scholarly journals Empagliflozin Treatment is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes

2021 ◽  
Author(s):  
Sharmaine Thirunavukarasu ◽  
Nicholas Jex ◽  
Amrit Chowdhary ◽  
Imtiaz Ul Hassan ◽  
Sam Straw ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Magnetic Resonance ◽  
Global Longitudinal Strain ◽  
Relative Reduction ◽  
Resonance Spectroscopy ◽  
Absolute Increase ◽  
Cellular Volume ◽  
The Mean

Sodium–glucose-cotransporter-2 (SGLT2) inhibitors reduce the risk of major adverse CV events and hospitalization for heart failure in type 2 diabetes (T2D) patients. Utilising cardiovascular magnetic resonance imaging (CMR) and 31phosphorus magnetic resonance spectroscopy(<sup>31</sup>P-MRS) in a longitudinal cohort study, we aimed to investigate the effects of the selective SGLT2i empagliflozin on myocardial energetics, cellular volume, function and perfusion. Eighteen T2D patients underwent CMR and <sup>31</sup>P-MRS scans before and after twelve-week empagliflozin treatment. Plasma N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) levels were measured. Ten volunteers with normal glycaemic control underwent an identical scan protocol on a single visit.<i> </i>Empagliflozin treatment was associated with significant improvements in PCr/ATP ratio (1.52 to 1.76, p=0.009). This was accompanied by a 7% absolute increase in the mean LVEF (p=0.001), 3% absolute increase in the mean global longitudinal strain (p=0.01), 8 ml/m2 absolute reduction in the mean myocardial cell volume (p=0.04) and 61% relative reduction in the mean NT-proBNP (p=0.05) from baseline measurements. No significant change in myocardial blood flow or diastolic strain was detected.<b> </b>Empagliflozin thus ameliorates the ‘cardiac energy-deficient’ state, regresses adverse myocardial cellular remodelling, and improves cardiac function, offering therapeutic opportunities to prevent or modulate heart failure in T2D.

scholarly journals Empagliflozin Treatment is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes

2021 ◽  
Author(s):  
Sharmaine Thirunavukarasu ◽  
Nicholas Jex ◽  
Amrit Chowdhary ◽  
Imtiaz Ul Hassan ◽  
Sam Straw ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Magnetic Resonance ◽  
Global Longitudinal Strain ◽  
Relative Reduction ◽  
Resonance Spectroscopy ◽  
Absolute Increase ◽  
Cellular Volume ◽  
The Mean

Sodium–glucose-cotransporter-2 (SGLT2) inhibitors reduce the risk of major adverse CV events and hospitalization for heart failure in type 2 diabetes (T2D) patients. Utilising cardiovascular magnetic resonance imaging (CMR) and 31phosphorus magnetic resonance spectroscopy(<sup>31</sup>P-MRS) in a longitudinal cohort study, we aimed to investigate the effects of the selective SGLT2i empagliflozin on myocardial energetics, cellular volume, function and perfusion. Eighteen T2D patients underwent CMR and <sup>31</sup>P-MRS scans before and after twelve-week empagliflozin treatment. Plasma N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) levels were measured. Ten volunteers with normal glycaemic control underwent an identical scan protocol on a single visit.<i> </i>Empagliflozin treatment was associated with significant improvements in PCr/ATP ratio (1.52 to 1.76, p=0.009). This was accompanied by a 7% absolute increase in the mean LVEF (p=0.001), 3% absolute increase in the mean global longitudinal strain (p=0.01), 8 ml/m2 absolute reduction in the mean myocardial cell volume (p=0.04) and 61% relative reduction in the mean NT-proBNP (p=0.05) from baseline measurements. No significant change in myocardial blood flow or diastolic strain was detected.<b> </b>Empagliflozin thus ameliorates the ‘cardiac energy-deficient’ state, regresses adverse myocardial cellular remodelling, and improves cardiac function, offering therapeutic opportunities to prevent or modulate heart failure in T2D.

scholarly journals Effects of Exenatide and Humalog Mix25 on Fat Distribution, Insulin Sensitivity, and β-Cell Function in Normal BMI Patients with Type 2 Diabetes and Visceral Adiposity

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Xinlei Wang ◽  
Xiaoqin Zhao ◽  
Yunjuan Gu ◽  
Xiaohui Zhu ◽  
Tong Yin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Magnetic Resonance ◽  
Cell Function ◽  
Visceral Adiposity ◽  
Fibroblast Growth Factor 21 ◽  
Resonance Spectroscopy

In China, most normal BMI (body mass index of ≥18.5 to <25 kg/m2) adults with type 2 diabetes (T2DM) exhibit visceral adiposity. This study compared the effects of exenatide and humalog Mix25 on normal BMI patients with T2DM and visceral adiposity. A total of 95 patients were randomized to receive either exenatide or humalog Mix25 treatment for 24 weeks. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were quantified by magnetic resonance imaging (MRI) and liver fat content (LFC) by liver proton magnetic resonance spectroscopy (1H MRS). Each patient’s weight, waist circumference, BMI, blood glucose, insulin sensitivity, pancreatic β-cell function, and fibroblast growth factor 21 (FGF-21) levels were measured. Data from 81 patients who completed the study (40 and 41 in the exenatide and humalog Mix25 groups, respectively) were analysed. The change in 2 h plasma blood glucose was greater in the exenatide group (P=0.039). HOMA-IR and MBCI improved significantly after exenatide therapy (P<0.01, P=0.045). VAT and LFC decreased in both groups (P<0.01 for all) but to a greater extent in the exenatide group, while SAT only decreased with exenatide therapy (P<0.01). FGF-21 levels declined more in the exenatide group (P<0.01), but were positively correlated with VAT in the entire cohort before (r=0.244, P=0.043) and after (r=0.290, P=0.016) the intervention. The effects of exenatide on glycaemic metabolism, insulin resistance, pancreatic β-cell function, and fat deposition support its administration to normal BMI patients with T2DM and visceral adiposity.

scholarly journals Characterization of Intra-myocellular Lipids Using 2d Localized Correlated Spectroscopy and Abdominal Fat Using Mri in Type 2 Diabetes

2012 ◽  
Vol 5 ◽  
pp. MRI.S10489 ◽  
Author(s):  
Preethi Srikanthan ◽  
Aparna Singhal ◽  
Cathy C. Lee ◽  
Rajakumar Nagarajan ◽  
Neil Wilson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Magnetic Resonance ◽  
Soleus Muscle ◽  
Subcutaneous Fat ◽  
Abdominal Fat ◽  
Resonance Spectroscopy ◽  
Model Assessment ◽  
Blood Draw

A major goal of this pilot study was to quantify intramyocellular lipids (IMCL), extra-myocellular lipids (EMCL), unsaturation index (UI) and metabolites such as creatine (Cr), choline (Ch) and carnosine (Car), in the soleus muscle using two-dimensional (2D) localized correlated spectroscopy (L-COSY). Ten subjects with type 2 diabetes (T2D), controlled by lifestyle management alone, and 9 healthy control subjects, were studied. In T2D patients only, the following measurements were obtained: body mass index (BMI); waist circumference (WC); abdominal visceral and subcutaneous fat quantified using breath-held magnetic resonance imaging (MRI); a fasting blood draw for assessment of glucose, insulin, and estimation of homeostasis model assessment of insulin resistance (HOMA-IR), HbA1c, and high-sensitivity c-reactive protein (hs-CRP). Analysis of the soleus muscle 2D L-COSY spectral data showed significantly elevated IMCL ratios with respect to Cr and decreased IMCL UI in T2D when compared to healthy subjects ( P < 0.05). In T2D subjects, Pearson correlation analysis showed a positive correlation of IMCL/Cr with EMCL/Cr (0.679, P < 0.05) and HOMA-IR (0.633, P < 0.05), and a non-significant correlation of visceral and subcutaneous fat with magnetic resonance spectroscopy (MRS) and other metrics. Characterization of muscle IMCL and EMCL ratios, UI, and abdominal fat, may be useful for the noninvasive assessment of the role of altered lipid metabolism in the pathophysiology of T2D, and for assessment of the effects of future therapeutic interventions designed to alter metabolic dysfunction in T2D.

scholarly journals Coronary microvascular dysfunction is only detectable in type 2 diabetes in the presence of obesity

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Chowdhary ◽  
S Thirunavukarasu ◽  
N Jex ◽  
C Bowers ◽  
R Cubbon ◽  
...  
Keyword(s):  
Heart Failure ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Magnetic Resonance ◽  
Myocardial Perfusion ◽  
Diabetic Cardiomyopathy ◽  
Microvascular Dysfunction ◽  
Left Ventricular Ejection ◽  
Coronary Microvascular Dysfunction

Abstract Background Heart failure (HF) is a leading cardiovascular complication of type 2 diabetes (T2D). Coronary microvascular dysfunction (CMD) precedes HF in diabetes and carries important prognostic information. CMD is also evident in metabolically healthy obese individuals without diabetes or hypertension. Whether diabetes causes CMD in the absence of obesity is uncertain. The interrelation among visceral adiposity and CMD has not been assessed previously. Objectives We sought to better understand the links between visceral and epicardial adipose tissue (VAT and EAT respectively) distribution, insulin resistance with myocardial perfusion, energetics and function in asymptomatic lean (LnT2D) and overweight/obese T2D patients (ObT2D) without cardiovascular disease. Methods 62 participants [27 Ob-T2D, 15 Ln-T2D, and 20 overweight controls] were recruited. Subjects underwent cardiac and abdominal magnetic resonance imaging and 31P-magnetic resonance spectroscopy, for measurements of EAT and VAT areas, rest and adenosine stress myocardial blood flow (MBF), cardiac function and phosphocreatine to ATP ratio (PCr/ATP). Fasting blood samples were taken for plasma homeostasis model assessment of insulin resistance (HOMA-IR) index calculations. Results The biochemical characteristics and multiparametric MR results are given in Table 1 and results of Pearson's regression analysis in the entire study population are given in Table 2. Stress MBF was lowest in ObT2D, while rest MBF was highest in LnT2D. Left ventricular ejection fraction (LVEF) and myocardial PCr/ATP were similarly reduced in diabetes groups. In the absence of obesity, there was no significant increase in VAT, EAT or HOMA-IR in T2D patients compared to controls. BMI and VAT, negatively correlated with LVEF, and strain parameters. PCr/ATP correlated with LVEF, but not HOMA-IR. BMI, EAT and VAT all correlated significantly with HOMA-IR, and HOMA-IR correlated with cardiac functional parameters. There was no association between HOMA-IR and myocardial perfusion. Conclusions In this study CMD was only evident in ObT2D patients, with normal rest and stress MBF in LnT2D patients. Despite normal perfusion and no significant increase in insulin resistance, LVEF and myocardial PCr/ATP were similarly reduced in LnT2D and ObT2D, and PCr/ATP correlated with LVEF. This suggests that alterations in cardiac energy metabolism are mechanistically more relevant for the pathophysiology of diabetic cardiomyopathy in LnT2D patients. In the absence of correlation between insulin resistance and myocardial perfusion, factors like inflammation and altered adipokine profile may play important roles for the pathophysiology of CMD in ObT2D patients. A better understanding of the underlying pathophysiological mechanisms of diabetic cardiomyopathy in LnT2D and ObT2D may help to develop contemporary tailored treatment and prevention strategies to tackle excess heart failure risk. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): BHFWellcome trust Table 1 Table 2

Prognostic utility of early systolic lengthening by speckle tracking echocardiography in patients with type 2 diabetes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Brainin ◽  
M.T Jensen ◽  
T Biering-Soerensen ◽  
R Moegelvang ◽  
T Fritz-Hansen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Speckle Tracking ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Major Adverse Cardiovascular Events ◽  
Forest Plot ◽  
Systolic Strain

Abstract Background Early systolic lengthening (ESL) has recently recognized as a predictor of cardiovascular events in patients with myocardial ischemia. Our aim was to evaluate the prognostic value of ESL in patients with type 2 diabetes. Methods In this prospective study we conducted speckle tracking examinations in 743 patients with type 2 diabetes (62% male; age 63±10 years; diabetes duration 11 [5, 17] years). Patients were free from interventricular conduction disturbances, atrial fibrillation, heart failure and ischemic heart disease at study inclusion. We assessed the ESL index, defined as: (−100 x [peak positive systolic strain / global longitudinal strain (GLS)]), and duration of ESL, defined as time from onset of QRS complex on the electrocardiogram to time of peak positive systolic strain. Measurements were averaged from 18 myocardial segments. Results During the median follow-up time of 4.8 years [IQR 4, 5.3 years], 93 (13%) patients experienced major adverse cardiovascular events (MACE), a composite of incident heart failure, myocardial infarction and cardiovascular death. Because GLS modified the association with MACE (P interaction &lt;0.05), the population was stratified by the median GLS value (low &gt;−15% and high ≤−15%). In patients with low GLS, the ESL index (HR 1.47 per 1% increase [1.12 to 1.93], P=0.005) and ESL duration (HR 1.73 per 1ms increase [1.10 to 2.72], P=0.017) were associated with MACE. Both associations remained significant in multivariable models adjusted for clinical, echocardiographic and speckle tracking measurements (Figure). No associations were found in patients with high GLS (Figure). Conclusion Assessment of ESL yields novel and independent prognostic information on major adverse cardiovascular events in patients with diabetes type 2 and reduced longitudinal strain. Forest plot: ESL and risk of MACE by GLS Funding Acknowledgement Type of funding source: None

scholarly journals The Impact of HbA1c level on heart failure with recovered rjection fraction in patients with Type 2 Diabetes

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
C.D Yang ◽  
X.Q Wang
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Hba1c Level ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Absolute Increase ◽  
The Impact

Abstract Background Heart failure (HF) with improved or recovered ejection fraction (EF, HFrecEF) has been recognized as a new type of HF with different underlying clinical phenotype, pathophysiology and prognosis. However, few studies have analyzed the relationship between type 2 diabetes and HFrecEF, and the impact of glycemic level on myocardial function recovery. Purpose In the present study, we sought to investigate the relation between HbA1c level and HFrecEF in patients with type 2 diabetes. Methods A total of 796 HF patients with reduced left-ventricular ejection fraction (LVEF, &lt;40%) and type 2 diabetes were consecutively enrolled from August 2012 to July 2020. During follow-up for up to 24 months, patients were classified into HFrecEF for whom developed recovered LVEF (≥40% and absolute increase ≥5%) and HFrEF for whose LVEF was persistently reduced (&lt;40%). The relation between HbA1c and the recovery of LV function was analyzed. Results HF patients with type 2 diabetes had significantly lower rates of LVEF recovery when having higher versus lower HbA1c levels in the baseline (the lowest tertile: 62.4%, intermediate tertile: 50.4%, the highest tertile: 46.8%; P&lt;0.001). There were stepwise decreases in changes of LVEF (P&lt;0.001) and increases in changes of LV end-systolic diameter (LVESD; P=0.093) with increasing tertiles of LVEF during follow-up. In the subgroup analysis, the impact of HbA1c on LVEF recovery was more prominent in patients with ischemic heart disease (P&lt;0.001) than those with dilated cardiomyopathy (P=0.536). A significant interaction term was present between HbA1c and etiology of heart failure with regard to LVEF recovery (P=0.012). After multivariate adjustment of conventional confounding factors, high HbA1c level remained to be an independent risk factor lower incidence of HFrecEF in patients type 2 diabetes. Conclusions Our study suggests that optimal glycemic control is an independent predictor for incidence of HFrecEF in patients with type 2 diabetes. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China, Shanghai Municipal Commission of Health and Family Planning

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