Intranasal oxytocin fails to acutely improve glucose metabolism in obese men.

The hypothalamic neuropeptide oxytocin not only modulates psychosocial function, but also contributes to metabolic regulation. We have recently shown that intranasal oxytocin acutely improves beta-cell responsivity and glucose tolerance in normal-weight men. In the present experiment, we investigated the acute glucoregulatory impact of oxytocin in obese men with impaired insulin sensitivity. Fifteen obese healthy men with an average body mass index of 35 kg/m2 and an average body fat content of 33% received a single intranasal dose (24 IU) of oxytocin before undergoing an oral glucose tolerance test. Results were analysed according to the oral minimal model and compared with our findings in normal-weight participants. In contrast to the results in normal-weight subjects, oxytocin did not blunt postprandial glucose and insulin excursions in obese men, and moreover failed to enhance beta-cell responsivity and glucose tolerance. These results indicate that pronounced obesity may be associated with a certain degree of resistance to the glucoregulatory impact of exogenous oxytocin, and underlines the need for further investigations into the potential of oxytocin to improve glucose homeostasis in the clinical context.

Visual food cues decrease postprandial glucose concentrations in lean and obese men without affecting food intake and related endocrine parameters.

The abundance of highly palatable food items in our environment represents a possible cause of overconsumption. Neuroimaging studies in humans have demonstrated that watching pictures of food increases activation in brain areas involved in homeostatic and hedonic food cue processing. Nevertheless, the impact of food cues on actual food intake and metabolic parameters has not been systematically investigated. We tested the hypothesis that watching high-calorie food cues increases food intake and modifies anticipatory blood parameters in lean and especially in obese men. In 20 normal-weight and 20 obese healthy fasted men, we assessed the effects of watching pictures of high-calorie food items versus neutral contents on food intake measured during a standardized test buffet and subsequent snacking as well as on glucose homeostasis and endocrine parameters. Compared to neutral pictures, viewing food pictures reduced postprandial blood glucose concentrations in lean (p = 0.016) and obese (p = 0.044) subjects, without any differences in insulin or C-peptide concentrations (all p > 0.4). Viewing food pictures did not affect total calorie intake during the buffet (all p > 0.5) and snack consumption (all p > 0.4). Concentrations of ghrelin, adrenocorticotropic hormone (ACTH), cortisol, and glucagon also remained unaffected (all p > 0.08). These data indicate that preprandial processing of food cues curbs postprandial blood glucose excursions, without immediately affecting eating behavior in normal-weight and obese men. Findings indicate that exposure to food cues does not acutely trigger calorie overconsumption but rather improves the glucoregulatory response to food intake.

Glucocorticoid replacement therapy in adrenal insufficiency--a challenge to physicians?

Adrenal insufficiency (AI) is a rare disease caused by destruction of the adrenal glands or dysfunction of the pituitary gland or the hypothalamus. Treatment usually requires lifelong replacement therapy with glucocorticoids. Correct use of glucocorticoids and early dose adjustments are essential to cover the increased glucocorticoid demand in stress. Repeated education of patients and their partners is the best strategy to avoid life-threatening emergencies. However, there is a debate whether physicians' knowledge regarding AI is sufficient, in part due to the rareness of this endocrine disorder. To determine the present specific knowledge of physicians in a large University Department of Internal Medicine with a clinically and scientifically active Division of Endocrinology, all interns, residents / fellows, specialists or senior physicians / consultants were asked to complete a questionnaire with various possible answers on the subject of AI (n=69, median age 30 years, range 23-49 years). The present data suggest that in the investigated University Hospital setting current physicians' knowledge of medical replacement strategies in AI may be insufficient depending on the level of education and experience. Even physicians with training in endocrinology in part demonstrated extensive knowledge gaps. There might be a need for additional structured information and training on AI, even in specialized hospitals.

Visual food cues decrease blood glucose and glucoregulatory hormones following an oral glucose tolerance test in normal-weight and obese men.

Previous experiments of our group have demonstrated that preprandial processing of food cues attenuates postprandial blood glucose excursions. Here we systematically re-evaluated the glucose-lowering effect of visual food cues by submitting 40 healthy fasted men (20 normal-weight men, mean age 24.8 ± 3.7 years, BMI 21.9 ± 0.3 kg/m2; 20 obese men, 26.8 ± 4.2 years, 34.3 ± 1.3 kg/m2) to an oral glucose tolerance test (OGTT) following exposure to pictures of high-calorie food items versus neutral items. OGTT-related changes in blood concentrations of glucose and relevant glucoregulatory hormones including GLP-1 were assessed and analyzed according to the oral minimal model. Independent of body weight, food-cue compared to neutral stimulus presentation reduced postprandial concentrations of glucose (p = 0.041), insulin (p = 0.026) and C-peptide (p = 0.007); accordingly, oral minimal model analyses yielded a food-cue induced decrease of dynamic-phase insulin secretion (p = 0.036). We also observed a trend towards lower GLP-1 levels directly after food cue stimulation in both body weight groups (p = 0.057), as well as a trend towards decreased heart rate (p = 0.093) and significantly decreased diastolic blood pressure (p = 0.019). While we did not detect indicators of an early rise in insulin levels in terms of a 'cephalic phase insulin response', our findings support the assumption that preprandial processing of food cues exerts marked effect on postprandial glucose regulation, with possible contributions of changes in GLP-1. The mechanisms linking food cue exposure and glucoregulatory improvements should be investigated in greater detail, to potentially open new treatment options for metabolic dysfunctions.

ERG expression in multiple myeloma-A potential diagnostic pitfall.

INTRODUCTION: ERG expression has been described as a frequent event in prostate cancer indicating poor prognosis and promoting oncogenesis. It has also been demonstrated in Ewing's sarcoma, acute myeloid leukemia and acute T-lymphoblastic leukemia but could not be found in other epithelial tumors, Hodgkin's or Non-Hodgkin's lymphoma. We aimed to analyze ERG expression in multiple myeloma, following an index case of a patient with metastases of unknown origin in the spine strongly expressing ERG, which were thought to be of prostatic origin but turned out to be plasmacytic lesions. MATERIAL AND METHODS: We subsequently selected 12 formalin-fixed, paraffin-embedded tissue samples of multiple myeloma from our archives and performed immunohistochemical staining for ERG. RESULTS: All 12 analyzed cases showed strong nuclear expression of ERG in >90% of tumor cells (myeloma cells). CONCLUSIONS: This report highlights a potential and critical diagnostic pitfall in biopsy specimens where morphology is only of limited assistance in reaching the correct diagnosis. It urges pathologists to exercise caution in cases where strong ERG-positivity implicates the presence of a prostatic neoplasia and illustrates the need for further immunohistochemical examination.

Oxytocin Improves ß-Cell Responsivity and Glucose Tolerance in Healthy Men.

In addition to its pivotal role in psychosocial behavior, the hypothalamic neuropeptide oxytocin contributes to metabolic control by suppressing eating behavior. Its involvement in glucose homeostasis is less clear, although pilot experiments suggest that oxytocin improves glucose homeostasis. We assessed the effect of intranasal oxytocin (24 IU) administered to 29 healthy, fasted male subjects on glucose homeostasis measured by means of an oral glucose tolerance test. Parameters of glucose metabolism were analyzed according to the oral minimal model. Oxytocin attenuated the peak excursion of plasma glucose and augmented the early increases in insulin and C-peptide concentrations in response to the glucose challenge, while slightly blunting insulin and C-peptide peaks. Oral minimal model analyses revealed that oxytocin compared with placebo induced a pronounced increase in ß-cell responsivity (PHItotal) that was largely due to an enhanced dynamic response (PHId), and a more than twofold improvement in glucose tolerance (disposition index). Adrenocorticotropic hormone (ACTH), cortisol, glucagon, and nonesterified fatty acid (NEFA) concentrations were not or were only marginally affected. These results indicate that oxytocin plays a significant role in the acute regulation of glucose metabolism in healthy humans and render the oxytocin system a potential target of antidiabetic treatment.

Clinical Scenario of the Metabolic Syndrome.

The term metabolic syndrome (MeS) refers to a cluster of associated symptoms composed of impaired fasting glucose, abdominal obesity, hypertension, and dyslipidemia. MeS is associated with an increased risk of cardiovascular and diabetes-associated morbidity and mortality. The increased amount of visceral fat together with a chronic inflammatory state predisposes to the development of arteriosclerosis. Furthermore, insulin resistance (IR) and dyslipidemia are associated with fatty liver disease. In addition, MeS is linked to non-cardiovascular diseases such as cancer as well as psychiatric or endocrine disorders. Here, we discuss the clinical impact of MeS in cardiovascular and non-cardiovascular diseases to highlight the importance of prevention, early diagnosis, and multifactorial treatment of high-risk individuals.

Intranasal insulin enhances postprandial thermogenesis and lowers postprandial serum insulin levels in healthy men.

OBJECTIVE: Animal studies indicate a prominent role of brain insulin signaling in the regulation of peripheral energy metabolism. We determined the effect of intranasal insulin, which directly targets the brain, on glucose metabolism and energy expenditure in humans. RESEARCH DESIGN AND METHODS: In a double-blind, placebo-controlled, balanced within-subject comparison, 19 healthy normal-weight men (18-26 years old) were intranasally administered 160 IU human insulin after an overnight fast. Energy expenditure assessed via indirect calorimetry and blood concentrations of glucose, insulin, C-peptide, and free fatty acids (FFAs) were measured before and after insulin administration and the subsequent consumption of a high-calorie liquid meal of 900 kcal. RESULTS: Intranasal insulin, compared with placebo, increased postprandial energy expenditure, i.e., diet-induced thermogenesis, and decreased postprandial concentrations of circulating insulin and C-peptide, whereas postprandial plasma glucose concentrations did not differ from placebo values. Intranasal insulin also induced a transient decrease in prandial serum FFA levels. CONCLUSIONS: Enhancing brain insulin signaling by means of intranasal insulin administration enhances the acute thermoregulatory and glucoregulatory response to food intake, suggesting that central nervous insulin contributes to the control of whole-body energy homeostasis in humans.