A Subtle Decline in Cardiac Mechanics is correlated with Albuminuria in Asymptomatic Normotensive Patients with Type 2 Diabetes Mellitus: A Two Dimensional Strain Echocardiography Study.

Background: Type 2 diabetes mellitus (T2DM) insidiously affects the myocardium with subsequent cardiomyopathy and induces microvascular damage in the kidneys reflected by albuminuria. We aimed to investigate the relationship between albuminuria and subclinical left ventricular (LV) systolic dysfunction in asymptomatic normotensive patients with T2DM assessed by two-dimensional speckle-tracking echocardiography. Materials and Methods and
Results: Sixty normotensive patients with T2DM were included and subdivided into two subgroups, each including thirty patients according to the presence of albuminuria, together with thirty control subjects. All underwent echocardiographic examination, including LV regional and global longitudinal strain (GLS) measurements. Laboratory tests were withdrawn, including serum glycated hemoglobin (HbA1C) and albumin-creatinine ratio (ACR). When compared to the control group, patients with T2DM had a significantly lower average peak systolic LV GLS (-16.18% ± 2.78% vs. -18.13% ± 2.86%, P < 0.001), however, there was no significant difference in average peak systolic LV GLS between both diabetic subgroups (-15.57% ± 2.77% in the albuminuric subgroup vs. -16.79% ± 2.70% in the nonalbuminuric subgroup, P = 0.077). Moreover, there was a significant correlation between ACR and reduction of GLS in patients with T2DM and albuminuria (r = 0.55, P = 0.002). However, this correlation was absent in patients with T2DM without albuminuria (r = 0.107, P = 0.573). Conclusions: Patients with T2DM have subclinical LV systolic dysfunction with a reduction of average LV GLS that correlates with ACR in patients with T2DM and albuminuria. Copyright:

INTRODUCTION

Cardiovascular disease (CVD) is one of the most common comorbidities and causes of death in patients with type 2 diabetes mellitus (T2DM).[1] However, in view of emerging evidence that T2DM represents a stronger predictor of mortality than coronary artery disease in cohorts with heart failure, diabetic cardiomyopathy (DCM) is increasingly recognized as a clinically relevant entity. DCM refers to a clinical condition of ventricular dysfunction in the absence of coronary atherosclerosis and hypertension in patients with diabetes mellitus.[2] The underlying mechanisms are proposed to be multifactorial yet likely to act synergistically, including microangiopathy, cardiomyocyte hypertrophy, deposition of glycation end products, and myocardial fibrosis with increased myocardial stiffness.[34]

It is essential to achieve an early diagnosis of DCM in asymptomatic diabetic patients to prevent the development of irreversible morphological changes, such as fibrosis, leading to impaired contractility.[5]

Speckle-tracking echocardiography is an imaging technique developed to quantify myocardial function and analyze cardiac motion and deformation objectively. It has the potential to unravel the transmural progression of myocardial dysfunction from subclinical stages to the development of heart failure and thus provide incremental information beyond the left ventricular ejection fraction (LVEF).[67] Therefore, assessment of peak systolic left ventricular (LV) global longitudinal strain (GLS) using speckle-tracking imaging may be able to identify subtle changes in cardiac mechanics that are not detectable with conventional echocardiography.[89]

Diabetic kidney disease is a life-threatening microvascular complication of T2DM and contributes to both cardiovascular morbidity and mortality. Albuminuria is an independent risk factor of the rapid progression of chronic kidney disease (CKD) and is considered a warning sign for CKD in T2DM. In patients with T2DM and CKD, the level of urinary albumin excretion has been associated with CVD.[10] Furthermore, albuminuria is known to be associated with increased LV mass and is theoretically related to multiple pathophysiological processes, including systemic inflammation and endothelial dysfunction.[1112]

Functioning in tandem, both the heart and kidney are pathologically implicated in T2DM. Thus, we hypothesize that the degree of microvascular involvement in T2DM, reflected by albuminuria and subtle DCM, measured by GLS, might be interrelated.

This study aimed to investigate the relationship between albuminuria and subclinical LV systolic dysfunction in asymptomatic normotensive patients with T2DM assessed by two-dimensional (2D) speckle-tracking echocardiography.

MATERIALS AND METHODS

This study was approved by our institutional review board and ethical committee, in accordance with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all individuals enrolled in the study.

Study population

This prospective observational study was conducted in the Cardiology Department university hospital, including 60 asymptomatic normotensive patients with T2DM, within 5 years of initial diagnosis and receiving conventional oral antidiabetic medications recruited from the outpatient clinic and 30 healthy controls. The 60 patients with T2DM were further subdivided into 30 normotensive patients withT2DM and albuminuria, defined as albumin–creatinine ratio (ACR) more than 30 mg/g (albuminuric subgroup), and 30 normotensive patients with T2DM but without albuminuria, defined as ACR <30 mg/g (nonalbuminuric subgroup).[13]

The study excluded patients with T2DM requiring insulin, previous history of ischemic heart disease or positive stress electrocardiography (ECG), significant CKD defined as an estimated creatinine clearance below 60 ml/min/1.73 m2, atrial flutter or fibrillation or frequent premature ventricular contractions, valvular heart disease (significant stenosis or regurgitation of mitral and aortic valves), LV dysfunction with LVEF <50%, resting echocardiography segmental wall motion abnormality, or suboptimal echocardiographic image quality.

Anthropometric measurements

Body mass index (BMI) and body surface area (BSA) were calculated for all included individuals. The Mosteller formula was used to calculate the BSA, which is the square root of the product of the weight in kg times the height in cm divided by 3600.[14]

Laboratory investigations

Urine analysis was done to calculate ACR. Other laboratory investigations included HbA1C and serum creatinine in addition to the calculation of estimated creatinine clearance by the Cockcroft–Gault formula.[15]

Exercise stress test

To rule out underlying ischemic heart disease, all patients in the study and control groups underwent exercise stress electrocardiography (GE Healthcare CASE version 6.6, United States).

Standard transthoracic echocardiographic study

All individuals were studied in the left lateral decubitus using an ultrasound system Vivid E9 General Electric machine (GE Vingmed Ultrasound AS, Horten, Norway) with an M4S matrix sector array probe of 2.5 MHz frequency. Standard 2D, M-mode, and Doppler echocardiograms were obtained according to the American Society of Echocardiography guidelines. All echocardiographic examinations and follow-up measurements were done by a senior echocardiographer with 10 years of experience performing echocardiograms. The echocardiographer was blinded to the laboratory results of the study population.[1617]

Basic measurements included LV wall thickness, LV internal dimensions, indexed LV end-diastolic and end-systolic volumes, LV mass index (LVMI), using the Devereux formula, and LVEF estimated by M-mode and modified Simpson's rule. Deceleration time (DT) and E/A ratio were measured by pulsed-wave Doppler and E/E’ by tissue Doppler imaging to assess LV diastolic function as recommended. Left atrial (LA) anterior–posterior dimensions and indexed LA volumes were also obtained.

Two-dimensional strain and strain rate imaging

2D echocardiography images were obtained from apical four- and two-chamber views and LV apical long-axis view by another echocardiographer blinded to the data obtained by the echocardiographer performing the standard transthoracic echocardiographic examination. All images were obtained during a breath-hold and stored in cine-loop format from three consecutive beats, at frame rates ranging from 50 to 90 frames per s. All data were transferred to a workstation for further offline analysis.

After defining the endocardial border manually and adjusting the range of interest width, an epicardial tracing was automatically developed by the software system in the following sequence: apical long axis, apical four-chamber, and apical two-chamber for LV. For each view, the endocardial border was manually traced in the end-systolic frame.

The software then automatically generated myocardial strain curves by frame-by-frame tracking of the natural acoustic markers throughout the cardiac cycle. If the automatically obtained tracking segments were adequate for analysis, the software system was allowed to interpret the data. In contrast, analytically inadequate tracking segments were either corrected manually or excluded from the study.

The myocardium of the LV was automatically divided into six walls, and all walls were then subdivided into three segments (apical, mid, and basal). The longitudinal peak systolic strain was calculated for each segment. The GLS for each view and average GLS were generated automatically by software, and bull's eye was generated for the whole LV at the end of the analysis [Figure 1].[181920]

Figure 1

Bull's eye view showing average peak systolic global longitudinal strain in one of the study group patients

Statistical analysis

All data were gathered, tabulated, and statistically analyzed on a PC using a commercially available statistical software package (SPSS, Inc., Chicago, IL, USA). Qualitative variables were expressed as frequency and percentage. Quantitative variables were expressed as mean ± standard deviation qualitative variables were compared using the Chi-squared test. Quantitative variables were assessed using paired t-test or one-way analysis of variance test (if more than two groups). ACR values deviated strongly from a (log) normal distribution (based on skewness/kurtosis), and the median and interquartile ranges were reported and subsequently analyzed by performing nonparametric tests (Mann–Whitney U test and Kruskal–Wallis test if more than two groups). Correlations were performed with linear regression and Pearson's coefficient. P < 0.05 was considered statistically significant, and P < 0.01 was considered highly significant.

RESULTS

Of 155 asymptomatic normotensive patients with T2DM recruited from the outpatient clinic, only 60 patients were enrolled in this study. Twenty-eight patients were accidentally discovered to have significant CKD and were ruled out; the remaining 67 patients were excluded from the study due to the presence of comorbidities that might affect the LV GLS values as atrial fibrillation (n = 11), asymptomatic significant valvular heart disease (n = 16), resting wall motion abnormality (n = 14), LV dysfunction defined as LVEF <50% (n = 10), or poor echocardiographic image quality (n = 16).

The mean age of the patients was 47.3 ± 8.5 years with almost equal sex distribution (males = 31 versus females 29) that was not statistically different from the control group. However, BMI was significantly higher in the diabetic study group (31.8 ± 6.8 vs. 26.1 ± 3.0, P < 0.001). Compared to the control group, the HbA1C and ACR were significantly higher in the diabetic study group, whereas the estimated creatinine clearance was significantly lower in the study group (106.8 ± 30.7 ml/min/1.73 m2 vs. 132.3 ± 30.7 ml/min/1.73 m2, P = 0.01), as shown in Table 1.

Table 1

Characteristics of the study group (patients with type 2 diabetes mellitus) and control group

	Study group (60)	Control group (30)	P
Age (years)	47.27±8.47	46.87±8.36	0.832
Male (%)	31 (51.7)	19 (63.3)	0.294
BMI (kg/m2)	31.82±6.78	26.13±2.99	<0.001
HbA1C (%)	6.75±1.14	5.26±0.46	<0.001
ACR (mg/g), median (IQR)	34.5 (11.5-191.5)	4.5 (2-8)	<0.001
Creatinine clearance (ml/min/1.73 m2)	106.8±30.7	132.3±30.7	0.01

BMI=Body mass index, HbA1C=Hemoglobin A1c, ACR=Albumin–creatinine ratio, IQR=Interquartile ranges

When comparing the results of both diabetic subgroups, there was no significant difference as regards glycemic control, as expressed by HbA1C values (6.93 ± 1.31 in the albuminuric subgroup vs. 6.56 ± 0.92 in the nonalbuminuric subgroup, P = 0.147). Regarding ACR in the diabetic nonalbuminuric subgroup, despite having normal ACR values, its median was significantly higher than the control group (median ACR: 11.5 mg/g vs. 4.5 mg/g, P < 0.001). On the other hand, it was significantly lower than the albuminuric subgroup (median ACR: 11.5 mg/g vs. 191.5 mg/g, P < 0.001) despite exhibiting similar creatinine clearance, as shown in Table 2.

Table 2

Characteristics of the diabetic subgroups and the control group

	Albuminuric subgroup (n=30)	Nonalbuminuric subgroup (n=30)	Control group (n=30)	P	Post hoc analysis by LSD
					P1	P2	P3
Age (years)	45.13±9.13	49.40±7.28	46.87±8.36	0.140	0.05	0.420	0.240
Male (%)	18 (60.0)	13 (43.3)	19 (63.3)	0.248	0.196	0.790	0.120
BMI (kg/m2)	32.78±7.90	30.86±5.41	26.13±2.99	0.000	0.204	<0.001	0.002
HbA1C (%)	6.93±1.31	6.56±0.92	5.26±0.46	<0.001	0.147	<0.001	<0.001
ACR (mg/g), median (IQR)	191.5 (89-280)	11.5 (8-15)	4.5 (2-8)	<0.001	<0.001	<0.001	<0.001
Creatinine clearance (ml/min/1.73 m2)	106.3±31.1	107.3±30.4	132.3±30.7	0.002	0.9	0.0019	0.0025

P1=P-value Group 1 versus Group 2, P2=P-value Group 1 versus control group, P3=P-value Group 2 versus control group, BMI=Body mass index, HbA1C=Hemoglobin A1c, ACR=Albumin–creatinine ratio, IQR=Interquartile ranges, LSD=Least Significant Difference

Regarding echocardiographic 2D findings, the diabetic study group had significantly larger LV indexed volumes (LV end-diastolic volume index and LV end-systolic volume index) and indexed LA volumes. Besides, the diabetic group had significantly higher LV wall thickness and indexed LV mass. Regarding LV diastolic parameters, the diabetic group showed significantly deteriorated diastolic function revealed by significantly higher DT and E/E’ with significantly lower E/A and lateral E’ values, as shown in Table 3.

Table 3

Echocardiographic findings in diabetic patients and control group

Echocardiographic data	Diabetic patients (n=60)	Control group (n=30)	P
Structural measures
LVEDD (mm)	50.82±4.49	48.83±2.61	0.028
LVESD (mm)	32.88±3.44	31.87±2.21	0.145
IVS (mm)	10.18±1.35	8.67±1.32	<0.001
PWT (mm)	10.10±1.20	8.87±1.01	<0.001
LVEDV index (ml/m2)	49.2±13.9	43.2±9.1	0.032
LVESV index (ml/m2)	17.7±7.33	16.5±3.02	0.001
LA volume index (ml/m2)	23.23±5.02	20.26±2.46	0.003
LV mass index (mg/m2)	92.97±20.07	76.47±13.41	<0.001
Diastolic measures
DT (ms)	179.35±41.22	147.97±25.35	<0.001
E/A	1.13±0.50	1.55±0.27	<0.001
Lateral E’	11.47±4.02	18.27±3.60	<0.001
E/e’	8.80±3.87	5.24±1.17	<0.001
Systolic measures (%)
LVEF	62.78±5.27	64.10±3.61	0.222
GLS-LAX	−16.18±3.10	−19.07±3.09	<0.001
GLS-2ch	−16.38±3.05	−18.43±2.34	0.002
GLS-4ch	−15.97±3.45	−18.13±2.86	0.004
GLS-average	−16.18±2.78	−18.57±2.46	<0.001

LV=Left ventricle, LVEDD=LV end-diastolic dimension, LVESD=LV end-systolic dimension, LVEDV=LV end-diastolic volume, LVESV=LV end-systolic volume, LVEF=LV ejection fraction, LA=Left atrial, DT=Deceleration time, GLS=Global longitudinal strain, LAX= long-axis, IVS= Interventricular septum, PWT= posterior wall thickness

Although the standard echocardiographic evaluation for LV systolic function (LVEF) revealed no significant difference between both diabetic and control groups (P = 0.22), all the measurements of deformation mechanics by GLS (four-chamber, two-chamber, Apical long axis (LAX), and average) were significantly lower in the diabetic group than the control group. This reflects the occurrence of subtle LV dysfunction in the diabetic group, as shown in Table 3 and illustrated in Figure 2.

Figure 2

Bar graph shows peak global longitudinal strain in all views in both patient and control groups

Diabetic subgroup echocardiographic analysis (albuminuric vs. nonalbuminuric)

Although the deformation mechanics were significantly affected in patients with diabetes than controls as stated, investigating LV systolic function in both diabetic subgroups did not show any statistical difference neither by conventional measurements (LVEF; 62.20% ± 5.31% in the albuminuric subgroup vs. 63.37% ± 5.26% in the nonalbuminuric subgroup, P = 0.348) nor by deformation mechanics (mean average GLS; −15.57% ± 2.77% in the albuminuric subgroup vs. −16.79% ± 2.70% in the nonalbuminuric subgroup, P = 0.077). A similar nonsignificant pattern was also witnessed in LV diastolic function parameters. The only significant difference between diabetic subgroups was the indexed LVEDV and LVESV, as well as LVEDD, being significantly higher in the albuminuric subgroup, as shown in Table 4.

Table 4

Echocardiographic findings in diabetic subgroups and control group

Echocardiographic data	Albuminuric subgroup (n=30)	Nonalbuminuric subgroup (n=30)	Control group (n=30)	P	Post hoc analysis by LSD
					P1	P2	P3
Structural measurements
LVEDD (mm)	51.97±4.54	49.67±4.20	48.83±2.61	0.007	0.024	0.002	0.407
LVESD (mm)	33.33±2.54	32.43±4.16	31.87±2.21	0.185	0.262	0.069	0.479
IVS (mm)	10.33±1.45	10.03±1.25	8.67±1.32	<0.001	0.388	<0.001	<0.001
PWT (mm)	10.23±1.07	9.97±1.33	8.87±1.01	<0.001	0.369	<0.001	<0.001
LVEDV index (ml/m2)	52.2±16.3	44.4±9.7	43.2±9.1	0.002	0.001	0.03	0.062
LVESV index (ml/m2)	20.3±8.7	15.2±4.4	16.5±3.02	0.004	0.005	0.003	0.216
LA volume index (ml/m2)	23.05±4.96	23.40±5.16	20.26±2.46	0.012	0.757	0.015	0.007
LV mass index (mg/m2)	96.63±19.01	89.30±20.75	76.47±13.41	<0.001	0.118	<0.001	0.007
Diastolic measurements
DT (ms)	177.30±37.50	181.40±45.19	147.97±25.35	0.001	0.668	0.003	0.001
E/A	1.21±0.53	1.05±0.46	1.55±0.27	<0.001	0.162	0.003	<0.001
Lateral E’	11.63±3.71	11.30±4.36	18.27±3.60	<0.001	0.742	<0.001	<0.001
E/e’	9.51±4.15	8.10±3.50	5.24±1.17	<0.001	0.093	<0.001	0.001
LA volume index (ml/m2)	23.05±4.96	23.40±5.16	20.26±2.46	0.012	0.757	0.015	0.007
Systolic measurements (%)
LVEF	62.20±5.31	63.37±5.26	64.10±3.61	0.306	0.348	0.128	0.555
GLS-LAX	−15.49±3.11	−16.88±2.98	−19.07±3.09	<0.001	0.081	<0.001	0.007
GLS-2ch	−15.98±3.65	−16.78±2.31	−18.43±2.34	0.004	0.282	0.001	0.026
GLS-4ch	−15.24±3.11	−16.71±3.67	−18.13±2.86	0.004	0.083	0.001	0.091
GLS-average	−15.57±2.77	−16.79±2.70	−18.57±2.46	<0.001	0.077	<0.001	0.011

P1=P-value Group 1 versus Group 2, P2=P-value Group 1 versus control group, P3=P-value Group 2 versus control group, LV=Left ventricle, LVEDD=LV end-diastolic dimension, LVESD=LV end-systolic dimension, LVEDV=LV end-diastolic volume, LVESV=LV end-systolic volume, LVEF=LV ejection fraction, LA=Left atrial, DT=Deceleration time, GLS=Global longitudinal strain, LAX= long-axis, IVS= Interventricular septum, LSD= Least Significant Difference, PWT= posterior wall thickness

Correlation between peak global longitudinal strain and albumin–creatinine ratio

On studying the correlation between average peak systolic GLS and ACR, there was a significant reduction in average peak systolic LV GLS with increasing ACR in patients with T2DM (r = 0.38, P = 0.003) [Figure 3a]. Furthermore, there was a moderately significant correlation between reduction in average GLS with increasing ACR in patients with T2DM and albuminuria (r = 0.55, P = 0.002) [Figure 3b]. However, this correlation was absent in patients with T2DM without albuminuria (r = 0.107, P = 0.573).

Figure 3

Correlation between average peak global longitudinal strain and albumin–creatinine ratio in the whole diabetic group (r = 0.38, P = 0.03) (a) and in the albuminuric diabetic subgroup (r = 0.55, P = 0.02) (b)

DISCUSSION

Although CAD is the primary cause of death in patients with diabetes mellitus, DCM is increasingly recognized as a clinically relevant distinct entity. In its early stages, DCM includes a hidden subclinical period characterized by structural and functional abnormalities, including LV hypertrophy, fibrosis, and cell signaling abnormalities. These pathophysiological changes of cardiac fibrosis and stiffness and associated subclinical diastolic dysfunction often evolve to heart failure with preserved ejection fraction (EF) and eventual systolic dysfunction accompanied by heart failure with reduced EF. Therefore, it is essential to detect myocardial dysfunction early in T2DM patients using advanced imaging modalities.

In this study, echocardiographic evidence of structural cardiac remodeling in T2DM, compared to the control group, is demonstrated, reflected by a statistically significant increment in indexed LV volumes (end-diastolic and end-systolic) and indexed LA volumes as well as indexed left ventricular mass (LVMI).

LV hypertrophy, an ominous prognostic sign, and an independent risk factor for cardiac events, is often present in patients with T2DM. This result agrees with Hirayama et al., who demonstrated that LVM and LVMI were significantly greater in the normotensive patients with T2DM than the normotensive control population.[21] Furthermore, this result is concordant with that of Santra et al., who demonstrated that LV hypertrophy is a common association in normotensive patients with T2DM predominantly without micro- or macrovascular complications and hypertension compared to the age- and sex-matched, normotensive nondiabetic controls.[22]

However, in the current study, there is no significant difference in the LVMI between the nonalbuminuric and albuminuric subgroups. This is discordant with the Strong Heart Study, which showed a stepwise increase in the prevalence of LV hypertrophy from no albuminuria to macroalbuminuria. This discordance in the results may be attributed to the possible interaction of hypertension in the Strong Heart Study because of prevalent hypertension among their study population. In addition, the relatively short duration since the initial diagnosis of T2DM in the current study with rather better glycemic control (lower mean HbA1C) compared to the Strong Heart Study might have contributed to the discordant result.[23] Not only T2DM is associated with structural remodeling, but also it is associated with functional remodeling in terms of significant changes in all measured diastolic parameters (DT, E/A, lateral E’, and E/E’), denoting significantly increased LV filling pressures. Regarding systolic parameters, although LVEF is not significantly different compared to the control group, GLS is significantly reduced. This adds to the body of published data that speckle-tracking use for deformation imaging is more sensitive than LVEF in detecting subtle changes in longitudinal fibers in the subendocardium that are initially affected in the course of DCM, even in the absence of hypertension and overt CVD. Moreover, GLS has been regarded as a prognostic marker, as shown by Liu et al., who demonstrated that impaired GLS in T2DM patients with no history of CVD was associated with cardiovascular events and provided incremental prognostic value.[24]

In our study, there is no significant difference in GLS between both subgroups (albuminuric versus nonalbuminuric). According to the thousand and one study that compared noncardiac type 1 diabetes mellitus (T1DM) patients with nondiabetic healthy control subjects, they found that GLS is reduced in patients with T1DM with albuminuria with no significant difference between control subjects and T1DM patients without albuminuria.[25] Our study did not show a significant difference in GLS between diabetic patients with or without albuminuria. This may be due to a possible difference in pathology between type 1 and T2DM. Our results also disagree with Jørgensen et al., who included patients with T2DM and stratified them according to albuminuria status into no albuminuria, microalbuminuria, and macroalbuminuria. Systolic functions were significantly reduced in patients with macroalbuminuria; this disagreement between our results may be attributed to the smaller number of diabetic patients with macroalbuminuria in our study population.[26]

The principal objective of this study was to study the correlation between albuminuria in asymptomatic normotensive T2DM patients and subclinical LV systolic dysfunction. In our study, there is a significant correlation between ACR and reduced average GLS in diabetic patients. In addition, there is a significant correlation between ACR and reduction in average GLS in patients with T2DM and albuminuria (r = 0.55), denoting that once the patients with T2DM commence developing albuminuria, progressive myocardial involvement ensues that mirrors the degree of albuminuria. This comes in agreement with the thousand and one study that showed a clear dose–response relationship between the degree of albuminuria and myocardial involvement.[25]

This finding may give insights into the delicate relationship between microvascular and myocardial involvements in the course of diabetes that denotes their simultaneous progression and intersection together with possibly stemming from shared pathophysiological mechanisms. This further reinforces the “common soil hypothesis,” where microalbuminuria is regarded as a marker of generalized endothelial dysfunction with perturbed vascular permeability, and these changes occur in conjunction with advanced glycation end products, oxidative stress, low-grade inflammation, and neovascularization of vasa vasorum can lead to macrovascular complications and DCM.[27] These accumulating data may help not only develop but also understand the effects of novel therapeutic interventions. One prominent example is the new class of antidiabetic medications (sodium-glucose co-transporter 2 “[SGLT-2]” inhibitors) with favorable renal and cardiovascular outcomes. A recently published randomized trial, EMPA-HEART CardioLink-6 trial, in patients with T2DM showed that empagliflozin treatment resulted in an early and significant reduction in LV mass as detected by cardiac magnetic resonance imaging, suggesting that reverse cardiac remodeling may be a possible contributor to the cardioprotective effects of SGLT-2 inhibitors.[28] Besides, results from the CREDENCE trial demonstrated the salutary effects of canagliflozin versus placebo on renal outcomes in patients with T2DM and albuminuric CKD. Both studies support the notion that renal protection and cardiovascular benefit induced by SGLT-2 inhibitors may be interlinked, thus reversing the concomitant adverse effects of T2DM on both myocardial and renal beds.[29]

Study limitations

The extensive exclusion criteria applied to the patients before enrollment in the study led to narrow eligibility criteria, with the exclusion of T2DM requiring insulin or patients with hypertension or underlying ischemic heart disease. The main objective of these extensive exclusion criteria was to try to document the presence of subtle changes in LV systolic function related to diabetic pathology and not to any other disease process. However, this limits the generalization of the study results to the whole population with T2DM. In addition, this study also comprised a few patients with T2DM and macroalbuminuria, possibly due to the inclusion of patients with a recent diagnosis of T2DM. Thus, further research on this patient cohort is recommended.

Correlation of decreased LV GLS in the diabetic population, especially those suffering albuminuria, and future development of LV systolic dysfunction defined as EF <50% using longer-term studies should be considered.

CONCLUSIONS

T2DM results in a reduction of average peak systolic LV GLS. There is a significant correlation between average peak systolic GLS and ACR in T2DM with albuminuria that may represent the actual start of myocardial systolic function decline, and thus, albuminuria can be used as a marker for risk stratification that identifies patients at risk of development of DCM.

Ethics approval and consent to participate

The study was approved by the ethics committee of the hospital, and all participants signed informed consent before the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.