ORIGINAL ARTICLE

The Correlation Between Insulin Resistance and Left Ventricular Systolic Function in Obese Women
Idrus Alwi*, S Harun*, Satrio Sukmoko**, Pradana Suwondo***, Maryantoro Oemardi***, Sarwono Waspadji***, Sidartawan Soegondo***

ABSTRACT Aim : to determine the correlation between insulin resistance and left ventricular systolic function in obese women. Methods : 44 obese (BMI > 25 kg/m2) and 45 normal weight women were studied. They had no other pathological conditions. Echocardiograms were undertaken in our echocardiographic laboratory following standard methods. The homeostasis model was used to assess insulin resistance (HOMA IR). Results : ejection fraction (p =0.22) and fractional shortening (p= 0.58) were not difference between obese women and the normal group. There was no correlation between insulin resistance and left ventricular systolic function. Conclusion : there was no correlation between insulin resistance and left ventricular ejection fraction. Key words : insulin resistance, obesity, left ventricular ejection fraction. INTRODUCTION

studies using echocardiography have shown abnormal diastolic function14 without consistent association with systolic dysfunction. 12,13 The precise nature of the association remains elusive, theoretical considerations have long suggested it may be mediated at least in part by insulin resistance.15 Obesity is characterized by a great variability of insulin sensitivity degree. Several studies have reported an independent correlations between circulating insulin level and cardiac mass in human subjects,16-17 others have not. 4,18 However, the correlation between insulin resistance and the left ventricular systolic function in obesity has not been reported. Our aim in this study was to determine the correlation between insulin resistance and the left ventricular systolic function in obese women.
METHODS

Obesity is associated with increased cardiovascular morbidity and mortality.1-3 Many studies have reported cardiac abnormalities in obesity.5-7 Obesity has been linked to a spectrum of more minor cardiovascular changes, ranging from a hyperdinamic circulation8 through subclinical cardiac structural changes9 to overt heart failure.10-11 Cardiac output is often higher in obesity, due to an augmented stroke volume and an increase in heart rate.8 Impairment of cardiac function has been reported to correlate with BMI and duration of obesity,12,13 with most

* Division of Cardiology, Department of Internal Medicine, ** Department of Internal Medicine, *** Division of Metabolic, Endocrinology and Diabetes, Department of Internal Medicine, Faculty of Medicine University of Indonesia/Cipto Mangunkusumo General Hospital, Jakarta

We selected 45 obese women (mean (SD) age, 36.7 (6.9) years; range 1454 years) and 45 non-obese control women (mean age, 36.4 (6.3) years; range 1544 years). Obesity was defined as a body mass index (BMI) of > 25 kg/m2, with clear evidence on physical examination of excessive subcutaneous adipose tissue. Inclusion criteria: no previous history or clinical evidence of coronary artery disease, heart failure, or cardiac valve disease; normal ECG; no respiratory disease; not suffering from any chronic or acute disease; not taking any drugs that could affect the heart and echocardiographic images had to be of sufficient quality to allow reproducible cross sectional, M-mode and 2-D studies. All subjects provided fully informed written consent for their participation in the study, and the protocol was approved by the ethics committee of our hospital. All participants provided information on age, family history, personal habits (alcohol intake, tobacco consumption, type and level of physical exercise, drug ingestion, known pathological conditions) and the duration of the obesity.
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Table 1. Baseline Characteristics Variable Age (years) Height (cm) Weight (kg) Body mass index (kg/m2) Waist Hip Waist hip ratio Visceral fat Systolic blood pressure Diastolic blood pressure Left ventricular mass Obese 36.70 (6.92) 154.01 (3.40) 77.00 (17.00) 32.07 (6.48) 93.82 (11.25) 109.08 (10.28) 0.86 (0.05) 362.29 (75.82) 113.05 (10.77) 70.64 (8.99) 156.01(44.45) Normal 36.44 (6.27) 155.33 (4.28) 53.49 (5.14) 22.15 (1.62) 71.88 (4.76) 94.64 (4.99) 0.76 (0.05) 276.20 (38.17) 106.93 (9.03) 65.4 (8.14) 105.09 (27.42) P 0.84 0.11 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00

Values are mean (SD). BMI, body mass index; BP, blood pressure; HR, heart rate.

Physical examination was conducted to exclude cardiac comorbidities. Height and weight were measured and the BMI was calculated as the weight (kg)/height2 (m2). A 12 lead ECG was obtained. Haematological and biochemical variables were determined from fasting blood samples and included fasting glucose. The homeostasis model was used to assess insulin resistance (HOMA IR).19 The formula for HOMA IR is as follows : insulin resistance (HOMA IR) = (fasting insulin(mU/ml) x fasting glucose (mmol/l)/22.5. A cross sectional echocardiogram was obtained from all participants (Philips). Echocardiograms were undertaken in our echocardiographic laboratory following standard methods.20-21 They included cross sectional, M mode, and Doppler studies. Measurements of all variables were made by one observer who was blinded to the patients clinical details. Left ventricular systolic functionLeft ventricular end diastolic (EDD) and end systolic diameter (ESD) and fractional shortening (FS) were obtained in the parasternal long axis views using M mode; left ventricular end diastolic (EDV) and end systolic volumes (ESV) and ejection fraction were measured from parasternal long axis view using the M mode echocardiography.
Statistical Analysis

RESULTS Baseline Characteristics

The characteristics of the patients studied are presented in table 1. There were no significant differences in age and height between obese and normal groups. Obese subjects had more weight, higher body mass index, waist, hip, waist hip ratio, more visceral fat, and higher systolic and diastolic blood pressure than normal subjects. The measured indices of the left ventricular systolic function are presented in table 2. There were no differences in LVEDD, LVESD, fraction shortening and ejection fraction between obese women and non obese women.
Table 2. Indices of Left Ventricular Systolic Function Obese LVEDD LVESD Fraction shortening Ejection fraction 45.65 (4.50) 26.70 (4.43) 41.61 (5.84) 71.59 (7.43) Normal 44.30 (7.14) 26.64 (4.14) 42.31 (5.83) 73.49 (6.99) P 0.29 0.94 0.58 0.22

EDD, end diastolic diameter; EDV, end diastolic volume; EF, ejection fraction; FS, fractional shortening.

Descriptive statistics were done on each of the variables to obtain the frequency distributions. Quantitative variables were described as mean (SD). Comparisons between the obese group and the normal weight group were analysed by t-tests. Correlations between clinical variables and left ventricular function were determined by Spearman Correlation. P < 0.05 were considered significant.

The measured indices of insulin resistance are presented in table 3. The glucose level, insulin level and HOMA IR were significantly higher in the obese subjects than the normal subjects.
Table 3. Indices of Insulin Resistance Obese Glucose level (fasting) Insulin level (fasting) HOMA IR 84.52 (11.19) 11.11 (6.18) 41.92 (29.03) Normal 79.71 (5.95) 4.33 (2.09) 15.41 (7.76) P 0.01 0.00 0.00

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The Correlation Between Insulin Resistance and Left Ventricular

Table 4. The Correlations Between Clinical Variables of Insulin Resistance and Left Ventricular Systolic Function Variables Fasting insulin Correlation coefficient Significant N Insulin resistance Correlation coefficient Significant N Ejection fraction Correlation coefficient Significant N Fraction shortening Correlation coefficient Significant N Fasting insulin 1.00 45 0.899* 0.00 45 -0.23 0.14 44 -0.21 0.18 44 Insulin resistance 0.899* 0.00 45 1.00 45 -0.27 0.08 44 -0.25 0.10 44 Ejection fraction -0.23 0.14 44 -0.27 0.08 44 1.00 44 0.88* 0.00 44 Fraction shortening -0.21 0.18 44 -0.25 0.10 44 0.88* 0.00 44 1.00 44

* Correlation is significant at the 0.01 level (2-tailed)

Correlations

The correlations between clinical variables of insulin resistance and left ventricular systolic function are shown in table 4. There was no correlation between insulin resistance and left ventricular systolic function.
DISCUSSION

In this study, there was no significant increase in the ejection fraction, and in the percentage of fractional shortening in obesity group compared with the normal group. Most echocardiographic studies using measurements of the ejection phases to evaluate systolic function in obese subjects have shown normal results.22-4 Studies in which these indices have been found to be reduced, albeit modestly, were done on patients with a considerable degree of obesity, suggesting that left ventricular systolic function is affected late in the course of obesity.22 These findings were similar to the previous findings, that LV systolic function is preserved in those with milder degrees of obesity.4,12 Pascual DA, et al12 reported that no patient with isolated obesity presented with subclinical systolic dysfunction, and there was a significant increase in ejection fraction and in the percentage of fractional shortening, but this only reached significance in slight and moderate obesity groups compared to the normal subjects. These findings could be explained on the basis that in the groups with lesser degrees of obesity there is a compensatory increase in systolic function. In the study by Iacobellis et al4 in uncomplicated obesity (in the absence of glucose intolerance, hyperten-

sion and dyslipidemia) the systolic function was changed in obese subjects. Left ventricular ejection fraction was higher in the obese subjects than in the normal subjects. He suggested that in obese subjects, an increase of cardiac work is necessary to supply a high oxygen consumption caused by an increase of body surface. The augmented preload and reduced afterload previously described in uncomplicated obese subjects could provide a further explanation for this supranormal LV function. In this study, we did not exclude the patients with glucose intolerance, hypertension and dyslipidemia. Several studies reported that there was a subclinical depression of LV function.22,25,26 The reason for this discrepancy probably relates to the techniques used for the assessment of systolic function. The previous smaller studies have focused on conventional methods such as LVEF and fractional shortening, which are relatively insensitive and thus unable to detect early preclinical changes. The more sensitive, newer echo techniques have been used to demonstrate the presence of subclinical LV changes in young obese women in a recent study.26 In this study there was no correlation between LV ejection fraction/fraction shortening and fasting insulin levels/insulin resistance. Wong CY et al,27 reported that insulin was significantly associated with systolic function, including strain. The study by Wong CY et al,27 provides observational findings that link obesity, insulin levels (and thereby insulin resistance), and myocardial disturbances. The reason for this discrepancy probably relates to the techniques used for the assessment of systolic function. Another reason may be the sample size
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that is too small. A recent study on young obese women further supported the notion that insulin resistance and alterations in myocardial substrate metabolism lead to myocardial contractile dysfunction associated with obesity.28
Limitations

The selection of the study sample, which included only women, precludes extrapolation of our results to the general population. The evaluation of LV systolic function still uses LV ejection fraction and fractional shortening, which are relatively insensitive.
CONCLUSION

There was no correlation between insulin resistance and left ventricular systolic function in obese women.
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