Hjärtats funktion och struktur hos patienter med diabetes –
undersökt med magnetisk resonanstomografi
Cardiac function and structure in patients with diabetes
examined with cardiovascular magnetic resonance imaging
Author: Darja Hamid
Spring term 2020
BLS, Degree Project in Medicine, Second Cycle, 30 Credits Thesis Course, MC2002
School of Health Sciences, Örebro University
Supervisor: Robert Jablonowski, MD, PhD, Lund University, Department of Clinical Sciences, Lund Examinator: Eewa Nånberg, Professor, School of Health Sciences, Örebro University
Abstract
Introduction: One of the main causes of death in the world is due to diabetes mellitus, a
metabolic disease characterized by chronic hyperglycemia. The disease is mainly divided into two groups, type 1 diabetes, an autoimmune disease, and type 2 diabetes caused by peripheral insulin resistance. Cardiovascular disease (CVD) is more frequent in patients with diabetes, but the link to blood sugar control is still not completely understood.
Aim: To investigate if cardiac function, extracellular volume and myocardial perfusion in
patients with diabetes are affected compared to healthy controls, and if there is a relationship to long-term blood sugar levels. Also, investigate if cardiac function is affected by acute hyperglycemia in patients with diabetes.
Method: The study included seven type 2 diabetic patients and twelve healthy controls. All
subjects performed a cardiac magnetic resonance imaging (CMR) at rest and during adenosine stress. All diabetic patients also performed a CMR during acute hyperglycemia. Left ventricular volumes, ejection fraction, extracellular volume (ECV), fibrosis and myocardial perfusion were calculated by delineation of CMR images. Hemoglobin A1c (HbA1c) was determined by blood test for all subjects. Non-parametric statistics were used to compare groups.
Results: All study participants had a normal left ventricular ejection fraction (LVEF) and there
was no relation between LVEF and HbA1c in patients with diabetes (R2 = 0.17, p=0.31). Patients
with diabetes had increased ECV (32±4% vs 25±4%, p=0.04) compared to healthy controls. There was a positive correlation between HbA1c and ECV in patients with diabetes (R2=0.73,
p=0.01). There was no difference in resting perfusion (ml/min/g) (diabetes 0.9 ± 0.2, controls 0.8 ± 0.1, p = 0.88) but during adenosine stress perfusion was significantly lower in subjects with diabetes (2.9 ± 0.4) compared to controls (3.9 ± 0.5, p=0.04). Myocardial perfusion ratio (stress/rest) was also significantly lower in patients with diabetes compared to controls (p=0.03). LVEF at peak hyperglycemia did not differ compared to baseline (57±5% vs. 59±6%, p=0.93) in patients with diabetes.
Conclusion: This study has demonstrated that diabetic patients had normal left ventricular
function, increased extracellular volume and impaired myocardial perfusion ratio suggestive of microvascular dysfunction.
Keywords: type 2 diabetes, CMR, diabetic cardiomyopathy, cardiac function, blood sugar
INTRODUCTION
Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia and is one of the main global burdens of disease [1]. The disease can be divided into two main subtypes; type 1 diabetes (T1D) which is an autoimmune disease that attacks the insulin-producing cells and results in inhibition of insulin production and type 2 diabetes (T2D) characterized by peripheral insulin resistance and together with high blood pressure and obesity it is a part of the metabolic syndrome [1]. According to statistics from the International Diabetes Federation (IDF), the global diabetes prevalence in 2019 was estimated to 9.3%, rising to 10.2% by 2030 and 10.9% by 2045 [2].
Patients with poorly controlled diabetes are at greater risk of developing microvascular complications that affect the eyes, nerves, kidneys as well as cardiovascular complications [3,4]. A well-regulated glucose level will reduce the risk of vascular complications in T2D [5] and similarly, good blood sugar control in T1D will reduce the risk of microvascular complications. The control of blood sugar levels are often made by testing blood samples and calculating the glycated hemoglobin A1c (HbA1c) level in the blood. It is used as an index of the average blood sugar level over a lifetime of erythrocytes, approximately 115 days [6,7].
Cardiovascular disease (CVD) is more frequent in patients with diabetes than others, but the mechanisms of its impact are still not completely understood [8]. The impact of blood sugar control and fluctuations in glucose levels, from hypoglycemia to hyperglycemia, are not studied enough to answer the question whether there is a link between blood sugar levels and CVD. Furthermore, individuals with diabetes have been found to have higher extracellular volume (ECV) in the heart muscle, as a result of e.g. fibrosis, compared to non-diabetics, which is associated with increased cardiovascular morbidity and mortality and longer hospital stays for heart failure [9]. Patients with diabetes have been shown to develop a special type of subclinical heart failure or cardiomyopathy, called diabetic cardiomyopathy. It is a complication in which ventricular remodeling typically results in a dysfunction of the left ventricle of the heart muscle. The changes also result in myocardial hypertrophy, myocardial necrosis and fibrosis, and collagen deposition as a result of impaired glucose tolerance [10]. The reasons behind this are not entirely clear, but changes in small blood vessels in the heart and changes in the structure of the heart muscle are part of the course of the disease. These changes are possible to study with cardiovascular magnetic resonance imaging (CMR) where the function and structure of the heart can be studied non-invasively and without dangerous ionizing radiation which enables safe
research on study participants [11].
The purpose of this project was to study morphological and microvascular changes in the heart of patients with T2D using CMR. The project will study long-term effects of high blood sugar (hyperglycemia) on the heart and how individual blood sugar control and duration of disease affect the function and structure of the heart.
The hypothesis was that morphological and microvascular changes in the myocardium are linked to how well-regulated the blood sugar levels are measured by HbA1c.
The specific aims of the study were to investigate if:
1. Cardiac function in patients with diabetes is affected compared to healthy controls, and if so, is there a relationship to HbA1c?
2. Extracellular volume and degree of fibrosis is altered in patients with diabetes compared to healthy controls and if there is a correlation to HbA1c?
3. Myocardial perfusion is affected in patients with diabetes compared to healthy controls? 4. Cardiac function is affected by acute hyperglycemia in patients with diabetes?
METHODS
Ethics approval and consent to participate
The study was approved by the National Research Ethics Committee (DNR 2016/208), and informed written consent was obtained from each participant. The projects' implementation follows the guidelines set by The General Data Protection Regulation (GDPR) and the Swedish Ethical Review Authority for corresponding research projects.
Study population
Seven patients (n=7) with documented type 2 diabetes (T2D) were recruited from the ANDIS register (the Swedish All New Diabetics in Scania/Alla Nya Diabetiker I Skåne) and included in the study. Severity and duration of T2D varied but they did not have any previously diagnosed coronary artery disease. Twelve (n=12) healthy controls were included as reference cohort (Figure 1).
Figure 1. Study flow chart. CMR acquisition
CMR examinations were performed on a clinical 1.5T scanner (Siemens Aera, Erlangen, Germany) with the study subjects in supine position.
Cardiac function: Imaging of cardiac function both at baseline and during hyperglycemia was
performed using cine imaging in breath hold both in short axis and long axis projections using steady-state free precession (cine-SSFP) sequences which provide good contrast between the heart muscle (myocardium) which appears dark in the images and the blood pool (bright). Image parameters were as follows: TR 2.7 ms, TE 1.2 ms, flip angle 60°, and slice thickness 8 mm with no slice gap.
Extracellular volume and fibrosis: A modified Look-Locker (MOLLI) T1 sequence was used to
generate T1 maps before and after gadolinium contrast agent administration. An inline extracellular volume map (ECV-map) was created after manual input of the hematocrit. Three short axis-slices were acquired at a basal, mid-ventricular and apical level. Macroscopic fibrosis was studied using a free breathing, motion corrected, late gadolinium enhancement (LGE) sequence acquired both in short and long axis projections. The inversion time was chosen to null remote myocardium. Specific parameters for the LGE sequence were: TR 2.8 ms, TE 1.2 ms, flip angle 50°, field of view 159 × 154 mm, pixel size 1.41 × 1.41 mm, no slice gap.
Myocardial perfusion: The acquisition of myocardial perfusion was made both at rest and during
stress where the latter was pharmacologically generated using an intravenous adenosine infusion (140 μg/kg/min). A basal, a mid-ventricular and an apical short-axis image were acquired both at rest and at stress. Details on image parameters have been previously published [12].
•Recruitment of patients with diabetes from ANDIS (n=7) and healthy controls (n=12)
•Baseline clinical assessment including blood pressure, ECG and blood tests including glucose and HbA1c
•Baseline CMR with adenosine provocation and perfusion imaging •Oral glucose intake, 75 g during 5 minutes
Image analysis
To assess information about LV structure and function Segment version 3.0 [13] a software solution with broad range of analysis tools for CMR was used for image processing.
Cardiac function and volumes: LV end diastolic volume (EDV), end systolic volume (ESV),
stroke volume (SV), ejection fraction (EF) and cardiac output (CO) were obtained by manually delineating endocardium and epicardium of the left ventricle at end-diastole and end-systole (Figure 2).
Extracellular volume and fibrosis: Tissue characterization was made by quantifying the
extracellular volume (ECV) which caters with information about the composition of the tissue, i.e. if it is healthy or not. For analysis of ECV, epi- and endocardium was delineated followed by drawing region of interest (ROI) in the myocardium in all three short-axis slices according to the AHA-17 segment model excluding the apex yielding 16 segments [14] (Figure 3). Obvious
image artifacts and coronary arteries were excluded from the ROIs. All the ROIs were averaged to calculate a global ECV for each subject.
Figure 2. Example of manual delineation of left ventricle endocardium (red dots) and epicardium (green dots) in the upper right panel using short axis cine images. Long axis images were used to optimize the delineation with the 2-chamber view (upper left), 3-chamber view (lower left) and 4-chamber view (lower right).
Figure 3. Example of extracellular volume (ECV) calculation by delineation of endocardium and epicardium in a short axis ECV map image. Red dots denote the endocardium and green dots the epicardium. The regions of interests (ROIs) are denoted by the blue line. Each pixel is directly proportional to the extracellular volume.
Myocardial perfusion: Myocardial perfusion in ml/min/g was also assessed regionally
according to the 17-segment model [14], excluding the apical segment, resulting in 16 segments per patient. Myocardial perfusion was assessed globally (average perfusion for all 16 segments). Myocardial perfusion reserve (MPR) was also calculated, defined as the ratio between perfusion at stress over rest.
Hyperglycemia CMR
In order to make the diabetic subjects hyperglycemic an equivalent amount of oral glucose was administered as in an oral glucose tolerance test. After the first CMR scan all patients with diabetes were given 75 g glucose to drink, a total of two deciliters of liquid. Blood glucose measurements at baseline and every 15 minutes were acquired for two hours. The CMR scan was initiated after 30 minutes following the completion of the glucose intake. Controls did not perform a hyperglycemic CMR scan.
Previous studies using CMR to study diabetic patients
In order to identify similarities and differences between this and other studies examining T2D patients with CMR, a summary analysis was compiled based on publications found on PubMed.
Search terms included: cardiovascular magnetic resonance, CMR, extracellular volume, ECV, diabetes and type 2 diabetes (T2D) was used separately and in different combinations with each other with the intention of finding articles and publications with aims and assessment comparable to this study. Studies that matched the search criteria were compiled and stratified according the presence of extracellular volume analysis. The myocardial perfusion sequence used in the current study has not been used in any study on diabetic patients and was therefore not included.
Glycemic status - measurement of HbA1c
HbA1c tests were analyzed by taking a venous blood sample from all participants using a small needle. After the needle was inserted in a vein, a small amount of blood was collected into a test tube. The blood samples were analyzed at the local clinical chemistry laboratory.
Statistical analysis
The program Graph Pad Prism 8.0 software (Graph Pad Software, Inc., La Jolla, CA, USA) was used for statistical analysis. Results are presented as mean±SD and nonparametric statistical methods were used to compare the study cohort against controls by using Mann-Whitney analysis method. Furthermore, linear regression was used to study the relationship between cardiac function, ECV and HbA1c. Differences with a p-value <0.05 were considered to denote statistical significance.
RESULTS
Study
population
The study sample consisting of 19 participants comprised seven patients with diabetes and twelve healthy controls. Baseline characteristics are presented in Table 1. The mean age of the
participants was 63 years in the diabetic group, two men and five women, and 50 years in the control group which consisted of only men. Patients with diabetes were slightly older and had a higher burden of comorbidity and disease severity than controls, including slightly higher blood pressure, medications and smoking habits. The HbA1c was significantly higher in the diabetes group compared to controls (56±10 vs. 35±4 mmol/L, p=0.03) and all patients with diabetes had pathological values >42mmol/L.
Table 1. Baseline characteristics of study participants. Diabetes (n=7) Controls (n=12) P Age (y) 63±11 50±12 0.54 Male gender, n (%) 2(29) 12(100) 0.09 LVEF (%) 59±6 60±4 0.30 LV-EDV (ml) 157±48 146±35 0.74 LV-ESV (ml) 62±17 55±85 0.85 LV-SV (ml) 100±24 102±17 0.77 LVM (g) 119±15 122±13 0.89 Systolic BP (mmHg) 135±14 123±6 0.93 Diastolic BP (mmHg) 75±9 70±4 0.88 Smoking, n (%) 2(16) 0(0) 0.08 Hypertension, n (%) 5(64) 0(0) 0.05 Beta-blocker, n (%) 3(100) 0(0) 0.06 Aspirin, n (%) 0(36) 0(0) 0.09 ACEi/ARB, n (%) 5(28) 0(0) 0.14 HbA1c (mmol/L) 56±10 35±3 0.03
LVEF=left ventricular ejection fraction, LV-EDV= left ventricular end diastolic volume, LV-ESV= left ventricular end systolic volume, LV-SV= left ventricular stroke volume, LVM= left ventricular mass, BP=blood pressure, ACEi= angiotensin converting enzyme inhibitors, ARB= angiotensin-receptor blockers, HbA1C=Glycosylated Hemoglobin A1c
Left ventricular function
All study subjects had a normal EF and no differences in EDV, ESV or left ventricular mass was seen between the groups (P = ns for all). There was no relation between EF and long-term glycemic control as measured by HbA1c in diabetic patients (R2 = 0.17, p=0.31), see Figure 4,
Figure 4. Left Panel - Correlation between HbA1c and ejection fraction. No significant correlations between blood sugar control and ejection fraction was seen (R2 = 0.17, p=0.31). Dashed line = linear regression.
Right Panel - Correlation between HbA1c and extracellular volume (ECV) showing significant interaction between the parameters (R2=0.73, p=0.01). In the small sample size data suggest that with increased HbA1c an increase in ECV is seen. Dashed line = linear regression.
Extracellular volume and fibrosis
Patients with diabetes showed a significant increase of extracellular volume (ECV) (32±4% vs 25±4%, p=0.04) compared to controls. There was a positive correlation between HbA1c and ECV in the diabetes group (R2=0.73, p=0.01), see Figure 4, right panel. There was no sign of
fibrous tissue in either group on late gadolinium enhancement CMR.
Myocardial perfusion
The perfusion assessment revealed no difference in resting perfusion (diabetes 0.9±0.2 vs. controls 0.8±0.1 ml/min/g, p=0.88). Whilst at adenosine stress, the perfusion was significantly lower in subjects with diabetes compared to controls (2.9±0.4 vs. 3.9±0.5 ml/min/g, p=0.04) indicating a limitation of vasodilatation in stress. Figure 6 shows an example of
adenosine-induced hypoperfusion in two patients with diabetes with normal rest perfusion. The ratio of stress and rest calculated as the myocardial perfusion reserve was significantly lower in patients with diabetes compared to controls (2.7±0.43 vs. 3.6±0.6 ml/min/g, p=0.03), see Figure 7.
Hyperglycemia
Six diabetes subjects performed a hyperglycemia CMR scan. One subject was nauseous after the baseline scan and did not perform a hyperglycemia CMR scan. At baseline blood test, blood
glucose level was 6.5±0.8 mmol/L in patients with diabetes and in during peak hyperglycemia at 60 minutes 14±3 mmol/L, p = 0.05. EF at peak hyperglycemia was 57±5%, which was similar to baseline EF (59±6%, p=0.93).
Figure 6. CMR perfusion images from two patients with diabetes at rest (top panels) and during adenosine stress (bottom panels) demonstrating perfusion deficits (dark areas denoted by blue arrows) during adenosine stress as a marker of a microvascular dysfunction. Pixels in image represent quantitative myocardial perfusion in ml/min/g.
Figure 7. CMR myocardial perfusion ratio (stress/rest) is significantly lower in T2D (2.7 ± 0.4ml/min/g) compared to controls (3.6 ± 0.6 ml/min/g, p=0.03), suggesting a deficiency in microvascular function in patients with diabetes.
Comparison to previous studies
A compilation of previous studies (n=14), in which LV volumes was measured in patients with type 2 diabetes was made to compare to the current results, see Table 2. Six studies investigated
ECV [15–18] and one study [17] analyzed patients in three strata dependent on HbA1c status.
Figure 8, left panel demonstrates all the compiled studies and the relation between the mean EF
and HbA1c where the data from the current study is added. No significant correlation was seen between the two parameters (R2=0.0005. p=0.92). Also, a comparison between the studies where
ECV was examined and the different studies mean HbA1c was performed (figure 8, right panel)
revealed no correlation (R2=0.03. p=0.72). However, 4 of 6 six studies that reported a
pathological HbA1c (>42 mmol/L) also reported a pathological ECV (>25% as assessed in controls in the current study).
Figure 8. Left Panel - Correlation between HbA1c and left ventricular ejection fraction (LVEF). Solid circles represent studies from Table 2 and the open circle represents data from the current study with data found in Table 1 in diabetic patients. There was no correlation between HbA1c and LVEF (R2=0.0005. p=0.92). Dashed line = linear regression.
Right Panel - Correlation between HbA1c and extracellular volume (ECV). Solid circles represent studies from Table 2 and the open circle represents data from the current study with data found in Table 1 in diabetic patients. There was no correlation between HbA1c and ECV (R2=0.03. p=0.72). Dashed line = linear regression.
Table 2. Summary of published studies on diabetic patients using CMR studying left ventricular function and extracellular volume.
Pat = # patients, SV = Stroke Volume, EDV = End Diastolic Volume, ESV = End Systolic Volume, EF = Ejection Fraction, ECV = Extracellular Volume, LGE = Late Gadolinium Enhancement, HbA1C = Glycosylated Hemoglobin A1c
Reference Pat (n) SV (ml) EDV (ml) ESV (ml) EF (ml) ECV (%) LGE (%) HbA1c
Duce L. S. et al
2015 [24] 55 43.7±8.2 66.9±12.8 22.4(11-55) 65.9±8.8 n/a 3(5.5) 65(41-115)
Kozakova et al
2017 [25] 125 72±17 n/a n/a 65±7 n/a n/a n/a
Larghat et al
2017 [28] 30 87.7 152.0 64.3 58.0 n/a n/a 51
Larghat et al
2017[28] 19 95.9 171.0 73.5 57.5 n/a n/a 70±6
Levelt E et al
2017 [20] 31 87±23 128±33 40±17 69±8 n/a n/a n/a
Ming-Yen Ng et
al 2020[19] 63 75.7±13.6 75.4±14.8 32.3 ± 10.5 57.6 ± 6.3 n/a 5 (7.9) 64±1.0
Rospleszcz S et al
2018 [21] 50 32.7±7.6 61.0±12.6 28.3±6.7 55.0±6.2 n/a 27.4±2.5 82 ± 13
Sørensen et al
2019 [26] 193 95±20 154±36 59±23 63±8 n/a n/a n/a
Wilmot et al
2014[27] 20 n/a 173.4(33.3) 78.3(17.6) 54.9(5.0) n/a n/a 63±15
Xi Liu et al 2018 [23] 40 43±13 73.31±10.38 30.41±9.36 58.86±8.93 n/a n/a 71±8 Yongning Shang et al 2016 [22] 25 36.5±4.7 60.1±7.7 24.6±5.9 60.1±6.7 n/a n/a 61(55-84) Ajay D. Rao et al 2014[18] 53 n/a 147.0±33.2 60.5±17.8 59.8±5.9 36±5 n/a 60 Albadri et al
2018[17] 12 n/a n/a n/a n/a 21.1(17.5-24.7) n/a 50(47-53)
Albadri et al
2018[17] 20 n/a n/a n/a n/a 27.6(24.8-30.3) n/a 61(58-64)
Albadri et al
2018[17] 15 n/a n/a n/a n/a 27.6(24.4-30.8) n/a 79(74-83)
Levelt et al 2016
[15] 46 86±21 124±27 37±13 70±7 29±2 n/a 46
Storz et al 2017
DISCUSSION
Left ventricular function and volumes
Our study has demonstrated that all study participants had a normal left ventricular ejection fraction (LVEF) and no alterations in left ventricular end diastolic volume, end systolic volume or left ventricular mass. Previously published studies did not show a significant decrease in EF or systolic dysfunction in patients with type 2 diabetes [29–31], with the exception of the Strong Heart Study where a direct correlation of ejection fraction was stated as associated with HbA1c levels [32]. However, no difference in left ventricular ejection fraction was found between normo- and hyperglycemia in patients with diabetes.
Extracellular volume
A previous study has shown that there is a correlation between HbA1c and ECV [33]. It has been suggested that the reason behind this was diabetes induced fibrosis in the myocardium leading to a diastolic dysfunction [16]. In our results no relation between LVEF and long-term glycemic control as measured by HbA1c appeared in our diabetic cohort. Yet all of the patients with diabetes showed a pathologically increase of ECV and HbA1c. A positive correlation between HbA1c and ECV was found in the diabetes group but, in contrast to previous studies, there was no sign of fibrous tissue in the type 2 diabetic cohort on late gadolinium enhancement CMR. Thus, the increased ECV found in the current study represents diffuse, interstitial fibrosis.
Myocardial perfusion
The perfusion assessment revealed no difference in resting perfusion between patients with diabetes and controls. However, at adenosine stress perfusion was significantly decreased in subjects with diabetes compared to controls indicating a limitation of vasodilatation in stress. The ratio of stress and rest calculated as the myocardial perfusion reserve was significantly lower in diabetic subjects compared to controls. Sørensen et al [26] presented a similar result, using a different perfusion sequence, stating that type 2 diabetics have higher global myocardial blood flow at rest and lower maximal myocardial blood flow during vasodilator-induced stress than controls. This could indicate that the reduced perfusion during stress is associated with microvascular complications and inversely correlated with diffuse myocardial fibrosis [26]. Our study has employed a perfusion sequence validated against PET and we corroborate the findings of Sørensen et al. The lower myocardial perfusion reserve in patients with diabetes found in our study is also indicative of coronary microvascular dysfunction [34] and may be a mechanistic
explanation to the interstitial fibrosis seen as increased ECV.
Comparison to previous studies
A compilation of previous studies in which left ventricular volumes in type 2 diabetics was measured, was made to study the compliance of achieved results against previously published results. Previous studies found in Table 2 corroborate our finding that there is no correlation between LVEF and HbA1c. Furthermore, there was no correlation between ECV and HbA1c but a majority of the studies demonstrated pathological ECV in type 2 diabetic patients. This provides evidence that even though the systolic function of the heart is normal, morphological composition may be pathological. CMR may as a result be beneficial compared to other imaging modalities, for example echocardiography, to discriminate patients with elevated ECV.
Mechanistic link to diabetic cardiomyopathy
Diabetes cardiomyopathy is a specific form of cardiac disease characteristic of diabetic patients [10]. Left ventricular diastolic dysfunction has been proposed to represent the first detectable stage of diabetic cardiomyopathy [29–31,35]. The findings in the current study, and also in previous studies, show that patients with diabetes have increased ECV as a sign of interstitial fibrosis and decreased myocardial perfusion provides a mechanistic link to diastolic dysfunction and possible therapeutic target. Similar to our study, increased ECV has also been confirmed in other studies where cardiac volumes in type 2 diabetes patients has been studied with CMR [36,37]. These studies also support the theory of elevated HbA1c being related to increased ECV. This suggests that good glycemic control is warranted to reduce risk of diabetes cardiomyopathy and increase of ECV [38].
Future of CMR in studying diabetic patients
Development of echocardiography enabled the diagnosis of diabetic cardiomyopathy before it had developed in to signs of heart failure. But even though echocardiography has a crucial role in cardiac diagnostics [37], CMR is becoming the golden standard in cardiac researches since it is a method that offers a broad, quantitative, reproducible alternative to investigate in the diabetic heart. With decreasing acquisition time, less reliance on breath-holding, and less technical demands on execution, CMR is becoming more accessible to clinical populations and for important research questions on subclinical disease because of its distinctive collection of sequences dedicated to myocardial function, structure, perfusion, and diffuse extracellular matrix expansion. Consequently also allowing easier investigation in the wide spectrum of phenotypes within the diabetic cardiovascular diseases [11,28,39].
Limitations
The results of this study should be viewed in the light of some limitations. First, correlation does not imply causality. Second, the entire sample size is small and only male controls were included. However, the study is part of an ongoing study and more subjects are planned for inclusion. Third, diastolic function was not assessed as it was out of the scope of the study but analysis of diastolic function may provide incremental understanding of the mechanistic link between CMR biomarkers.
CONCLUSION
Our study has demonstrated that the patients with diabetes had normal cardiac function but with an increased ECV and lower perfusion ratio compared to controls. Higher HbA1c was correlated to higher ECV in diabetic patients. These results suggest that a contrast-enhanced CMR can detect subclinical myocardial dysfunction and impaired myocardial microvascular perfusion in patients with diabetes before the onset of apparent cardiac disease.
ABBREVIATIONS
AHA – American Health Organization
CMR – Cardiovascular magnetic resonance imaging CO – Cardiac output
CVD – Cardiovascular disease ECV – Extracellular volume EDV - End diastolic volume EF – Ejection fraction ESV - End systolic volume
HbA1c – Glycosylated Hemoglobin, Type A1C IDF – International Diabetes Federation
LGE – Late Gadolinium enhancement LV – left ventricle
MRI – magnetic resonance imaging SV – stroke volume
T1D – type one diabetes T2D – type two diabetes
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