52
replicate test of the standard glucose preparation was utilized in calculating the plasma glucose levels in the test sample. Glucose level was estimated using the formula:
Plasma glucose = OD of sample x concentration of standard OD of standard
Glycated haemoglobin (HbA1c) concentration was estimated by microchromatographic method using A1C Now+ (multi-test A1C system) diagnostic kit. Venous blood from the patient was mixed well within the lithium-heparin bottle. A 5µL of blood was sucked up into the blood collector. The blood collector was fully inserted into the sampler body. The sampler body was shaken to mix the blood with the solution contained within it. The base of the sampler body was removed and the diluted sampler dispensed unto the cartridge. Digital results were displayed in the display window of the monitor after 5 minutes.
Good glycaemic control was defined as FBS between 70-130mg/dl and HbA1c of < 7.0%.92 Fasting lipid profile was carried out. The procedure was as follows:
53
C. It was mixed and incubated for 10 minutes at 20-25o C.
D. The absorbance of the sample and standard against the reagent blank was measured at 500nm within 60 minutes.
E. Calculation= 553 X sample absorbance (mg/dl) 3. HDL- CHOLESTEROL ASSAY
A. 500µL of sample/standard was into pipetted centrifuge tubes B. 1000µL of precipitant was added into each tube
C. It was mixed and allowed to stand for 10 minutes at room temperature.
D. It was centrifuged for 10 minutes at 4000rpm
E. The clear supernatant was separated off within 2 hours and the HDL-Cholesterol content determined.
F. 100µL of supernatant/standard/distilled water was pipetted into test tube.
G. 1000µL of reagent was added into each test tube H. It was mixed and incubated for 10 minutes at 20-25o C.
I. The absorbance of the sample and standard against the reagent blank was measured at 500nm within 60 minutes.
J. Calculation= 180 X sample absorbance (mg/dl) 4. LDL-CHOLESTEROL CALCULATION
The LDL-Cholesterol was calculated using the Friedewald’s formula,
LDL-Cholesterol = Total Cholesterol - [ HDL-Cholesterol – Triglyceride/5].93
Dyslipidaemia was defined as TC>200mg/dl, LDL>130mg/dl, TG≥150mg/dl, HDL<40mg/dl (male) and HDL<50mg/dl (female).94
Electrocardiography
54
A standard 12 lead ECG was done using a Schiller AT-1 Smart Print ECG machine. The ECG strips were scrutinized for evidence of myocardial ischaemia or old infarcts (pathologic Q waves, inverted T waves) which was an exclusion criteria.
Echocardiography
A 2-dimensionally guided M-mode echocardiography was done for each subject with a 3.5MHz phased array transducer in the partial left lateral decubitus position using a standard commercial echocardiography machine (Sonoscape SSI-5000). Left ventricular measurements were made with the M-mode beam positioned just beyond the mitral leaflets tips (mitral chordal level) perpendicular to the long axis of the ventricle. Standard echocardiographic measurements of diastolic and systolic left ventricular internal dimension (LVID) and (LVIDS), posterior wall thickness (PWT), and interventricular septal thickness (IVST) dimensions were made at end- diastole and end-systole over 3 cardiac cycles and the mean calculated. These were done according to American Society of Echocardiography (ASE) recommendation.95
Left ventricular mass (LVM) was calculated using the formula: 41 0.8X [1.04X (LVIDd + IVSd + PWd)3 – (LVIDd)3] + 0.6
This has been shown to yield values closely related to necropsy left ventricular weight.
[Normal reference value; women= 67- 162g, men= 88- 224g]41
Left ventricular mass index (LVMI) was calculated using the formula:
LVM/BSA (where BSA is the body surface area)
[Normal reference value; women= 43- 95g/m2, men= 49- 115g/m2]41
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Left ventricular systolic performance was assessed using the fractional shortening of the left ventricle and the ejection fraction.
LV ejection fraction was calculated using the Teicholz calculation formula.
LVEF % = EDV-ESV/EDV x 100
FS was calculated by the formula FS % = (LVIDd – LVIDs)/LVIDd x 100
Normal left ventricular systolic function was defined by LVEF ≥50% and FS ≥ 25%96
Left ventricular diastolic function was evaluated by studying mitral inflow, pulmonary venous flow using Doppler, as well as tissue Doppler imaging of the mitral annulus.
Pulsed-wave Doppler of the transmitral inflow velocity in diastole was obtained in the apical 4-chamber view. The parameters that were measured included peak velocity of early filling (E-wave), peak velocity of atrial contraction (A-wave), and E/A ratio was calculated by dividing E-wave peak velocity by A-wave peak velocity. The normal reference value of E/A ratio is 0.9-1.5. LVDD was defined by E/A ratio of <0.9 for impaired relaxation or grade I , 0.9-1.5 for pseudonormalization pattern or grade II, >1.8 for reversible restrictive pattern or grade III and >2.0 for irreversible restrictive pattern or grade IV.41
The deceleration time (DT) was measured as the time interval between the peak of E-wave velocity and the baseline. Normal value for DT is 140-240 milliseconds. LVDD was defined by DT >240ms for impaired relaxation or grade I, 140-200ms for pseudonormalization or grade II, <140ms for reversible restrictive or grade III, and <130ms for irreversible restrictive or grade IV.41
56
Isovolumetric relaxation time (IVRT) was measured as the interval between the aortic valve closure and the beginning of mitral valve opening with the simultaneous visualization of the aortic and mitral inflow. Normal reference value for IVRT is 70-90ms. LVDD was defined by IVRT>90ms for impaired relaxation or grade I, 60-90ms for pseudonormalization pattern or grade II, and < 70ms for both reversible and irreversible restrictive patterns (grade III and IV).41
Pulmonary venous flow was interrogated using pulse-wave Doppler with sample volume located 1-2cm into the right upper pulmonary vein, proximal to its insertion into the left atrium. The systolic peak velocity (S), diastolic peak velocity (D), the S/D ratio, atrial systolic reversal velocity (Ar) were measured. The difference in duration between Ar and mitral A-wave (Ar-A) was calculated. Normal LV diastolic function was defined as S≥D.
LVDD was defined by S>D with prolonged Ar duration for impaired relaxation(grade I), S≤D with prolonged Ar duration for pseudonormalization pattern (grade II), S<<D with prolonged Ar duration for both restrictive patterns (grade III and IV). The difference in duration of Ar and mitral A-wave duration (Ar-A) >30ms defined LVDD.41
Tissue Doppler imaging assessment of myocardial velocities was done by placing the cursor across the septal and lateral aspects of the mitral annulus respectively. The e′ (average of septal and lateral e′) and E/e′ were calculated. The normal reference value for septal e’ is
>10cm/s. LVDD was defined by e’ <10cm/s for impaired relaxation or grade I, <8cm/s for pseudonormalization pattern or grade II, <5cm/s for both restrictive patterns (grade III and IV). The normal reference value for lateral e’ is >12cm/s. LVDD was defined by e’ <10cm/s for impaired relaxation or grade I, <8cm/s for pseudonormalization pattern or grade II and both restrictive patterns (grade III and IV). The normal reference value for E/e’ is < 8.
57
LVDD was defined by E/e’ <8 for impaired relaxation or grade I, 9-12 for pseudonormalization pattern or grade II, >15 for both restrictive patterns (grade III and IV).41
DATA ANALYSIS
The data collected were entered into an Excel spreadsheet and exported into the SPSS (Statistical Package for Social Sciences) Software version 20. Data was described for both cases (diabetics) and controls. Continuous variables were expressed as the mean (±SD) while categorical variables were expressed as percentages. Comparison between cases and controls was done using Chi-square for categorical and discrete variables and independent t test for continuous variables. Pearson’s correlation statistics was used to determine correlation of echocardiographic variables with continuous clinical and metabolic variables. Logistic regression analysis was used to determine independent predictors of left ventricular dysfunction. For all tests, p < 0.05 was considered as significant.
CHAPTER 5
58 RESULTS
A total of three hundred and twenty seven individuals were recruited for this study. Two hundred and forty five had type 2 diabetes mellitus while eighty one served as healthy controls.
5.1: The demographic and clinical characteristics of the study population is summarized in Table 1. The mean age of the diabetics was 51.14 ±7.04 years while that of the control group was 49.91±7.91 years. There was no statistical difference. There was a female preponderance in the study population with a F:M ratio of 1.4:1. The mean duration of DM was 6.87±4.08 years. The mean height of the control was slightly higher than that of the diabetic subjects, though not statistically significant. The mean weight of the diabetics was significantly higher than that of the control (P=0.008). The mean body mass index of the diabetics was higher than that of the control (26.74±3.43 vs. 24.91±3.79) and was statistically significant (P<0.0001). The mean waist to hip ratio was higher in the diabetics compared to the control group and was statistically significant (P<0.0001). The SBP and DBP were normal but higher in the diabetics. There was a statistically significant difference in the DBP (P=0.012).
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TABLE 1: DEMOGRAPHIC AND CLINICAL CHARACERISTICS OF DIABETIC SUBJECTS AND CONTROLS
Variable Cases (n=245) Control (n=81) t-value p-value Age (yrs) 51.14 ± 7.04 49.91 ± 7.91 1.315 0.189 Sex M 103 (42.0%)
142 (58.0%)
34 (42.0%) 47 (58.0%)
--- ---
--- --- F
DODM (yrs) 6.87±4.08 --- --- ---
HT (m) 1.68 ± 0.07 1.69 ± 0.07 -0.791 0.430
WT (Kg) 76.48 ± 11.30 72.05 ± 13.34 2.681 0.008*
BMI (Kg/m2) 26.70 ± 3.43 24.91 ± 3.79 4.036 <0.0001*
WHR 0.95 ± 0.09 0.88 ± 0.08 6.598 <0.0001*
BSA (m2) 1.89 ± 0.26 1.83 ± 0.18 1.920 0.056
SBP (mmHg) 120.69 ± 9.47 118.96 ± 11.72 1.205 0.231 DBP (mmHg) 78.90 ± 7.04 76.47 ± 7.58 2.544 0.012*
*Significant where p<0.05. DODM- Duration of Diabetes Mellitus , HT- Height, WT-weight, BMI- Body Mass Index, , WHR-Waist to Hip Ratio, BSA-Body Surface Area, SBP-Systolic Blood Pressure, DBP- Diastolic Blood Pressure.
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5.2: The table below shows the biochemical characteristics of the study participants. The FBS, HBA1C, TC, TG and LDL were higher among the diabetics, while the HDL was lower in the diabetics and the difference statistically significant (P<0.0001).
61
TABLE 2: BIOCHEMICAL CHARACTERISTICS OF DIABETIC SUBJECTS AND CONTROL
Cases (n=245) Controls(n=81)
Variable Mean± SD Mean± SD t-value p-value
FPG (mg/dl) 153.20 ± 69.55 82.20 ± 10.87 15.419 <0.0001*
HBA1C (%) 8.61 ± 2.30 5.28 ± 0.48 21.258 <0.0001*
TC (mg/dl) 208.34 ± 47.56 172.98 ± 38.55 6.065 <0.0001*
TG (mg/dl) 176.12 ± 59.46 118.31 ± 33.45 10.878 <0.0001*
LDL (mg/dl) 149.04 ± 44.75 120.07 ± 29.39 6.673 <0.0001*
HDL (mg/dl) 44.71 ± 9.02 50.31 ± 9.35 -4.796 <0.0001*
*Significant where p<0.05
FPG-Fasting plasma glucose, HBA1C- Glycated haemoglobin, TC-Total cholesterol, TG- Triglyceride, LDL- Low density lipoprotein, HDL- High density lipoprotein.
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5.3: The table below shows the echocardiographic indices of LV structure and function of the diabetic subjects and controls. The IVSD, LVIDD and LVIDS are higher in the patients than in the control group and statistically significant (P<0.0001, P=0.019, P=0.005 respectively). The LVMI was higher in the diabetics compared with the control (105.69±19.85g/m2 vs. 95.84±18.76g/m2) and showed significant statistical difference (P<0.0001). The comparison of the parameters of LV systolic function revealed normal mean ejection fraction (EF) and fractional shortening (FS) in both the diabetic and control group but were lower in the diabetics (EF: 61.09±6.49% vs. 63.8±5.93%), (FS:
32.51±4.84% vs. 34.53±4.55%) and statistically significant (P=0.001, P=0.001 respectively)
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TABLE 3: ECHOCARDIOGRAPHIC INDICES OFLV STRUCTURE AND FUNCTION OF DIABETIC SUBJECTS AND CONTROL
Cases (n=245) Controls (n=81)
Mean± SD Mean± SD t-value p-value
IVSD (cm) 1.06 ± 0.13 0.99 ± 0.15 4.054 <0.0001*
IVSS (cm) 1.54± 0.15 1.46± 0.22 3.385 0.001*
LVIDD (cm) 5.00 ± 0.41 4.89 ± 0.34 2.372 0.019*
LVIDS (cm) 3.31 ± 0.44 3.17 ± 0.35 2.867 0.005*
LVPWD (cm) 1.02 ± 0.14 0.94 ± 0.15 4.337 <0.0001*
LVPWS (cm) 1.50± 0.17 1.44± 0.19 2.678 0.008*
EDV (ml) 117.01 ± 21.85 112.53 ± 17.75 1.853 0.066
ESV (ml) 46.10 ± 15.21 40.59 ± 11.17 3.493 0.001*
SV (ml) 70.70 ± 11.43 71.88 ± 11.26 -0.804 0.422
EF (%) 61.09 ± 6.49 63.80 ± 5.93 -3.328 0.001*
FS (%) 32.51 ± 4.84 34.53 ± 4.55 -3.293 0.001*
LVM (g) 199.28 ± 42.91 177.36 ± 44.77 3.942 <0.0001*
LVMI (g/m2 ) 105.69 ± 19.85 95.84 ± 18.76 3.923 <0.0001*
*Significant where p<0.05; EDV- End-diastolic volume; ESV- End-systolic volume; EF-ejection fraction; FS- fractional shortening; LVIDD- Left Ventricular Internal Dimension in Diastole; LVIDS- Left Ventricular Internal Dimension in Systole; LVM- Left Ventricular Mass; LVMI- left ventricular mass index; LVPWD- Left ventricular posterior wall thickness in diastole; SV- Stroke volume
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5.4: The table below shows the comparison of diastolic function parameters between the diabetics and control group. The mean E/A was higher in the control group (1.21±0.37 vs.
1.02±.37) and was statistically significant (P<0.0001). The mean DT was higher in the diabetic group (214.07±32.47ms vs. 204.98±27.35ms) and showed significant statistical difference (P=0.014). The mean IVRT was significantly higher in the diabetic group (88.97±12.96 ms vs. 83.56±10.7 ms, P<0.0001). The E/e′ was significantly higher in the diabetics compared to the control (8.06±2.75 vs. 6.93±1.95, P<0.0001). The S/D was higher in the control than the diabetic, though not statistically significant. The ArV and Ar-A were higher in the diabetics and was statistically significant (P<0.0001).
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TABLE 4: ECHOCARDIOGRAPHIC INDICES OF LV DIASTOLIC FUNCTION OF DIABETIC SUBJECTS AND CONTROL
*Significant where p<0.05 ; E- peak velocity of early left ventricular filling; A- peak velocity of atrial contraction; DT- deceleration time; IVRT- isovolumetric relaxation time; e′(s)- septal e-prime wave; e′(l)- lateral e-prime wave; e′(av)- average e-prime wave; S- peak velocity of systolic wave of pulmonary venous flow ; D- peak velocity of diastolic wave of pulmonary venous flow; ArV- retrograde atrial wave peak velocity; Ar-A - difference between Ar and A wave duration
Cases (n=245) Control s(n=81)
Mean SD Mean SD t-value p-value
E(m/s) 0.77 ± 0.18 0.83 ± 0.18 -2.649 0.008*
A(m/s) 0.85 ± 0.68 0.74 ± 0.18 1.507 0.133
E/A 1.02 ± 0.37 1.21 ± 0.32 -4.359 <0.0001*
DT (ms) 214.07 ± 32.47 204.98 ± 27.35 2.473 0.014*
IVRT (ms) 88.91 ± 12.95 83.56 ± 10.70 3.693 <0.0001*
e′(s) (cm/s) 9.86 ± 3.05 11.9364 ± 3.03 -5.320 <0.0001*
e′(l) (cm/s) 10.87 ± 3.45 13.269 ± 3.58 -5.376 <0.0001*
e′(av) (cm/s) 10.33 ± 3.13 12.5977 ± 3.15 -5.636 <0.0001*
E/e′ 8.08 ± 2.75 6.9363 ± 1.96 4.088 <0.0001*
S/D 1.14 ± 0.28 1.1769 ± 0.21 1.128 0.260
ArV (cm/s) 30.13 ± 6.55 26.15 ± 5.66 5.277 <0.0001*
Ar-A (ms) 6.36 ± 16.05 -2.67 ± 9.19 5.795 <0.0001*
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5.5: Left ventricular systolic function as measured by ejection fraction (EF) and fractional shortening were normal in all the diabetic subjects and the controls. Among the diabetic subjects ninety five persons (38%) had normal diastolic function, one hundred and seven (43.7%) had impaired LV relaxation, while forty three (17.5%) had pseudonormal filling pattern. Seventy (86.4%) of the control subjects had normal diastolic function while eleven (13.6%) had an impaired LV relaxation pattern. None of the diabetics or control subjects had restrictive pattern of diastolic dysfunction.
5.6: The table below shows the comparison of diastolic function between diabetic subjects and controls with normal BMI, WHR and lipids. The prevalence of diastolic dysfunction was higher among the diabetic subjects and showed statistical significance in the normal BMI and WHR groups.
67
TABLE 5: COMPARISON OF DIASTOLIC FUNCTION BETWEEN DIABETIC SUBJECTS AND CONTROLS WITH NORMAL BMI, WHR AND LIPIDS
DIASTOLIC FUNCTION
Cases Control
n (%) n (%) Chi-square test BMI (normal)
Normal 23 (52.3) 28 (93.3) X2= 14.040
Abnormal 21 (47.7) 2 (6.7) df= 1
Total 44 (100.0) 30 (100.0) p <0.0001*
WHR (normal)
Normal 41 (70.7) 39 (90.7) X2 =6.002
Abnormal 17 (29.3) 4 (9.3) df= 1
Total 58 (100.0) 43 (100.0) p= 0.014*
LIPIDS (normal)
Normal 22 (59.5) 31 (79.5) X2 =3.609
Abnormal 15 (40.5) 8 (20.5) df= 1
Total 37 (100.0) 39 (100.0) p= .057
*Significant where P<0.05
68
5.7: The table below shows the relationship between LV diastolic function and duration of diabetes. Majority of the patients with normal LVF were diabetic for <5 years, while majority of those with abnormal LVF were diabetic for 5 to 9 years.
69
TABLE 6: RELATIONSHIP BETWEEN LV DIASTOLIC FUNCTION AND DURATION OF DM
Duration of DM (years)
DIASTOLIC FUNCTION
Normal Abnormal Total
n (%) n (%) n (%) X2 p-value
<5 41 (43.2) 43 (28.7) 84 (34.3)
5-9 35 (36.8) 55 (36.7) 90 (36.7) 8.160c 0.041*
10-14 15 (15.8) 44 (29.3) 59 (24.1)
15-19 4 (4.2) 8 (5.3) 12 (4.9)
>20 0 (0.0) 0 (0.0) 0 (0.0)
Total 95 (100.0) 150 (100.0) 245 (100.0)
*Significant where p<0.05 c: corrected chi, df=4
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5.8: The table below shows the relationship between LV diastolic function and control of DM. The frequency of LV diastolic dysfunction was higher among subjects with poor glycaemic control and it was statistically significant (P=0.001).
71
TABLE 7: RELATIONSHIP BETWEEN LV DIASTOLIC FUNCTION AND GLYCAEMIC CONTROL OF DM
Glycaemic control
DIASTOLIC FUNCTION
Normal Abnormal Total
n (%) n (%) n (%) X2 p-value Good 35 (36.8) 26 (17.3) 61 (24.9) 11.838 0.001*
Poor 60 (63.2) 124 (82.7) 184 (75.1)
Total 95 (100.0) 150 (100.0) 245 (100.0)
*Significant where p<0.05, df=1
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5.9: The table below shows the relationship between clinical characteristics of the diabetic subjects and indices of left ventricular structure and systolic function using Pearson’s correlation. The LVMI correlated positively with age of the diabetic subjects, duration of DM, height, weight, BMI, WHR, BSA, SBP and DBP and showed statistical significance. The EF and FS showed significant negative correlation with the age of the diabetics, duration of DM, height, weight, WHR, BSA, SBP and DBP.
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TABLE 8: CORRELATION BETWEEN CLINICAL CHARACTERISTICS AND ECHOCARDIOGRAPHIC INDICES OF LV STRUCTURE AND SYSTOLIC FUNCTION
EDV ESV SV EF FS LVM LVMI
AGE r 0.187** 0.210** 0.081 -0.209** -0.207** 0.269** 0.329**
DODM r 0.159* 0.179** 0.078 -0.164* -0.166** 0.078 0.179**
HT r 0.381** 0.375** 0.233** -0.253** -0.258** 0.233** 0.375**
WT r 0.502** 0.437** 0.370** -0.232** -0.246** 0.370** 0.437**
BMI r .334** 0.263** 0.279** -0.106 -0.118 0.279** 0.263**
WHR r 0.485** 0.500** 0.250** -0.380** -0.354** 0.250** 0.500**
BSA r 0.414** 0.344** 0.236** -0.195** -0.193** 0.236** 0.344**
SBP r 0.181** 0.178** 0.074 -0.127* -0.109 0.074 0.178**
DBP r 0.355** 0.287** 0.150* -0.284** -0.265** 0.150* 0.287**
**. Correlation is significant at the P < 0.01 level (2-tailed).
*. Correlation is significant at the P < 0.05 level (2-tailed).
.
74
5.10: The figure below shows the correlation between duration of diabetes mellitus and left ventricular systolic function using Pearson’s correlation. The ejection fraction was found to decrease with increasing duration of diabetes mellitus.
75
FIGURE 1: CORRELATION BETWEEN DURATION OF DIABETES MELLITUS AND LEFT VENTRICULAR SYSTOLIC FUNCTION (EJECTION FRACTION)
Pearson’s coefficient ( r ) = -0.164, P =0.01
76
5.11: The table below shows the relationship between mitral inflow indices and clinical characteristics of the diabetic subjects using Pearson’s correlation. The E/A ratio was negatively correlated with the age of the subjects and duration of DM and was significant.
The deceleration time (DT) was negatively correlated with the age of the subjects and showed statistical significance. The IVRT was positively correlated with the age of the subjects and was statistically significant.
77
TABLE 9: CORRELATION BETWEEN CLINICAL CHARACTERISTICS AND ECHOCARDIOGRAPHIC INDICES OF LV DIASTOLIC FUNCTION OF DIABETIC SUBJECTS (1)
E A E/A DT IVRT AGE r -0.122 0.108 -0.209** 0.180** 0.221**
DODM r -0.173** -0.005 -0.185** 0.161* 0.111
HT r 0.063 0.015 0.011 0.039 -0.019
WT r 0.097 0.117 0.067 -0.004 -0.103
BMI r 0.058 0.132* 0.054 -0.016 -0.097
WHR r -0.068 -0.017 -0.032 0.039 0.067
BSA r 0.025 0.083 -0.028 0.052 -0.041
SBP r -0.108 -0.076 -0.109 0.080 0.092
DBP r -0.028 0.030 -0.080 0.068 -0.012
**. Correlation is significant at the P < 0.01 level (2-tailed).
*. Correlation is significant at the P < 0.05 level (2-tailed).
78
5.12: The table below shows the relationship between clinical characteristics and TDI and pulmonary venous flow parameters of diastolic function of the diabetic subjects using Pearson’s correlation. The septal and lateral e′ velocities were negatively correlated with the age of the subjects, duration of DM, height, weight, BMI, WHR, BSA, SBP, DBP and showed statistical significance. The E/e′ was positively correlated with age of subjects, height, weight, BMI, WHR, BSA and DBP and was statistically significant. The ArV showed significant positive correlation with the age of the subjects, duration of DM, height, weight, WHR, BSA, SBP, DBP. The Ar-A showed significant positive correlation with age of the subjects, duration of DM, height, weight, WHR, BSA, SBP, DBP
79
TABLE 10: CORRELATION BETWEEN CLINICAL CHARACTERISTICS AND ECHOCARDIOGRAPHIC INDICES OF LV DIASTOLIC FUNCTION IN DIABETIC SUBJECTS (2)
e′(S) e′(l) e′(AV) E/e′
S/D ArV Ar-A AGE r -0.291** -0.345** -0.326** 0.161* 0.014 0.185** 0.150* DODM r -0.307** -0.326** -0.327** 0.084 -0.003 0.170** 0.146* HT r -0.296** -0.273** -0.299** 0.273** -0.077 0.201** 0.156* WT r -0.304** -0.277** -0.299** 0.313** -0.069 0.189** 0.126* BMI r -0.173** -0.155* -0.165** 0.185** -0.012 0.098 0.037 WHR r -0.538** -0.436** -0.499** 0.378** -0.093 0.557** 0.312**
BSA r -0.222** -0.224** -0.231** 0.198** -0.066 0.052 0.130* SBP r -0.255** -0.185** -0.224** 0.103 -0.006 0.174** 0.052 DBP r -0.385** -0.348** -0.379** 0.284** -0.069 0.268** 0.187**
**. Correlation is significant at the P < 0.01 level (2-tailed).
*. Correlation is significant at the P < 0.05 level (2-tailed).
80
5.13: The figure below shows the correlation between duration of diabetes mellitus and left ventricular diastolic function (E/A ratio) using Pearson’s correlation. The duration of diabetes mellitus was found to be inversely related to the E/A ratio.
81
FIGURE 2: CORRELATION BETWEEN DURATION OF DIABETES MELLITUS AND LEFT VENTRICULAR DIASTOLIC FUNCTION ( E/A )
Pearson’s coefficient ( r ) = -0.185, P =0.004
82
5.14: The table below shows the relationship between the biochemical parameters and indices of left ventricular structure and systolic function in the diabetic subjects using Pearson’s correlation. HBA1c was negatively correlated with ejection fraction (EF) and positively correlated with LVMI which was statistically significant. TC, TG and LDL were negatively correlated with EF, FS and positively correlated with LVMI with statistical significance.
HDL was positively correlated with EF, FS and negatively correlated with LVMI and was statistically significant.
83
TABLE 11: CORRELATION BETWEEN BIOCHEMICAL CHARACTERISTICS AND ECHOCARDIOGRAPHIC INDICES OF LV STRUCTURE AND FUNCTION OF DIABETIC SUBJECTS
EDV ESV SV EF FS LVM LVMI
FPG r -0.183** -0.067 -0.234** -0.049 -0.011 0.080 0.105
HBA1C r -0.160* -0.024 -0.260** -0.129* -0.088 0.176** 0.264**
TC r 0.222** 0.365** -0.047 -0.412** -0.406** 0.270** 0.282**
TG r 0.291** 0.395** 0.031 -0.467** -0.462** 0.281** 0.253**
LDL r 0.316** 0.443** 0.014 -0.503** -0.491** 0.321** 0.320**
HDL r -0.177** -0.211** -0.061 0.238** 0.216** -0.216** -0.200**
**. Correlation is significant at the P < 0.01 level (2-tailed).
*. Correlation is significant at the P < 0.05 level (2-tailed).
84
5.15: The figure below shows the correlation between glycaemic control (HBA1C) and left ventricular systolic function (ejection fraction) using Pearson’s correlation. There was reduction in left ventricular ejection fraction with increasing levels of HBA1C (worsening glycaemic control).
85
FIGURE 3: CORRELATION BETWEEN GLYCAEMIC CONTROL (HBA1C) AND LEFT VENTRICULAR SYSTOLIC FUNCTION ( EJECTION FRACTION)
Pearson’s coefficient ( r ) = -0.129, P =0.043
86
5.16 : The figure below shows the correlation between Total cholesterol levels and left ventricular systolic function (ejection fraction) using Pearson’s correlation. There was reduction in left ventricular ejection fraction with increasing levels of total cholesterol.
87
FIGURE 4: CORRELATION BETWEEN TOTAL CHOLESTEROL LEVELS AND LEFT VENTRICULAR SYSTOLIC FUNCTION (EJECTION FRACTION)
Pearson’s coefficient ( r ) = -0.412, P = < 0.0001
88
5.17: The figure below shows the correlation between glycaemic control (HBA1C) and left ventricular diastolic function (E/A ratio) using Pearson’s correlation. The glycaemic control (HBA1C) was found to be inversely related to the E/A ratio.
89
FIGURE 5: CORRELATION BETWEEN GLYCAEMIC CONTROL ( HBA1C ) AND LEFT VENTRICULAR DIASTOLIC FUNCTION ( E/A )
Pearson’s coefficient ( r ) = -0.06, P = 0.347
90
5.18 The figure below shows the correlation between total cholesterol levels and left ventricular diastolic function (E/A ratio) using Pearson’s correlation. The total cholesterol level was inversely related to E/A ratio.
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FIGURE 6: CORELATION BETWEEN TOTAL CHOLESTEROL LEVELS AND LEFT VENTRICULAR DIASTOLIC FUNCTION ( E/A )
Pearson’s coefficient ( r ) = -0.061, P = 0.344
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5.19: The table below shows the relationship between biochemical characteristics of the diabetic subjects and mitral inflow parameters of diastolic function using Pearson’s correlation . FPG and HBA1c were positively correlated with IVRT and showed statistical significance. HDL was negatively correlated with DT and was statistically significant. TC, TG, LDL were negatively correlated with E/A and positively correlated with DT and IVRT but did not show any statistical significance.
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TABLE 12: CORRELATION BETWEEN BIOCHEMICAL CHARACTERISTICS AND ECHOCARDIOGRAPHIC INDICES OF LV DIASTOLIC FUNCTION IN DIABETIC SUBJECTS (1)
E A E/A DT IVRT
FPG r -0.155* -0.057 -0.045 0.064 0.175**
HBA1c r -0.188** -0.067 -0.060 0.013 0.175**
TC r -0.021 0.048 -0.061 0.092 0.096
TG r 0.010 0.065 -0.040 0.058 0.012
LDL r 0.017 0.046 -0.039 0.061 0.011
HDL r 0.027 -0.018 0.059 -0.128* -0.076
** Correlation is significant at the P < 0.01 level (2-tailed) *Correlation is significant at the P < 0.05 level (2-tailed).
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5.20: Table 14 shows the relationship between the biochemical characteristics of the diabetic subjects, TDI and pulmonary venous flow parameters of LV diastolic function using Pearson’s correlation. FPG and HBA1c were positively correlated with ArV and showed statistical significance. TC and LDL were negatively correlated with septal and lateral e′, positively correlated with E/e′, ArV and Ar-A and was statistically significant. TG was negatively correlated with septal and lateral e′, S/D, positively correlated with E/e′, ArV and Ar-A and was statistically significant. HDL was positively correlated septal and lateral e′, negatively correlated with E/e′ and ArV and was statistically significant.
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TABLE 13: CORRELATION BETWEEN BIOCHEMICAL CHARACTERISTICS AND ECHOCARDIOGRAPHIC INDICES OF LV DIASTOLIC FUNCTION IN DIABETIC SUBJECTS (2)
e’(S) e’(l) e’(AV) E/e’
S/D ArV Ar-A FPG r -0.080 0.063 -0.007 -0.045 0.079 0.152* -0.072 HBA1c r -0.123 -0.018 -0.067 -0.035 0.010 0.318** 0.024 TC r -0.311** -0.303** -0.315** 0.197** -0.050 0.274** 0.151* TG r -0.358** -0.384** -0.383** 0.276** -0.147* 0.298** 0.239**
LDL r -0.372** -0.393** -0.395** 0.301** -0.124 0.285** 0.210**
HDL r 0.187** 0.187** 0.185** -0.132* 0.033 -0.209** -0.105 ** Correlation is significant at the P < 0.01 level (2-tailed)
*Correlation is significant at the P < 0.05 level (2-tailed).
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5.21: The table below shows logistic regression analysis of the predictors of left ventricular diastolic dysfunction in subjects with type 2 DM. Age, WHR and LVMI were found to be independent predictors of left ventricular diastolic dysfunction.
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TABLE 14: LOGISTIC REGRESSION ANALYSIS OF PREDICTORS OF LEFT VENTRICULAR DYSFUNCTION AMONG PATIENTS WITH TYPE 2 DM
VARIABLE Odds Ratio
95% C.I.
(Lower - Upper) p-value
AGE 1.089 (1.032 - 1.150) 0.002*
DODM 1.052 (0.964 - 1.149) 0.253
WT 0.981 (0.920 - 1.047) 0.566
BMI 0.923 (0.777 - 1.096) 0.360
WHR 1.078 (1.025- 1.134) 0.004*
BSA 2.347 (0.434 - 12.695) 0.322
SBP 1.007 (0.969 - 1.045) 0.730
DBP 0.971 (0.921 - 1.024) 0.284
FBS 0.997 (0.991 - 1.003) 0.362
HBA1C 1.076 (0.877 - 1.321) 0.481
TC 1.005 (0.988 - 1.022) 0.553
TG 1.004 (0.996 - 1.012) 0.285
LDL 0.988 (0.971 - 1.006) 0.187
HDL 0.962 (0.920 - 1.007) 0.094
LVMI 1.041 (1.018 - 1.066) 0.001*
*Significant where P <0.05
98 CHAPTER 6
DISCUSSION
This study found a high level of LV diastolic dysfunction (61.2%) among Type 2 diabetics compared to 13.6% in the control group. The prevalence of left ventricular diastolic dysfunction found among the diabetics in this study is similar to the findings of Poirier et al59 and Dodiyi-Manuel et al63 who found a left ventricular diastolic dysfunction of 60.0% and 65.6% respectively among their diabetic subjects . However Boyer et al87, Aigbe et al57 and Ojji et al58 found a much higher prevalence of left ventricular diastolic dysfunction of 75%, 72% and 71% respectively in their diabetic subjects. Zabalgoitia et al61 and Rothangpui et al56 however found a much lower prevalence of 47% and 40% respectively. The difference in prevalence may be due to the use of different parameters (Tissue Doppler imaging compared to mitral inflow) in assessing left ventricular diastolic function. The mean body mass index (BMI), waist to hip ratio (WHR) and lipids were abnormal in the diabetics. However on comparing a subset of both the diabetic and control group who had normal BMI, WHR and lipids the prevalence of diastolic dysfunction was still higher among the diabetics. This is suggestive of diabetes mellitus being the most likely cause of the increased prevalence of diastolic dysfunction and not the abnormality in BMI, WHR and lipid fraction found in the diabetic group. In this study 43.7 % of the diabetic subjects had impaired relaxation while 17.5% had pseudonormal pattern. Dodiyi-Manuel et al63 found that of the diabetics in their study 57.8% had impaired relaxation, 6.7% had pseudo normal filling, and 1.1% had restrictive filling pattern. Poirier et al59 found that (32%) had impaired relaxation while 13 (28%) had pseudo- normalized filling while Ojji et al58 found that 58% had impaired relaxation, 7% had pseudo- normalized filling, and 6% had restrictive filling.
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This study did not find evidence of left ventricular systolic dysfunction in the diabetic subjects and controls though the mean ejection fraction was lower in the diabetics and this was statistically significant, suggesting that diabetes mellitus impairs left ventricular systolic function. Poirier et al59 , Zabalgoitia et al61, Aigbe et al57 and Omo-olaye et al55 equally did not find evidence of left ventricular systolic dysfunction in their studies. These studies as well as the present study used a LVEF of ≥50% as cut-off for normal systolic function. On the other hand Dodiyi-Manuel et al63 found a systolic dysfunction of 15.65% and 4.4% in their diabetic and control subjects respectively while Rothangpui et al56 found a systolic dysfunction of 8% in their diabetic subjects in their studies which used EF≥55% as cut-off for normal systolic function. The difference in the findings is most likely due to the cut-off used as normal systolic function. Dodiyi-Manuel et al63 and Danbauchi et al54 found lower ejection fraction in their diabetic subjects compared to the controls just as the present study unlike Aigbe et al57 who found a higher ejection fraction in the diabetics compared to the controls.
The LVMI was found to be higher in the diabetic subjects compared to the control group in this study and this was similar to the findings of Aigbe et al57, Danbauchi et al54, Omo-olaye et al55 and Dodiyi-Manuel et al63. The increase in left ventricular mass has been postulated to possibly result from increased apoptosis and necrosis observed in diabetics, causing increased deposition of collagen in diffuse manner as a result of replacement fibrosis and connective tissue proliferation.
This study found that a longer duration of diabetes mellitus was associated with increased prevalence of left ventricular diastolic dysfunction. This finding was similar to the studies done by Kim et al75 , Noh et al 76 who equally noticed an increase in the prevalence of left ventricular diastolic dysfunction with increasing duration of diabetes mellitus. However Di Bonito et al74 and Attali et al73 did not find any correlation between left ventricular diastolic
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dysfunction and duration of diabetes mellitus. In this study duration of diabetes mellitus was found to be inversely related to the LVEF and FS demonstrating that longer durations of diabetes are associated with a decline in left ventricular systolic function. This is similar to the findings of Annonu et al77 who found that an inverse relationship existed between the duration of diabetes and left ventricular ejection fraction.
Poor glycaemic control was related to an increase in the prevalence of left ventricular diastolic dysfunction in this study which is similar to the findings of Patil et al62. Vanninen et al67, Hirayama et al68 found that there was a significant improvement in left ventricular diastolic function following a period of improved glycaemic control in their studies. Similar studies by Puzengruber et al69 and Pitale et al72 did not find any change in left ventricular diastolic or systolic function following a period of improved glycaemic control. This may have been due to the fact that the patients in their studies had reached an advanced stage of diabetic cardiomyopathy which is irreversible.
The E/A ratio was negatively correlated with the age of the subjects and was significant. The deceleration time (DT) was negatively correlated with the age of the subjects and showed statistical significance. The IVRT was positively correlated with the age of the subjects and was statistically significant. The E/e′ was positively correlated with age of subjects, BMI, WHR, BSA and DBP and was statistically significant. The age of subjects, BMI, WHR, BSA, SBP and DBP as clinical parameters were associated with the presence of left ventricular diastolic dysfunction.
TC, TG and LDL were negatively correlated with EF, FS and positively correlated with LVMI with statistical significance. HDL was positively correlated with EF, FS and negatively correlated with LVMI and was statistically significant. This shows that dyslipidaemia is associated with reduction in left ventricular systolic function and changes