Myocardial Involvement in Chagas Disease and Insulin Resistance: A Non-Metabolic Model of Cardiomyopathy

Abstract

Background: Heart failure (HF) and type 2 Diabetes Mellitus (T2DM) represent two chronic interrelated conditions accounting for significant morbidity and mortality worldwide. Insulin resistance (IR) has been identified as a risk factor for HF; however, the risk of IR that HF confers has not been well elucidated. The present study aims to analyze the association between myocardial involvement in Chronic Chagas Cardiomyopathy (CCM) and IR, taking advantage of this non-metabolic model of the disease. Methods: Cross-sectional study performed during the period 2015-2016. Adults with a serological diagnosis of Chagas disease were included, being divided into two groups: CCM and non-CCM. IR was determined by HOMA-IR index. Bivariate analysis and multivariate logistic regression were performed to determine the association between IR as an outcome and CCM as primary exposure. Results: 200 patients were included in the study, with a mean age of 54.7 years and a female predominance (53.5%). Seventy-four (37.0%) patients were found to have IR, with a median HOMA-IR index of 3.9 (Q1 = 3.1; Q3 = 5.1). Multiple metabolic variables were significantly associated with IR. In a model analyzing only individuals with an altered HWI, an evident association between CCM and IR was observed (OR 4.08; 95% CI 1.55-10.73, p = 0.004). Conclusion: CCM was significantly associated with IR in patients with an altered HWI. The presence of this association in a non-metabolic model of HF (in which the myocardial involvement is expected to be mediated mostly by the parasitic infection) may support the evidence of a direct unidirectional correlation between this last and IR.

Benznidazole decreases the risk of chronic Chagas disease progression and cardiovascular events: A long-term follow up study

“…Many factors may be involved in the risk of developing chronic Chagas heart disease and/or megasyndromes including age, sex, geographical origin, parasite load, genetic heterogeneity of T. cruzi and its discrete typing units (DTU, TcI–TcVI), immunological aspects of the host, severity of the initial acute infection, transmission route, exposure to T. cruzi reinfection in areas with sustained vector transmission, nutritional status, presence of comorbidities, and the social context and quality of life of CD patients [ 39 , 40 ].…”

Diretriz da SBC sobre Diagnóstico e Tratamento de Pacientes com Cardiomiopatia da Doença de Chagas – 2023

“… 176 Muitos fatores estão envolvidos no risco de progressão da FIDC para a CCDC, tais como: idade; sexo masculino; origem geográfica; intensidade da carga parasitária; cepa do T. cruzi e suas “ discrete typing units ” (TcI–TcVI e Tc-bat); aspectos genéticos do hospedeiro; gravidade da infecção aguda inicial relacionada com a via de transmissão; exposição à reinfecção pelo parasito em áreas com transmissão vetorial sustentada; estado nutricional e presença de comorbidades; contexto social; qualidade de vida dos indivíduos com DC; e ausência de tratamento antiparasitário. 247 , 297 , 510 - 517 …”

“… 176 Several factors are involved in the risk for IFCD progression to CCCD, such as: age; male sex; geographical origin; parasite load intensity; T. cruzi strain and its discrete typing units (TcI–TcVI and Tc-bat); host’s genetic aspects; severity of the initial acute infection related to the transmission mode; exposure to reinfection with the parasite in sustained vectorial transmission areas; host’s nutritional status and presence of comorbidities; social context; quality of life of individuals with CD; and absence of trypanocidal treatment. 247 , 297 , 510 - 517 …”

“…176 Muitos fatores estão envolvidos no risco de progressão da FIDC para a CCDC, tais como: idade; sexo masculino; origem geográfica; intensidade da carga parasitária; cepa do T. cruzi e suas "discrete typing units" (TcI-TcVI e Tc-bat); aspectos genéticos do hospedeiro; gravidade da infecção aguda inicial relacionada com a via de transmissão; exposição à reinfecção pelo parasito em áreas com transmissão vetorial sustentada; estado nutricional e presença de comorbidades; contexto social; qualidade de vida dos indivíduos com DC; e ausência de tratamento antiparasitário. 247,297,[510][511][512][513][514][515][516][517] A despeito do pouco conhecimento sobre a história natural da DC, é importante enfatizar que a FIDC tem geralmente bom prognóstico, 509,518,519 sendo a própria mortalidade superponível à da população geral não infectada, enquanto o ECG for normal. 404 O indivíduo com a FIDC pode permanecer por muitas décadas nessa condição, 299,300 sendo que a realização anual ou mesmo bianual do ECG, de maneira seriada, pode detectar a evolução para CCDC.…”

Fat tissue regulates the pathogenesis and severity of cardiomyopathy in murine chagas disease

“…Cardiac fat tissue (epicardial and pericardial fat tissue) is located in proximity to heart muscle and probably plays an important role in regulating cardiac parasite load, inflammation, and metabolic functions [10]. Clinical studies have shown an association between body mass index (BMI), fat mass, dyslipidemia, nutritional status, and CCC severity [11,12]. However, it is not known whether adipocytes directly regulate the pathogenesis of CCC.…”