[Comprehensive nutrition therapy in hospitals - Wishful thinking or reality? A survey-based cross-sectional study of the nutritional therapy in hospitals of Baden-Württemberg]. / Flächendeckende Ernährungstherapie ­ Wunsch oder Wirklichkeit? Eine fragebogengestützte Querschnittsstudie zur ernährungstherapeutischen Versorgung in baden-württembergischen Krankenhäusern.

INTRODUCTION: Malnutrition is widespread in German hospitals, has a negative impact on therapeutic success and quality of life, and it leads to increasing costs. An individualized nutritional support by nutritional professionals in accordance with current guidelines was shown to reduce mortality of malnourished inpatients. Ideally, nutritional support is conducted by an interdisciplinary nutrition support team. Current data on the nutritional therapy in German hospitals is missing. METHODS: In order to ascertain the current status of nutritional support in hospitals in the federal state of Baden-Württemberg, clinic managements of all hospitals in Baden-Württemberg received an online questionnaire. Affiliated hospitals, specialist hospitals, as well as hospitals with less than 50 beds were excluded from the analysis. RESULTS: The response rate was 84% (n = 94). The presence of a nutrition support team was reported by 34% of the hospitals. Twelve percent of the hospitals meet the structural characteristic of the OPS Code 8-98j Ernährungsmedizinische Komplexbehandlung, which means that their nutrition support team includes a physician. A validated nutritional risk screening is performed in 72% of the hospitals. Only 40% of the hospitals report that this is performed throughout every department. Nutrition support teams are more often concerned with malnutrition, enteral and parenteral nutrition as compared to nutritionists who are not organized in a team. Moreover, nutrition support teams have a wider range of tasks and more often a physician as a team member. Also, nutritional risk screenings are more often applied in hospitals with nutrition support teams. DISCUSSION: Compared with a nationwide survey from 2004, there are markedly more nutrition support teams available in hospitals in Baden-Württemberg. When compared internationally, however, the rate of nutrition support teams is still low. In addition, there is no comprehensive nutritional care available. High-quality nutritional support is more often found in hospitals with nutrition support teams. CONCLUSION: There is still a great potential of improving clinical nutritional care in hospitals in Baden-Württemberg. Moreover, an increase in nutrition support teams, also comprising medical members, should be achieved. Therefore, legal regulations and a sufficient refinancing are indispensable.

Empagliflozin Improves Insulin Sensitivity of the Hypothalamus in Humans With Prediabetes: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial.

OBJECTIVE: Insulin action in the human brain reduces food intake, improves whole-body insulin sensitivity, and modulates body fat mass and its distribution. Obesity and type 2 diabetes are often associated with brain insulin resistance, resulting in impaired brain-derived modulation of peripheral metabolism. So far, no pharmacological treatment for brain insulin resistance has been established. Since sodium-glucose cotransporter 2 (SGLT2) inhibitors lower glucose levels and modulate energy metabolism, we hypothesized that SGLT2 inhibition may be a pharmacological approach to reverse brain insulin resistance. RESEARCH DESIGN AND METHODS: In this randomized, double-blind, placebo-controlled clinical trial, 40 patients (mean ± SD; age 60 ± 9 years; BMI 31.5 ± 3.8 kg/m2) with prediabetes were randomized to receive 25 mg empagliflozin every day or placebo. Before and after 8 weeks of treatment, brain insulin sensitivity was assessed by functional MRI combined with intranasal administration of insulin to the brain. RESULTS: We identified a significant interaction between time and treatment in the hypothalamic response to insulin. Post hoc analyses revealed that only empagliflozin-treated patients experienced increased hypothalamic insulin responsiveness. Hypothalamic insulin action significantly mediated the empagliflozin-induced decrease in fasting glucose and liver fat. CONCLUSIONS: Our results corroborate insulin resistance of the hypothalamus in humans with prediabetes. Treatment with empagliflozin for 8 weeks was able to restore hypothalamic insulin sensitivity, a favorable response that could contribute to the beneficial effects of SGLT2 inhibitors. Our findings position SGLT2 inhibition as the first pharmacological approach to reverse brain insulin resistance, with potential benefits for adiposity and whole-body metabolism.

No modulation of postprandial metabolism by transcutaneous auricular vagus nerve stimulation: a cross-over study in 15 healthy men.

Experimental evidence suggests a crucial role of the autonomic nervous system in whole body metabolism with major regulatory effects of the parasympathetic branch in postprandial adaptation. However, the relative contribution of this mechanism is still not fully clear in humans. We therefore compared the effects of transcutaneous auricular vagus nerve stimulation (taVNS, Cerbomed Nemos) with sham stimulation during an oral glucose tolerance test in a randomized, single-blind, cross-over design in 15 healthy lean men. Stimulation was performed for 150 min, 30 min before and during the entire oral glucose tolerance test with stimulation cycles of 30 s of on-phase and 30 s of off-phase and a 25 Hz impulse. Heart rate variability and plasma catecholamine levels were assessed as proxies of autonomic tone in the periphery. Neither analyzed heart rate variability parameters nor plasma catecholamine levels were significantly different between the two conditions. Plasma glucose, insulin sensitivity and insulin secretion were also comparable between conditions. Thus, the applied taVNS device or protocol was unable to achieve significant effects on autonomic innervation in peripheral organs. Accordingly, glucose metabolism remained unaltered. Therefore, alternative approaches are necessary to investigate the importance of the autonomic nervous system in postprandial human metabolism.

Insulin Action in the Hypothalamus Increases Second-Phase Insulin Secretion in Humans.

BACKGROUND: Animal studies and initial correlative data in humans indicate that insulin action in the brain may affect pancreatic insulin secretion. An important brain region for this process is the hypothalamus, an area that can develop insulin resistance. METHODS: Fifteen young, healthy men (27 ± 3 years) with a wide BMI spectrum (20-30 kg/m2) underwent 2 hyperglycemic clamps (target blood glucose: 10 mmol/L). In this double-blind study, subjects received 160 U of insulin or placebo as a nasal spray on 2 days in randomized order. On another day, insulin sensitivity of the hypothalamus was determined by functional magnetic resonance imaging. RESULTS: Glucose levels were comparable on both study days. In the whole group, C-peptide levels were not significantly different between conditions. Though, there was a significant interaction between insulin sensitivity of the hypothalamus × nasal spray × time on C-peptide levels (p = 10-6). The group was therefore divided according to median hypothalamic insulin sensitivity. C-peptide concentrations were higher after intranasal insulin compared to placebo spray in the group with a strong hypothalamic insulin response (p < 0.0001, ß = 6.00 ± 1.24) and lower in the brain insulin-resistant group (p = 0.005, ß = -2.68 ± 0.95). Neither somatostatin nor glucagon kinetics was altered by the nasal spray. CONCLUSIONS: In participants with high hypothalamic insulin sensitivity, insulin action in the brain enhanced second-phase insulin secretion from pancreatic beta cells. This reaction could, for example, contribute to late postprandial glucose regulation by suppressing hepatic glucose production by portal venous insulin.

Dietary Niacin Intake Predicts the Decrease of Liver Fat Content During a Lifestyle Intervention.

Niacin inhibits fatty acid flux from adipose tissue to liver, reduces hepatic triglyceride synthesis and increases hepatic lipid oxidation. Thus, niacin may have a role in the regulation of liver fat content in humans. We tested if dietary intake of niacin predicts change of liver fat content during a lifestyle intervention. To this end, we estimated the composition of diet from diaries of 202 healthy subjects at risk of type 2 diabetes undergoing lifestyle intervention comprising physical activity and diet counselling. Total-, subcutaneous- and visceral adipose tissue mass were measured by magnetic resonance (MR) tomography and liver fat content by 1H-MR spectroscopy at baseline and after 9 months of follow-up. Among fat compartments, liver fat content showed the largest decrease (-32%, p < 0.0001). High baseline niacin intake predicted a larger decrease of liver fat (p = 0.004). Subjects in the highest quartile of niacin intake at baseline also had the largest decrease of liver fat (1st:-10%; 2nd:-27%; 3rd:-35%; 4th:-37%). Among 58 subjects with nonalcoholic fatty liver disease (NAFLD) at baseline, NAFLD resolved in 23 subjects during the lifestyle intervention. For one standard deviation increase in niacin intake, the odds ratio for resolution of NAFLD was 1.77 (95% CI, 1.00-3.43). High dietary niacin intake may have a favorable effect on the reduction of liver fat during lifestyle intervention.

Preadipocytes of obese humans display gender-specific bioenergetic responses to glucose and insulin.

BACKGROUND/OBJECTIVES: Although the prevalence of obesity and its associated metabolic disorders is increasing in both sexes, the clinical phenotype differs between men and women, highlighting the need for individual treatment options. Mitochondrial dysfunction in various tissues, including white adipose tissue (WAT), has been accepted as a key factor for obesity-associated comorbidities such as diabetes. Given higher expression of mitochondria-related genes in the WAT of women, we hypothesized that gender differences in the bioenergetic profile of white (pre-) adipocytes from obese (age- and BMI-matched) donors must exist. SUBJECTS/METHODS: Using Seahorse technology, we measured oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) of (pre-)adipocytes from male (n = 10) and female (n = 10) deeply-phenotyped obese donors under hypo-, normo- and hyperglycemic (0, 5 and 25 mM glucose) and insulin-stimulated conditions. Additionally, expression levels (mRNA/protein) of mitochondria-related genes (e.g. UQCRC2) and glycolytic enzymes (e.g. PKM2) were determined. RESULTS: Dissecting cellular OCR and ECAR into different functional modules revealed that preadipocytes from female donors show significantly higher mitochondrial to glycolytic activity (higher OCR/ECAR ratio, p = 0.036), which is supported by a higher ratio of UQCRC2 to PKM2 mRNA levels (p = 0.021). However, no major gender differences are detectable in in vitro differentiated adipocytes (e.g. OCR/ECAR, p = 0.248). Importantly, glucose and insulin suppress mitochondrial activity (i.e. ATP-linked respiration) significantly only in preadipocytes of female donors, reflecting their trends towards higher insulin sensitivity. CONCLUSIONS: Collectively, we show that preadipocytes, but not in vitro differentiated adipocytes, represent a model system to reveal gender differences with clinical importance for metabolic disease status. In particular preadipocytes of females maintain enhanced mitochondrial flexibility, as demonstrated by pronounced responses of ATP-linked respiration to glucose.

Treatment of malnutrition decreases complication rates and shortens the length of hospital stays in a radiation oncology department.

PURPOSE: The nutritional status of inpatients influences the therapeutic outcome. Malnutrition is a common comorbidity in oncological patients. Both radio- and radiochemotherapy may contribute to the additional deterioration of the nutritional status. The aim of this study was to evaluate the impact of specialized treatment of malnutrition as a clinical routine. METHODS: The nutritional status of inpatients was assessed by the Nutritional risk screening (NRS-2002) on the day of admission to the University Department of Radiation Oncology. In case of significantly elevated NRS-2002 (NRS ≥ 3), a guideline-compliant, individual nutritional treatment was initiated by a specialized nutrition support team. The influence of the nutritional status and nutritional treatment on length of stay and complication rate was assessed. RESULTS: Of 840 included patients, 344 patients (40.95%) were at risk for malnutrition. Malnutrition was a significant, independent risk factor for both prolonged hospital stay, represented by the deviation between the actual length of stay and the DRG-associated mean length of stay (dLOS at risk: 0.88 days, dLOS not at risk: -0.88 days, p = 0.0047), as well as for the occurrence of complications (OR: 1.758 CI: [1.286-2.402], p = 0.0006). In the group of 337 (40.12%) rehospitalized patients the nutritional management was able to assimilate the values of length of stay as well as the complication rates to standard values. CONCLUSIONS: The high risk for malnutrition and the negative consequences for patients and hospitals underline the urgent need for malnutrition screening on admission and treatment of malnutrition. A specialized, interdisciplinary nutrition support team positively influences patient outcome and should be established routinely in all oncological disciplines.

Effects of resveratrol supplementation on liver fat content in overweight and insulin-resistant subjects: A randomized, double-blind, placebo-controlled clinical trial.

We performed the largest randomized, placebo-controlled clinical trial to date (N = 112, 12-week intervention) to investigate the effects and safety of resveratrol supplementation on liver fat content and cardiometabolic risk parameters in overweight and obese and insulin-resistant subjects. At baseline the variability in liver fat content was very large, ranging from 0.09% to 37.55% (median, 7.12%; interquartile range, 3.85%-12.94%). Mean (SD) liver fat content was 9.22 (6.85) % in the placebo group and 9.91 (7.76) % in the resveratrol group. During the study liver fat content decreased in the placebo group (-0.7%) but not in the resveratrol group (-0.03%) (differences between groups: P = .018 for the intention-to-treat [ITT] population; N = 54, resveratrol, N = 54, placebo and P = .0077 for the per protocol [PP] population). No effects of resveratrol supplementation on cardiometabolic risk parameters were observed. Resveratrol supplementation was well tolerated and safe. In conclusion, these data suggest that resveratrol supplementation is safe and that it does not considerably impact liver fat content or cardiometabolic risk parameters in humans.

Leptin Replacement Reestablishes Brain Insulin Action in the Hypothalamus in Congenital Leptin Deficiency.

OBJECTIVE: Human obesity is associated with impaired central insulin signaling, and in very rare cases, severe obesity can be caused by congenital leptin deficiency. In such patients, leptin replacement results in substantial weight loss and improvement in peripheral metabolism. RESEARCH DESIGN AND METHODS: In a leptin-deficient patient, we investigated the impact of leptin substitution on central insulin action, as quantified by changes in neuronal activity after intranasal insulin application. This was assessed before and during the first year of metreleptin substitution. RESULTS: After only 1 year, treatment with metreleptin reestablishes brain insulin sensitivity, particularly in the hypothalamus and, to a lesser degree, in the prefrontal cortex. Results are depicted in comparison with a control group. In our patient, brain activation changes were accompanied by substantial weight loss, reduced visceral adipose tissue, reduced intrahepatic lipid content, and improved whole-body insulin sensitivity. CONCLUSIONS: Leptin replacement and weight loss improved homeostatic insulin action in the patient in question.

Detection thresholds for four different fatty stimuli are associated with increased dietary intake of processed high-caloric food.

BMI-specific differences in food choice and energy intake have been suggested to modulate taste perception. However, associations between body composition and fat taste sensitivity are controversial. The objective of this study was to examine the association between body composition, dietary intake and detection thresholds of four fatty stimuli (oleic acid, paraffin oil, canola oil, and canola oil spiked with oleic acid) that could be perceived via gustatory and/or textural cues. In 30 participants, fat detection thresholds were determined in a repeated measurements design over twelve days. Weight status was examined by measuring the participants' BMI, waist circumference and waist-to-hip ratio. The habitual food intake was assessed via several questionnaires and twelve, non-consecutive 24-hour food diaries. In this study, a negative correlation was found between fat detection thresholds and the intake of food rich in vitamins and fibre. Moreover, a positive correlation was identified between the intake of high-fat food and fat detection thresholds. No differences in fat detection thresholds were observed due to variations in BMI or waist-to-hip ratio. These findings indicate that a regular intake of fatty foods might decrease an individuals' perceptual response to fats which might lead to excess fat intake on the long term.

Oil Perception-Detection Thresholds for Varying Fatty Stimuli and Inter-individual Differences.

Multiple lines of research have demonstrated that humans can perceive fat in the form of free fatty acids (FFAs). However, the dietary concentration of FFAs is generally very low and fat is mainly consumed as triacylglycerol (TAG). The aim of this study was to examine the perception of different fatty stimuli and possible associations between them. Therefore, detection thresholds for 4 fatty stimuli (oleic acid [FFA], paraffin oil [mixture of hydrocarbon molecules], canola oil [TAG-rich], and canola oil spiked with oleic acid [rich in TAGs and FFAs]) were determined in 30 healthy participants. Additionally, inter-individual differences in fat perception were examined. It was observed that oleic acid was perceivable at significantly lower concentrations than all other stimuli (P < 0.001). Similarly, canola oil with oleic acid was detectable at lower concentrations than canola oil alone (P < 0.001). Moreover, canola oil detection thresholds were significantly lower than paraffin oil detection thresholds (P = 0.017). Participants who were sensitive for low concentrations for oleic acid showed lower detection thresholds for canola oil with and without oleic acid, compared with participants that were less sensitive for oleic acid. The results of this study demonstrate that the higher the concentrations of FFAs in the stimuli, the lower the individual fat detection threshold. Moreover, participants being sensitive for lower concentrations of FFAs are also more likely to detect low concentrations of TAG-rich fats as it is found in the human diet.

Hypothalamic insulin responsiveness is associated with pancreatic insulin secretion in humans.

CONTEXT: Activity of the hypothalamus - the major brain area controlling peripheral metabolism - is specifically modulated by insulin. Research in animals suggests that brain insulin action influences pancreatic insulin secretion. OBJECTIVE: We investigated the association between hypothalamic insulin sensitivity and pancreatic insulin secretion in humans. DESIGN AND SETTING: This was a clinical-experimental trial in an university hospital setting. PARTICIPANTS: 48 healthy volunteers (21 women and 27 men) were included. MAIN OUTCOME MEASURES: Insulin sensitivity of the hypothalamus was quantified by cerebral blood flow (CBF) using MRI in combination with intranasal insulin administration. On a different day, a 75g oral glucose tolerance test with glucose, insulin, and C-peptide levels measured at five time points was performed. Three established insulin secretion indices (insulinogenic index [IGI], corrected insulin response [CIR], and AUCC-peptide0-30/AUCglucose0-30) were then analyzed for correlations with hypothalamic insulin sensitivity independent of whole-body insulin sensitivity. RESULTS: Hypothalamic insulin sensitivity showed a significant association with all three investigated insulin secretion indices (IGI p=0.0043; CIR p=0.06; AUCCpep0-30/AUCgluc0-30 p=0.0179). Participants with a strong hypothalamic insulin effect (i.e. decreased CBF after intranasal insulin administration) had lower insulin secretion during the OGTT, whereas participants with hypothalamic insulin resistance had substantially higher insulin secretion. No correlations with the occipital cortex, a control region, were detected. CONCLUSIONS: Our data suggest that hypothalamic insulin resistance might contribute to pancreatic insulin hypersecretion. Alternatively, common pathogenetic mechanisms could introduce both brain insulin resistance and beta cell hypersecretion.

Hypothalamic and Striatal Insulin Action Suppresses Endogenous Glucose Production and May Stimulate Glucose Uptake During Hyperinsulinemia in Lean but Not in Overweight Men.

Intranasal spray application facilitates insulin delivery to the human brain. Although brain insulin modulates peripheral metabolism, the mechanisms involved remain elusive. Twenty-one men underwent two hyperinsulinemic-euglycemic clamps with d-[6,6-2H2]glucose infusion to measure endogenous glucose production and glucose disappearance. On two separate days, participants received intranasal insulin or placebo. Insulin spillover into circulation after intranasal insulin application was mimicked by an intravenous insulin bolus on placebo day. On a different day, brain insulin sensitivity was assessed by functional MRI. Glucose infusion rates (GIRs) had to be increased more after nasal insulin than after placebo to maintain euglycemia in lean but not in overweight people. The increase in GIRs was associated with regional brain insulin action in hypothalamus and striatum. Suppression of endogenous glucose production by circulating insulin was more pronounced after administration of nasal insulin than after placebo. Furthermore, glucose uptake into tissue tended to be higher after nasal insulin application. No such effects were detected in overweight participants. By increasing insulin-mediated suppression of endogenous glucose production and stimulating peripheral glucose uptake, brain insulin may improve glucose metabolism during systemic hyperinsulinemia. Obese people appear to lack these mechanisms. Therefore, brain insulin resistance in obesity may have unfavorable consequences for whole-body glucose homeostasis.

Potential Predictors of Plasma Fibroblast Growth Factor 23 Concentrations: Cross-Sectional Analysis in the EPIC-Germany Study.

BACKGROUND: Increased fibroblast growth factor 23 (FGF23), a bone-derived hormone involved in the regulation of phosphate and vitamin D metabolism, has been related to the development of cardiovascular disease (CVD) in chronic kidney disease patients and in the general population. However, what determines higher FGF23 levels is still unclear. Also, little is known about the influence of diet on FGF23. The aim of this study was therefore to identify demographic, clinical and dietary correlates of high FGF23 concentrations in the general population. METHODS: We performed a cross-sectional analysis within a randomly selected subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany comprising 2134 middle-aged men and women. The Human FGF23 (C-Terminal) ELISA kit was used to measure FGF23 in citrate plasma. Dietary data were obtained at baseline via validated food frequency questionnaires including up to 148 food items. RESULTS: Multivariable adjusted logistic regression showed that men had a 66% lower and smokers a 64% higher probability of having higher FGF23 (≥ 90 RU/mL) levels compared, respectively, with women and nonsmokers. Each doubling in parathyroid hormone, creatinine, and C-reactive protein was related to higher FGF23. Among the dietary factors, each doubling in calcium and total energy intake was related, respectively, to a 1.75 and to a 4.41 fold increased probability of having higher FGF23. Finally, each doubling in the intake of iron was related to an 82% lower probability of having higher FGF23 levels. Results did not substantially change after exclusion of participants with lower kidney function. CONCLUSIONS: In middle-aged men and women traditional and non-traditional CVD risk factors were related to higher FGF23 concentrations. These findings may contribute to the understanding of the potential mechanisms linking increased FGF23 to increased CVD risk.

Selective insulin resistance in homeostatic and cognitive control brain areas in overweight and obese adults.

OBJECTIVE: Impaired brain insulin action has been linked to obesity, type 2 diabetes, and neurodegenerative diseases. To date, the central nervous effects of insulin in obese humans still remain ill defined, and no study thus far has evaluated the specific brain areas affected by insulin resistance. RESEARCH DESIGN AND METHODS: In 25 healthy lean and 23 overweight/obese participants, we performed magnetic resonance imaging to measure cerebral blood flow (CBF) before and 15 and 30 min after application of intranasal insulin or placebo. Additionally, participants explicitly rated pictures of high-caloric savory and sweet food 60 min after the spray for wanting and liking. RESULTS: In response to insulin compared with placebo, we found a significant CBF decrease in the hypothalamus in both lean and overweight/obese participants. The magnitude of this response correlated with visceral adipose tissue independent of other fat compartments. Furthermore, we observed a differential response in the lean compared with the overweight/obese group in the prefrontal cortex, resulting in an insulin-induced CBF reduction in lean participants only. This prefrontal cortex response significantly correlated with peripheral insulin sensitivity and eating behavior measures such as disinhibition and food craving. Behaviorally, we were able to observe a significant reduction for the wanting of sweet foods after insulin application in lean men only. CONCLUSIONS: Brain insulin action was selectively impaired in the prefrontal cortex in overweight and obese adults and in the hypothalamus in participants with high visceral adipose tissue, potentially promoting an altered homeostatic set point and reduced inhibitory control contributing to overeating behavior.

Resting-state functional connectivity of the human hypothalamus.

The hypothalamus is of enormous importance for multiple bodily functions such as energy homeostasis. Especially, rodent studies have greatly contributed to our understanding how specific hypothalamic subregions integrate peripheral and central signals into the brain to control food intake. In humans, however, the neural circuitry of the hypothalamus, with its different subregions, has not been delineated. Hence, the aim of this study was to map the hypothalamus network using resting-state functional connectivity (FC) analyses from the medial hypothalamus (MH) and lateral hypothalamus (LH) in healthy normal-weight adults (n = 49). Furthermore, in a separate sample, we examined differences within the LH and MH networks between healthy normal-weight (n = 25) versus overweight/obese adults (n = 23). FC patterns from the LH and MH revealed significant connections to the striatum, thalamus, brainstem, orbitofrontal cortex, middle and posterior cingulum and temporal brain regions. However, our analysis revealed subtler distinctions within hypothalamic subregions. The LH was functionally stronger connected to the dorsal striatum, anterior cingulum, and frontal operculum, while the MH showed stronger functional connections to the nucleus accumbens and medial orbitofrontal cortex. Furthermore, overweight/obese participants revealed heightened FC in the orbitofrontal cortex and nucleus accumbens within the MH network. Our results indicate that the MH and LH network are tapped into different parts of the dopaminergic circuitry of the brain, potentially modulating food reward based on the functional connections to the ventral and dorsal striatum, respectively. In obese adults, FC changes were observed in the MH network.

Evaluation of various biomarkers as potential mediators of the association between coffee consumption and incident type 2 diabetes in the EPIC-Potsdam Study.

BACKGROUND: The inverse association between coffee consumption and the risk of type 2 diabetes (T2D) is well established; however, little is known about potential mediators of this association. OBJECTIVE: We aimed to investigate the association between coffee consumption and diabetes-related biomarkers and their potential role as mediators of the association between coffee consumption and T2D. DESIGN: We analyzed a case-cohort study (subcohort: n = 1610; verified incident T2D cases: n = 417) nested within the European Prospective Investigation into Cancer and Nutrition-Potsdam study involving 27,548 middle-aged participants. Habitual coffee consumption was assessed with a validated, semiquantitative food-frequency questionnaire. We evaluated the association between coffee consumption and several T2D-related biomarkers, such as liver markers (reflected by γ-glutamyltransferase, fetuin-A, and sex hormone-binding globulin), markers of dyslipidemia (high-density lipoprotein cholesterol and triglycerides), inflammation [C-reactive protein (CRP)], an adipokine (adiponectin), and metabolites, stratified by sex. RESULTS: Coffee consumption was inversely associated with diacyl-phosphatidylcholine C32:1 in both sexes and with phenylalanine in men, as well as positively associated with acyl-alkyl-phosphatidylcholines C34:3, C40:6, and C42:5 in women. Furthermore, coffee consumption was inversely associated with fetuin-A (P-trend = 0.06) and CRP in women and γ-glutamyltransferase and triglycerides in men. Coffee consumption tended to be inversely associated with T2D risk in both sexes, reaching significance only in men [HR (95% CI): women: ≥4 compared with >0 to <2 cups coffee/d: 0.78 (0.46, 1.33); men: ≥5 compared with >0 to <2 cups coffee/d: 0.40 (0.19, 0.81)]. The association between coffee consumption and T2D risk in men was slightly reduced after adjustment for phenylalanine or lipid markers. CONCLUSIONS: Coffee consumption was inversely associated with a diacyl-phosphatidylcholine and liver markers in both sexes and positively associated with certain acyl-alkyl-phosphatidylcholines in women. Furthermore, coffee consumption showed an inverse trend with CRP in women and with triglycerides and phenylalanine in men. However, these markers explained only to a small extent the inverse association between long-term coffee consumption and T2D risk.

Central insulin administration improves whole-body insulin sensitivity via hypothalamus and parasympathetic outputs in men.

Animal studies suggest that insulin action in the brain is involved in the regulation of peripheral insulin sensitivity. Whether this holds true in humans is unknown. Using intranasal application of insulin to the human brain, we studied the impacts of brain insulin action on whole-body insulin sensitivity and the mechanisms involved in this process. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic glucose clamp before and after intranasal application of insulin and placebo in randomized order in lean and obese men. After insulin spray application in lean subjects, a higher glucose infusion rate was necessary to maintain euglycemia compared with placebo. Accordingly, clamp-derived insulin sensitivity index improved after insulin spray. In obese subjects, this insulin-sensitizing effect could not be detected. Change in the high-frequency band of heart rate variability, an estimate of parasympathetic output, correlated positively with change in whole-body insulin sensitivity after intranasal insulin. Improvement in whole-body insulin sensitivity correlated with the change in hypothalamic activity as assessed by functional magnetic resonance imaging. Intranasal insulin improves peripheral insulin sensitivity in lean but not in obese men. Furthermore, brain-derived peripheral insulin sensitization is associated with hypothalamic activity and parasympathetic outputs. Thus, the findings provide novel insights into the regulation of insulin sensitivity and the pathogenesis of insulin resistance in humans.

Olive oil aroma extract modulates cerebral blood flow in gustatory brain areas in humans.

BACKGROUND: Low- and high-fat meals affect homeostatic and gustatory brain areas differentially. In a previous study, we showed that a high-fat meal decreased cerebral blood flow (CBF) in homeostatic brain areas (hypothalamus), whereas a low-fat meal increased CBF in gustatory regions (anterior insula). OBJECTIVE: The aim of this study was to investigate the long-lasting effect of fat-free flavor-active compounds of olive oil on the brain and whether those aroma components can trigger fat-associated brain responses in homeostatic and gustatory regions. DESIGN: Eleven healthy male subjects participated in a functional magnetic resonance imaging study. On 2 measurement days, subjects consumed single-blinded a plain low-fat yogurt or low-fat yogurt mixed with a fat-free aroma extract of olive oil. Resting CBF was measured before and 30 and 120 min after yogurt intake. Hunger was rated before each measurement. Blood samples were collected at 6 time points. RESULTS: The extract-containing yogurt elicited higher CBF in the frontal operculum 30 and 120 min after a meal. Furthermore, the activity change in the anterior insula after 30 min correlated positively with the glucose change in the extract condition only. No effects were observed in the hypothalamus. CONCLUSIONS: The anterior insula and the frontal operculum are regarded as the primary taste cortex. Modulation of the frontal operculum by the yogurt containing the olive oil extract suggests that it might be possible to simulate fat-triggered sensations in the brain on the gustatory level, possibly by ingredients the body implicitly associates with fat. This trial was registered at clinicaltrials.gov as NCT01716286.