Myocardial Insulin Resistance: An Overview of Its Causes, Effects, and Potential Therapy

Toit, E. Du; Donner, D.

doi:10.5772/50619

Cited by 14 publications

(14 citation statements)

References 280 publications

(343 reference statements)

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“…Across multiple populations [ 79 , 80 ], male patients presenting with a total fat mass >25% are classified as obese, with incremental increases in fat mass percentage associated with increasing risk of developing type 2 diabetes (T2DM) [ 81 ]. Additionally, visceral fat mass is independently associated with decreased insulin sensitivity [ 82 ], likely mediated by the hyperlipidemic consequences of energy utilisation from this fat depot [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…In men, testosterone deficiency is defined by a low circulating testosterone of <12 nmol/L (<346 ng/dL) accompanied by characteristic clinical symptoms including erectile dysfunction, loss of libido and/or sarcopenia [ 21 – 23 ]. TD may also contribute to the increased prevalence of cardiovascular risk factors [ 24 ] and abnormal glucose metabolism [ 25 ] seen in older men, which are predictors of adverse cardiovascular outcomes [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Impact of Diet-Induced Obesity and Testosterone Deficiency on the Cardiovascular System: A Novel Rodent Model Representative of Males with Testosterone-Deficient Metabolic Syndrome (TDMetS)

et al. 2015

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IntroductionCurrent models of obesity utilise normogonadic animals and neglect the strong relationships between obesity-associated metabolic syndrome (MetS) and male testosterone deficiency (TD). The joint presentation of these conditions has complex implications for the cardiovascular system that are not well understood. We have characterised and investigated three models in male rats: one of diet-induced obesity with the MetS; a second using orchiectomised rats mimicking TD; and a third combining MetS with TD which we propose is representative of males with testosterone deficiency and the metabolic syndrome (TDMetS).MethodsMale Wistar rats (n = 24) were randomly assigned to two groups and provided ad libitum access to normal rat chow (CTRL) or a high fat/high sugar/low protein “obesogenic” diet (OGD) for 28 weeks (n = 12/group). These groups were further sub-divided into sham-operated or orchiectomised (ORX) animals to mimic hypogonadism, with and without diet-induced obesity (n = 6/group). Serum lipids, glucose, insulin and sex hormone concentrations were determined. Body composition, cardiovascular structure and function; and myocardial tolerance to ischemia-reperfusion were assessed.ResultsOGD-fed animals had 72% greater fat mass; 2.4-fold greater serum cholesterol; 2.3-fold greater serum triglycerides and 3-fold greater fasting glucose (indicative of diabetes mellitus) compared to CTRLs (all p<0.05). The ORX animals had reduced serum testosterone and left ventricle mass (p<0.05). In addition to the combined differences observed in each of the isolated models, the OGD, ORX and OGD+ORX models each had greater CK-MB levels following in vivo cardiac ischemia-reperfusion insult compared to CTRLs (p<0.05).ConclusionOur findings provide evidence to support that the MetS and TD independently impair myocardial tolerance to ischemia-reperfusion. The combined OGD+ORX phenotype described in this study is a novel animal model with associated cardiovascular risk factors and complex myocardial pathology which may be representative of male patients presenting with TDMetS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of Diet-Induced Obesity and Testosterone Deficiency on the Cardiovascular System: A Novel Rodent Model Representative of Males with Testosterone-Deficient Metabolic Syndrome (TDMetS)

et al. 2015

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“…Circulating lipid levels correlate with changes in energy use from the visceral fat depot, and reductions in adiposity lead to concomitant reductions in serum lipids, described elsewhere (15).…”

Section: Effects Of Androgens On Serum Lipid Profilementioning

confidence: 97%

“…Lastly, hearts from animal models of obesity and insulin resistance (89), isolated insulin resistance (90), or diabetes (91) have a reduced tolerance to I-R and suffer increased damage due to the myocardium's dependency on ATP generation from anaerobic glucose metabolism during ischemia, reviewed by ourselves elsewhere (15).…”

Section: Androgen Effects On Myocardial Tolerance To I-rmentioning

confidence: 99%

“…Although there are additional criteria that have been suggested for the diagnosis of the MetS, it is consistently characterized by increased visceral adiposity, dyslipidaemia, and insulin resistance (9 -11) and increases cardiovascular risk by 2-fold (12). TD impairs myocardial tolerance to ischemia reperfusion (I-R) both directly (13) and indirectly through myocardial desensitization to insulin (14,15).…”

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confidence: 99%

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Trenbolone Improves Cardiometabolic Risk Factors and Myocardial Tolerance to Ischemia-Reperfusion in Male Rats With Testosterone-Deficient Metabolic Syndrome

et al. 2016

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The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. After 8 weeks of feeding, rats underwent sham surgery or an orchiectomy (ORX). Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN were implanted in HF/HS+ORX rats. Body composition, fat distribution, lipid profile, and insulin sensitivity were assessed. Infarct size was quantified to assess myocardial damage after in vivo ischaemia reperfusion, before cardiac and prostate histology was performed. The HF/HS+ORX animals had increased sc and visceral adiposity; circulating triglycerides, cholesterol, and insulin; and myocardial damage, with low circulating TEST compared with CTRLs. Both TEST and TREN protected HF/HS+ORX animals against sc fat accumulation, hypercholesterolaemia, and myocardial damage. However, only TREN protected against visceral fat accumulation, hypertriglyceridaemia, and hyperinsulinaemia and reduced myocardial damage relative to CTRLs. TEST caused widespread cardiac fibrosis and prostate hyperplasia, which were less pronounced with TREN. We propose that TEST replacement therapy may have contraindications for males with TD and obesity-related MetS. TREN treatment may be more effective in restoring androgen status and reducing cardiovascular risk in males with TD and MetS.

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Phenotypes of Atopic Dermatitis Depending on the Timing of Onset and Progression in Childhood

et al. 2017

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and the PASTURE study group IMPORTANCE Atopic dermatitis is an inflammatory, pruritic skin disease that often occurs in early infancy with a chronic course. However, a specific description of subtypes of atopic dermatitis depending on the timing of onset and progression of the disease in childhood is lacking.OBJECTIVE To identify different phenotypes of atopic dermatitis using a definition based on symptoms before age 6 years and to determine whether some subtypes are more at risk for developing other allergic diseases. DESIGN, SETTING, AND PARTICIPANTSThe Protection Against Allergy Study in Rural Environments (PASTURE) is a European birth cohort where pregnant women were recruited between August 2002 and March 2005 and divided in 2 groups dependent on whether they lived on a farm. Children from this cohort with data on atopic dermatitis from birth to 6 years of age were included.EXPOSURES Atopic dermatitis, defined as an itchy rash on typical locations from birth to 6 years. MAIN OUTCOMES AND MEASURESThe latent class analysis was used to identify subtypes of atopic dermatitis in childhood based on the course of symptoms. Multivariable logistic regressions were used to analyze the association between atopic dermatitis phenotypes and other allergic diseases. RESULTSWe included 1038 children; of these, 506 were girls. The latent class analysis model with the best fit to PASTURE data separated 4 phenotypes of atopic dermatitis in childhood: 2 early phenotypes with onset before age 2 years (early transient [n = 96; 9.2%] and early persistent [n = 67; 6.5%]), the late phenotype with onset at age 2 years or older (n = 50; 4.8%), and the never/infrequent phenotype (n = 825; 79.5%), defined as children with no atopic dermatitis. Children with both parents with history of allergies were 5 times more at risk to develop atopic dermatitis with an early-persistent phenotype compared with children with parents with no history of allergies. Both early phenotypes were strongly associated with food allergy. The risk of developing asthma was significantly increased among the early-persistent phenotype (adjusted odds ratio, 2.87; 95% CI, 1.31-6.31). The late phenotype was only positively associated with allergic rhinitis. CONCLUSIONS AND RELEVANCEUsing latent class analysis, 4 phenotypes of atopic dermatitis were identified depending on the onset and course of the disease. The prevalence of asthma and food allergy by 6 years of age was strongly increased among children with early phenotypes (within age 2 years), especially with persistent symptoms. These findings are important for the development of strategies in allergy prevention.

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Myocardial Insulin Resistance: An Overview of Its Causes, Effects, and Potential Therapy

Cited by 14 publications

References 280 publications

Impact of Diet-Induced Obesity and Testosterone Deficiency on the Cardiovascular System: A Novel Rodent Model Representative of Males with Testosterone-Deficient Metabolic Syndrome (TDMetS)

Impact of Diet-Induced Obesity and Testosterone Deficiency on the Cardiovascular System: A Novel Rodent Model Representative of Males with Testosterone-Deficient Metabolic Syndrome (TDMetS)

Trenbolone Improves Cardiometabolic Risk Factors and Myocardial Tolerance to Ischemia-Reperfusion in Male Rats With Testosterone-Deficient Metabolic Syndrome

Phenotypes of Atopic Dermatitis Depending on the Timing of Onset and Progression in Childhood

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