In anorexia nervosa, even a small increase in abdominal fat is responsible for the appearance of insulin resistance

Context The aim of treatment in patients affected by anorexia nervosa (AN) is weight recovery. However, during weight gain, anorectic patients’ body composition is changed, with an increase in abdominal fat, particularly in the visceral compartment. Objective We hypothesized that changes in body composition, particularly in abdominal fat, are responsible for the variability in insulin sensitivity (IS) in different stages of AN. Design and Measurements We compared 20 anorectic patients in the acute stage, 19 in the weight‐recovery stage and 21 controls. All subjects underwent an oral glucose tolerance test, hyperinsulinaemic euglycaemic clamp and dual energy X‐ray absorptiometry to measure body composition. Results The percentage of trunk fat was higher in weight recovery than in the acute phase (47·7 ± 8·4%vs 34·6 ± 7·6%; P ≤ 0·01) and in the control group (33·4 ± 7·6; P < 0·01 vs weight recovery). Although the recovery group gained weight, their body mass index (BMI) was not statistically different from that of the acute group (14·4 ± 1·1 vs 13·6 ± 1·8 kg/m²). Insulin sensitivity was lower in the weight‐recovery group than the acute group (4·7 ± 1·5 vs 7·8 ± 1·6 mg/kg/min; P < 0·01) and controls (7·7 ± 1·4 mg/kg/min; P < 0·01). A linear negative correlation was found between IS and the percentage of abdominal fat in the weight‐recovery and acute groups (r = ?0·51; P = 0·04 and r = ?0·53; P = 0·04 respectively), while IS did not correlate with BMI. Conclusion Although weight‐recovery represents the main aim of treatment in AN, refeeding is associated with an increase in abdominal fat which might be responsible of the onset of insulin resistance. As BMI and weight‐recovery were associated with impaired IS, they cannot be considered the only aim of treatment of AN.     

The size of adrenal incidentalomas correlates with insulin resistance. Is there a cause‐effect relationship?

Context Adrenal incidentalomas (AI) have often been associated with a high prevalence of insulin resistance (IR) and cardiovascular risk factors, although direct measurement of insulin sensitivity (IS) has never been carried out. Objective We aimed to investigate whether the morphological and hormonal features of AI correlate with the presence and severity of IR, using the hyperinsulinaemic euglycaemic clamp (HEC). Design and Measurements Forty patients with AI (22 women) with a mean age of 58·5 ± 11·1 years underwent hormonal and morphological evaluation. Nineteen patients with AI without known history of diabetes mellitus (DM) or impaired glucose tolerance (IGT) and 17 matched controls underwent oral glucose tolerance test (OGTT) and hyperinsulinaemic euglycaemic clamp (HEC). Results Diabetes mellitus was observed in 13 patients (33%), while three (8%) had IGT. Thirty‐one of the AI were nonfunctioning (82·5%), whereas two (5%) secreted cortisol (Cushing’s syndrome) and seven (12·5%) showed subclinical secretion of cortisol. The 19 patients with nonfunctioning AI were more insulin resistant than controls (glucose up‐take: 4·58 ± 1·80 vs 5·85 ± 2·48 mg/kg/min respectively; P = 0·01); IS was inversely related to the mass size (r = ?0·57; P = 0·04), free urinary cortisol (r = ?0·68; P = 0·01), serum cortisol after 1‐mg dexamethasone suppression (?0·65; P = 0·02) and percentage of trunk fat mass (?0·77; P = 0·02) and directly related to serum adreno cortico tropic hormone (ACTH) (r = 0·62; P = 0·03). After performing multivariate regression, the mass size was found to be the most powerful predictor of IR. Conclusion Our study showed a high prevalence of insulin resistance in patients with nonfunctioning AI and suggests its possible involvement in AI growth.     

Critical role of chemokine (C-C motif) receptor 2 (CCR2) in the KKAy + Apoe -/- mouse model of the metabolic syndrome

Aims/hypothesis  

Chemokines and their receptors such as chemokine (C-C motif) receptor 2 (CCR2) may contribute to the pathogenesis of the metabolic syndrome via their effects on inflammatory monocytes. Increased accumulation of CCR2-driven inflammatory monocytes in epididymal fat pads is thought to favour the development of insulin resistance. Ultimately, the resulting hyperglycaemia and dyslipidaemia contribute to development of the metabolic syndrome complications such as cardiovascular disease and diabetic nephropathy. Our goal was to elucidate the role of CCR2 and inflammatory monocytes in a mouse model that resembles the human metabolic syndrome.     

Cardiovascular magnetic resonance of cardiac tumors and masses

Cardiac masses diagnosis and treatment are a true challenge, although they are infrequently encountered in clinical practice. They encompass a broad set of lesions that include neoplastic (primary and secondary), non-neoplastic masses and pseudomasses. The clinical presentation of cardiac tumors is highly variable and depends on several factors such as size, location, relation with other structures and mobility. The presumptive diagnosis is made based on a preliminary non-invasive diagnostic work-up due to technical difficulties and risks associated with biopsy, which is still the diagnostic gold standard. The findings should always be interpreted in the clinical context to avoid misdiagnosis, particularly in specific conditions (e.g., infective endocarditis or thrombi). The modern multi-modality imaging techniques has a key role not only for the initial assessment and differential diagnosis but also for management and surveillance of the cardiac masses. Cardiovascular magnetic resonance (CMR) allows an optimal non-invasive localization of the lesion, providing multiplanar information on its relation to surrounding structures. Moreover, with the additional feature of tissue characterization, CMR can be highly effective to distinguish pseudomasses from masses, as well as benign from malignant lesions, with further differential diagnosis of the latter. Although histopathological assessment is important to make a definitive diagnosis, CMR plays a key role in the diagnosis of suspected cardiac masses with a great impact on patient management. This literature review aims to provide a comprehensive overview of cardiac masses, from clinical and imaging protocol to pathological findings.     

Can vitamin D deficiency cause diabetes and cardiovascular diseases? Present evidence and future perspectives

Several studies have shown that vitamin D may play a role in many biochemical mechanisms in addition to bone and calcium metabolism. Recently, vitamin D has sparked widespread interest because of its involvement in the homeostasis of the cardiovascular system. Hypovitaminosis D has been associated with obesity, related to trapping in adipose tissue due to its lipophilic structure. In addition, vitamin D deficiency is associated with increased risk of cardiovascular disease (CVD) and this may be due to the relationship between low vitamin D levels and obesity, diabetes mellitus, dyslipidaemia, endothelial dysfunction and hypertension. However, although vitamin D has been identified as a potentially important marker of CVD, the mechanisms through which it might modulate cardiovascular risk are not fully understood. Given this background, in this work we summarise clinical retrospective and prospective observational studies linking vitamin D levels with cardio-metabolic risk factors and vascular outcome. Moreover, we review various randomised controlled trials (RCTs) investigating the effects of vitamin D supplementation on surrogate markers of cardiovascular risk. Considering the high prevalence of hypovitaminosis D among patients with high cardiovascular risk, vitamin D replacement therapy in this population may be warranted; however, further RCTs are urgently needed to establish when to begin vitamin D therapy, as well as to determine the dose and route and duration of administration.     

Association of the Chronotype Score with Circulating Trimethylamine N-Oxide (TMAO) Concentrations

Individual differences in the chronotype, an attitude that best expresses the individual circadian preference in behavioral and biological rhythms, have been associated with cardiometabolic risk and gut dysbiosis. Up to now, there are no studies evaluating the association between chronotypes and circulating TMAO concentrations, a predictor of cardiometabolic risk and a useful marker of gut dysbiosis. In this study population (147 females and 100 males), subjects with the morning chronotype had the lowest BMI and waist circumference (p < 0.001), and a better metabolic profile compared to the other chronotypes. In addition, the morning chronotype had the highest adherence to the Mediterranean diet (p < 0.001) and the lowest circulating TMAO concentrations (p < 0.001). After adjusting for BMI and adherence to the Mediterranean diet, the correlation between circulating TMAO concentrations and chronotype score was still kept (r = −0.627, p < 0.001). Using a linear regression analysis, higher chronotype scores were mostly associated with lower circulating TMAO concentrations (β = −0.479, t = −12.08, and p < 0.001). Using a restricted cubic spline analysis, we found that a chronotype score ≥59 (p < 0.001, R² = −0.824) demonstrated a more significant inverse linear relationship with circulating TMAO concentrations compared with knots <59 (neither chronotype) and <41 (evening chronotype). The current study reported the first evidence that higher circulating TMAO concentrations were associated with the evening chronotype that, in turn, is usually linked to an unhealthy lifestyle mostly characterized by low adherence to the MD.     

Passage of radio-iodinated insulin through the intestinal wall of the rat

Summary ¹³¹I-insulin was given intravenously to normal rats, and the passage of radioactivity into the duodenal loop containing a proteasis inhibitor was studied by two techniques. In the first, the ¹³¹I-insulin was separated from the intestinal content by electrophoresis; whereas in the second, the radioactivity that remained on an ion-exchange resin, directly introduced into the small intestine, was measured. It was found that within 15 minutes from the injection a small amount of ¹³¹I-insulin passes into the gut lumen. — The absorption of ¹³¹I-insulin from small intestine into the blood was studied after introduction of ¹³¹I-insulin along with a proteasis inhibitor into the intestinal loop. The autoradiograph of the electrophoresis of serum showed plasma-protein-bound radioactivity but no radioactivity due to unbound (free) insulin-¹³¹I. — These findings show that the passage of insulin through the intestinal wall of rats can be demonstrated by neutralizing the proteolytic activity in the intestinal tract. The possible role of this passage in protein-losing enteropathy is pointed out.

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Passage von radiojodmarkiertem, Insulin durch die Darmwand der Ratte

Zusammenfassung Normale Ratten erhielten ¹³¹I-Insulin i.V., und der Übertritt der Radioaktivität in das Lumen des Zwölffingerdarms, das einen Proteasen-Inhibitor (Trasylol) enthielt, wurde mittelszweier Verfahren untersucht. Bei dem ersten wurde das ¹³¹I-Insulin durch Elektrophorese vom Darminhalt getrennt, während beim zweiten ein Ionenaustauscher direkt in den Darm eingeführt und dann die daran haftende Radioaktivität gemessen wurde. Dabei fand sich, daß 15 Minuten nach der Injektion eine kleine Menge ¹³¹I-Insulin in das Darmlumen übertritt. — Die Absorption von ¹³¹I-Insulin aus dem Dünndarm in das Blut wurde nach Einbringen von ¹³¹I-Insulin zusammen mit einem Proteasen-Hemmer in die Darmschleife untersucht. Die Autoradiographie der Serumelektrophorese zeigte an Plasmaeiweiß gebundene Radioaktivität, jedoch kein nichtgebundenes (freies) ¹³¹I-Insulin. — Aus diesen Untersuchungen geht hervor, daß sich der Durchtritt von Insulin durch die Darmwand bei Ratten nach Neutralisierung der proteolytischen Aktivität im Verdauungstrakt nachweisen läßt. Es wird auf die mögliche Bedeutung dieser Passage bei Enteropathien mit Eiweißverlust hingewiesen.

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Passage d'insuline marquée à l'iode radioactif à travers la paroi intestinale du rat

Résumé Des rats normaux ont reçu de l'insuline-¹³¹I par voie intraveineuse et le passage de la radioactivité à l'intérieur du duodénum, contenant un inhibiteur de la protéolyse (Trasylol), a été déterminé par deux méthodes. Pour la première, l'insuline-¹³¹I a été séparée du contenu intestinal par électrophorèse, tandis que pour la deuxième, nous avons mesuré la radioactivité fixée sur résine échangeuse d'ions introduite directement dans l'intestin. Nous avons trouvé que 15 minutes après l'injection une petite quantité d'insuline passe dans la lumière intestinale. — L'absorption d'insuline-¹³¹I de l'intestin grêle vers le sang a été déterminée après introduction combinée d'insuline-¹³¹I avec un inhibiteur de la protéolyse dans une anse intestinale. L'autoradiographie de l'électrophorèse du sérum a montré une radioactivité liée aux protéines du plasma, mais pas d'insuline-¹³¹I non-liée (libre). — Ces recherches montrent que le passage d'insuline à travers la paroi intestinale du rat peut être démontré après neutralisation de l'activité protéolytique dans l'intestin. Un rôle possible de ce passage dans les entéropathies avec perte de protéines est suggéré.

     

Association Between Haptoglobin Phenotype and Microvascular Obstruction in Patients With STEMI: A Cardiac Magnetic Resonance Study

ObjectivesThis study aimed to evaluate the correlation between different haptoglobin (Hp) phenotypes and myocardial infarction characteristics as detected by cardiac magnetic resonance (CMR) in consecutive patients after ST-segment elevation myocardial infarction (STEMI).BackgroundHp is a plasma protein that prevents iron-mediated oxidative tissue damage. CMR has emerged as the gold standard technique to detect left ventricular ejection fraction (LVEF), extent of scar with late gadolinium enhancement (LGE) technique, microvascular obstruction (MVO), and myocardial hemorrhage (MH) in patients with STEMI treated by primary percutaneous coronary intervention (pPCI).MethodsA total of 145 consecutive STEMI patients (mean age 62.2 ± 10.3 years; 78% men) were prospectively enrolled and underwent Hp phenotyping and CMR assessment within 1 week after STEMI.ResultsCMR showed an area at risk (AAR) involving 26.6 ± 19.1% of left ventricular (LV) mass with a late LGE extent of 15.2 ± 13.1% of LV mass. MVO and MH occurred in 38 (26%) and 12 (8%) patients, respectively. Hp phenotypes 1-1, 2-1, 2-2 were observed in 15 (10%), 62 (43%), and 68 (47%), respectively. Multivariable analysis demonstrated that body mass index, Hp2-2, diabetes, and peak troponin I were independent predictors of MVO with Hp2-2 associated with the highest odds ratio (OR) (OR: 5.5 [95% confidence interval [CI]: 2.1 to 14.3; p < 0.001]). Hp2-2 significantly predicted both the presence (area under the curve [AUC]: 0.63 [95% CI: 0.53 to 0.72; p = 0.008]) and extent of MVO (AUC: 0.63 [95% CI: 0.54 to 0.72; p = 0.007]).ConclusionsHp phenotype is an independent predictor of MVO. Therefore, Hp phenotyping could be used for risk stratification and may be useful in assessing new therapies to reduce myocardial reperfusion injury in patients with STEMI.