Sabina Smajis

Pericardial- Rather than Intramyocardial Fat Is Independently Associated with Left Ventricular Systolic Heart Function in Metabolically Healthy Humans.

Background Obesity is a major risk factor to develop heart failure, in part due to possible lipotoxic effects of increased intramyocardial (MYCL) and/or local or paracrine effects of pericardial (PERI) lipid accumulation. Recent evidence suggests that MYCL is highly dynamic and might rather be a surrogate marker for disturbed energy metabolism than the underlying cause of cardiac dysfunction. On the other hand, PERI might contribute directly by mechanic and paracrine effects. Therefore, we hypothesized that PERI rather than MYCL is associated with myocardial function. Methods To avoid potential confounding of metabolic disease 31 metabolically healthy subjects (age: 29±10yrs; BMI: 23±3kg/m2) were investigated using 1H-magnetic resonance spectroscopy and imaging. MYCL and PERI, as well as systolic and diastolic left ventricular heart function were assessed. Additionally, anthropometric data and parameters of glucose and lipid metabolism were analyzed. Correlation analysis was performed using Pearson’s correlation coefficient. Linear regression model was used to show individual effects of PERI and MYCL on myocardial functional parameters. Results Correlation analysis with parameters of systolic heart function revealed significant associations for PERI (Stroke Volume (SV): R = -0.513 p = 0.001; CardiacIndex (CI): R = -0.442 p = 0.014), but not for MYCL (SV: R = -0.233; p = 0.207; CI: R = -0.130; p = 0.484). No significant correlations were found for E/A ratio as a parameter of diastolic heart function. In multiple regression analysis CI was negatively predicted by PERI, whereas no impact of MYCL was observed in direct comparison. Conclusions Cardiac fat depots impact left ventricular heart function in a metabolically healthy population. Direct comparison of different lipid stores revealed that PERI is a more important predictor than MYCL for altered myocardial function.

Whole-Body Insulin Sensitivity Rather than Body-Mass-Index Determines Fasting and Post-Glucose-Load Growth Hormone Concentrations

Background Obese, non-acromegalic persons show lower growth hormone (GH) concentrations at fasting and reduced GH nadir during an oral glucose tolerance test (OGTT). However, this finding has never been studied with regard to whole-body insulin-sensitivity as a possible regulator. Methods In this retrospective analysis, non-acromegalic (NonACRO, n = 161) and acromegalic (ACRO, n = 35), non-diabetic subjects were subdivided into insulin-sensitive (IS) and –resistant (IR) groups according to the Clamp-like Index (CLIX)-threshold of 5 mg·kg−1·min−1 from the OGTT. Results Non-acromegalic IS (CLIX: 8.8±0.4 mg·kg−1·min−1) persons with similar age and sex distribution, but lower (p<0.001) body-mass-index (BMI = 25±0 kg/m2, 84% females, 56±1 years) had 59% and 70%, respectively, higher (p<0.03) fasting GH and OGTT GH area under the curve concentrations than IR (CLIX: 3.5±0.1 mg·kg−1·min−1, p<0.001) subjects (BMI = 29±1 kg/m2, 73% females, 58±1 years). When comparing on average overweight non-acromegalic IS and IR with similar anthropometry (IS: BMI: 27±0 kg/m2, 82% females, 58±2 years; IR: BMI: 27±0 kg/m2, 71% females, 60±1 years), but different CLIX (IS: 8.7±0.9 vs. IR: 3.8±0.1 mg·kg−1·min−1, p<0.001), the results remained almost the same. In addition, when adjusted for OGTT-mediated glucose rise, GH fall was less pronounced in IR. In contrast, in acromegalic subjects, no difference was found between IS and IR patients with regard to fasting and post-glucose-load GH concentrations. Conclusions Circulating GH concentrations at fasting and during the OGTT are lower in non-acromegalic insulin-resistant subjects. This study seems the first to demonstrate that insulin sensitivity rather than body-mass modulates fasting and post-glucose-load GH concentrations in non-diabetic non–acromegalic subjects.

Chronic Intranasal Insulin Does Not Affect Hepatic Lipids but Lowers Circulating BCAAs in Healthy Male Subjects

Context Nonalcoholic fatty liver disease and elevated circulating branched-chain amino acids (BCAAs) are common characteristics of obesity and type 2 diabetes. In rodents, brain insulin signaling controls both hepatic triglyceride secretion and BCAA catabolism. Whether brain insulin signaling controls similar metabolic pathways in humans is unknown. Objective Here we assessed if intranasal insulin, a method to preferentially deliver insulin to the central nervous system, is able to modulate hepatic lipid content and plasma BCAAs in humans. Design/Setting We conducted a randomized, double-blind, placebo-controlled trial at the Medical University of Vienna. Participants/Intervention We assessed if a chronic 4-week intranasal insulin treatment (40 IU, 4 times daily) reduces hepatic triglyceride content and circulating BCAAs in 20 healthy male volunteers. Main Outcome Measures Hepatic lipid content was assessed noninvasively by 1H-magnetic resonance spectroscopy, and BCAAs were measured by gas chromatography mass spectrometry at defined time points during the study. Results Chronic intranasal insulin treatment did not alter body weight, body mass index, and hepatic lipid content but reduced circulating BCAA levels. Conclusions These findings support the notion that brain insulin controls BCAA metabolism in humans. Thus, brain insulin resistance could account at least in part for the elevated BCAA levels observed in the insulin-resistant state.

Clinical presentation in insulinoma predicts histopathological tumour characteristics.

Insulinomas are rare neuroendocrine tumours (NETs) of the pancreas, characterized clinically by neuroglycopenic symptoms during periods of substrate deficiency. The gold standard test for diagnosing an insulinoma is a 72‐h fast. However, the prognostic value of parameters in the standardized 72‐h fast on histopathological tumour criteria and clinical presentation has not been examined.

HORMONE SUBSTITUTION AFTER GASTRIC BYPASS SURGERY IN PATIENTS WITH HYPOPITUITARISM SECONDARY TO CRANIOPHARYNGIOMA

OBJECTIVE Craniopharyngiomas (CPs) are benign brain tumors presenting frequently in childhood and are treated by surgery with or without radiotherapy. About 50% of cured patients suffer from eating disorders and obesity due to hypothalamic damage, as well as hypopituitarism, necessitating subsequent hormone substitution therapy. Gastric bypass surgery has been reported to be an efficient treatment strategy for morbid hypothalamic obesity. However, so far it is unknown whether oral hormone substitution is affected by impaired intestinal drug absorption, potentially leading to severe hypopituitarism or pituitary crisis. METHODS Four morbidly obese CP patients with panhypopituitarism treated by gastric bypass surgery were included in this retrospective analysis. Dosages of hormone substitution therapy, blood concentrations of hormones, potential complications of impaired drug absorption, and anthropometric characteristics were investigated pre- and postoperatively after 6 to 14 months and 13 to 65 months. RESULTS In all CP patients (3 female/1 male; baseline body mass index, 49 ± 7 kg/m(2)), gastric bypass resulted in distinct weight loss (-35 ± 27 kg). In follow-up examinations, mean daily dosage of thyroid hormone (levothyroxinebaseline 156 ± 44 μg/day versus levothyroxinefollow-up 150 ± 30 μg/day), hydrocortisone (hydrocortisonebaseline 29 ± 12 mg/day versus hydrocortisonefollow-up 26 ± 2 mg/day), growth-hormone (somatotropinbaseline 0.9 ± 0.5 mg/day versus somatotropinfollow-up 1.0 ± 0.4 mg/day), and desmopressin (desmopressinbaseline 222 ± 96 μg/day versus desmopressinfollow-up 222 ± 96 μg/day) substitution was unchanged. No patient developed adrenal insufficiency. Oral thyroid/hydrocortisone absorption testing performed in 1 patient indicated sufficient gastrointestinal drug absorption after bariatric surgery. CONCLUSION Our preliminary results suggest that oral hormone substitution therapy is not impaired following gastric bypass operation in CP patients with morbid obesity, indicating that it might be a safe and effective treatment strategy.

Absolute Quantification of Phosphor-Containing Metabolites in the Liver Using 31P MRSI and Hepatic Lipid Volume Correction at 7T Suggests No Dependence on Body Mass Index or Age: Absolute 31P Quantification in Liver at 7T

Hepatic disorders are often associated with changes in the concentration of phosphorus‐31 (31P) metabolites. Absolute quantification offers a way to assess those metabolites directly but introduces obstacles, especially at higher field strengths (B0 ≥ 7T).