scholarly journals Effect of carvedilol versus nebivolol on insulin resistance among non-diabetic, non-ischemic cardiomyopathy with heart failure

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Yasser Gaber Metwally ◽  
Heba Kamal Sedrak ◽  
Inass Fahiem Shaltout
Keyword(s):  
Heart Failure ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Ischemic Cardiomyopathy ◽  
Diabetic Patients ◽  
Promising Strategy ◽  
Improve Insulin Resistance ◽  
First Choice ◽  
The Difference

Abstract Background Although B-blockers provide unequivocal benefits in heart failure (HF) management, some B-blockers worsen insulin resistance. It will be a promising strategy to recruit such a B blocker that did not worsen or can even improve insulin resistance (IR). So, this study aimed to assess the effect of two of the third-generation B-blockers (carvedilol versus nebivolol) on insulin sensitivity state in non-diabetic patients with non-ischemic cardiomyopathy with heart failure. Results Out of 43 patients enrolled, 58.1% represented the carvedilol group while 41.9% represented the nebivolol group. Nebivolol improves insulin resistance-related variables (fasting glucose, fasting insulin, and HOMA-IR; P < 0.001, 0.01, and 0.01 respectively). The percentage of change at homeostasis model of assessment (HOMA-IR), indicative of insulin sensitivity status, between baseline versus at 3-months follow-up level of intra-group comparison was increased by 4.58% in the carvedilol arm whereas it was decreased by 11.67% in the nebivolol arm, and the difference on the intragroup level of comparison was significant (P < 0.001 and 0.01 respectively). Conclusion Nebivolol improves insulin resistance-related variables .Nebivolol may be recommended as the B blocker of the first choice for those with non-ischemic cardiomyopathy heart failure with evident insulin resistance; however, larger scaled prospective multicenter randomized trials are needed for confirming our favorable results.

scholarly journals 2-es típusú diabetes mellitus, inzulinrezisztencia és májrák idült hepatitis C-fertőzésben. Északkelet-magyarországi adatok

2019 ◽  
Vol 160 (40) ◽  
pp. 1591-1602
Author(s):  
Béla Lombay ◽  
Roland Szilágyi ◽  
Ferenc Szalay
Keyword(s):  
Hepatocellular Carcinoma ◽  
Insulin Resistance ◽  
Hepatitis C ◽  
Insulin Sensitivity ◽  
Antiviral Therapy ◽  
Virological Response ◽  
Diabetic Patients ◽  
Female Ratio ◽  
Insulin Resistant

Abstract: Introduction: Liver cirrhosis (20–25%), hepatocellular carcinoma (1.5–3%), insulin resistance (30–40%) and type 2 diabetes (25–30%) are common complications in patients with chronic hepatitis C virus (HCV) infection; however, data are missing from Hungary. Aim: To determine the prevalence of diabetes and insulin resistance in Hungarian HCV patients; to evaluate treatment-induced metabolic changes in relation to diabetes/insulin resistance and virological response and to perform a sustained follow-up for hepatocellular carcinoma detection. Method: We enrolled 150 Hungarian HCV genotype 1 patients (mean age: 48.55 ± 8.55 years, male/female ratio: 45/55%) from 2007–2012. We analysed their baseline, week 12, and end of therapeutic follow-up (24 weeks after interferon-based therapy completion) laboratory data. We performed a 5-year follow-up (2012–2017). Results: The prevalence of insulin sensitivity, insulin resistance and diabetes was 37.4%, 35.3% and 27.3%, respectively. Insulin resistant and diabetic patients showed a decrease in fasting glucose from baseline to end of follow-up (5.47 ± 0.66 vs. 5.08 ± 0.60, p<0.001; 7.90 ± 2.67 vs. 7.04 ± 2.75, p = 0.006), as did both the sustained responder and non-responder groups. Treatment efficacy rate was poor in diabetic vs. insulin sensitive and insulin resistant groups (17% vs. 46% and 40%); insulin sensitivity was not a predictor of virological response. Three participants with diabetes were diagnosed with hepatocellular carcinoma during follow-up by regular ultrasound examinations. Conclusion: Hungarian HCV patients showed high prevalence of diabetes and insulin resistance, though antiviral therapy caused favourable changes in their carbohydrate metabolism. Antiviral therapy was less effective in diabetic patients. Follow-up ultrasound examinations are required for hepatocellular carcinoma in HCV patients, especially those with diabetes. Orv Hetil. 2019; 160(40): 1591–1602.

scholarly journals SAT0111 THE RELATIONSHIP BETWEEN THE ADMINISTRATION OF IL-6 INHIBITORS AND INSULIN RESISTANCE IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 989.3-989
Author(s):  
A. Jitaru ◽  
C. Pomirleanu ◽  
M. M. Leon-Constantin ◽  
F. Mitu ◽  
C. Ancuta
Keyword(s):  
Rheumatoid Arthritis ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Beneficial Effect ◽  
Disease Activity ◽  
Interleukin 6 ◽  
Normal Weight ◽  
Diabetic Patients ◽  
Model Assessment ◽  
Inflammatory Status

Background:Rheumatoid arthritis (RA) is associated with an increased cardiovascular (CV) risk, due not only to the traditional risk factors (hypertension, insulin resistance/diabetes, obesity, smoking), but to the inflammatory status as well. The blockade of interleukin-6 (IL-6) can regulate the glucose metabolism, reducing the glucose level and insulin resistance (IR). This beneficial effect is seen more in patients with normal values of body mass index (BMI), compared to the obese population.Objectives:Given the mentioned existing data, we aim to demonstrate the positive effect of IL-6 inhibitors in active RA patients with normal or increased BMI.Methods:We recruited 56 consecutive patients with definite and active RA, non-responders/partial responders to conventional synthetic Drug Modifying Anti-Rheumatic Drugs (csDMARDs)/biological therapy. For a period of 52 weeks, patients received subcutaneous Tocilizumab (TCZ) in a dose of 162mg once a week, according to European League Anti Rheumatism (EULAR) recommendation and National Protocol. We assessed demographics, RA-related parameters (clinical, inflammatory and immune) and metabolic markers, as well as the peripheral response to insulin, quantified by Homeostasis Model Assessment for insulin resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI). We did not include in the study the patients known with diabetes mellitus (DM) and those undergoing glucocorticoids.Results:After 52 weeks of treatment, most of the patients showed a statistically significant reduction of HOMA-IR (3.61 ± 1.21 at the onset vs. 2.45 ± 1.46 at the end of the study, p<0.001), while QUICKI registered a slight increase (0.32 ± 0.01 at the onset vs. 0.33 ± 0.01 at the end of the study, p<0.001). Also, the decrease in insulin and glucose levels were more obvious in patients with normal BMI, strictly related to disease activity.Conclusion:Long-term administration of TCZ in active RA is associated with a significant reduction of disease activity and IR, especially in normal weight patients. This confirms that obesity, as a CV risk factor, represents one of the main causes of IR.References:[1]Castañeda S, Remuzgo-Martínez S, López-Mejías R et al. Rapid beneficial effect of the IL-6 receptor blockade on insulin resistance and insulin sensitivity in non-diabetic patients with rheumatoid arthritis.Clin Exp Rheumatol. 2019; 37(3):465-473.[2]Lehrskov LL, Christensen RH. The role of interleukin-6 in glucose homeostasis and lipid metabolism.Semin Immunopathol. 2019; 41(4):491-499.[3]Ursini F, Russo E, Ruscitti P, Giacomelli R, De Sarro G. The effect of non-TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis.Autoimmun Rev. 2018 Apr;17(4):399-404.Disclosure of Interests:Alexandra Jitaru: None declared, Cristina Pomirleanu: None declared, Maria-Magdalena Leon-Constantin: None declared, Florin Mitu: None declared, CODRINA ANCUTA Consultant of: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly

Twin peaks diversity with sacubitril/valsartan treatment responses in cardiomyopathic heart failure patients of non-ischemic compared to ischemic etiologies

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H.Y Chang ◽  
W.R Chiou ◽  
P.L Lin ◽  
C.Y Hsu ◽  
C.T Liao ◽  
...  
Keyword(s):  
Heart Failure ◽  
Primary Endpoint ◽  
Ischemic Cardiomyopathy ◽  
Ventricular Remodeling ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Heart Failure Patients ◽  
Twin Peaks ◽  
All Cause Mortality

Abstract Background Ischemic cardiomyopathy (ICM) has been associated with increased mortality when compared with non-ischemic cardiomyopathy (NICM) from several heart failure (HF) cohorts. Instead, PARADIGM study demonstrated similar event rates of cardiovascular (CV) death, all-cause mortality and HF readmissions between ICM and NICM patients. Although the beneficiary effect of sacubitril/valsartan (SAC/VAL) compared to enalapril on these endpoints was consistent across etiologic categories, PARADIGM study did not analyze the effect of ventricular remodeling of SAC/VAL on patients with different HF etiologies, which may significantly affect treatment outcomes. Purpose We aim to compare alterations of left ventricular ejection fraction (LVEF) following SAC/VAL treatment and its association with clinical outcomes in patients with different HF etiologies. Methods Treatment with angiotensin receptor neprilysin inhibitor for Taiwan heart failure patients (TAROT-HF) study is a multicenter study which enrolled 1552 patients with LVEF &lt;40%, whom had been on SAC/VAL treatment from 9 hospitals between 2017 and 2018. After excluding patients without having follow-up echocardiographic studies, patients were grouped by HF etiologies and by LVEF changes following treatment for 8-month period. LVEF improvement ≥15% was defined as “significant improvement”, 5–15% as “marginal improvement”, and &lt;5% or worse as “lack of improvement”. The primary endpoint was a composite of CV death or a first hospitalization for HF. Mean follow-up period was 726 days. Results A total of 1230 patients were analyzed. Patients with ICM were significantly older, more male, and prone to have associated hypertension and diabetes. On the other hand, patients with NICM had lower LVEF and higher likelihood of atrial fibrillation. LVEF increase was significantly greater in patients with NICM compared to those with ICM (11.2±12.4% vs. 6.9±9.8, p&lt;0.001). The effect of ventricular remodeling of SAC/VAL on patients with NICM showed twin peaks diversity (Significant improvement 37.1%, lack of improvement 42.3%), whereas in patients with ICM the proportions of significant, marginal and lack of improvement groups were 19.4%, 28.2% and 52.4%, respectively. The primary endpoint showed twin peaks diversity also in patients with NICM in line with LVEF changes: adjusted HR for patients with NICM and significant improvement was 0.41 (95% CI 0.29–0.57, p&lt;0.001), for patients with NICM and lack of improvement was 1.54 (95% CI 1.22–1.94, p&lt;0.001). Analyses for CV death, all-cause mortality, and HF readmission demonstrated consistent results. Conclusion Patients with NICM had higher degree of LVEF improvement than those with ICM following SAC/VAL treatment, and significant improvement of LVEF in NICM patients may indicate favorable outcome. NICM patients without response to SAC/VAL treatment should serve as an indicator for poor clinical outcome and warranted meticulous HF management. Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Cheng Hsin General Hospital

scholarly journals Cardiac mechanics as predictors of left ventricular reverse remodelling in patients with dilated non-ischemic cardiomyopathy

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Ferrandez ◽  
F Islas ◽  
A Travieso ◽  
J Diz-Diaz ◽  
A Restrepo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ischemic Cardiomyopathy ◽  
Multimodality Imaging ◽  
Global Longitudinal Strain ◽  
Cardiac Mechanics ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Imaging Parameters ◽  
Reverse Remodelling

Abstract Background and purpose The appearance of left ventricular reverse remodelling (LVRR) is associated with a better prognosis in patients with dilated non-ischemic cardiomyopathy (DCM). Our aim was to identify cardiac imaging parameters, including speckle tracking by transthoracic echocardiography (TTE) and feature tracking by CMR, associated with LVRR in a prospective cohort of patients with DCM. Methods From 2014 to 2021, 182 patients with DCM and left ventricle ejection fraction (LVEF) &lt;40% were prospectively evaluated in our hospital. LVRR was defined as an increase in LVEF ≥10 points or absolute LVEF ≥50%, associated with a reduction in left ventricular end- diastolic diameter ≥10%. Patients underwent multimodality imaging evaluation including CMR with a 1.5 Tesla scanner, and TTE. Cardiac mechanics, including global longitudinal strain (GLS), strain rate (SR) and mechanical dispersion (MD) were measured. Results Median age of our cohort was 62.3 (14.4) years, and 67.7% were male. Most patients (&gt;90%) were treated with beta-blockers or RASS blockers, and 67% with mineralocorticoid receptor antagonists. 30% had cardiac resynchronization therapy (CRT) and 37% had ICD as primary prevention. Mean LVEF was 31.3%. During a mean follow-up period of 35.9 (35.4) months, 38.3% of patients had LVRR. Age and gender distribution were similar in both groups. Regarding cardiovascular risk factors and pharmacological treatment, no differences were found between patients with and without LVRR. Baseline CRT therapy was not associated with LVRR (22.6% vs 34.7%; p=0.249). However, there was a trend towards higher LVRR in those who received CRT during follow-up 18.8% vs 0%; p=0.069). Patients who experienced LVRR had lower basal LVEF (23.4% vs 29%; p&lt;0.008), as well as poorer RV function, including lower RVEF (40.5% vs 51%; p=0.006) and lower TAPSE (16 mm vs 19 mm; p=0.021). Regarding cardiac mechanics, those patients with lower GLS (−9% vs −12%; p=0.001), and higher MD (73 mm vs 55 mm; p=0,050) had LVRR more frequently during follow-up. The presence of a left bundle branch block (LBBB) contraction pattern by strain was associated with higher rate of LVRR (83.3% vs 30.4%; p=0.011). The burden of fibrosis measured by LGE with CMR was not associated with LVRR (14% vs 12%; p=NS). Patients with LVRR had a lower cardiovascular mortality (3.3 vs 14.3%; p=0.117), lower mortality due to heart failure (0% vs 12.2%; p=0.046), less heart failure hospitalizations (20% vs 46.9%; p=0.016), and a lower incidence of ventricular tachyarrhythmias (3.3% vs 18.4%; p=0.051). Conclusions LVRR in patients with DCM receiving optimized medical therapy is associated with a better prognosis. Imaging parameters, including a lower basal LVEF, RVEF, GLS and higher MD, as well as LBBB echo pattern, were associated with a higher frequency of LVRR, and might help to identify patients who could benefit from CRT/and may be helpful to stratify patients's risk. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Susceptibility to oxidative stress, insulin resistance, and insulin secretory response in the development of diabetes from obesity

2007 ◽  
Vol 64 (6) ◽  
pp. 391-397 ◽  
Author(s):  
Radivoj Kocic ◽  
Dusica Pavlovic ◽  
Gordana Kocic ◽  
Milica Pesic
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Lipid Peroxidation ◽  
Insulin Sensitivity ◽  
Healthy Subjects ◽  
Critical Role ◽  
Secretory Response ◽  
Diabetic Patients ◽  
Apparent Difference ◽  
Insulin Secretory Response

Background/Aim. Oxidative stress plays a critical role in the pathogenesis of various diseases. Recent reports indicate that obesity may induce systemic oxidative stress. The aim of the study was to potentiate oxidative stress as a factor which may aggravate peripheral insulin sensitivity and insulinsecretory response in obesity in this way to potentiate development of diabetes. The aim of the study was also to establish whether insulin-secretory response after glucagonstimulated insulin secretion is susceptible to prooxidant/ antioxidant homeostasis status, as well as to determine the extent of these changes. Methods. A mathematical model of glucose/insulin interactions and C-peptide was used to indicate the degree of insulin resistance and to assess their possible relationship with altered antioxidant/prooxidant homeostasis. The study included 24 obese healthy and 16 obese newly diagnozed non-insulin dependent diabetic patients (NIDDM) as well as 20 control healthy subjects, matched in age. Results. Total plasma antioxidative capacity, erythrocyte and plasma reduced glutathione level were significantly decreased in obese diabetic patients, but also in obese healthy subjects, compared to the values in controls. The plasma lipid peroxidation products and protein carbonyl groups were significantly higher in obese diabetics, more than in obese healthy subjects, compared to the control healthy subjects. The increase of erythrocyte lipid peroxidation at basal state was shown to be more pronounced in obese daibetics, but the apparent difference was obtained in both the obese healthy subjects and obese diabetics, compared to the control values, after exposing of erythrocytes to oxidative stress induced by H2O2. Positive correlation was found between the malondialdehyde (MDA) level and index of insulin sensitivity (FIRI). Conclusion. Increased oxidative stress together with the decreased antioxidative defence seems to contribute to decreased insulin sensitivity and impaired insulin secretory response in obese diabetics, and may be hypothesized to favour the development of diabetes during obesity.

scholarly journals Clinical Outcomes in Patients with Ischemic versus Non-Ischemic Cardiomyopathy after Angiotensin-Neprilysin Inhibition Therapy

2021 ◽  
Vol 10 (21) ◽  
pp. 4989
Author(s):  
Mohammad Abumayyaleh ◽  
Christina Pilsinger ◽  
Ibrahim El-Battrawy ◽  
Marvin Kummer ◽  
Jürgen Kuschyk ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Tachyarrhythmias ◽  
Ventricular Ejection Fraction ◽  
One Year ◽  
The Impact

Background: The angiotensin receptor-neprilysin inhibitor (ARNI) decreases cardiovascular mortality in patients with chronic heart failure with a reduced ejection fraction (HFrEF). Data regarding the impact of ARNI on the outcome in HFrEF patients according to heart failure etiology are limited. Methods and results: One hundred twenty-one consecutive patients with HFrEF from the years 2016 to 2017 were included at the Medical Centre Mannheim Heidelberg University and treated with ARNI according to the current guidelines. Left ventricular ejection fraction (LVEF) was numerically improved during the treatment with ARNI in both patient groups, that with ischemic cardiomyopathy (n = 61) (ICMP), and that with non-ischemic cardiomyopathy (n = 60) (NICMP); p = 0.25. Consistent with this data, the NT-proBNP decreased in both groups, more commonly in the NICMP patient group. In addition, the glomerular filtration rate (GFR) and creatinine changed before and after the treatment with ARNI in both groups. In a one-year follow-up, the rate of ventricular tachyarrhythmias (ventricular tachycardia and ventricular fibrillation) tended to be higher in the ICMP group compared with the NICMP group (ICMP 38.71% vs. NICMP 17.24%; p = 0.07). The rate of one-year all-cause mortality was similar in both groups (ICMP 6.5% vs. NICMP 6.6%; log-rank = 0.9947). Conclusions: This study shows that, although the treatment with ARNI improves the LVEF in ICMP and NICMP patients, the risk of ventricular tachyarrhythmias remains higher in ICMP patients in comparison with NICMP patients. Renal function is improved in the NICMP group after the treatment. Long-term mortality is similar over a one-year follow-up.

scholarly journals Common Risk Factors in Relatives and Spouses of Patients with Type 2 Diabetes in Developing Prediabetes

Healthcare ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1010
Author(s):  
Wei-Hao Hsu ◽  
Chin-Wei Tseng ◽  
Yu-Ting Huang ◽  
Ching-Chao Liang ◽  
Mei-Yueh Lee ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Diabetic Patients ◽  
Β Cell ◽  
Tyg Index ◽  
Β Cell Function

Prediabetes should be viewed as an increased risk for diabetes and cardiovascular disease. In this study, we investigated its prevalence among the relatives and spouses of patients with type 2 diabetes or risk factors for prediabetes, insulin resistance, and β-cell function. A total of 175 individuals were included and stratified into three groups: controls, and relatives and spouses of type 2 diabetic patients. We compared clinical characteristics consisting of a homeostatic model assessment for insulin resistance (HOMA-IR) and beta cell function (HOMA-β), a quantitative insulin sensitivity check index (QUICKI), and triglyceride glucose (TyG) index. After a multivariable linear regression analysis, the relative group was independently correlated with high fasting glucose, a high TyG index, and low β-cell function; the relatives and spouses were independently associated with a low QUICKI. The relatives and spouses equally had a higher prevalence of prediabetes. These study also indicated that the relatives had multiple factors predicting the development of diabetes mellitus, and that the spouses may share a number of common environmental factors associated with low insulin sensitivity.

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.

scholarly journals The association of hyperglycaemia and insulin resistance with incident depressive symptoms over 4 years of follow-up: The Maastricht Study

Diabetologia ◽  
2020 ◽  
Vol 63 (11) ◽  
pp. 2315-2328 ◽  
Author(s):  
Anouk F. J. Geraets ◽  
Sebastian Köhler ◽  
Rutendo Muzambi ◽  
Casper G. Schalkwijk ◽  
Anke Oenema ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Depressive Symptoms ◽  
Insulin Sensitivity ◽  
Cox Regression ◽  
Temporal Association ◽  
Sensitivity Index ◽  
Skin Autofluorescence ◽  
Insulin Sensitivity Index ◽  
Increased Risk

Abstract Aims/hypothesis Depression is twice as common in individuals with type 2 diabetes as in the general population. However, it remains unclear whether hyperglycaemia and insulin resistance are directly involved in the aetiology of depression. Therefore, we investigated the association of markers of hyperglycaemia and insulin resistance, measured as continuous variables, with incident depressive symptoms over 4 years of follow-up. Methods We used data from the longitudinal population-based Maastricht Study (n = 2848; mean age 59.9 ± 8.1 years, 48.8% women, 265 incident depression cases, 10,932 person-years of follow-up). We assessed hyperglycaemia by fasting and 2 h post-load OGTT glucose levels, HbA1c and skin autofluorescence (reflecting AGEs) at baseline. We used the Matsuda insulin sensitivity index and HOMA-IR to calculate insulin resistance at baseline. Depressive symptoms (nine-item Patient Health Questionnaire score ≥10) were assessed at baseline and annually over 4 years. We used Cox regression analyses, and adjusted for demographic, cardiovascular and lifestyle risk factors. Results Fasting plasma glucose, 2 h post-load glucose and HbA1c levels were associated with an increased risk for incident depressive symptoms after full adjustment (HR 1.20 [95% CI 1.08, 1.33]; HR 1.25 [1.08, 1.44]; and HR 1.22 [1.09, 1.37] per SD, respectively), while skin autofluorescence, insulin sensitivity index and HOMA-IR were not (HR 0.99 [0.86, 1.13]; HR 1.02 [0.85, 1.25]; and HR 0.93 [0.81, 1.08], per SD, respectively). Conclusions/interpretation The observed temporal association between hyperglycaemia and incident depressive symptoms in this study supports the presence of a mechanistic link between hyperglycaemia and the development of depressive symptoms.

Sarcolemmal fatty acid uptake vs. mitochondrial β-oxidation as target to regress cardiac insulin resistanceThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 34 (3) ◽  
pp. 473-480 ◽  
Author(s):  
Joost J.F.P. Luiken
Keyword(s):  
Heart Failure ◽  
Insulin Resistance ◽  
Fatty Acid ◽  
Peer Review Process ◽  
Diabetic Patients ◽  
Central Feature ◽  
Acid Uptake ◽  
Cpt I ◽  
Rate Limiting

Cardiomyopathy and heart failure are frequent comorbid conditions in type-2 diabetic patients. However, it has become increasingly evident that insulin resistance, type-2 diabetes, and cardiomyopathy are not independent variables, and are linked through changes in metabolism. Specifically, elevated intracellular levels of long-chain fatty acid (LCFA) metabolites are a central feature in the development of cardiac insulin resistance, and their prolonged accumulation is an important cause of heart failure. In the insulin-resistant heart, the abundance of the LCFA transporters CD36 and FABPpm at the sarcolemma of cardiac myocytes appears to be markedly increased. Because circulating LCFA levels are increased in insulin resistance, the cardiac LCFA metabolizing machinery is confronted with drastic increases in substrate supply. Indeed, LCFA esterification into triacylglycerol and other lipid intermediates is increased, as is β-oxidation and reactive oxygen species production. Therapeutic strategies to normalize the cardiac LCFA flux would be most successful when the target is the rate-limiting step in cardiac LCFA utilization. Carnitine palmitoyltransferase (CPT)-I has long been considered to be this rate-limiting site and, accordingly, pharmacological inhibition of CPT-I, or β-oxidation enzymes, has been proposed as an insulin-resistance-antagonizing strategy. However, recent evidence indicates that, instead, sarcolemmal LCFA transport mediated by CD36 in concert with FABPpm provides a major site of flux control. In this review, it is proposed that a pharmacologically imposed net internalization of CD36 and FABPpm is the preferable strategy to limit LCFA entry and accumulation of LCFA metabolites, to regress cardiac insulin resistance and, eventually, prevent diabetic heart failure.

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