Is there a link between glucose levels and heart failure? An update

Abstract

SUMMARYIt has been well documented that there is an increased prevalence of standard cardiovascular (CV) risk factors in association with diabetes and with diabetes-related abnormalities. Hyperglycemia, in particular, also plays an important role. Heart failure (HF) has become a frequent manifestation of cardiovascular disease (CVD) among individuals with diabetes mellitus. Epidemiological studies suggest that the effect of hyperglycemia on HF risk is independent of other known risk factors. Analysis of datasets from populations including individuals with dysglycemia suggests the pathogenic role of hyperglycemia on left ventricular function and on the natural history of HF. Despite substantial epidemiological evidence of the relationship between diabetes and HF, data from available interventional trials assessing the effect of a glucose-lowering strategy on CV outcomes are limited. To provide some insight into these issues, we describe in this review the recent important data to understand the natural course of CV disease in diabetic individuals and the role of hyperglycemia at different times in the progression of HF. Arq Bras Endocrinol Metab. 2010;54(5):488-97 Keywords Prediabetic state; blood glucose; hyperglycemia; ventricular dysfunction, left; heart failure SUMÁRIO Já foi bem documentado um aumento da prevalência dos fatores de risco cardiovascular convencional em portadores de diabetes melito e em pessoas com as anormalidades relacionadas ao diabetes. A hiperglicemia, particularmente, teria um papel crítico. A insuficiência cardíaca (IC) tem se tornado uma manifestação frequente da doença cardiovascular em indivíduos com diabetes. Estudos epidemiológicos sugerem que o efeito da hiperglicemia no risco para IC é independente dos outros fatores de risco. A análise dos dados de populações que incluem indivíduos com disglicemia sugere um papel patogênico da hiperglicemia na função do ventrículo esquerdo na história natural da IC. A despeito de evidências epidemiológicas na relação entre diabetes e IC, os dados disponíveis de estudos clínicos de intervenção para avaliar o efeito da estratégia de redução da glicose sobre os desfechos cardiovasculares ainda são limitados. Para trazer alguma compreensão nesse tópico, descrevemos nesta revisão os dados recentes e importantes para entender a história natural da doença cardiovascular em indivíduos com diabetes e o papel da hiperglicemia em diferentes períodos na progressão da doença. Arq Bras Endocrinol Metab. 2010;54(5):488-97 Descritores

Left ventricle structural remodelling in the prediabetic Goto-Kakizaki rat

“…While further functional assessment of the LV and study in the GK rat with an extended time course are warranted, it is noteworthy that diastolic dysfunction has been previously reported in the 8-week-old prediabetic Otsuka Long Evans Tokushima Fatty rat (Mizushige et al 2000) In summary, our work highlights the possibility that ventricular decompensation, frequently reported in HF of diabetic origin, may be linked to an early remodelling of cardiac parenchyma triggered by the cardiotoxic effects of moderate, early changes in glucose metabolism and presents the likelihood of TGFβ1 involvement in this process. From a clinical standpoint, our findings are corroborated by emerging current recommendations encouraging a stringent degree of glycaemic control to compensate for the low threshold of glucose perturbation that apparently engenders the onset of cardiac consequences (Nielsen & Lange, 2005;Bergman, 2010;Schainberg et al 2010). Finally, it is estimated that patients may be exposed to a decade of mild-to-moderate hyperglycaemia before a diagnosis of overt DM is made (Schainberg et al 2010).…”

“…Indeed, past work and theoretical mechanisms are consistent with the proposition that increasing glucose has a continuous association with risk for HF and adverse cardiovascular outcomes even at concentrations below the range defined for a diagnosis of diabetes; i.e. in the dysglycaemia of impaired glucose tolerance (IGT; also impaired fasting glucose), used interchangeably with the term 'prediabetes' (Nielsen & Lange, 2005;Bergman, 2010;Schainberg et al 2010).…”

“…Taken together, our findings are significant in that they demonstrate a possible role for the dysglycaemia of IGT in the pathophysiology of developing cardiac complications via early effects on ventricle structural remodelling. This concept finds resonance in recent clinical reports of concentric remodelling and LV hypertrophy in IGT (Fujita et al 2007;Schainberg et al 2010). …”

“…The relationship of HG to HF is complicated by converse observations that improved glycaemic control does not improve cardiac function and hence prevent HF (Nielsen & Lange, 2005) and also that HF can, in turn, induce insulin resistance and DM (Schainberg et al 2010). Genetic heterogeneity of sample populations, intercurrent events, such as acute coronary syndromes, sex-pooled analyses and environmental risk factors are amongst other caveats confounding interpretation of clinical studies.…”

“…Hyperglycaemia (HG) is the primary diagnostic feature of diabetes mellitus (DM), the target for anti-diabetic therapy and, together with glycated haemoglobin, the principal marker of glucose control (Schainberg et al 2010). It follows that several lines of epidemiological evidence have accumulated to suggest an independent effect of HG on HF, in the absence of confounding comorbidities/risk factors.…”