Glucagon-like peptide 1 (GLP-1).

BACKGROUND: The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential. Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of insulin secretion, decrease of gastric emptying, inhibition of food intake, increase of natriuresis and diuresis, and modulation of rodent ß-cell proliferation. GLP-1 also has cardio- and neuroprotective effects, decreases inflammation and apoptosis, and has implications for learning and memory, reward behavior, and palatability. Biochemically modified for enhanced potency and sustained action, GLP-1 receptor agonists are successfully in clinical use for the treatment of type-2 diabetes, and several GLP-1-based pharmacotherapies are in clinical evaluation for the treatment of obesity. SCOPE OF REVIEW: In this review, we provide a detailed overview on the multifaceted nature of GLP-1 and its pharmacology and discuss its therapeutic implications on various diseases. MAJOR CONCLUSIONS: Since its discovery, GLP-1 has emerged as a pleiotropic hormone with a myriad of metabolic functions that go well beyond its classical identification as an incretin hormone. The numerous beneficial effects of GLP-1 render this hormone an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, and neurodegenerative disorders.

Fetal auditory evoked responses to onset of amplitude modulated sounds. A fetal magnetoencephalography (fMEG) study.

The human fetal auditory system is functional around the 25th week of gestational age when the thalamocortical connections are established. Fetal magnetoencephalography (fMEG) provides evidence for fetal auditory brain responses to pure tones and syllables. Fifty-five pregnant women between 31 and 40 weeks of gestation were included in the study. Fetal MEG was recorded during the presentation of an amplitude modulated tone (AM) with a carrier frequency of 500 Hz to the maternal abdomen modulated by low modulation rates (MRs) - 2/s and 4/s, middle MR - 8/s and high MRs - 27/s, 42/s, 78/s and 91/s. The aim was to determine whether the fetal brain responds differently to envelope slopes and intensity change at the onset of the AM sounds. A significant decrease of the response latencies of transient event-related responses (ERR) to high and middle MRs in comparison to the low MRs was observed. The highest fetal response rate was achieved by modulation rates of 2/s, 4/s and 27/s (70%, 57%, and 86%, respectively). Additionally, a maturation effect of the ERR (response latency vs. gestational age) was observed only for 4/s MR. The significant difference between the response latencies to low, middle, and high MRs suggests that still before birth the fetal brain processes the sound slopes at the onset in different integration time-windows, depending on the time for the intensity increase or stimulus power density at the onset, which is a prerequisite for language acquisition.

The protective effect of human renal sinus fat on glomerular cells is reversed by the hepatokine fetuin-A.

Renal sinus fat (RSF) is a perivascular fat compartment located around renal arteries. In this in vitro and in vivo study we hypothesized that the hepatokine fetuin-A may impair renal function in non alcoholic fatty liver disease (NAFLD) by altering inflammatory signalling in RSF. To study effects of the crosstalk between fetuin-A, RSF and kidney, human renal sinus fat cells (RSFC) were isolated and cocultured with human endothelial cells (EC) or podocytes (PO). RSFC caused downregulation of proinflammatory and upregulation of regenerative factors in cocultured EC and PO, indicating a protective influence of RFSC. However, fetuin-A inverted these benign effects of RSFC from an anti- to a proinflammatory status. RSF was quantified by magnetic resonance imaging and liver fat content by 1H-MR spectroscopy in 449 individuals at risk for type 2 diabetes. Impaired renal function was determined via urinary albumin/creatinine-ratio (uACR). RSF did not correlate with uACR in subjects without NAFLD (n = 212, p = 0.94), but correlated positively in subjects with NAFLD (n = 105, p = 0.0005). Estimated glomerular filtration rate (eGRF) was inversely correlated with RSF, suggesting lower eGFR for subjects with higher RSF (r = 0.24, p < 0.0001). In conclusion, our data suggest that in the presence of NAFLD elevated fetuin-A levels may impair renal function by RSF-induced proinflammatory signalling in glomerular cells.

An extended fatty liver index to predict non-alcoholic fatty liver disease.

BACKGROUND: In clinical practice, there is a strong interest in non-invasive markers of non-alcoholic fatty liver disease (NAFLD). Our hypothesis was that the fold-change in plasma triglycerides (TG) during a 2-h oral glucose tolerance test (fold-change TGOGTT) in concert with blood glucose and lipid parameters, and the rs738409 C>G single nucleotide polymorphism (SNP) in PNPLA3 might improve the power of the widely used fatty liver index (FLI) to predict NAFLD. METHODS: The liver fat content of 330 subjects was quantified by 1H-magnetic resonance spectroscopy. Blood parameters were measured during fasting and after a 2-h OGTT. A subgroup of 213 subjects underwent these measurements before and after 9 months of a lifestyle intervention. RESULTS: The fold-change TGOGTT was closely associated with liver fat content (r=0.51, P<0.0001), but had less power to predict NAFLD (AUROC=0.75) than the FLI (AUROC=0.79). Not only was the fold-change TGOGTT independently associated with liver fat content and NAFLD, but so also were the 2-h blood glucose level and rs738409 C>G SNP in PNPLA3. In fact, a novel index (extended FLI) generated from these and the usual FLI parameters considerably increased its power to predict NAFLD (AUROC=0.79-0.86). The extended FLI also increased the power to predict changes in liver fat content with a lifestyle intervention (n=213; standardized beta coefficient: 0.23-0.29). CONCLUSION: This study has provided novel data confirming that the OGTT-derived fold-change TGOGTT and 2-h glucose level, together with the rs738409 C>G SNP in PNPLA3, allow calculation of an extended FLI that considerably improves its power to predict NAFLD.

Gestational diabetes alters the fetal heart rate variability during an oral glucose tolerance test: a fetal magnetocardiography study.

OBJECTIVE: Gestational diabetes mellitus (GDM) potentially harms the child before birth. We previously found GDM to be associated with developmental changes in the central nervous system. We now hypothesise that GDM may also impact on the fetal autonomic nervous system under metabolic stress like an oral glucose tolerance test (OGTT). DESIGN: We measured heart rate variability (HRV) of mothers and fetuses during a three-point OGTT using fetal magnetocardiography (fMCG). SETTING: Measurements were performed in the fMEG Centre in Tübingen. POPULATION: After exclusion of 23 participants, 13 pregnant women with GDM and 36 pregnant women with normal glucose tolerance were examined. METHODS: All women underwent the same examination setting with OGTT during which fMCG was recorded three times. MAIN OUTCOME MEASURE(S): Parameters of heart rate variability were measured. RESULTS: Compared with mothers with normal glucose regulation, mothers with GDM showed increased heart rate but no significant differences of maternal HRV. In contrast, HRV in fetuses of mothers with GDM differed from those in the metabolically healthy group regarding standard deviation normal to normal beat (SDNN) (P = 0.012), low-frequency band (P = 0.008) and high-frequency band (P = 0.031). These HRV parameters exhibit a decrease only in GDM fetuses during the second hour of the OGTT. CONCLUSIONS: These results show an altered response of the fetal autonomic nervous system to metabolic stress in GDM-complicated pregnancies. Hence, disturbances in maternal glucose metabolism might not only impact on the central nervous system of the fetus but may also affect the fetal autonomic nervous system. TWEETABLE ABSTRACT: Metabolic stress reveals a different response of fetal autonomic nervous system in GDM-complicated pregnancies.

Association between omentin-1, adiponectin and bone health under consideration of osteoprotegerin as possible mediator.

PURPOSE: Several studies implicated a crosstalk between bone and fat in the pathogenesis of osteoporosis. Few studies indicated an association between adiponectin and omentin-1 on the bone remodeling process and bone mineral density, and suggested osteoprotegerin (OPG) as a mediator of this relationship. However, only limited evidence on this relationship is available in humans. Therefore, this study aimed to investigate the association between omentin-1, adiponectin and broadband ultrasound attenuation (BUA) in peri-/premenopausal and postmenopausal women, and to assess the role of OPG as a possible mediator. METHODS: Data from the German population-based EPIC-Potsdam cohort comprising 637 women were analyzed. Multivariable-adjusted ANCOVA including age, BMI, waist circumference, smoking status, education, physical activity, adiponectin or omentin-1 and hormone use was used to investigate potential relationships between the adipokines and BUA levels. A mediation analysis assessed the mediating effect of OPG on the association of BUA and omentin-1 levels. RESULTS: Peri-/premenopausal women had higher BUA levels (112.5 ± 10.1 dB/MHz), compared to postmenopausal women (106.3 ± 10.0 dB/MHz). In peri-/premenopausal women neither adiponectin nor omentin-1 was significantly associated with BUA. In postmenopausal women, adiponectin was not associated with BUA, but 10 % increase in the omentin-1 concentration was significantly associated with 0.44 dB/MHz lower BUA levels (p = 0.01). Omentin-1 was positively associated with OPG (p = 0.02); however, OPG was not significantly related to BUA (p = 0.62). CONCLUSION: Our study provides evidence for an inverse association between circulating omentin-1 and BUA levels in postmenopausal women. However, the present findings do not support a mediating effect of OPG in the adipose tissue-bone pathway.

Oxytocin's inhibitory effect on food intake is stronger in obese than normal-weight men.

BACKGROUND/OBJECTIVES: Animal studies and pilot experiments in men indicate that the hypothalamic neuropeptide oxytocin limits food intake, and raise the question of its potential to improve metabolic control in obesity. SUBJECTS/METHODS: We compared the effect of central nervous oxytocin administration (24 IU) via the intranasal route on ingestive behaviour and metabolic function in 18 young obese men with the results in a group of 20 normal-weight men. In double-blind, placebo-controlled experiments, ad libitum food intake from a test buffet was examined in fasted subjects 45 min after oxytocin administration, followed by the assessment of postprandial, reward-driven snack intake. Energy expenditure was repeatedly assessed by indirect calorimetry and blood was sampled to determine concentrations of blood glucose and hormones. RESULTS: Oxytocin markedly reduced hunger-driven food intake in the fasted state in obese but not in normal-weight men, and led to a reduction in snack consumption in both groups, whereas energy expenditure remained generally unaffected. Hypothalamic-pituitary-adrenal axis secretion and the postprandial rise in plasma glucose were blunted by oxytocin in both groups. CONCLUSIONS: Oxytocin exerts an acutely inhibitory impact on food intake that is enhanced rather than decreased in obese compared with normal-weight men. This pattern puts it in contrast to other metabolically active neuropeptides and bodes well for clinical applications of oxytocin in the treatment of metabolic disorders.

Metabolic profiles during an oral glucose tolerance test in pregnant women with and without gestational diabetes.

BACKGROUND/AIM: Gestational diabetes (GDM) is a complex metabolic condition associated with hyperpglycemia that is diagnosed in an oral glucose tolerance test (OGTT) during pregnancy. For a deeper understanding of the pathology of the disease, further investigations during pregnancy are required, ideally under metabolic challenging conditions. METHODS: We performed targeted metabolomics in a group of 24 well-matched women during an oral glucose tolerance test (OGTT). 231 plasma metabolites were profiled and compared to conventional clinical diagnostics. RESULTS: A pattern of 8 metabolites differed between GDM and healthy controls as early as 30 min in an OGTT (AUC 0.977±0.008), and an increase in acylcarnitine C18:0, decreased concentrations of diacyl phosphatidylcholines (PC aa) C34:4, PC aa C36:4, PC aa C38:5, Lyso PC C20:4 and arachidonic acid were associated with insulin resistance. CONCLUSION: Our data suggest an additional value of metabolite pattern in the diagnosis of GDM and describe altered pathways that might be subjected to a more precise diagnosis and individualized therapy.

[Liver volume, intrahepatic fat and body weight in the course of a lifestyle interventional study: Analysis with quantitative MR-based methods]. / Lebervolumen, Leberfettanteil und Körpergewicht im Verlauf einer Lebensstilinterventionsstudie : Eine Analyse mit quantitativen MR-basierten Methoden.

OBJECTIVES: The aim of this study was to investigate potential associations between changes in liver volume, the amount of intrahepatic lipids (IHL) and body weight during lifestyle interventions. MATERIAL AND METHODS: In a prospective study 150 patients with an increased risk for developing type 2 diabetes mellitus were included who followed a caloric restriction diet for 6 months. In the retrospective analysis 18 women and 9 men (age range 22-71 years) with an average body mass index (BMI) of 32 kg/m(2) were enrolled. The liver volume was determined at the beginning and after 6 months by three-dimensional magnetic resonance imaging (3D-MRI, echo gradient, opposed-phase) and IHLs were quantified by volume-selective MR spectroscopy in single voxel stimulated echo acquisition mode (STEAM). Univariable and multivariable correlation analyses between changes of liver volume (Δliver volume), intrahepatic lipids (ΔIHL) and body weight (ΔBW) were performed. RESULTS: Univariable correlation analysis in the whole study cohort showed associations between ΔIHL and ΔBW (r = 0.69; p < 0.0001), ΔIHL and Δliver volume (r = 0.66; p = 0.0002) as well as ΔBW and Δliver volume (r = 0.5; p = 0.0073). Multivariable correlation analysis revealed that changes of liver volume are primarily determined by changes in IHL independent of changes in body weight (ß = 0.0272; 95% CI: 0.0155-0.034; p < 0.0001). CONCLUSION: Changes of liver volume during lifestyle interventions are independent of changes of body weight primarily determined by changes of IHL. These results show the reversibility of augmented liver volume in steatosis if it is possible to reduce IHLs during lifestyle interventions.

Compromised white matter integrity in obesity.

Obesity is associated with both structural and functional changes of the central nervous system. While gray matter alterations in obesity point to a consistent reduction with increasing body mass index (BMI), volumetric changes in white matter are more complex and less conclusive. Hence, more recently, diffusion tensor imaging (DTI) has been employed as a highly sensitive tool to investigate microstructural changes in white matter structure. Parameters of diffusivity and anisotropy are used to evaluate white matter and fibre integrity as well as axonal and myelin degeneration. Fractional anisotropy (FA) is the most commonly used parameter as it is the best estimate of fibre integrity. The focus of this review was on the relationship between obesity and brain alterations assessed by DTI. Altogether, these studies have shown a loss of white matter integrity with obesity-related factors, especially in tracts within the limbic system and those connecting the temporal and frontal lobe. More specifically, multiple studies found an inverse association between BMI and FA in the corpus callosum, fornix, cingulum and corona radiata in elderly and young adults as well as children. Furthermore, significant interactions were observed between BMI and age, pointing to accelerated ageing of white matter structure in obese.

Insulin action in the human brain: evidence from neuroimaging studies.

Thus far, little is known about the action of insulin in the human brain. Nonetheless, recent advances in modern neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) or magnetoencephalography (MEG), have made it possible to investigate the action of insulin in the brain in humans, providing new insights into the pathogenesis of brain insulin resistance and obesity. Using MEG, the clinical relevance of the action of insulin in the brain was first identified, linking cerebral insulin resistance with peripheral insulin resistance, genetic predisposition and weight loss success in obese adults. Although MEG is a suitable tool for measuring brain activity mainly in cortical areas, fMRI provides high spatial resolution for cortical as well as subcortical regions. Thus, the action of insulin can be detected within all eating behaviour relevant regions, which include regions deeply located within the brain, such as the hypothalamus, midbrain and brainstem, as well as regions within the striatum. In this review, we outline recent advances in the field of neuroimaging aiming to investigate the action of insulin in the human brain using different routes of insulin administration. fMRI studies have shown a significant insulin-induced attenuation predominantly in the occipital and prefrontal cortical regions and the hypothalamus, successfully localising insulin-sensitive brain regions in healthy, mostly normal-weight individuals. However, further studies are needed to localise brain areas affected by insulin resistance in obese individuals, which is an important prerequisite for selectively targeting brain insulin resistance in obesity.

[Phenotypes of prediabetes and type 2 diabetes]. / Phänotypen des Prädiabetes und des Typ-2-Diabetes.

Type 2 Diabetes is a heterogeneous disease which harbors several different pathomechanistic entities. For a successful prevention, it is important to understand the exact pathomechanisms. Overt type 2 Diabetes usually develops through an intermediary state called prediabetes, which is also heterogeneous. This state is especially important, because it already confers a higher risk for diabetes-associated complications. Therefore, detection of prediabetes and prevention of its progression to diabetes would be desirable. In this review, we describe the phenotypes of prediabetes and type 2 diabetes. We also try to envision the first steps of a future phenotype-oriented diabetes therapy.

Association between erythrocyte membrane fatty acids and biomarkers of dyslipidemia in the EPIC-Potsdam study.

BACKGROUND/OBJECTIVE: Blood proportions of fatty acids (FAs) and FA-ratios reflecting desaturase activity are associated with the risk of chronic diseases like type 2 diabetes mellitus or cardiovascular diseases. Biomarkers of dyslipidemia are considered as potential mediators of this association. We evaluated associations of erythrocyte membrane proportions of individual disease-related polyunsaturated fatty acids (PUFAs), trans-FAs, dairy-derived saturated FAs (SFAs) (15:0, 17:0) and FA-ratios with biomarkers of dyslipidemia (high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, non-HDL-cholesterol, triglycerides). SUBJECTS/METHODS: We conducted a cross-sectional analysis of a subsample (n=1759) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study. Associations of individual FAs and FA-ratios with plasma biomarkers of dyslipidemia were evaluated by linear multivariable regression. RESULTS: Most notably, FA-ratios reflecting activity of Δ6-desaturase (D6D) and stearoyl-coenzyme A-desaturase (SCD) were positively associated with triglyceride and LDL-cholesterol concentrations (adjusted means (95% confidence interval (CI)) of triglycerides (mg/dl) across D6D tertiles: men--102 (94.7-110), 111 (104-120), 144 (134-156) and women--73.5 (70.0-77.2), 82.9 (79.0-86.9), 94.2 (89.7-98.9)); across SCD tertiles: men--99.0 (91.8-107), 115 (107-124), 144 (134-156) and women--72.4 (69.0-76.0), 81.5 (77.8-85.5), 97.2 (92.6-102)), whereas inverse associations with triglycerides were observed for the estimated Δ5-desaturase (D5D) activity (adjusted means (95% CI) of triglycerides (mg/dl) across D5D tertiles: men--128 (119-138), 121 (113-131), 106 (97.9-114) and women--92.0 (87.6-96.6), 82.8 (78.9-86.9), 75.3 (71.6-79.1), P-values for trend at least 0.0006). Furthermore, we observed generally weaker and less consistent associations of dairy-derived SFAs (mainly 17:0) with triglycerides and HDL-cholesterol. Individual PUFAs and trans-FAs were, if at all, only weakly associated with dyslipidemia markers. CONCLUSIONS: Our findings suggest that triglyceride and LDL-cholesterol concentrations may be mediators that link intake and metabolism of FAs to metabolic risk.

Age-dependent association of serum prolactin with glycaemia and insulin sensitivity in humans.

The dopamine agonist bromocriptine has been approved for the treatment of type 2 diabetes in the United States. Bromocriptine inhibits prolactin secretion, and patients with hyperprolactinaemia display impaired insulin sensitivity. We therefore hypothesized that low prolactin levels are associated with lower glycaemia and higher insulin sensitivity in healthy subjects. Prolactin levels were determined from fasting serum in participants without diabetes from the cross-sectional Tübingen family study for type 2 diabetes (m/f = 562/1,121, age = 40 ± 13 years, BMI = 30 ± 9 kg/m(2)). A 75 g oral glucose tolerance test was performed, and the area under the glucose curve (AUC(0-120)Glucose) and insulin sensitivity index were calculated. A subgroup (n = 494) underwent hyperinsulinaemic-euglycaemic clamp tests. Prolactin associated positively with insulin sensitivity (p = 0.001, adjusted for gender, age, and BMI). Age strongly interacted (p < 0.0001) with the effect of prolactin on insulin sensitivity, inverting the positive relationship to a negative one in younger participants. Glycated haemoglobin (HbA1c) and AUC(0-120)Glucose correlated negatively with prolactin, and an interaction with age was found as well. Higher prolactin levels are associated with improved insulin sensitivity and lower glucose in individuals without diabetes. This relationship turns to its opposite in younger persons. As prolactin is a proxy for the dopaminergic tone in the central nervous system, these associations may indicate an age-dependent influence of the brain on peripheral insulin sensitivity.

Plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, e-selectin and C-reactive protein levels in response to 4-week very-high-fructose or -glucose diets.

BACKGROUND/OBJECTIVES: High intake of added sweeteners is considered to have a causal role in the pathogenesis of cardiometabolic disorders. Especially, high-fructose intake is regarded as potentially harmful to cardiometabolic health. It may cause not only weight gain but also low-grade inflammation, which represents an independent risk factor for developing type 2 diabetes and cardiovascular disease. In particular, fructose has been suggested to induce plasminogen activator inhibitor-1 (PAI-1) expression in the liver and to increase circulating inflammatory cytokines. We therefore aimed to investigate, whether high-fructose diet has an impact on PAI-1, monocyte chemoattractant protein-1 (MCP-1), e-selectin and C-reactive protein (CRP) concentrations in healthy humans. SUBJECTS/METHODS: We studied 20 participants (12 males and 8 females) of the TUebingen FRuctose Or Glucose study. This is an exploratory, parallel, prospective, randomized, single-blinded, outpatient, hypercaloric, intervention study. The participants had a mean age of 30.9 ± 2.1 years and a mean body mass index of 26.0 ± 0.5 kg/m(2) and they received 150 g of either fructose or glucose per day for 4 weeks. RESULTS: There were neither significant changes of PAI-1, MCP-1, e-selectin and CRP after fructose (n=10) and glucose (n=10) intervention nor treatment effects (all P>0.2). Moreover, we did not observe longitudinal associations of the inflammatory parameters with triglycerides, liver fat, visceral fat and body weight in the fructose group. CONCLUSIONS: Temporary high-fructose intake does not seem to cause inflammation in apparently healthy people in this secondary analysis of a small feeding trial.

Altered brain activity in severely obese women may recover after Roux-en Y gastric bypass surgery.

OBJECTIVE: Neuroimaging studies have demonstrated alterations in brain activity in obese (OB) subjects that might be causally linked to their disorder. Roux-en Y gastric bypass (RYGB) surgery induces a marked and sustained weight loss and may affect brain activity. The aim of this study was to compare brain activity pattern between severely OB women (n=11), normal-weight women (NW, n=11) and previously severely OB women who had undergone RYGB surgery (RYGB, n=9) on average 3.4±0.8 years (all >1 year) before the experiment. DESIGN: Brain activity was assessed by functional magnetic resonance imaging during a one-back task containing food- and non-food-related pictures and during resting state. Hunger and satiety were repeatedly rated on a visual analog scale during the experiment. RESULTS: As compared with NW and also with RYGB women, OB women showed (1) a higher cerebellar and a lower fusiform gyrus activity during the visual stimulation independently of the picture category, (2) a higher hypothalamic activation during the presentation of low- vs high-caloric food pictures, (3) a higher hippocampal and cerebellar activity during the working memory task and (4) a stronger functional connectivity in frontal regions of the default mode network during resting state. There were no differences in brain activity between the NW and RYGB women, both during picture presentation and during resting state. RYGB women generally rated lower on hunger and higher on satiety, whereas there were no differences in these ratings between the OB and NW women. CONCLUSION: Data provide evidence for an altered brain activity pattern in severely OB women and suggest that RYGB surgery and/or the surgically induced weight loss reverses the obesity-associated alterations.

[Rare cause of recurrent hypoglycaemia in type 1 diabetes mellitus--case 6/2013]. / Seltene ursache rezidivierender hypoglykämien bei diabetes mellitus typ 1--fall 6/2013.

HISTORY AND ADMISSION FINDINGS: We report on a 44-year-old patient with type 1 diabetes who suffered from vomiting and diarrhoea for 10 days as well as episodes of recurrent hypoglycaemia with reduced insulin requirements. Medical history was remarkable for nasopharyngeal carcinoma that had been treated by radiation and chemotherapy five years earlier. INVESTIGATIONS: Laboratory results showed hyponatraemia, reduced free thyroxine with normal thyroid- stimulating hormone and diminished morning serum cortisol levels. Short synacthen test revealed inadequate stimulation of cortisol. Corticotropin-releasing hormone test showed a subnormal stimulation of cortisol with a strong increase of adrenocorticotropin. Besides, testosterone, luteinizing hormone and insulin- like growth factor-1 levels were reduced. The growth hormone-releasing hormone-arginine test revealed complete growth hormone deficiency. A MRI of the sella revealed no abnormalities in hypothalamus and pituitary gland. DIAGNOSIS, TREATMENT AND COURSE: Findings were consistent with panhypopituitarism following radiotherapy for nasopharyngeal carcinoma. A replacement therapy was started comprising hydrocortisone, L-thyroxine and testosterone. Accordingly, symptomatology improved. CONCLUSIONS: Obscure recurrent hypoglycaemia requires endocrinological tests to clarify possible underlying hypocortisolism.

Working memory-related brain activity is associated with outcome of lifestyle intervention.

OBJECTIVE: Lifestyle interventions including reduction of caloric intake are still the most pursued option to treat obesity. However, their outcome in terms of weight loss strongly differs between participants. In our study, we hypothesized that initial differences in brain activation in a food specific memory task are associated with weight change during a lifestyle intervention. DESIGN AND METHODS: Magnetic brain activity was recorded during a one-back visual memory task with food and nonfood pictures in 33 overweight and obese subjects before they underwent a lifestyle intervention. The intervention lasted 6 months and aimed for a reduction in daily caloric intake by 400 kcal. Body mass index (BMI) was determined before and after the intervention. RESULTS: Differences between outer tertiles representing people who increased their BMI by 1.4% ± 1.1% (non-responders) and who reduced their BMI by -6.9% ± 2.6% (responders) are reported. Neuronal activity was related to BMI change in sensor and source space. Non-responders showed higher activation in right inferior frontal and left occipital visual areas, whereas responders showed increased activation in right temporal areas including hippocampus and fusiform gyrus. CONCLUSIONS: Differences in the cerebral response during a food specific memory task indicate an altered cognitive control over food intake. These differences might determine the ability to eat less and successfully lose weight.

[Arthroscopically assisted therapy of avascular necrosis of the femoral head]. / Arthroskopisch gestützte Behandlung der aseptischen Hüftkopfnekrose.

OBJECTIVE: Preservation of the hip joint function by treatment of the avascular necrosis of the femoral head in adults or at least avoiding progression. INDICATIONS: Avascular necrosis of the femoral head in adults in Steinberg stages I-III. In patients with Steinberg stage IVa (subchondral collapse ≤ 15% of the articular surface, depression < 2 mm) hip joint salvage therapy in early stages of femoral head collapse. CONTRAINDICATIONS: Manifest osteoarthritis of the hip joint. Joint infection. Relative contraindications: subchondral collapse > 15% of the articular surface or depression > 2 mm (Steinberg stage IVb and above). Persisting risk factors for a progression of avascular necrosis (e.g., alcohol abuse, chemotherapy, local irradiation, high-dose cortisone therapy) and obesity (BMI > 40). SURGICAL TECHNIQUE: Arthroscopy of the hip joint in case of cartilage defects and/or potential collapse of the femoral head. Without collapse of the femoral head and absence of severe damage of the cartilage: core decompression using a guiding sleeve through a lateral approach (Steinberg II, III). Subsequently curettage of the necrotic area through a central drill hole and insertion of autogenic bone cylinders using an OATS harvester (Steinberg II b/c, III b/c). In Steinberg stage IVa, reconstruction of the outline of the femoral head is attempted by reduction of the impressed portion (under intraoperative fluoroscopy). POSTOPERATIVE MANAGEMENT: Limited weight bearing (10 kg) of the operated leg for 6 weeks. In cases of large necrotic defects located directly beneath the subchondral bone (Steinberg IIIc) as well as subchondral collapse with flattening of the femoral head (Steinberg IVa) limited weight bearing (10 kg) for 12 weeks. RESULTS: Early results of femoral head preserving therapy in 53 patients (56 hips, consecutively treated between June 2004 and December 2009) after 33 ± 20 months: success rate (no arthroplasty, no reoperation, no radiological progress associated with clinical symptoms) 86% for patients treated with Steinberg stages I-III. Failure of the head preserving therapy with concern to the mentioned criteria depending on the initial Steinberg stage: 0 (0%) for stage I, 2 (10%) for stage II, 3 (25%) for stage III, and 4 (31%) for stage IVa.