Gastrointestinal Hormones in Healthy Adults: Reliability of Repeated Assessments and Interrelations with Eating Habits and Physical Activity.

Background: Gastrointestinal hormones (GIHs) are crucial for the regulation of a variety of physiological functions and have been linked to hunger, satiety, and appetite control. Thus, they might constitute meaningful biomarkers in longitudinal and interventional studies on eating behavior and body weight control. However, little is known about the physiological levels of GIHs, their intra-individual stability over time, and their interaction with other metabolic and lifestyle-related parameters. Therefore, the aim of this pilot study is to investigate the intra-individual stability of GIHs in normal-weight adults over time. Methods: Plasma concentrations of ghrelin, leptin, GLP-1 (glucagon-like-peptide), and PP (pancreatic polypeptide) were assessed by enzyme-linked immunosorbent assay (ELISA) in 17 normal-weight, healthy adults in a longitudinal design at baseline and at follow-up six months later. The reliability of the measurements was estimated using intra-class correlation (ICC). In a second step, we considered the stability of GIH levels after controlling for changes in blood glucose and hemoglobin A1 (HbA1c) as well as self-reported physical activity and dietary habits. Results: We found excellent reliability for ghrelin, good reliability for GLP1 and PP, and moderate reliability for leptin. After considering glucose, HbA1c, physical activity, and dietary habits as co-variates, the reliability of ghrelin, GLP1, and PP did not change significantly; the reliability of leptin changed to poor reliability. Conclusions: The GIHs ghrelin, GLP1, and PP demonstrated good to excellent test-retest reliability in healthy individuals, a finding that was not modified after adjusting for glucose control, physical activity, or dietary habits. Leptin showed only moderate to poor reliability, which might be linked to weight fluctuations, albeit small, between baseline and follow-up assessment in our study sample. Together, these findings support that ghrelin, GLP1, and PP might be further examined as biomarkers in studies on weight control, with GLP1 and PP serving as anorexic markers and ghrelin as an orexigenic marker. Additional reliability studies in obese individuals are necessary to verify or refute our findings for this cohort.

Supraphysiological effects of pancreatic polypeptide on gastric motor function and nutrient tolerance in humans.

Pancreatic polypeptide (PP) is known to affect food intake. In this exploratory study, we set out to investigate its supraphysiological effect on food tolerance, gastric accommodation, and emptying. In 12 healthy volunteers, 0, 3, or 10 pmol*kg-1 *min-1 PP was administered intravenously (PP0, PP3 or PP10). Thirty minutes thereafter, nutrient drink infusion (60 ml*min-1 ) through a nasogastric feeding tube was started until maximum satiation. Gastric accommodation was assessed by measuring the intragastric pressure (IGP; nasogastric manometry). In a separate test, the effect of PP0 or PP10 on gastric emptying was tested in 10 healthy volunteers and assessed using the 13 C breath test. Results are presented as mean ± SEM, and p < 0.05 was considered significant. For the IGP test, PP increased ingested nutrient volume: 886 ± 93, 1059 ± 124, and 1025 ± 125 ml for PP0, PP3, and PP10, respectively (p = 0.048). In all groups, Nadir IGP values were reached upon food intake (transformed values: 1.5 ± 0.2, 1.7 ± 0.3, and 1.6 ± 0.3 mmHg for PP0, PP3, and PP10, respectively; NS) to return to baseline thereafter. For the gastric emptying study, volunteers ingested a similar nutrient volume: 802 ± 119 and 1089 ± 128 ml (p = 0.016), and gastric half-emptying time was 281 ± 52 and 249 ± 37 min for PP0 and PP10, respectively (NS). No significant correlation between tolerated nutrient volume and IGP drop (R² < 0.01; p = 0.88 for PP0 vs. PP3 and R² =0.07; p = 0.40 for PP0 vs. PP10, respectively) or gastric half-emptying time (R² = 0.12; p = 0.32) was found. A supraphysiological PP dose enhances food tolerance; however, this effect is not mediated through gastric motility. CLINICAL TRIAL REGISTRY NUMBER: NCT03854708 is obtained from clinicaltrials.gov.

Urinary Dopamine Excretion Rate Decreases during Acute Dietary Protein Deprivation and Is Associated with Increased Plasma Pancreatic Polypeptide Concentration.

Background: Dopamine, a key neurotransmitter in the autonomic nervous system participating in the homeostatic balance between sympathetic and parasympathetic divisions, is involved in food intake regulation. Objective: We investigated whether dopamine is altered by acute fasting or overfeeding diets with varying macronutrient content. Design: Ninety-nine healthy subjects underwent 24-h dietary interventions including eucaloric feeding, fasting, and five different overfeeding diets in a crossover design. Overfeeding diets (200% of eucaloric requirements) included one diet with 3%-protein (low-protein high-fat overfeeding-LPF: 46%-fat), three diets with 20%-protein, and a diet with 30%-protein (44%-fat). Urine was collected for 24 h and urinary dopamine concentration was quantified by high-performance liquid chromatography. Plasma pancreatic polypeptide (PP) concentration, an indirect marker of parasympathetic activity, was measured prior to and after each diet after an overnight fast. Results: During 24-h of fasting, dopamine decreased on average by ~14% compared to eucaloric conditions, whereas PP increased by two-fold (both p < 0.001). Lower dopamine during 24-h fasting correlated with increased PP (r = -0.40, p < 0.001). Similarly, on average urinary dopamine decreased during LPF by 14% (p < 0.001) and lower dopamine correlated with increased PP (r = -0.31, p = 0.01). No changes in dopamine and PP concentrations were observed during other overfeeding diets (all p > 0.05). Conclusions: Dopamine concentrations decrease during short-term fasting and overfeeding with a low-protein diet. As both dietary conditions have in common protein deficit, the correlation between dopamine and PP suggests a compensatory mechanism underlying the shift from sympathetic to parasympathetic drive during dietary protein deprivation.

Effect of Acute Sprint Exercise on Myokines and Food Intake Hormones in Young Healthy Men.

Physical exercise is known to influence hormonal mediators of appetite, but the effect of short-term maximal intensity exercise on plasma levels of appetite hormones and cytokines has been little studied. We investigated the effect of a 30 s Wingate Test, followed by a postprandial period, on appetite sensations, food intake, and appetite hormones. Twenty-six physically active young males rated their subjective feelings of hunger, prospective food consumption, and fatigue on visual analogue scales at baseline, after exercise was completed, and during the postprandial period. Blood samples were obtained for the measurement of nesfatin-1, ghrelin, leptin, insulin, pancreatic polypeptide (PP), human growth factor (hGH) and cytokine interleukin-6 (IL-6), irisin and plasma lactate concentrations, at 30 min before exercise, immediately (210 s) after exercise, and 30 min following a meal and at corresponding times in control sedentary males without ad libitum meal intake, respectively. Appetite perceptions and food intake were decreased in response to exercise. Plasma levels of irisin, IL-6, lactate, nesfatin-1 and ghrelin was increased after exercise and then it was returned to postprandial/control period in both groups. A significant rise in plasma insulin, hGH and PP levels after exercise was observed while meal intake potentiated this response. In conclusion, an acute short-term fatiguing exercise can transiently suppress hunger sensations and food intake in humans. We postulate that this physiological response involves exercise-induced alterations in plasma hormones and the release of myokines such as irisin and IL-6, and supports the notion of existence of the skeletal muscle-brain-gut axis. Nevertheless, the detailed relationship between acute exercise releasing myokines, appetite sensations and impairment of this axis leading to several diseases should be further examined.

Plasma Protein Panels for Mild Cognitive Impairment Among Elderly Chinese Individuals with Different Educational Backgrounds.

To explore plasma protein panels as potential biomarkers to screen for mild cognitive impairment (MCI) among elderly Chinese individuals with different educational backgrounds. Forty-four illiterate, 36 lower education (1-6 years), and 55 higher education (7 years or more) elderly individuals were included in the present study. Among all subjects, 67 were healthy individuals and 68 were diagnosed with MCI. Fifty plasma proteins in blood samples collected from these subjects were analyzed via the Luminex assay. Binary logistic regression was utilized to explore diagnostic models for MCI among the three educational subgroups. Then, receiver operating characteristic (ROC) curves were conducted for the clinical validity of the MCI models. Among the analyzed proteins, clusterin was used in the model of MCI among the total sample with a sensitivity (se) of 67.6%, a specificity (sp) of 59.7%, and a classification rate of 63.68%. The MCI model for the illiterate group included cystatin C, plasminogen activator inhibitor-1, and apolipoprotein A-I (se: 71.4%, sp.: 82.6%, accuracy: 77.25%). The sensitivity, specificity, and classification rate of the diagnostic model of MCI in elderly adults with lower education (human serum albumin) were each 75.0%. Additionally, the sensitivity, specificity, and accuracy rate of the diagnostic model for MCI elderly individuals with higher education (alpha-acid glycoprotein + soluble intercellular adhesion molecule-1 + pancreatic polypeptide) were 77.8%, 89.3%, and 83.60%, respectively. The performance of diagnostic models for MCI based on different educational levels is superior to that of diagnostic models for MCI without grouping by educational level.

A novel method of sacral nerve stimulation for colonic inflammation.

BACKGROUND: Vagal nerve stimulation has been reported to treat inflammation with promising results. The aims of our study were to optimize sacral nerve stimulation (SNS) methodologies for colonic inflammation in a rodent model of colitis and to investigate autonomic and cytokine mechanisms. METHODS: Three major efforts were made in optimizing SNS: (a) to determine the best stimulation duration: SNS-0.5h daily, SNS-1h daily, and SNS-3h daily with the parameters set at 5 Hz, 10 seconds on, 90 seconds off; (b) to determine the best stimulation position: bilateral, bipolar, and unipolar stimulation; (c) to determine the best stimulation parameters: our 5 Hz intermittent stimulation vs 14 Hz-210 µs continuous stimulation. Inflammatory responses were assessed by the disease activity index (DAI), histological analyses, and the myeloperoxidase (MPO) activity. Levels of inflammatory cytokines, norepinephrine (NE), and pancreatic polypeptide (PP) in both plasma and colon tissues were assessed. KEY RESULTS: Both SNS-1h and SNS-3h significantly ameliorated intestinal inflammation; SNS-1h was superior to SNS-3h. Bipolar but not bilateral or unipolar stimulation improved the inflammation in colitis. SNS with 5 Hz intermittent stimulation but not the 14 Hz continuous SNS was better for treating colitis in rats. SNS with the optimized stimulation parameters increased vagal activity and decreased sympathetic activity. CONCLUSION & INFERENCES: Bipolar stimulation for 1 hour daily using intermittent 5 Hz parameters is most effective in improving colonic inflammation in TNBS-treated rats by inhibiting pro-inflammatory cytokines and increasing anti-inflammatory cytokines via the modulation of the autonomic function.

Changes in post-oral glucose challenge pancreatic polypeptide hormone levels following metabolic surgery: A comparison of gastric bypass and sleeve gastrectomy.

BACKGROUND: Pancreatic polypeptide (PP) hormone is a 36-amino-acid peptide released from the pancreas, the serum levels of which have been shown to rise upon food intake. The underlying mechanism for metabolic surgery in the treatment of patients with type 2 diabetes mellitus (T2DM) remains intriguing. We compared post-oral glucose challenge PP levels between patients undergoing laparoscopic gastric bypass (GB) and sleeve gastrectomy (SG) at 1 year after surgery. METHODS: This hospital-based, prospective study followed up a total of 12 laparoscopic GB and 12 laparoscopic SG patients and evaluated their glucose homeostasis. One year after metabolic surgery, 75-g oral glucose tolerance tests (OGTTs) were performed in the patients in the GB and SG groups and the blood levels of PP were evaluated. RESULTS: The laparoscopic GB group had stable serum PP levels within 120 min after OGTT; however, the levels were significantly higher in the laparoscopic SG group at 30 min after OGTT. The patients with complete T2DM remission did not exhibit significantly different PP levels at fasting and post-OGTT than those in patients without remission after GB. Similarly, after SG, patients with T2DM remission did not show significantly different PP levels at fasting and post-OGTT than those in patients without T2DM remission. CONCLUSIONS: No significant difference was found in plasma PP levels after OGTT in T2DM patients that received either GB or SG, or in T2DM remitters or non-remitters 1 year after metabolic surgery.

Dairy products influence gut hormone secretion and appetite differently: A randomized controlled crossover trial.

Little is known about how dairy products with different nutrient contents and food matrices affect appetite sensation and gut hormone secretion. The objective of this study was to investigate how appetite sensation and gut hormone secretion in healthy adults are affected by meals with the same amount of fat but from different dairy products. Forty-seven healthy adults (70% women) were recruited to a randomized controlled crossover study with 4 dairy meals consisting of butter, cheese, whipped cream, or sour cream, corresponding to 45 g (approximately 60 energy percent) of fat. Plasma samples were collected for analysis of cholecystokinin (CCK), pancreatic polypeptide (PP), peptide YY (PYY), and ghrelin concentrations at 0, 2, 4, and 6 h after the meals and analyzed as the incremental area under the curve (iAUC0-6h) in a mixed model. Hunger, satiety, and appetite sensations were measured with a visual analog scale (VAS) immediately after finishing the meals and at 4 and 6 h postprandially. Intake of cheese induced a higher level of plasma PP-iAUC0-6h compared with butter or whipped cream, and a higher level of plasma CCK-iAUC0-6h compared with whipped cream. Intake of whipped cream increased VAS appetite at 4 h compared with cheese or sour cream, and at 6 h compared with cheese or butter. No significant meal effect was found for hunger, satiety, plasma PYY, or plasma ghrelin concentration. Intake of cheese increased postprandial plasma PP and CCK concentrations and decreased appetite compared with whipped cream but not with sour cream. These findings encourage further investigations of how different dairy products affect gut hormone secretion and appetite sensation.

Utility of the plasma pancreatic polypeptide response to modified sham feeding in diabetic gastroenteropathy and non-ulcer dyspepsia.

BACKGROUND: The relationship between cardiovascular and gastrointestinal (ie, plasma pancreatic polypeptide [PP] response to modified sham feeding [MSF]) indices of vagal function is unclear. Hyperglycemia inhibits PP secretion via vagally mediated mechanisms. Our aims were to (a) compare the PP response, (b) its relationship with glycemia, and (c) the relationship between PP response to MSF, gastric emptying (GE) of solids, and symptoms during GE study in healthy controls, patients with diabetic gastroenteropathy (DM), and non-ulcer dyspepsia (NUD). METHODS: In 24 healthy controls, 40 DM, and 40 NUD patients, we measured plasma PP concentrations during MSF, cardiovagal functions, GE, and symptoms during a GE study. KEY RESULTS: Baseline PP concentrations were higher in DM than in controls and NUD (P = .01), and in type 2 than in type 1 DM patients (P < .01). The PP increment during MSF was normal (≥20 pg/mL) in 70% of controls, 54% of DM, and 47% of NUD patients. Overall, the PP response and cardiovagal tests were concordant (P = .01). Among patients with a reduced PP increment with MSF, 7/10 of T1DM and 1/7 of T2DM patients had moderate or severe cardiovagal dysfunctions (P < .05). The PP response to MSF was not associated with GE. CONCLUSIONS & INFERENCES: Up to 30% of healthy controls have a reduced PP increment during MSF, limiting the utility of this test to detect vagal injury. The PP response is more useful when it is normal than abnormal. A reduced PP response is more likely to be associated with cardiovagal dysfunctions in T1DM than in T2DM.

Sacral nerve stimulation with appropriate parameters improves constipation in rats by enhancing colon motility mediated via the autonomic-cholinergic mechanisms.

Although sacral nerve stimulation (SNS) has been applied for treating constipation, its parameters were adopted from SNS for fecal incontinence, its effects are limited, and mechanisms are largely unknown. We investigated the effects and mechanism of SNS with appropriate parameters on constipation in rats treated with loperamide. First, using rectal compliance as an outcome measure, an experiment was performed to derive effective SNS parameters. Then, a 7-day SNS was performed in rats with constipation induced by loperamide. Autonomic functions were assessed by spectral analysis of heart rate variability (HRV) derived from an electrocardiogram. Serum levels of pancreatic polypeptide (PP), norepinephrine (NE), and acetylcholine (ACh) in colon were assessed. 1) Acute SNS at 5 Hz, 100 µs was found effective in enhancing rectal compliance and accelerating distal colon transit (P < 0.05 vs. sham SNS). 2) The 7-day SNS normalized loperamide-induced constipation, assessed by the number, weight, and water content of fecal pellets, and accelerated the distal colon transit (29.4 ± 3.7 min with sham SNS vs. 16.4 ± 5.3 min with SNS but not gastric emptying or intestinal transit. 3) SNS significantly increased vagal activity (P = 0.035) and decreased sympathetic activity (P = 0.012), assessed by spectral analysis of HRV as well as by the serum PP. 4) SNS increased ACh in the colon tissue; atropine blocked the accelerative effect of SNS on distal colon transit. We concluded that SNS with appropriate parameters improves constipation induced by loperamide by accelerating distal colon motility, mediated via the autonomic-cholinergic function.NEW & NOTEWORTHY Although sacral nerve stimulation (SNS) has been applied for treating constipation, its parameters were adopted from SNS for fecal incontinence, effects are limited, and mechanisms are largely unknown. This paper shows that SNS with appropriate parameters improves constipation induced by loperamide by accelerating distal colon motility mediated via the autonomic-cholinergic function.

Metabolic hormones and breast cancer risk among Mexican American Women in the Mano a Mano Cohort Study.

C-peptide, insulin, leptin, and other metabolic hormones are assumed to play roles in breast cancer development; though, results are inconsistent. In this prospective case-control study nested within the Mano a Mano Cohort Study, we assessed the risk of breast cancer with regard to plasma levels of c-peptide, gastric inhibitory polypeptide, insulin, leptin, monocyte chemoattractant protein-1, pancreatic polypeptide, and peptide YY. Among women followed for a median of 8.5 years, 109 breast cancer cases were identified and frequency-matched to 327 controls at a ratio of 1:3. Overall, only c-peptide was observed significantly associated with breast cancer risk. High c-peptide levels (≥ the median level of controls) were significantly associated with increased breast cancer risk (odds ratio [OR] = 1.39, 95% confidence interval [CI]: 1.01, 2.44). In an analysis of participants stratified by age, the significant association between c-peptide levels and breast cancer risk was evident in only women age ≥51 years (OR = 1.53, 95% CI: 1.02, 3.27). Among women age <51 years, high leptin levels were significantly associated with decreased breast cancer risk (OR = 0.49, 95% CI: 0.24, 0.82). Our findings suggest that selected metabolic hormones are associated with breast cancer development in Mexican American women.

Effects of Acute Eccentric Exercise on Appetite-Related Hormones and Food Preferences in Men.

Eccentric exercise has been suggested to improve muscle atrophy, muscle function, and insulin sensitivity. The aim of this study was to examine the effect of acute eccentric exercise on appetite-related hormones, food preferences, and food intake. Fourteen moderately active men were recruited to participate in this study (age 24.2 ± 5.5 years; BMI 23.4 ± 3.3 kg/m2; VO2max 48.9 ± 3.1 ml/kg/min). Three different conditions were implemented; no exercise, flat running "inclination 0" and downhill running "inclination -12%." Appetite-related hormones, subjective appetite sensations, food preference and reward, and ad libitum food intake were measured at pre-, immediately post-, and 24 h post exercise. There were no significant median changes in total ghrelin or pancreatic peptide concentrations between conditions. There were also no median differences in subjective appetite ratings or energy intake between conditions, but the median change in explicit liking of sweet versus savory foods differed significantly between pre-exercise and 24 h post exercise (p = .013). Post-hoc analysis observed a significant difference in the pre-exercise to 24 h post exercise change between front running and downhill running (p = .023), and indicated greater liking of savory foods over sweet foods in downhill running than front running. However, no further differences were seen between conditions for the remaining food preference parameters, suggesting there were no systematic trends in these data. In conclusion, there was no effect of front and downhill running on eating behavior as compared to a nonexercise control condition, but these data need to be replicated in a larger and more heterogeneous sample.

Association of serum gastric inhibitory polypeptide and pancreatic polypeptide levels with prolonged esophageal acid exposure time in refractory gastroesophageal reflux disease.

BACKGROUND: Acid exposure time (AET) prolongation plays an important role in the pathogenesis of gastroesophageal reflux disease (GERD). Gastric inhibitory polypeptide (GIP) and pancreatic polypeptide (PP) participate in the regulation of gastric acid secretion, blood glucose and lipid levels, and food intake. In this study, we evaluated the serum GIP and PP levels in refractory GERD patients and analyzed their metabolic and motility characteristics. METHODS: Seventy-three refractory GERD patients were enrolled in this study from September 2015 to September 2017. We investigated the clinical characteristics, severity, and duration of GERD symptoms. High-resolution manometry and 24 hours impedance-pH monitoring were performed to assess esophageal motility and reflux parameters. The patients were divided into the AET- group (AET <4.2%) and AET+ group (AET >4.2%). GIP and PP levels were determined in all subjects and their associations with other parameters evaluated. RESULTS: Age and GERDQ score were significantly higher (P < .05) and acid reflux and heartburn more frequent in the AET+ group than in the AET- group. The contraction front velocity was increased in the AET- group, while there was no significant difference in the distal contraction integral, peristalsis interruption, distal latency, or resting pressures of the lower and upper esophageal sphincters between the 2 groups (P > .05). The serum levels of GIP (P = .003) and PP (P = .012) were significantly increased in the AET+ group. Increased GIP and PP levels were associated with abnormal upright AET (correlation coefficients 0.307 and 0.233, P = .008 and P = .047). There was a positive correlation between GIP and triglyceride levels (correlation coefficient 0.279, P = .017). CONCLUSION: The serum levels of GIP and PP in refractory GERD patients with prolongation of AET are significantly elevated, mainly in the upright position.

Whey Proteins Reduce Appetite, Stimulate Anorexigenic Gastrointestinal Peptides and Improve Glucometabolic Homeostasis in Young Obese Women.

INTRODUCTION: Proteins, particularly whey proteins, represent the most satiating macronutrient in animals and humans. A dietetic regimen based on proteins enriched preload before eating might be a strategy to counteract obesity. AIMS AND METHODS: The aim of the present study was to evaluate the effects of an isocaloric drink containing whey proteins or maltodextrins (preload) on appetite (satiety/hunger measured by a visual analogue scale or VAS), glucometabolic control (blood glucose/insulin), and anorexigenic gastrointestinal peptides (pancreatic polypeptide or PP, glucagon-like peptide 1 or GLP-1 and peptide YY or PYY) in a cohort of obese young women (n = 9; age: 18.1 ± 3.0 years; body mass index, BMI: 38.8 ± 4.5 kg/m²). After two and a half hours, they were administered with a mixed meal at a fixed dose; satiety and hunger were measured by VAS. RESULTS: Each drink significantly augmented satiety and reduced hunger, and the effects were more evident with whey proteins than maltodextrins. Similarly, there were significant increases in GLP-1 and PYY levels (but not PP) after the ingestion of each drink; these anorexigenic responses were higher with whey proteins than maltodextrins. While insulinemia identically increased after each drink, whey proteins induced a lower glycemic response than maltodextrins. No differences in satiety and hunger were found after the meal, which is presumably due to the late administration of the meal test, when the hypophagic effect of whey proteins was disappearing. CONCLUSIONS: While whey proteins actually reduce appetite, stimulate anorexigenic gastrointestinal peptides, and improve glucometabolic homeostasis in young obese women, further additional studies are mandatory to demonstrate their hypophagic effects in obese subjects, when administered as preload before eating.

Postprandial Effects of Blueberry (Vaccinium angustifolium) Consumption on Glucose Metabolism, Gastrointestinal Hormone Response, and Perceived Appetite in Healthy Adults: A Randomized, Placebo-Controlled Crossover Trial.

The consumption of blueberries, as well as the phenolic compounds they contain, may alter metabolic processes related to type 2 diabetes. The study investigated the effects of adding 140 g of blueberries to a higher-carbohydrate breakfast meal on postprandial glucose metabolism, gastrointestinal hormone response, and perceived appetite. As part of a randomized crossover design study, 17 healthy adults consumed a standardized higher-carbohydrate breakfast along with 2 treatments: (1) 140 g (1 cup) of whole blueberries and (2) a placebo gel (matched for calories, sugars, and fiber of the whole blueberries). Each subject participated in two 2-h meal tests on separate visits ≥8 days apart. Venous blood samples and perceived appetite ratings using visual analog scales were obtained prior to and at 30, 60, 90, and 120 min after consuming the breakfast meals. Results show that glucose metabolism, several gastrointestinal hormones, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY) concentrations and perceived appetite did not change significantly with blueberry consumption. However, pancreatic polypeptide (PP) concentrations were statistically significantly higher (p = 0.0367), and the concentrations were higher during 30, 60, 90, and 120 min after consumption of the blueberry breakfast meal than the placebo breakfast meal. Additional research is needed to determine whether blueberries and other flavonoid-rich foods reduce type 2 diabetes risk by modifying gastrointestinal hormones and perceived appetite.

Diabetes of the exocrine pancreas.

Diabetes of the exocrine pancreas (DEP) is a form of diabetes that occurs due to pancreatic disease. It is far more common than has been previously considered, with a recent study showing 1.8% of adults with new-onset diabetes should have been classified as DEP. The majority is misdiagnosed as type 2 diabetes mellitus (T2DM). Patients with DEP exhibit varying degrees of exocrine and endocrine dysfunction. Damage to the islet of Langerhans effects the secretion of hormones from the ß, α, and pancreatic polypeptide cells; the combination of low insulin, glucagon, and pancreatic polypeptide contributes to rapid fluctuations in glucose levels. This form of "brittle diabetes" may result in the poorer glycemic control observed in patients with DEP, when compared with those with T2DM. Diabetes of the exocrine pancreas has a different natural history to other forms of diabetes; patients are more likely to require early insulin initiation compared with those with T2DM. Therefore, individuals with DEP should be advised about the symptoms of decompensated hyperglycemia, although they are less likely to develop ketoacidosis. Clinicians should screen for DEP in patients with acute or chronic pancreatitis, following pancreatic resection, or with co-existing cystic fibrosis or hemochromatosis. Incident diabetes may herald the onset of pancreatic ductal carcinoma in a small subset of patients. Once identified, patients with DEP can benefit from specific lifestyle advice, pancreatic enzyme replacement therapy, metformin treatment, appropriate insulin dosing, and monitoring. Further research is needed to establish the ideal treatment regimens to provide optimal clinical outcomes for this unique form of diabetes.

Role of biomarker tests for diagnosis of neuroendocrine tumours.

Neuroendocrine tumours (NETs) are neoplasms that arise from neuroendocrine cells. Neuroendocrine cells and their tumours can secrete a wide range of amines and polypeptide hormones into the systemic circulation. This feature has triggered widespread investigation into circulating biomarkers for the diagnosis of NETs as well as for the prediction of the biological behaviour of tumour cells. Classic examples of circulating biomarkers for gastroenteropancreatic NETs include chromogranin A, neuron-specific enolase and pancreatic polypeptide as well as hormones that elicit clinical syndromes, such as serotonin and its metabolites, insulin, glucagon and gastrin. Biomarker metrics of general markers for diagnosing all gastroenteropancreatic NET subtypes are limited, but specific hormonal measurements can be of diagnostic value in select cases. In the past decade, methods for detecting circulating transcripts and tumour cells have been developed to improve the diagnosis of patients with NETs. Concurrently, modern scanning techniques and superior radiotracers for functional imaging have markedly expanded the options for clinicians dealing with NETs. Here, we review the latest research on biomarkers in the NET field to provide clinicians with a comprehensive overview of relevant diagnostic biomarkers that can be implemented in dedicated situations.

Comparison of Fasting Human Pancreatic Polypeptide Levels Among Patients With Pancreatic Ductal Adenocarcinoma, Chronic Pancreatitis, and Type 2 Diabetes Mellitus.

OBJECTIVES: Human pancreatic polypeptide (HPP) is a hormone secreted by the ventral pancreas. While postprandial HPP levels have been studied in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC), there are limited data on fasting HPP in these diseases. METHODS: Fasting serum HPP was measured in the following groups of patients: CP with diabetes mellitus (DM) (n = 16), CP without DM (n = 34), PDAC with new-onset DM (n = 50), PDAC without DM (n = 49), new-onset type 2 DM (n = 50), and controls without DM (n = 49). Sixty-six had type 3c DM (CP with DM, n = 16; PDAC with new-onset DM, n = 50). RESULTS: Median fasting HPP levels (in picograms per milliliter) were similar among all groups. Median (interquartile range) HPP levels in new-onset type 2 DM (n = 50; 288.3 [80.1-1072.1]) were similar to those in type 3c DM (n = 66; 242.3 [64.9-890.9]) (P = 0.71). In PDAC (n = 99), HPP values were similar in pancreatic head (n = 75) versus body/tail (n = 24) tumors (245.3 [64.3-1091.3] vs 334.7 [136.1-841.5]; P = 0.95), regardless of DM. CONCLUSIONS: Fasting HPP levels are similar in CP, PDAC, and controls regardless of glycemic status.

Novel essential amino acid supplements enriched with L-leucine facilitate increased protein and energy intakes in older women: a randomised controlled trial.

BACKGROUND: Inadequate protein intake (PI), containing a sub-optimal source of essential amino acids (EAAs), and reduced appetite are contributing factors to age-related sarcopenia. The satiating effects of dietary protein per se may negatively affect energy intake (EI), thus there is a need to explore alternative strategies to facilitate PI without compromising appetite and subsequent EI. METHODS: Older women completed two experiments (EXP1 and EXP2) where they consumed either a Bar (565 kJ), a Gel (477 kJ), both rich in EAAs (7.5 g, 40% L-leucine), or nothing (Control). In EXP1, participants (n = 10, 68 ± 5 years, mean ± SD) consumed Bar, Gel or Control with appetite sensations and appetite-related hormonal responses monitored for one hour, followed by consumption of an ad libitum breakfast (ALB). In EXP2, participants (n = 11, 69 ± 5 years) ingested Bar, Gel or Control alongside an ALB. RESULTS: In EXP1, EI at ALB was not different (P = 0.674) between conditions (1179 ± 566, 1254 ± 511, 1206 ± 550 kJ for the Control, Bar, and Gel respectively). However, total EI was significantly higher in the Bar and Gel compared to the Control after accounting for the energy content of the supplements (P < 0.0005). Analysis revealed significantly higher appetite Area under the Curve (AUC) (P < 0.007), a tendency for higher acylated ghrelin AUC (P = 0.087), and significantly lower pancreatic polypeptide AUC (P = 0.02) in the Control compared with the Bar and Gel. In EXP2, EI at ALB was significantly higher (P = 0.028) in the Control (1282 ± 513 kJ) compared to the Bar (1026 ± 565 kJ) and Gel (1064 ± 495 kJ). However, total EI was significantly higher in the Bar and Gel after accounting for the energy content of the supplements (P < 0.007). CONCLUSIONS: Supplementation with either the Bar or Gel increased total energy intake whether consumed one hour before or during breakfast. This may represent an effective nutritional means for addressing protein and total energy deficiencies in older women. TRIAL REGISTRATION: Clinical trial register: retrospectively registered, ISRCTN12977929 on.

Pancreatic Polypeptide in Parkinson's Disease: A Potential Marker of Parasympathetic Denervation.

BACKGROUND AND OBJECTIVES: Parkinson's disease (PD) patients experience several non-motor symptoms from the gastrointestinal tract that may partly be caused by parasympathetic deficiency. The pancreas is densely innervated by the vagus nerve, which mediates early meal-induced secretion of pancreatic polypeptide (PP). Early secretion after sham feeding has been validated as a marker of vagal integrity. Thus, the aim was to evaluate the ratio of increased PP plasma levels after sham feeding in PD and correlate findings with gastrointestinal transit time (GITT). METHODS: Twenty-five PD patients and 17 controls were included. PP, insulin, and blood glucose levels were measured before, during, and after sham feeding with white bread and chocolate spread. GITT was measured using radiopaque markers. Furthermore, faeces samples were analyzed for pancreatic elastase enzyme as a marker of exocrine pancreatic function. RESULTS: PD patients showed significantly lower PP ratio levels after sham feeding, which was most pronounced at 10 minutes. No significant association was seen between attenuated PP response and GITT in PD patients. No between-group differences were seen in glucose or insulin levels over time, but PD patients showed generally lower insulin levels compared to controls. No difference was found in faeces pancreatic elastase. CONCLUSIONS: Early-to-moderate stage PD patients demonstrated significantly decreased PP response after sham feeding suggestive of vagal denervation.