis and classification of DM criteria [11] or patients who are on oral antidiabetic drugs and 59 nondiabetic age- and sex-matched controls completed the study.

Exclusion criteria were hypertension (blood pressure ≥140/90 mmHg or use of antihypertensive drugs); age above 65 years; albuminuria; serum creatinine of ≥1.5 mg/dL; chest deformity or long-standing chest disease evidenced on chest X-ray; sickle cell disease; urinary tract infection; pregnancy; cardiac conditions such as arrhythmia, HF, valvular heart disease, pericardial disease, congenital heart disease; and ischemic heart disease (IHD) as evidenced by clinical, electrocardiographic, and echocardiographic features.

Age, sex, and duration of DM were recorded for each participant; weight using Hanson's weighing scale in kilogram (kg), height using a stadiometer, waist and hip circumferences (WC and HC) using tape rule were measured in centimeter (cm). Body mass index (BMI), body surface area (BSA), and waist–hip ratio (WHR) were calculated. Blood pressure was measured after at least 15 min rest in sitting position; using Accoson mercury sphygmomanometer and appropriate sized cuff at brachial artery. Korotkoff phase 1 was used for systolic BP (SBP) and phase 5 for diastolic BP (DBP); pulse rate (PR) was measured at radial artery. The mean of three consecutive measurements taken at 5-min intervals were recorded. An overnight fasting venous blood sample was collected for measurement of plasma glucose, creatinine, urea, and lipid profile using standard protocols.

A two-step microalbuminuria screening process was conducted. Combur 10 test strip (obtained from Roche Diagnostics GmbH D-68298 Mannheim, Germany), a visual colorimetric semi-quantitative urine test strip was used to test for protein, blood, nitrite, and leukocyte. If all were absent then detection of microalbuminuria was performed on the same urine.

Microalbuminuria was determined using the Micral test strips an optically read semi-quantitative immunoassay method (from Roche Diagnostics Australia Pty Ltd., Australia) with a sensitivity and specificity of 80% and 88%, respectively.[12] There are four color blocks on the test strip corresponding to negative (or 0), 20, 50, and 100 mg/L of albumin. The test was done on two occasions; the first was random urine samples and second was first-morning void (FMV) urine samples of participants. Microalbuminuria was considered to be present when the two urine samples tested produced a reaction color corresponding to 20 mg/L or more. The result gotten from the FMV urine sample was recorded as the MCA status of the participant. Participants that have proteinuria or microalbuminuria were excluded from the study.

Echocardiographic examination was performed with the patient in left lateral decubitus position using a Hewlett-Packard Sonos 4500 Echocardiography machine with a 3.5 MHz transducer, measurements were taken under two-dimensional-guided M-mode as recommended by the American Society of Echocardiography.[13]

LV systolic and diastolic function were estimated according to the standard recommendations.[14],[15] Pulmonary artery systolic pressure was estimated from peak tricuspid regurgitant flow using continuous wave Doppler. Tissue Doppler echocardiography was not used because as at the time, the study was conducted the ECHO machine used did not have the particular facility.

LV mass was calculated using Devereux modified cubed formula which had been shown to have good interstudy reproducibility.[16]

LV mass was indexed to BSA to give LV mass index (LVMI) in g/m 2. Left ventricular hypertrophy (LVH) was defined as LVMI ≥134 g/m 2 in men and ≥110 g/m 2 in women, respectively.[17]

Relative wall thickness (RWT) was calculated as: RWT = (PWTd + IVSTd)/left ventricular internal dimension in diastole (LVIDd). A partition value of 0.45 for RWT was used for both men and women which represents the 96th percentile in normal participants.[18] LV geometry was classified into the following:

Data analysis

Data obtained were analyzed using STATA 10 (STATA Corp, Texas, USA). Continuous variables were expressed as mean ± standard deviation and categorical variables as percentages. Categorical variables were analyzed using Chi-square. Student's t-test and Analysis of variance were used to analyze continuous variables. Predictors of LV dysfunction was assessed using logistic regressions. The P ≤ 0.05 was considered as statistically significant.

  Results Top

One hundred and nine participants comprising of 50 normotensive T2DM patients with normoalbuminuria and 59 controls were studied. The mean age for all the participants was 48 years.

[Table 1] shows the clinical characteristics of the two study groups. The weight, WC, waist–hip ratio and PR were significantly higher in diabetic patients than controls (P = 0.026, P = 0.001, P = 0.001 and P = 0.0298), respectively. Height, BMI, BSA, SBP, DBP, and PP were comparable between the two groups.
Table 1: Sociodemographic and anthropometric data (mean±standard deviation) variation between healthy controls and normotensive normoalbuminuric diabetics

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[Table 2] shows that renal function as assessed by estimated glomerular filtration rate (eGFR) using Cockcroft Gault formula was reasonably preserved among the two groups, but serum urea concentration was significantly higher in the diabetic group (P = 0.004).
Table 2: Laboratory data (mean±standard deviation) variation between healthy controls and normotensive normoalbuminuric diabetics

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The mean values of lipid components were normal and comparable except, LDL cholesterol and atherogenic ratio (AR) which were significantly higher in the diabetics than the controls (P = 0.0314 and P = 0.0015), respectively. FBS was also significantly higher in the diabetic group compared to controls (P < 0.001).

[Table 3] compares the echocardiographic parameters of LV geometry and functions between the two groups; IVSTd, PWTd, LVIDd, and RWT show significant increase in the diabetics compare to the controls (P = 0.0002, P = 0.0011, P = 0.0274, and P = 0.0006).
Table 3: Comparison of echocardiographic parameters (mean±standard deviation) of left ventricular geometry and functions between healthy controls and normotensive normoalbuminuria diabetics

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The mean values of EF and FS were normal and comparable between the two groups. Doppler echocardiographic parameters show some degree of diastolic dysfunction more pronounced in diabetic groups; E velocity (P = 0.0009), E/A ratio (P = 0.0006), portal vein flows (P = 0.0004), PVFd (P = 0.0005) were significantly reduced in patients than controls.

The prevalence of abnormal LV geometry was significantly higher in patients than controls 70% versus 36%. The most common abnormal geometric pattern was CR; 68% of patients and 32% of controls have CR, while 2% of patients versus 1.69% of controls had CH [Figure 1]. These observed differences were statistically significant (χ2 = 14.5827, P = 0.002).
Figure 1: Comparison of prevalence and pattern of left ventricular geometry between diabetics and controls. Chi-square was used to do the analysis. Seventy percent of diabetic patients versus 36% of controls had abnormal left ventricular geometry. The most common abnormal geometry pattern was concentric remodeling. (χ2 = 14.5827, P = 0.002)

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[Figure 2] shows the prevalence and pattern of LVDD between the two groups. The prevalence of LVDD was significantly higher in patients (54%) than controls (27%). The most common grade of DD is grade 1. Grade 1 DD occurred in 40% of diabetic and grade 1 was the only type of DD found in the control group. In normoalbuminuric diabetics group, 12% had grade 2 pattern of DD while 2% had grade 3 pattern. None of the controls had grades 2 and 3 LVDD. These observed differences were statistically significant (χ2 = 14.58, P = 0.007).
Figure 2: Comparison of the prevalence and pattern of left ventricular diastolic dysfunction between diabetic patients and controls, Chi-square was used to do the analysis. The prevalence of left ventricular diastolic dysfunction was significantly higher in patients (54%) than controls (27%). The most common grade of DD was grade 1. None of thecontrols have grade 2 nor 3 left ventricular diastolic dysfunction. (χ2 = 14.58, P = 0.007)

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[Table 4] shows BMI and age correlated significantly with RWT (P = 0.0451, P = 0.0247) while BMI and pulse pressure also correlated significantly with LVMI (P = 0.0118, P = 0.0160).
Table 4: Correlation coefficient of clinical and biochemical variables compared with relative wall thickness and left ventricular mass index in normotensive diabetic patients (significant if P<0.05)

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eGFR correlated significantly with both E/A ratio and DT (P = 0.0005, P = 0.0276). In addition, age also correlated with E/A ratio (P = 0.0055) as shown in [Table 5].
Table 5: Correlation coefficient of clinical and biochemical variables compared with mitral inflow early velocity/mitral inflow atrial velocity ratio and isovolumic relaxation time in normotensive diabetic patients (significant if P<0.05)

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In multivariate logistic regression, after adjusting for all the other factors in the multivariate model, age and presence of DM were the independent predictor of LVDD in the participants, the model shows that for every 1 year increase in age, there was a 5% increased risk of developing DD (odds ratio [OR] =1.05, 95% confidence interval [CI] of 1.01–1.11, P = 0.0273) and that patients with DM are three more likely to develop DD than patients without DD (OR = 2.70, 95% CI of 1.12–6.53, P = 0.0273) as shown in [Table 6].
Table 6: Multivariate logistic regression model to determine predictors of left ventricular diastolic dysfunction in the normotensive diabetics and healthy controls

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  Discussion Top

This cross-sectional study demonstrated that LVDD and LV geometry remodeling were significantly more common in normotensive normoalbuminuric patients with diabetes than controls. This group of diabetics are predominantly without microvascular nor macrovascular complications and were not on antihypertensive therapy. The prevalence of LVDD in this diabetic group is closer to the lower border of the range of 40%–75% reported by studies done on normotensive diabetics within [19] and outside the country.[20] Likewise, the prevalence of LV geometry remodeling was comparable to the previous reports in literature within and outside the country.[7],[19],[21],[22] Grade 1 LVDD was the most common form and was significantly more in normotensive normoalbuminuric patients with diabetes than controls (P = 0.007). Grades 2 and 3 though rare were exclusively seen in the diabetic group [Figure 2]. Aigbe et al.[19] and Patil et al.[20] reported similar findings. Lower rates of LVDD were reported by Liu et al.[23] Among American Indian with T2DM, 16% in normo-, 26% in micro-, and 31% in the macroalbuminuric group probably because diastolic function assessment was only based on transmitral flow parameters, with no distinctions made between normal and grade 2 DD. Thus, patients with pseudonormalized pattern were not included in their analysis.

Systolic dysfunction was rare in the two groups, which is similar to the previous report.[3] An higher value of 15.56% reported by Dodiyi-Manuel et al.[5] may probably be due to the higher EF cutoff value of 55% used to define systolic dysfunction. These findings suggest that alteration of both relaxation and filling usually precede alteration of systolic function in T2DM patients, also that systolic dysfunction detected by conventional echocardiography is not an early feature of DMCMP.[24] However, more sophisticated imaging technology such as speckle-tracking imaging used to assess myocardial strain and strain rate have permitted the detection of subtle systolic dysfunction in the diabetic myocardium.[25]

The significant correlation of E/A ratio with age (P = 0.005) and eGFR (P = 0.0005) in the normotensive normoalbuminuric T2DM and the fact that only age (OR = 1.05, 95% CI of 1.01–1.11, P = 0.0273) and presence of DM (OR = 2.70, 95% CI of 1.12–6.53, P = 0.0273)were the independent predictor of LVDD in the participants after controlling for other variables, imply that there may be worsening of LVDD in normotensive diabetic patients as they grow older and renal function starts declining even in the absence of albuminuria.

Likewise, Danbauchi et al.[26] reported significant correlation of LVDD with age, FBG and 2-h postprandial glucose in T2DM. Yazici et al.[27] in their study on 76 T2DM of Turkish origin documented that E/A ratio correlated significantly with age, glycated hemoglobin, and DMdur. It is commonly believed that grade 1 LVDD in patients above 65 years may represent relaxation abnormality associated with aging process; however, patients younger than 65 years may represent impaired relaxation due to other conditions that may be a precursor to more advanced diastolic impairment if not treated.

In the present study, patients older than 65 years were excluded, the absence of grade 2 and 3 LVDD in the control group and the fact that pseudonormal and restrictive LV filling patterns are usually pathological phenomenons;[28] further suggest that the higher proportion of LVDD seen in the diabetic group is linked not only to aging but also to the effect of DM without albuminuria.

We also observed that PWTd and IVSTd were significantly thicker in normotensive normoalbuminuic diabetics than healthy controls. These resulted in increased RWT and LV geometric remodeling, which were significantly more prevalent in the diabetic group. CR was the most common form of abnormal LV geometry, while both CH and EH were rare in the participants [Figure 1]. Bayauli et al. 2012 reported that among 60 consecutive diabetes that had echocardiographic study, CR (43%) was more common in the group with normal renal function while LVH (37%) was more common in the group with chronic kidney disease.[22] Likewise, Magnusson et al.[29] reported a lower prevalence of LVH (9.6%) in asymptomatic diabetics with no known CAD, whose mean albumin excretion rate was 2.1 μg/min, which is within the normal range.

In contrast, Aigbe et al.[19] found CH as the most common form occurring in 55% of one hundred and fifty normotensive patients with DM. Wu et al.[30] reported among 333 Asian diabetics that higher percentages of those with normoalbuminuria (53%) and microalbuminuria (66.3%) had abnormal geometry patterns. From the Strong Heart Study involving North American Indians, Liu et al.[23] reported that 23% of normoalbuminuric T2DM had LVH estimated from echocardiographic parameters.

CR may predominate in early stage of DMCMP due to the predominating pressure overload,[30] CR may predispose patient to increase all-cause mortality due to elevated arterial load, reduced coronary flow reserve, elevated neuroendocrine components, and abnormal growth factors as suggested by Milani et al. in the Ochsner studies.[31] Later, in the course of the disease CH and EH progressively takes over with further increase in LV mass (LVM) and later reduction in wall thickness due to increase in volume overload. EH is noted to be associated with lowest global LV systolic function and possibly an herald to progressive systolic impairment,[32] this explains its rarity in this study because all patients studied had preserved systolic function.

The significant deleterious effect of obesity on LV geometry remodeling as suggested in the Oschner study was demonstrated in this study. Both LVMI and RWT correlated significantly with BMI. RWT correlated with age and LVMI with pulse pressure. Similarly, Kamal et al.[33] demonstrated among American diabetics that LVM and LVMI correlated significantly with weight, BMI, BSA and DMdur. Among Indian diabetics, Santra et al.[34] also reported a significant association of LVH with BMI, HbA1c and DMdur.

CR which progresses to CH is an ominous prognostic sign.[35] It represents remodeling of heart architecture to normalize wall stress. Initially, it is an adaptive process but once a critical mass is reached, then it becomes pathological and has been shown to be a powerful predictor of cardiovascular morbidity and mortality in DM.[35],[36] There is thus a high background prevalence of cardiovascular disease risk factors in normoalbuminuric, normotensive diabetic patients with short DMdur similar to findings in another study.[37]

In addition to echocardiographic findings, this study shows that although the lipid profile and AR in the patients and controls were within normal limits, the LDL values and AR for uncomplicated diabetics were significantly more than the controls (P = 0.03 and P = 0.0015). These findings may be early indicators of the worse lipid and AR metabolic changes that are frequently seen in T2DM of long durations and which predispose to IHD.[38]

  Conclusions Top

From our observations, significant precursors of cardiomyopathy and IHD can be detected early in diabetic patients before albuminuria and hypertension complicate these cases. This calls for more energetic efforts in primary prevention of DM.

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Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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