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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 41  |  Issue : 2  |  Page : 76-85

Relation of glycosylated hemoglobin and obesity indices with diastolic dysfunction in participants with type 2 diabetes mellitus


Department of Medicine, Krishna Institute of Medical Sciences, Karad, Maharashtra, India

Date of Submission30-Mar-2020
Date of Decision09-Jun-2020
Date of Acceptance17-Jul-2020
Date of Web Publication02-Sep-2020

Correspondence Address:
Dr. Aniket Bhaskar Avhad
Department of Medicine, Krishna Institute of Medical Sciences Deemed to be University, Karad, Satara, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jmedsci.jmedsci_67_20

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  Abstract 


Background: Diabetes is an important risk factor of cardiomyopathy which can eventually lead to acute or chronic heart failure. Many factors such as obesity, hyperglycemia, suboptimal glycemic control, and hyperlipidemia predispose as well as aggravate long-term complications in diabetes mellitus (DM). Aim: The present study was conducted to assess the relation of glycosylated hemoglobin (HbA1c) and obesity indices (body mass index [BMI], waist circumference [WC]) with diastolic dysfunction in participants with type 2 DM (T2DM). Methods: This was a cross-sectional study conducted at the teaching hospital during a 1-year period. All 100 consecutive T2DM participants were investigated for HbA1c, blood sugars and lipid profile parameters, and echocardiography. Standardized transthoracic echocardiographic examination was performed (American Society of Echocardiography) using Vivid S6 ultrasound machine with 4–5 MHz probe. Left ventricular diastolic dysfunction (LVDD) was labeled if 3 or more of these variables were abnormal: “Septal e <7 cm/s, lateral e <10 cm/s, E/e' >14, LA volume index >34 mL/m2, and Peak TR velocity >2.8 m/s.” Results: Out of the total 100 diabetics, 37% had diastolic dysfunction (Grade I: 30 [81.08%] and Grade II: 7 [18.91%]). The peak early transmitral filling wave velocity (E) in diabetics with obesity was low as compared to diabetics with normal weight (44 ± 11 cm/s vs. 52 ± 7.5 cm/s). Higher BMI was associated with higher peak late transmitral velocity (A) (61 ± 14 cm/s vs. 38 ± 6.24 cm/s). The mean of E/A ratio was significantly lower in diabetics with obesity. The E/e' ratio was higher in diabetics with obesity (14.8 ± 2.8 vs. 12.86 ± 2.14). The mean of WC was 90.18 ± 6.82 cm in participants of diastolic dysfunction, whereas it was 86.46 ± 6.42 cm in those without dysfunction. Diastolic dysfunction was present in participants with a suboptimal glycemic control, HbA1c ≥ 6.% (40%), with longer duration of diabetes (62.16%) (P = 0.003). Thus, a higher BMI was associated with higher diastolic dysfunction (P = 0.027). Conclusions: The present study reveals burden of LVDD in asymptomatic T2DM participants with its significant association with age, obesity indices (WC and BMI), HbA1c levels, and longer duration of diabetes. This highlights the magnitude of obesity and suboptimal glycemic control that should be considered in the management of cardiac complications in the form of development of diastolic dysfunction. It will benefit in triage for the optimal management of diabetes.

Keywords: Anthropometric variables, body mass index, diastolic dysfunction, diabetes mellitus, glycosylated hemoglobin


How to cite this article:
Patil VC, Avhad AB. Relation of glycosylated hemoglobin and obesity indices with diastolic dysfunction in participants with type 2 diabetes mellitus. J Med Sci 2021;41:76-85

How to cite this URL:
Patil VC, Avhad AB. Relation of glycosylated hemoglobin and obesity indices with diastolic dysfunction in participants with type 2 diabetes mellitus. J Med Sci [serial online] 2021 [cited 2021 Jul 31];41:76-85. Available from: https://www.jmedscindmc.com/text.asp?2021/41/2/76/294295




  Introduction Top


The incidence of diabetes mellitus (DM) is increasing worldwide. According to recent studies, diabetes is also an important risk factor of cardiomyopathy which can eventually lead to acute or chronic heart failure. The hyperglycemia, hyperlipidemia, hypertension, and obesity predispose as well as aggravate cardiovascular complications in DM.[1] Due to the involvement of numerous molecular, epigenetic, and neuroendocrine mechanisms, the etiopathogenesis of diabetic cardiomyopathy is less understood. The first structural and functional change is the diastolic dysfunction seen in the left ventricle (LV).[1],[2] Approximately 37% decrease in the microvascular complications is seen even if the glycosylated hemoglobin (HbA1c) is reduced by only 1%.[2] The relation with coronary artery disease is well established. Atherosclerotic cardiovascular disease (CVD) is the foremost cause of death. Studies have shown a high prevalence of preclinical diastolic dysfunction in diabetic participants. Transthoracic two-dimensional (2D) echocardiography can help us screen participants susceptible to cardiovascular complications. The assessment of diastolic dysfunction with risk factor and variables of DM may aid the early and precise identification of individuals at risk of having diabetic cardiomyopathy. Echocardiographic correlation with age, obesity indices, and HbA1c will help in triage for the optimal management of diabetes as well as the prevention of diastolic heart failure. This cross-sectional, observational study conducted to estimates the parameters and grades of diastolic dysfunction to severity of DM and obesity indices (body mass index [BMI] and waist circumference [WC]).


  Methods Top


Aim

The aim of this study is to study the relation of HbA1c and obesity indices (BMI and WC) with diastolic dysfunction in participants with type 2 DM (T2DM). To find the relation between the parameters of diastolic dysfunction with HbA1c and obesity indices.

Study design and setting

This was a cross-sectional, observational study on participants with DM carried out over a period of 1 year. The study was conducted at Krishna Hospital and Medical Research Center, a tertiary care hospital and teaching institute in Maharashtra.

Source of data

The study was carried on participants with the diagnosis of DM (diagnosed by ADA guidelines) who were admitted in wards over the period of (January 2019–December 2019) in Krishna Institute of Medical Sciences, Karad. Ethical clearance: The study approved by the Institutional Ethical Committee (Protocol number 176/2019–2020).

Study population

A total 100 participants will be included in this study satisfying the inclusion criteria. Informed and written consent of the participant: The appropriate written and informed consent was obtained from the participant of study. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Inclusion criteria

Participants between 18 and 60 years of age and participants with T2DM.

Exclusion criteria

Participants with hypertension, coronary artery disease, congenital heart disease, valvular heart disease, documented systolic dysfunction, hypertrophic obstructive cardiomyopathy, dilated cardiomyopathy, and pericardial effusion will be excluded from the study. Participants with liver dysfunction, renal dysfunction, and chronic obstructive pulmonary disease will be excluded from the study.

Data collection

All enrolled subjects underwent anthropometric measurements calculated for BMI, WC. They were investigated for blood sugars, HbA1c, lipid profile and 2D echodcardiography with Pulse wave Doppler, tissue Doppler imaging (TDI). DM: Fasting blood sugar ≥126 mg/dL or HbA1c ≥6.% (diagnosed by ADA guidelines).[3]

Obesity indices

The study participants were considered normal weight if BMI <23.0 kg/m2 and Overweight or obese if BMI ≥23.0–27.4 kg/m2, WC – men ≥90 cm, women ≥80 cm.[4],[5]

Echocardiographic analysis

The left ventricular (LV) diastolic function was evaluated using mitral annular velocity and mitral inflow velocity. An apical 4-chamber view (A-4-CH view) was used to assess Peak E and A velocity of the mitral inflow and then E/A ratio was calculated. The mean value of e' velocities measured by TDI from septal and lateral annulus was calculated and E/e' ratio was used as an indicator of LV filling pressure. An apical two (A-2-CH view), standard parasternal long axis (PLAX), short axis (PSAX), conventional techniques (transthoracic 2D echocardiography, Pulsed-wave were also used. Definition of diastolic dysfunction was as follows: LV diastolic dysfunction (LVDD) was labeled if 3 or more of these variables were abnormal:[6]”Septal e' <7 cm/s, lateral e' <10 cm/s, E/e' >14, LA volume index >34 mL/m2, and Peak TR velocity >2.8 m/s”. Diastolic dysfunction was divided into three grades (Grade I: impaired LV relaxation, Grade II: pseudo-normal filling pattern, and Grade III: restrictive filling pattern) [Figure 1].
Figure 1: Transthoracic two-dimensional echocardiography Pulsed-wave, Tissue Doppler imaging

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Statistical analysis

The data collected were entered in Microsoft Excel sheet. Data was analyzed for mean, percentage, standard deviation, and Chi-square test for quantitative data by using the IBM SPSS Statistics for Windows, Version 21.0 (Armonk, NY: IBM Corp.) was used for data analysis. The P < 0.05 was considered as statistically significant.


  Results Top


The present study conducted in a tertiary care hospital over a period of 1 year and was designed to determine the prevalence of diastolic dysfunction in T2DM. It also assessed the risk factors contributing to its cardiovascular complications. The mean age of participants having diastolic dysfunction with DM was 56.07 ± 12.02 years while those without dysfunction was 53.33 ± 13.36 years (P = 0.04). WC was comparatively higher in participants having diastolic dysfunction (90.18 ± 6.82 cm) as compared to (86.46 ± 6.42) participants without diastolic dysfunction (P = 0.05). Mean of BMI was higher in participants of DM with diastolic dysfunction (26.6 ± 3.24 [kg/m2]) than those without dysfunction (22.8 ± 2.82 [kg/m2]) (P = 0.027). Similarly, the mean duration was significantly higher in diabetic participants (10.33 ± 6.1 years) with diastolic dysfunction than in those without dysfunction (7.23 ± 3.83 years). The mean of HbA1c was 8.75 ± 1.34% in cases with obesity, while it was 6.4 ± 1.26% in cases who were normal weight (P = 0.009). Total cholesterol levels were observed to be more in participants with obesity and diabetes as compared with the participants with normal weight (180.28 ± 48.46 vs. 151.67 ± 43.90 [mg/dl]) (P = 0.002). The mean of triglyceride levels was significantly higher 195.22 ± 76.62 (mg/dl) in participants of diabetes with diastolic dysfunction while it was lower in those not having diastolic dysfunction (143.93 ± 63.69 [mg/dl]) (P = 0.031). High-density lipoprotein (HDL) cholesterol value was observed on lower side 43.28 ± 9.86 (mg/dl) in cases of diastolic dysfunction in comparison to 48.53 ± 16.36 (mg/dl), seen in cases without diastolic dysfunction [Table 1] and [Graph 1].
Table 1: Mean and standard deviation of variables of the study population (n=100)

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The peak early trans-mitral filling wave velocity (E) in diabetic par with obesity was low as compared to diabetics with normal weight (44 ± 11 cm/s vs. 52 ± 7.5 cm/s). Higher BMI was associated with higher peak late trans-mitral velocity (A) (61 ± 14 cm/s vs. 38 ± 6.24 cm/s). Similar to (E), the early diastolic mitral annulus velocity (e') was lower in overweight/obese diabetics as compared to normal weight. The e' septal (9.1 ± 1.88 [cm/s] vs. 9.8 ± 1.82 [cm/s]) and e' lateral (9.8 ± 1.92 [cm/s] vs. 9.9 ± 1.88 [cm/s]) were also on lower side in cases with obesity versus without obesity, respectively. The mean of E/A ratio was significantly lower in diabetics with obesity as compared to normal weight diabetics. The E/e' ratio was higher in diabetic group with obesity (14.8 ± 2.8) as compared to normal weight diabetic group (12.86 ± 2.14). Diabetic participants with obesity had significantly higher TR jet (2.84 ± 1.2 vs. 0.9 ± 0.36 [m/s]), higher LA volume index (30. 4 ± 14.46 vs. 22.4 ± 4.66 [ml/m2]), and LVMI (170 ± 42.6 vs. 116 ± 28.4 [g/m2]) as compared to diabetics with a normal BMI, respectively [Table 2] and [Graph 2].
Table 2: Mean and standard deviation of parameters in diastolic dysfunction with body mass index ≥23 kg/m2 and body mass index <23 kg/m2

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Age, BMI, WC, duration of DM, and HbA1c had negative correlation with parameters of LVDD (E [cm/s], E/A, e') and positive correlation with E/e', TR jet. The variable of T2DM and their relation to parameters of echocardiography as depicted in [Table 3], [Graph 3] and [Graph 4].
Table 3: Correlation of parameters of diastolic dysfunction with biochemical profile and obesity indices

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The prevalence of diastolic dysfunction was 37%. A total of 30 participants (81.08%) had Grade I diastolic dysfunction. A total of 7 participants had grade II dysfunction (18.91%). Out of 37 participants of diastolic dysfunction, 28 participants (75.76%) were above 40 years of age (P = 0.044) and 9 participants below 40 years of age (24.32%). A total of 15 males (40.54%) and 22 females (59.4%) had diastolic dysfunction. A total of 26 diabetics with diastolic dysfunction had higher BMI (70.27%) (P = 0.027). Eleven participants (29.72%) had normal weight. The prevalence of diastolic dysfunction was significantly higher in 23 participants with diabetes of longer duration (62.16%) as compared to 14 participants with diabetes <5 years (37.83%). Thirty-four participants with HbA1c ≥6.5 (40%) (P = 0.139) had diastolic dysfunction. Out of 37 participants of diastolic dysfunction, 17 subjects (45.94%) had total cholesterol <00 mg/dl, while 20 participants (54.0%) had total cholesterol ≥200 mg/dl. Similarly, hypertriglyceridemia was present in 30 diabetic participants with diastolic dysfunction (81.08%) as compared to 7 participants with normal triglyceride level (18.91%). HDL level was <40 mg/dl in 20 diabetics with diastolic dysfunction (54.0%) in comparison to 17 participants having HDL ≥40 mg/dl (45.94%) [Table 4].
Table 4: Relation of biochemical and obesity indices with diastolic dysfunction

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  Discussion Top


Obesity is the most important causative factor in spectrum of both T2DM and Heart Failure. The increasing trend of sedentary lifestyle has led to vulnerability to various lifestyle-related disorders such as T2DM, metabolic syndrome, further complicated by CVD. In preventing obesity, major part of coronary heart disease morbidity is prevented. Diabetic cardiomyopathy involves the changes in cardiac structure and function without hypertension or coronary artery disease.[7] It is considered that LVDD precedes the systolic dysfunction. The pathogenesis of diabetic cardiomyopathy is multifactorial. The presence of chronic hyperglycemia, insulin resistance, obesity increases glycation of interstitial proteins such as collagen products that have harmful effects on the myocardium.[8] Heart failure with preserved ejection fraction, a disease where no therapy has been shown to significantly improve the prognosis.[9] Chronic increases in plasma glucose level in T2DM participants is associated with aortic stiffening and consequent increase in LV afterload, as well as with LV mass increment. Even before the onset of DM, myocardial dysfunction has already become established.[10] Thus, an adequate glycemic control and weight reduction can prevent the myocardial dysfunction. TDI is more sensitive method that measures “the velocity of the longitudinal motion (shortening and lengthening) of the mitral annulus” and it is a sensitive method for the early detection of diastolic dysfunction.[11] The early identification and correction of the main determinants of subclinical diastolic dysfunction, such as obesity and glycemic status, are vital for decreasing the morbidity and mortality in these individuals. Only few studies have described an independent association between diabetes and heart failure, especially because this association is confounded by the simultaneous presence of other risk factors. The current cross-sectional observational study assesses the parameters and grades of diastolic dysfunction with severity of DM and obesity indices, especially association with abdominal obesity and glycemic control and LVDD

Age and diastolic dysfunction: Of 37 participants with diastolic dysfunction, 28 participants (75.76%) were above 40 years of age, and 9 participants below 40 years of age (24.32%) in the present study (P = 0.044). Zuo et al. observed that age of diastolic dysfunction group was older (59.17 ± 10.77 years).[2] Sharavanan et al. quoted the highest prevalence of LVDD in the female population and in the individuals belonging to the age group of more than 45 years.[12] Similarly, diastolic dysfunction was significantly higher in participants with age >45 years, compared to age <45 years as stated by Ashour[13] Chaudhary et al. also found a higher incidence of LVDD in older subjects group, especially above 50 years.[14]

Association between BMI and diastolic dysfunction: In present study, 26 participants (70.27%) were overweight or obese with LVDD as compared to 11 participants (29.72%) with normal weight with LVDD (P = 0.027). Similarly, Zuo et al. also found a higher proportion of diastolic dysfunction in participants with higher BMI (68.29%).[2] This result was supported by Sharavanan et al. wherein 63.63% subjects had LVDD with BMI of more than 23 kg/m2.[12] Ashour found no significant difference in the mean of BMI between diabetics and control group.[13] Similarly, Chaudhary et al. observed that BMI was not found to be correlated with LVDD.[14] These two studies were not in agreement with the present study, this could be because of difference of population characteristics and criteria and cutoffs used to label diastolic dysfunction and obesity.

Relation of diastolic dysfunction with duration of T2DM and HbA1c: We observed that the prevalence of diastolic dysfunction was significantly higher in 23 participants with diabetes of longer duration (62.16%) as compared to 14 participants with diabetes <5 years (37.83%). The mean duration of diabetes was (10.33 ± 6.1) years in subjects of diastolic dysfunction as compared to (7.23 ± 3.83) years in those without diastolic dysfunction. The course of type-2 DM was 7.68 ± 6.24 years in the normal group and 11.34 ± 7.07 years in the dysfunction group.[2] Ashour noted that there is a direct relation between the duration of DM and the presence of preclinical diastolic dysfunction.[13] In our study, twenty-three subjects with HbA1c ≥6.5 (72.97%) (P = 0.009) had diastolic dysfunction and 10 subjects had HbA1c <6.5 (27.02%). Similarly, the diastolic dysfunction in diabetics also correlated with the poor glycemic control and HbA1c level in a study by Ashour and Chaudhary et al. also found that mean HbA1c level of LVDD group was higher as compared to those without LVDD.[13],[14]

Dyslipidemia and diastolic dysfunction: Hypertriglyceridemia was observed in cases of obesity (P = 81.08%). Study by Zuo et al. there were no significant differences in HbA1c level, total cholesterol, HDL, LVDD.[2] We observed that a total of 17 subjects (45.94%) had total cholesterol <200 mg/dl while 20 subjects (54.0%) had total cholesterol ≥200 mg/dl. Similarly, hypertriglyceridemia was present in 30 diabetic subjects with diastolic dysfunction (81.08%) as compared to 7 subjects with normal triglyceride level (18.91%). HDL level was <40 mg/dl in 20 diabetics with diastolic dysfunction (54.0%) in comparison to 17 subjects having HDL ≥40 mg/dl (45.94%). Chaudhary et al. found serum cholesterol not to be related with LVDD. This could be attributed to the duration of diabetes in these subjects.[14]

Echocardiographic parameters of diastolic dysfunction: The present study observed that the prevalence of diastolic dysfunction (LVDD) was 37% with 30 (81.08%) participants had Grade I diastolic dysfunction, 7 (18.91%) participants had grade II dysfunction, and no patient had restrictive filling pattern (Grade III) diastolic dysfunction. Similarly, in a study by Sharavanan et al. quoted 5% diabetic participants were detected with LVDD with 72% had Grade I, 16% had a Grade II.[12] Chaudhary et al. quoted 41% incidence of LVDD (Grade 1 LVDD: 87.80%).[14] Kozakova et al. observed 35.2% T2DM subjects had e′ velocity lower than that expected for age (against 7.9% in healthy volunteers; P < 0.0001), and 71 (56.8%) had LV mass higher than that expected for body size. HbA1c was related to LV mass in T2DM participants. T2DM subjects with HbA1c ≥6.% (n = 85) had a higher prevalence of LV hypertrophy (P = 0.01) and lower e′ velocity.[15] Diastolic dysfunction was more prevalent in the particiants with higher HbA1c as observed by Fontes-Carvalho et al.[7] the E velocity in diabetic participants with obesity was low as compared to diabetics with normal weight (44 ± 11 cm/s vs. 52 ± 7.5 cm/s). Higher BMI was associated with higher “A” (61 ± 14 cm/s vs. 38 ± 6.24 cm/s). The e' was lower in overweight/obese diabetics as compared to normal weight. The e' septal (9.1 ± 1.88 [cm/s] vs. 9.8 ± 1.82 [cm/s]) and e' lateral (9.8 ± 1.92 [cm/s] vs. 9.9 ± 1.88 [cm/s]) were also on lower side in cases with obesity and without obesity, respectively. The E/e' ratio was higher in diabetic group with obesity (14.8 ± 2.8) as compared to normal weight diabetic group (12.86 ± 2.14) in present study. Similarly Seo et al. observed overweight had lower e' and E/e' ratio than normal weight (P < 0.05). BMI was associated with higher A, lower e', and higher E/e'. The risk of LVDD was significantly higher among overweight. BMI had positive association with peak 'A' velocity and E/E' ratio. In contrast, BMI was negatively associated with E/A ratio and e' velocity. There were significant correlations between higher LV mass index and lower E/A ratio, lower e' velocity, and higher E/e' ratio.[16] This was in accordance as noted by Seferovi et al. that with advancing age and BMI increase the risk of heart failure in T2DM.[17] Bouthoorn et al. in their study stated that among type 2 diabetics, LVDD and heart failure with preserved LVEF was high.[18],[19] We observed that diabetic participants with obesity had significantly higher TR jet (2.84 ± 1.2 vs. 0.9 ± 0.36 [m/s]), higher LA volume index (30. 4 ± 14.46 vs. 22.4 ± 4.66 [ml/m2]), and LVMI (170 ± 42.6 vs. 116 ± 28.4 [g/m2]) as compared to diabetics with a normal BMI. Ashour observed that mean E/A ratio in the diabetics was significantly lower and E/e' ratio was higher.[13] Fontes-Carvalho et al. found that participants with T2DM showed lower e' velocity and increased E/e' ratio. HbA1c levels are positively associated with LV mass and a negative impact on early diastolic velocity e′.[7] The LV mass index A and E/e' were higher, E, E/A were lower in the overweight and obese groups. Age, gender, BMI, and systolic blood pressure correlated positively with E/e'. In men, E/e' correlated positively with age and BMI or WC. In women, only age had a positive correlation with E/E'.[20] In the present study, the prevalence of diastolic dysfunction was 37%. A total 81.08% participants had Grade I diastolic dysfunction and 18.91% subjects had grade II dysfunction. Similarly, Zakriaa et al. observed that 80% subjects had diastolic dysfunction, classified as 27% type 1 diastolic dysfunction, 47% type 2 pseudo-normal diastolic dysfunction, and 7% participants with type 3 diastolic dysfunction. 21 Echocardiographic, subclinical diastolic worsening leading to overt heart failure can be anticipated.[22] Zheng et al. observed a significant positive association between the metabolic risk factor clustering and the risk of LVDD. Abdominal obesity, hypertension, and elevated blood glucose were the major contributors to the greater dysfunction risk.[23] Similarly, in the present study, E/A ratio negative correlation with (−0.34) WC and positive correlation with E/e' (0.48) and LVMI (0.37). The comparison of various studies is shown in [Table 5].
Table 5: Comparison of various studies with the present study

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  Conclusions Top


The present study highlighted that obesity indices (WC and BMI) had significant association with the LVDD. About one-third of participants with T2DM had LVDD and statistically correlated with obesity, longer duration of diabetes, sub-optimal glycemic control, and hypertriglyceridemia. Early echocardiographic evaluation of diabetic participants will benefit in triage for the optimal management of diabetes and also preclusion of diastolic heart failure as obesity is a self-determining and most commanding risk factor in band of both diseases. This study highlights the consequence of unbalanced variables associated with diabetes that should be considered in the management of cardiac complications. Along with monitoring of HbA1c levels, echocardiographic screening of subtle LV diastolic abnormalities will help in deciding early pharmacological intervention in participants with DM. It has emphasized the key role of lifestyle modification, balanced nutrition, and regular exercise in primary prevention of obesity.

Limitations

The sample size was small. Fasting insulin levels or HOMA-IR was not done in the present study.

Financial support and sponsorship

Krishna Institute of Medical Sciences Deemed to be University, Karad.

Conflicts of interest

There are no conflicts of interest.



 
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Chaudhary AK, Aneja GK, Shukla S, Razi SM. Study on diastolic dysfunction in newly diagnosed type 2 diabetes mellitus and its correlation with glycosylated haemoglobin (HbA1C). J Clin Diagn Res 2015;9:OC20-2.  Back to cited text no. 14
    
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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