In previous publications the authors have reported

In previous publications, the authors have reported on targeted analyses of plasma from this same cohort using a different platform, identifying correlation of specific bile acids, phosphatidylcholines and several essential BGB-324 with gut permeability or HAZ index (,,). Tryptophan, citrulline and ornithine, identified previously and also in other studies () are shown in the current report as negatively correlating with L:M ratio, engendering confidence that these amino acids may truly represent biomarkers of EED in children. However, other metabolites identified in the previous publications on this cohort are not replicated in the current study, as acknowledged by the authors. This study highlights nicely the current limitations of using metabolomics as a tool: procedural differences between the different platforms and the choice of statistical methods influence the set of specific metabolites that is identified every time. Regardless, the study warrants further exploration of metabolites identified herein in future studies.
A number of prospective studies have suggested that obesity and type 2 diabetes (T2D) promote a state of relative natriuretic peptide (NP) deficiency, so-called “natriuretic handicap” (). This observation led to the hypothesis that NP deficiency contributes to the susceptibility of obese individuals to hypertension. Considering that obesity/T2D are characterized by insulin resistance and that insulin resistance is a risk factor of hypertension, it has been proposed that insulin resistance triggers NP deficiency in obesity/T2D (). Insulin resistance defines a pathophysiological state where higher insulin levels are required to maintain blood glucose concentrations in the normal range. Hyperinsulinemia and hyperglycemia in the fasting and postprandial state are common features of obesity and T2D. Researchers therefore assumed that systemic factors from the pro-insulin resistant obese milieu, such as hyperinsulinemia and hyperglycemia, could inhibit atrial proANP expression/secretion. A recent study in cultured human embryonic stem cell-derived cardiomyocytes indicate that glucose down-regulate ANP mRNA levels by inducing miR-425, a negative regulator of its expression (). These findings were comforted by experiments showing a 27% reduction of plasma NT-proANP levels in healthy humans challenged with a high carbohydrate drink. One study in obese subjects also suggested that hyperinsulinemia may contribute to lower levels of NP by up-regulating NP clearance receptor (NPRC) expression in subcutaneous fat tissue (). In light of these observations, hyperglycemia and hyperinsulinemia may be the mechanisms underlying NP deficiency in obesity and T2D. Since T2D is also characterized by elevated blood glucagon levels (), it is not possible to discriminate the specific effect of high glucose levels on ANP secretion independently of insulin and glucagon levels. In this issue of , aimed to assess this question in a series of clinical studies in healthy individuals with normal and impaired glucose tolerance. In a first experimental study, they examined cardiac ANP secretion by measuring plasma NT-proANP in lean healthy individuals infused with either glucagon alone or in combination with somatostatin while blood glucose levels were clamped. No acute effect of glucagon and somatostatin on cardiac ANP secretion were observed. In a second longitudinal study, they investigated the influence of acute hyperinsulinemia during euglycemic conditions on cardiac ANP secretion before and after a 7-days bed rest (BR). BR induced a significant reduction of plasma NT-proANP levels by 25% and a concomitant state of insulin resistance and glucose intolerance. However no relationship between changes in plasma NT-proANP, the M-value and the Matsuda index was noted. No effect of acute euglycemic hyperinsulinemia was observed before and after the BR. In a third cross-sectional study, assessed the relationship between impaired glucose regulation and circulating NT-proANP levels. Impaired glucose regulation in middle-aged men and women was not associated with changes in plasma NT-proANP despite mild insulin resistance. Together this study highlights that acute changes in plasma insulin and glucagon do not influence cardiac proANP secretion.