Abnormal in vivo myocardial energy substrate uptake in diet-induced type 2 diabetic cardiomyopathy in rats

2010 ◽  
Vol 298 (5) ◽  
pp. E1049-E1057 ◽  
Author(s):  
Sébastien L. Ménard ◽  
Etienne Croteau ◽  
Otman Sarrhini ◽  
Roselle Gélinas ◽  
Pascal Brassard ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Mrna Expression ◽  
Oxidative Metabolism ◽  
Left Ventricular ◽  
Glucose Clamp ◽  
Left Ventricular Ejection ◽  
Myocardial Oxidative Metabolism

The purpose of this study was to determine in vivo myocardial energy metabolism and function in a nutritional model of type 2 diabetes. Wistar rats rendered insulin-resistant and mildly hyperglycemic, hyperinsulinemic, and hypertriglyceridemic with a high-fructose/high-fat diet over a 6-wk period with injection of a small dose of streptozotocin (HFHFS) and control rats were studied using micro-PET (μPET) without or with a euglycemic hyperinsulinemic clamp. During glucose clamp, myocardial metabolic rate of glucose measured with [18F]fluorodeoxyglucose ([18F]FDG) was reduced by ∼81% ( P < 0.05), whereas myocardial plasma nonesterified fatty acid (NEFA) uptake as determined by [18F]fluorothia-6-heptadecanoic acid ([18F]FTHA) was not significantly changed in HFHFS vs. control rats. Myocardial oxidative metabolism as assessed by [11C]acetate and myocardial perfusion index as assessed by [13N]ammonia were similar in both groups, whereas left ventricular ejection fraction as assessed by μPET was reduced by 26% in HFHFS rats ( P < 0.05). Without glucose clamp, NEFA uptake was ∼40% lower in HFHFS rats ( P < 0.05). However, myocardial uptake of [18F]FTHA administered by gastric gavage was significantly higher in HFHFS rats ( P < 0.05). These abnormalities were associated with reduced Glut4 mRNA expression and increased Cd36 mRNA expression and mitochondrial carnitine palmitoyltransferase 1 activity ( P < 0.05). HFHFS rats display type 2 diabetes complicated by left ventricular contractile dysfunction with profound reduction in myocardial glucose utilization, activation of fatty acid metabolic pathways, and preserved myocardial oxidative metabolism, suggesting reduced myocardial metabolic efficiency. In this model, increased myocardial fatty acid exposure likely occurs from circulating triglyceride, but not from circulating plasma NEFA.

scholarly journals Association between adipocyte fatty acid-binding protein with left ventricular remodelling and diastolic function in type 2 diabetes: a prospective echocardiography study

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Mei-Zhen Wu ◽  
Chi-Ho Lee ◽  
Yan Chen ◽  
Shuk-Yin Yu ◽  
Yu-Juan Yu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Diastolic Dysfunction ◽  
Fatty Acid Binding Protein ◽  
Cox Regression ◽  
Left Ventricular ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Lv Mass

Abstract Background The relationship between adipocyte fatty acid-binding protein (AFABP) and cardiac remodelling has been reported in cross-sectional studies, although with conflicting results. Type 2 diabetes mellitus (T2DM) is associated with left ventricular (LV) hypertrophy and diastolic dysfunction, as well as elevated circulating AFABP levels. Here we investigated prospectively the association between AFABP with the longitudinal changes of cardiac remodelling and diastolic dysfunction in T2DM. Methods Circulating AFABP levels were measured in 176 T2DM patients without cardiovascular diseases (CVD) at baseline. All participants received detailed transthoracic echocardiography both at baseline and after 1 year. Multivariable linear and Cox regression analyses were used to evaluate the associations of circulating AFABP levels with changes in echocardiography parameters and incident major adverse cardiovascular events (MACE), respectively. Results The median duration between baseline and follow-up echocardiography assessments was 28 months. Higher sex-specific AFABP quartiles at baseline were associated with increase in LV mass and worsening of average E/e′ (all P < 0.01). Multivariable linear regression demonstrated that AFABP in the highest quartile was independently associated with both increase in LV mass (β = 0.89, P < 0.01) and worsening of average E/e′ (β = 0.57, P < 0.05). Moreover, multivariable Cox regression analysis showed that elevated baseline circulating AFABP level independently predicted incident MACE (HR 2.65, 95% CI 1.16–6.05, P < 0.05) after adjustments for age, sex, body mass index, glycated haemoglobin, hypertension, dyslipidemia and presence of chronic kidney disease. Conclusion Circulating AFABP level at baseline predicted the development of LV hypertrophy, diastolic dysfunction and MACE in T2DM patients without CVD.

3269Impact of type 2 diabetes on incidence and phenotype of heart failure in patients with atrial fibrillation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Polovina ◽  
I Milinkovic ◽  
G Krljanac ◽  
I Veljic ◽  
I Petrovic-Djordjevic ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Type 2 Diabetes ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Diabetic Patients ◽  
History Of ◽  
New Onset

Abstract Background Type 2 diabetes (T2DM) portends adverse prognosis in patients with atrial fibrillation (AF). Whether T2DM independently increases the risk of incident heart failure (HF) in AF is uncertain. Also, HF phenotype developing in patients with vs. those without T2DM has not been characterised. Purpose In AF patients without a history of prior HF, we aimed to assess: 1) the impact of T2DM on the risk of new-onset HF; and 2) the association between T2DM and HF phenotype developing during the prospective follow-up. Methods We included diabetic and non-diabetic AF patients, without a history of HF. Baseline T2DM status was inferred from medical history, haemoglobin A1c levels and oral glucose tolerance test. Study outcome was the first hospital admission or emergency department treatment for new-onset HF during the prospective follow-up. The phenotype of new-onset HF was determined by echocardiographic exam performed following clinical stabilisation (at hospital discharge, or within a month after HF diagnosis). HF phenotype was defined as HFrEF (left ventricular ejection fraction [LVEF] <40%), HFmrEF (LVEF 40–49%) or HFpEF (LVEF≥50%). Cox regression analyses adjusted for age, sex, baseline LVEF, comorbidities, smoking status, alcohol intake, AF type (paroxysmal vs. non-paroxysmal) and T2DM treatment was used to analyse the association between T2DM and incident HF. Results Among 1,288 AF patients without prior HF (mean age: 62.1±12.7 years; 61% male), T2DM was present in 16.5%. Diabetic patients had higher mean baseline LVEF compared with nondiabetic patients (50.0±6.2% vs. 57.6±9.0%; P<0.001). During the median 5.5-year follow-up, new-onset HF occurred in 12.4% of patients (incidence rate, 2.9; 95% confidence interval [CI], 2.5–3.3 per 100 patient-years). Compared with non-diabetic patients, those with T2DM had a hazard ratio of 2.1 (95% CI, 1.6–2.8; P<0.001) for new-onset HF, independent of baseline LVEF or other factors. In addition, diabetic patients had a significantly greater decline in covariate-adjusted mean LVEF (−10.4%; 95% CI, −9.8% to −10.8%) at follow-up, compared with nondiabetic patients (−4.0%; 95% CI, −3.8% to −4.2%), P<0.001. The distribution of HF phenotypes at follow-up is presented in Figure. Among patients with T2DM, HFrEF (56.9%) was the most common phenotype of HF, whereas in patients without T2DM, HF mostly took the phenotype of HFpEF (75.0%). Conclusions T2DM is associated with an independent risk of new-onset HF in patients with AF and confers a greater decline in LVEF compared to individuals without T2DM. HFrEF was the most prevalent presenting phenotype of HF in AF patients with T2DM.

1407Drug effect of luseogliflozin and voglibose on heart failure with preserved ejection fraction in diabetic patients: a multicenter randomized-controlled trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Ejiri ◽  
T Miyoshi ◽  
H Kihara ◽  
Y Hata ◽  
T Nagano ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

Abstract Background Recent randomized, placebo-controlled trial in patients with type 2 diabetes demonstrated that the sodium-glucose cotransporter 2 inhibitors reduced mortality, cardiovascular events and hospitalization for heart failure. However, those trials were not specialized design to investigate the effect of sodium-glucose cotransporter 2 inhibitors in patients with heart failure, in particular with heart failure with preserved ejection fraction. Purpose The aim of this study was to evaluate the drug efficacy of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, compared with voglibose, an alpha-glucosidase inhibitor, using brain natriuretic peptide (BNP) in type 2 diabetes patients with heart failure with preserved ejection fraction. Methods This study was a prospective, multicenter, open-label, randomized-controlled trial, comparing luseogliflozin 2.5 mg once daily or voglibose 0.2 mg three times daily in patients with type 2 diabetes suffering from heart failure with preserved ejection fraction (left ventricular ejection fraction >45% and BNP ≥35 pg/ml2) in a 1:1 randomization fashion. Randomization was undertaken using a computer-generated random sequence web response system. The primary outcome was the difference from baseline in BNP after 12 weeks of treatment between two drugs. The key secondary outcomes were the change from baseline in left ventricular ejection fraction and E/e' in echocardiographic parameters, body weight, glycohemoglobin level after 12 weeks of treatment. The safety outcomes included the incidence of major adverse cardiovascular events, hypoglycemic adverse events, and urinary tract infection. Results Between December 2015 and September 2018, 173 patients from 16 hospitals and clinics have been included in this study. Of those, 83 patients were assigned to receive luseogliflozin and 82 to receive voglibose. There was no significant difference in the reduction in the BNP concentration after 12 weeks from baseline between the two groups; the ratio of the average values at week 12 to the baseline value was 0.91 in the luseoglifllzin group as compared with 0.98 in the voglibose group (percent change, −9.0% vs. −1.9%, ratio of change with luseogliflozin vs. voglibose, 0.93; 95% confidence interval, 0.78 to 1.10; p=0.26). The key secondary outcomes including left ventricular ejection fraction, E/e', body weight, glycohemoglobin level and the safety outcomes did not differ significantly between the two groups. Conclusions In type 2 diabetes patients with heart failure with preserved ejection fraction, the administration of luseogliflozin did not lead to a significant reduction in the BNP concentration than that of voglibose. Left ventricular ejection fraction, E/e', body weight and glycohemoglobin level after 12 weeks of treatment, comparing with at baseline did not differ significantly between the two groups. (UMIN Clinical Trial Registry number, UMINehz748.005618395) Acknowledgement/Funding Novartis

The clinical and experimental analysis of ventricular rhythm disturbances in the patients with type 2 diabetes mellitus suffering from diastolic cardiac insufficiency

2015 ◽  
Vol 61 (2) ◽  
pp. 21-27
Author(s):  
I P Tatarchenko ◽  
N V Pozdnyakova ◽  
A G Denisova ◽  
O I Morozova
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diastolic Dysfunction ◽  
Left Ventricular ◽  
Cardiac Insufficiency ◽  
Left Ventricular Ejection ◽  
Ventricular Extrasystole ◽  
Ventricular Ejection Fraction

The present study was focused on the assessment of electrophysiological, structural, and functional characteristics of the heart associated with ventricular rhythm disturbances in the patients with type 2 diabetes mellitus (DM2) suffering from diastolic cardiac insufficiency. The study involved a total of 128 patients with DM2 and coronary heart disease (CHD) exhibiting signs of functional class I-III chronic cardiac insufficiency and left ventricular ejection fraction over 50%. The patients were divided into three groups. Group 1 (n=55) included patients presenting with left ventricular relaxation. Group 2 (n=44) was comprised of the patients with the pseudo-normal type of diastolic dysfunction. Group 3 (n=29) consisted of the patients with restrictive diastolic dysfunction. The patients of the latter group were characterized by the high frequency of complicated forms of ventricular arrhythmia, such as Grade IV-V ventricular extrasystole (48.3%) and Grade III ventricular extrasystole (34.5%). Restrictive type of diastolic dysfunction was associated with the delayed fragmented activity in the end part of the ventricular complex in 72.4% of the patients. The close correlation between the left ventricular diastolic function and parameters of myocardial electrical remodeling was documented.

scholarly journals Type 2 diabetes and heart failure: Characteristics and prognosis in preserved, mid-range and reduced ventricular function

2018 ◽  
Vol 15 (6) ◽  
pp. 494-503 ◽  
Author(s):  
Isabelle Johansson ◽  
Ulf Dahlström ◽  
Magnus Edner ◽  
Per Näsman ◽  
Lars Rydén ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction ◽  
Reduced Ejection Fraction

Objective: To study the characteristics and prognostic implications of type 2 diabetes in different heart failure entities from a nationwide perspective. Methods: This observational study comprised 30,696 heart failure patients prospectively included in the Swedish Heart Failure Registry (SwedeHF) 2003–2011 from specialist care, with mortality information available until December 2014. Patients were categorized into three heart failure entities by their left ventricular ejection fraction (heart failure with preserved ejection fraction: ⩾50%, heart failure with mid-range ejection fraction: 40%–49% and heart failure with reduced ejection fraction: <40%). All-cause mortality stratified by type 2 diabetes and heart failure entity was studied by Cox regression. Results: Among the patients, 22% had heart failure with preserved ejection fraction, 21% had heart failure with mid-range ejection fraction and 57% had heart failure with reduced ejection fraction. The proportion of type 2 diabetes was similar, ≈25% in each heart failure entity. Patients with type 2 diabetes and heart failure with preserved ejection fraction were older, more often female and burdened with hypertension and renal impairment compared with heart failure with mid-range ejection fraction and heart failure with reduced ejection fraction patients among whom ischaemic heart disease was more common. Type 2 diabetes remained an independent mortality predictor across all heart failure entities after multivariable adjustment, somewhat stronger in heart failure with left ventricular ejection fraction below 50% (hazard ratio, 95% confidence interval; heart failure with preserved ejection fraction: 1.32 [1.22–1.43], heart failure with mid-range ejection fraction: 1.51 [1.39–1.65], heart failure with reduced ejection fraction: 1.46 [1.39–1.54]; p-value for interaction, p = 0.0049). Conclusion: Type 2 diabetes is an independent mortality predictor across all heart failure entities increasing mortality risk by 30%–50%. In type 2 diabetes, the heart failure with mid-range ejection fraction entity resembles heart failure with reduced ejection fraction in clinical characteristics, risk factor pattern and prognosis.

scholarly journals [18F]FDG Uptake in Adipose Tissue Is Not Related to Inflammation in Type 2 Diabetes Mellitus

2020 ◽  
Vol 23 (1) ◽  
pp. 117-126
Author(s):  
Melanie Reijrink ◽  
Stefanie A. de Boer ◽  
Ines F. Antunes ◽  
Daan S. Spoor ◽  
Hiddo J. L. Heerspink ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mrna Expression ◽  
Ex Vivo ◽  
Expression Levels ◽  
Fdg Uptake ◽  
Mrna Expression Levels

Abstract Purpose 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) uptake is a marker of metabolic activity and is therefore used to measure the inflammatory state of several tissues. This radionuclide marker is transported through the cell membrane via glucose transport proteins (GLUTs). The aim of this study is to investigate whether insulin resistance (IR) or inflammation plays a role in [18F]FDG uptake in adipose tissue (AT). Procedures This study consisted of an in vivo clinical part and an ex vivo mechanistic part. In the clinical part, [18F]FDG uptake in abdominal visceral AT (VAT) and subcutaneous AT (SAT) was determined using PET/CT imaging in 44 patients with early type 2 diabetes mellitus (T2DM) (age 63 [54–66] years, HbA1c [6.3 ± 0.4 %], HOMA-IR 5.1[3.1–8.5]). Plasma levels were measured with ELISA. In the mechanistic part, AT biopsies obtained from 8 patients were ex vivo incubated with [18F]FDG followed by autoradiography. Next, a qRT-PCR analysis was performed to determine GLUT and cytokine mRNA expression levels. Immunohistochemistry was performed to determine CD68+ macrophage infiltration and GLUT4 protein expression in AT. Results In vivo VAT [18F]FDG uptake in patients with T2DM was inversely correlated with HOMA-IR (r = − 0.32, p = 0.034), and positively related to adiponectin plasma levels (r = 0.43, p = 0.003). Ex vivo [18F]FDG uptake in VAT was not related to CD68+ macrophage infiltration, and IL-1ß and IL-6 mRNA expression levels. Ex vivo VAT [18F]FDG uptake was positively related to GLUT4 (r = 0.83, p = 0.042), inversely to GLUT3 (r = − 0.83, p = 0.042) and not related to GLUT1 mRNA expression levels. Conclusions In vivo [18F]FDG uptake in VAT from patients with T2DM is positively correlated with adiponectin levels and inversely with IR. Ex vivo [18F]FDG uptake in AT is associated with GLUT4 expression but not with pro-inflammatory markers. The effect of IR should be taken into account when interpreting data of [18F]FDG uptake as a marker for AT inflammation.

Sign in / Sign up

Export Citation Format

Share Document