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Early detection of cystic fibrosis (CF) related diabetes (CFRD) improves health outcomes and reduces CF-related mortality. The study aims to evaluate the ratio of islet amyloid polypeptide (IAPP) to C-peptide in CF patients with diabetes and without diabetes.Cross-sectional analysis was carried out in a prospective cohort of 33 participants (CF [n = 16] and CFRD [n = 18]). We examined the association of plasma IAPP:C-peptide ratio with clinical information, including glycated hemoglobin, and lung function markers.The median (interquartile range) IAPP:C-peptide ratio was significantly (P = 0.004) higher in people with CFRD (4.8 [4.5]) compared with participants without CFRD (12.1 [19.7]). The ratio of IAPP to C-peptide significantly accounted for a 38% variation in the diabetes status in patients with CF (r2 = 0.399, P0.001). Islet amyloid polypeptide is strongly correlated with serum ferritin levels (r = 0.683, P = 0.005) and forced expiratory volume in CFRD, but not in nondiabetic participants with CF.Islet amyloid polypeptide:C-peptide ratio could be a potential marker of CFRD in adults with CF. Further research requires validation of this marker in longitudinal cohort studies to confirm the capability of IAPP:C-peptide to predict CFRD.

Epidemiological and interventional studies have linked saturated fatty acids (SFA) with elevated levels of low-density lipoprotein cholesterol (LDL-C) and increased CVD risk. However, the effects of the SFA chain length on postprandial lipemia in humans are not well elucidated. The aim of this study was to investigate the impact of short, medium and long-chain SFA on postprandial blood lipids in healthy volunteers. Sixteen healthy volunteers consumed test biscuits containing 40 g of either butter (BB), coconut oil (CB) or lard (LB) in a single-blinded, randomized crossover design. Blood samples were collected fasting and 2, 3, 4, and 6 hours postprandially and assessed for blood lipids (total cholesterol, TC; high-density lipoprotein cholesterol, HDL-C; LDL-C and triglyceride, TG). The postprandial TG response following CB was 59.8% lower than following BB (p 0.01) and 58.8% lower than LB (p 0.01), although no difference was observed between the BB and the LB responses. The net area under the LDL-C concentration curve was significantly larger after consumption of the CB compared to the BB, despite no significant differences in postprandial net area under the TC and HDL-C concentration curves. Consumption of medium-chain SFA as CB resulted in lower postprandial TG excursions compared to short-chain SFA as BB and long-chain SFA as LB, despite their identical fat and caloric content. These results suggest that SFA differ in their potential to elevate postprandial lipid levels, and that coconut oil, a rich source of medium-chain SFA may not be as hyperlipidemic as animal fats rich in long chain SFA. ANZCTR IDENTIFIER: 12617000903381. CLINICAL TRIAL REGISTRY NUMBER: The study was registered with the Australia New Zealand Trial registry as ACTRN12617000903381.

AIM Overweight and obesity are frequently reported in young persons with type 1 diabetes, however its relative magnitude in comparison to the general population is not well understood. This study compared the prevalence of overweight and obesity in young persons with type 1 diabetes to a reference population and explored possible associated factors, including gender, age, HbA1c , insulin regimen, age at diagnosis, diabetes duration, socio-economic status and cardiovascular disease risk factors. METHODS A cross-sectional review was undertaken of data collected from youth (3-17 years) in 2016 and young adults (18-30 years) in 2015 with a diagnosis of type 1 diabetes for > 3 months attending diabetes centres in Newcastle, Australia. Rates of overweight and obesity were compared with matched population survey results. RESULTS Data from 308 youth and 283 young adults were included. In girls, significantly higher prevalence of overweight and obesity were seen in the 5-8 (43% vs. 18%), 13-16 (41% vs. 27%), 18-24 (46% vs. 34%) and 25-30 (60% vs. 43%) years age groups; whereas in boys increased prevalence was observed in the 5-8 years age group only (41% vs. 18%). Rates of overweight and obesity increased with age across sexes. In youth, BMI standard deviation score was correlated with socio-economic status, insulin regimen, blood pressure and blood lipids (P

AIMS Hyperglycaemia following antenatal corticosteroids is common in women with diabetes in pregnancy, and validated algorithms to maintain pregnancy-specific glucose targets are lacking. The Pregnancy-IVI, an intravenous-insulin (IVI) algorithm, has been validated in gestational diabetes; however, its performance in pre-existing diabetes (Type 1 and Type 2 diabetes) is not known. We hypothesised that Pregnancy-IVI would be superior to a generic Adult-IVI protocol (prior standard of care) following betamethasone in women with pre-existing diabetes. METHODS A retrospective cohort study enrolled all women with pre-existing diabetes at a tertiary centre receiving betamethasone and treated with IVI according to one of two protocols: Adult-IVI (n = 73, 2014-2017) or Pregnancy-IVI (n = 62, 2017-2020). The primary outcome was on-IVI glycaemic time-in-range (capillary blood glucose (BGL) 3.8-7.0 mmol/L). Secondary outcomes included time with critical hyperglycaemia (BGL > 10 mmol/L); occurrence of maternal hypoglycaemia (BGL

Background: Hypertriglyceridemia-associated acute pancreatitis (HTGAP) has been linked with increased severity and morbidity. In this study, triglyceride levels were measured in all patients admitted with acute pancreatitis (AP) to establish the incidence of HTGAP in an Australian center. Methods: A prospective cohort with AP was collated over an 18-month period in a single tertiary referral hospital. HTGAP was defined as AP with triglycerides &ge, 11.2 mmol/L (1000 mg/dL). Incidence, clinical co-morbidities, severity and management strategies were recorded. Results: Of the 292 episodes of AP, 248 (85%) had triglycerides measured and were included. HTGAP was diagnosed in 10 of 248 (4%) AP cases. Type 2 diabetes, obesity, alcohol misuse and gallstones were common cofactors. The HTGAP group demonstrated severe hypertriglyceridemia compared to the non-HTGAP group (median 51 mmol/L vs. 1.3 mmol/L). Intensive care unit (ICU) admissions were significantly increased (odds ratio (OR) 16, 95% CI 4&ndash, 62) in the HTGAP group (5/10 vs. 14/238 admissions, p &lt, 0.001) and constituted 26% (5/19) of total ICU admissions for AP. Four patients received intravenous insulin with fasting and had a rapid reduction in triglyceride levels by 65&ndash, 77% within 24 h, one patient had mild hypoglycemia secondary to therapy. Conclusion: HTGAP occurred in 4% of AP cases and was associated with higher risk of ICU admission. Intravenous insulin and fasting appear safe and efficacious for acutely lowering triglyceride levels in HTGAP.

This review examined the risk of cardiovascular disease in adults with metabolically healthy overweight/obesity. A systematic review and meta-analysis using data from Medline, EMBASE, SCOPUS and Cochrane Library searched from inception up to 31st October 2019. We included prospective cohort studies of adults who are metabolically healthy or unhealthy. Outcomes were fatal and nonfatal cardiovascular events, all-cause mortality. Pooled relative risk was calculated for each outcome in populations with metabolically healthy overweight and metabolically healthy obesity using metabolically healthy normal weight as reference. A random-effects model was used for meta-analysis, and risk of bias assessment tool for nonrandomized studies assessed risk of bias within each study. Twenty-three prospective cohort studies with 4,492,723 participants were included. Cardiovascular disease risk was increased in metabolically healthy groups with overweight (RR = 1.34, CI: 1.23-1.46, n = 20, I2 = 90.3%) and obesity (RR = 1.58, CI: 1.34-1.85, n = 21, I2 = 92.2) compared with a reference group with metabolically healthy normal weight. Cardiovascular disease risk was similar irrespective of the number of risk factors used to define metabolically healthy and the risk remained in the group with no metabolic risk factors. Cardiovascular disease risk is increased in populations with overweight and obesity classified as metabolically healthy even when there were no metabolic risk factors.

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 β, 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.

To assess the relationship between insulin resistance (IR), retinopathy and maculopathy in young adults with Type 1 diabetes mellitus.A cross-sectional study at a regional Australian tertiary hospital. Retinal pathology, assessed by colour fundus photography, was correlated with two surrogate measures of IR: estimated Glucose Disposal Rate (eGDR) and Insulin Sensitivity Score (ISS), where lower scores reflect greater IR.107 patients were recruited, with mean age 24.7years, 53% male, and mean duration of disease 10.8years. Mean eGDR scores (5.6vs 8.0 p0.001) and ISS (4.7vs 7.9, p0.001) were lower in subjects having at least moderate non-proliferative diabetic retinopathy (NPDR; relative to nil/mild-NPDR). Similarly, mean eGDR (4.2vs 6.2, p=0.001) and ISS (3.8vs 6.1, p=0.003) were lower in patients with maculopathy. Multivariate logistic regression modelling was used to control for confounding. For retinopathy severity, a unit increase in eGDR or ISS (representing lower IR) was associated with a 50% decrease in odds of moderate-NPDR or worse (eGDR OR 0.5, 95%CI 0.32-0.77, p=0.002; ISS OR 0.49, 95%CI 0.29-0.84, p=0.01). A unit increase in eGDR or ISS was associated with a 46-56% decrease in odds of maculopathy (eGDR OR 0.54, 95%CI 0.37-0.81, p=0.003; ISS OR 0.44, 95%CI 0.22-0.88, p=0.02).IR correlates with more severe retinopathy in young adults with Type 1DM. This is the first description of a correlation between IR and maculopathy in Type 1DM, warranting further evaluation. Prospective studies examining whether reducing IR can improve microvascular complications are required.

Background Nerves and neurotrophic growth factors are emerging promoters of cancer growth. The precursor for Nerve Growth Factor (proNGF) is overexpressed in thyroid cancer, but its potential role as a clinical biomarker has not been reported. Here we have examined the value of proNGF as a serum and biopsy-rinse biomarker for thyroid cancer diagnosis. Methods Patients presenting for thyroid surgery or biopsy were enrolled in separate cohorts examining serum (n = 204, including 46 cases of thyroid cancer) and biopsy-rinse specimens (n = 188, including 26 cases of thyroid cancer). ProNGF levels in clinical samples were analysed by ELISA. Univariate and multivariate statistical analyses were used to compare proNGF levels with malignancy status and clinicopathological parameters. Results ProNGF was not detected in the majority of serum samples (176/204, 86%) and the detection of proNGF was not associated with thyroid cancer diagnosis. In the few cases where proNGF was detected in the serum, thyroidectomy did not affect proNGF concentration, demonstrating that the thyroid was not the source of serum proNGF. Intriguingly, an association between hyperthyroidism and serum proNGF was observed (OR 3.3, 95% CI 1.6–8.7 p = 0.02). In biopsy-rinse, proNGF was detected in 73/188 (39%) cases, with no association between proNGF and thyroid cancer. However, a significant positive association between follicular lesions and biopsy-rinse proNGF was found (OR 3.3, 95% CI 1.2–8.7, p = 0.02). Conclusions ProNGF levels in serum and biopsy-rinse are not increased in thyroid cancer and therefore proNGF is not a clinical biomarker for this condition.

Metastatic thyroid cancer is an uncommon condition to be present at the time of pregnancy, but presents a challenging paradigm of care. Clinicians must balance the competing interests of long-term maternal health, best achieved by iatrogenic hyperthyroidism, regular radioiodine therapy and avoidance of dietary iodine, against the priority to care for the developing foetus, with inevitable compromise. Additionally, epidemiological and cellular data support the role of oestrogen as a growth factor for benign and malignant thyrocytes, although communicating the magnitude of this risk to patients and caregivers, as well as the uncertain impact of any pregnancy on long-term prognosis, remains challenging. Evidence to support treatment decisions in this uncommon situation is presented in the context of a case of a pregnant teenager with known metastatic papillary thyroid cancer and recent radioiodine therapy. Learning points: Pregnancy is associated with the growth of thyroid nodules due to stimulation from oestrogen receptors on thyrocytes and HCG cross-stimulation of the TSH receptor. Thyroid cancer diagnosed during pregnancy has not been shown to be associated with increased rates of persistent or recurrent disease in most studies. There is little evidence to guide the management of metastatic thyroid cancer in pregnancy, where both maternal and foetal wellbeing must be carefully balanced.

Diabetes is a chronic, complex condition requiring sound knowledge and self-management skills to optimize glycemic control and health outcomes. Dietary intake and physical activity are key diabetes self-management (DSM) behaviors that require tailored education and support. Electronic health (eHealth) technologies have a demonstrated potential for assisting individuals with DSM behaviors. This review provides examples of technologies used to support nutrition and physical activity behaviors in the context of DSM. Technologies covered include those widely used for DSM, such as web-based programs and mobile phone and smartphone applications. In addition, examples of novel tools such as virtual and augmented reality, video games, computer vision for dietary carbohydrate monitoring, and wearable devices are provided. The challenges to, and facilitators for, the use of eHealth technologies in DSM are discussed. Strategies to support the implementation of eHealth technologies within practice and suggestions for future research to enhance nutrition and physical activity behaviors as a part of broader DSM are provided.

AIMS Marked hyperglycaemia is common following betamethasone administration in women with gestational diabetes (GDM), and may contribute to neonatal hypoglycaemia. Validated protocols to deliver glycaemic stability following betamethasone are lacking. We hypothesized that an intravenous insulin (IVI) protocol for pregnancy-specific glycaemic targets (Pregnancy-IVI) would achieve greater at-target glycaemic control than a generic adult intravenous insulin protocol (Adult-IVI), and may reduce neonatal hypoglycaemia. METHODS A retrospective cohort study of the performance Adult-IVI and Pregnancy-IVI following betamethasone in GDM, sequentially implemented at a tertiary hospital, without change in indication for IVI. Cases were identified by electronic record search. Primary outcome was percentage of on-IVI time with at-target glycaemia [blood glucose level (BGL) 3.8-7 mmol/l]. Secondary outcomes were time with critical hyperglycaemia (BGL > 10 mmol/l), occurrence of maternal hypoglycaemia (BGL

OBJECTIVE Post-thyroidectomy hypocalcaemia is a significant cause of morbidity and prolonged hospitalization, usually due to transient parathyroid gland damage, treated with calcium and vitamin D supplementation. We present a randomized, double-blinded placebo-controlled trial of preoperative loading with high-dose cholecalciferol (300 000 IU) to reduce post-thyroidectomy hypocalcaemia. PATIENTS AND MEASUREMENTS Patients (n = 160) presenting for thyroidectomy at tertiary hospitals were randomized 1:1 to cholecalciferol (300 000 IU) or placebo 7 days prior to thyroidectomy. Ten patients withdrew prior to surgery. The primary outcome was post-operative hypocalcaemia (corrected calcium

Background Medium-chain saturated fatty acids (MCFAs) may affect circulating lipids and lipoproteins differently than long-chain saturated fatty acids (LCSFAs), but the results from human intervention trials have been equivocal. Objective The aim of this study was to determine whether MCFAs and LCSFAs have differential impacts on blood lipids and lipoproteins. Design Five databases were searched (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus) until April 2018, and published clinical trials investigating the differential effects of dietary MCFAs and LCSFAs on blood lipids were included. Searches were limited to the English language and to studies with adults aged >18 y. Where possible, studies were pooled for meta-analysis using RevMan 5.2. The principle summary measure was the mean difference between groups calculated using the random-effects model. Results Eleven eligible crossover and 1 parallel trial were identified with a total of 299 participants [weighted mean ± SD age: 38 ± 3 y; weighted mean ± SD body mass index (kg/m2): 24 ± 2]. All studies were pooled for the meta-analysis. Diets enriched with MCFAs led to significantly higher high-density lipoprotein (HDL) cholesterol concentrations than diets enriched with LCSFAs (0.11 mmol/L; 95% CI: 0.07, 0.15 mmol/L) with no effect on triglyceride, low-density lipoprotein (LDL) cholesterol, and total cholesterol concentrations. Consumption of diets rich in MCFAs significantly increased apolipoprotein A-I (apoA-I) concentrations compared with diets rich in LCSFAs (0.08 g/L; 95% CI: 0.02, 0.14 g/L). There was no evidence of statistical heterogeneity for HDL cholesterol, apoA-I, and triglyceride concentrations; however, significant heterogeneity was observed for the total cholesterol (I2 = 49%) and LDL cholesterol analysis (I2 = 58%). Conclusion The findings of this research demonstrate a differential effect of MCFAs and LCSFAs on HDL cholesterol concentrations. Further investigations are warranted to elucidate the mechanism by which the lipid profile is altered. This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42017078277.

SummaryObjective The insulin tolerance test (ITT) is contraindicated in a proportion of patients with suspected ACTH deficiency. The aim of this study was to investigate the diagnostic accuracy of the glucagon stress test (GST) compared with the overnight metyrapone test (OMT) in patients with contraindications to ITT. Design This was a prospective comparison of the GST to the OMT in patients with suspected ACTH deficiency and contraindications to the ITT. The OMT was used as the standard for comparison. The study was conducted at two tertiary referral centres for pituitary disease. Patients Seventy-eight patients underwent contemporaneous OMT and GST of whom 61 had sufficient suppression of cortisol during the OMT to be included in the comparison. Forty had suffered traumatic brain injury, 36 had organic pituitary disorders and two were classified as ‘other’. Measurements ACTH sufficiency was defined as 0800h 11-deoxycortisol ≥ 200 nmol/l on OMT and peak cortisol ≥ 440 nmol/l on GST, as per local reference ranges. Results There was significant discrepancy between the proportion of patients diagnosed with ACTH deficiency using the OMT (39%) and GST (89%). From our data, a GST peak cortisol cut-off of ≥350 nm provides the combination of optimal sensitivity (71%) and specificity (57%), compared with a higher sensitivity (88%) but poor specificity (11%) using a cut-off of ≥440 nm. Conclusions The GST should be used with caution as a diagnostic test of ACTH reserve. The OMT should be used in preference to the GST to assess the hypothalamic pituitary adrenal axis where ITT is contraindicated.

Aim There is a high incidence of neonatal hypoglycaemia in neonates born to mothers with pre-existing diabetes. This often necessitates admission to the neonatal intensive care. Guidelines suggest maintaining intrapartum blood glucose levels (BGLs) of 4–7 mmol/l in women with diabetes to reduce the risk of neonatal hypoglycaemia. This study assessed whether intrapartum BGLs in women with pre-gestational Type 1 and 2 diabetes were predictive of neonatal hypoglycaemia. Methods A retrospective analysis of 261 births delivered at a tertiary hospital in Australia from 2009 to 2014. Results There were 122 cases of neonatal hypoglycaemia (glucose ≤ 2.6 mmol/l) in 261 births (47%). The mothers in the neonatal hypoglycaemia group spent less time with BGL in the range 4–7 mmol/l [55 ± 37% vs. 65 ± 35%, P = 0.02; odds ratio (OR) 0.992, P = 0.03] and more time with BGL in the 7–10 mmol/l range (31 ± 34% vs. 18 ± 27%, P = 0.003; OR 1.013, P = 0.003) compared with those without neonatal hypoglycaemia. Although statistically significant, receiver operating characteristic (ROC) curve analysis showed that time spent with maternal BGLs in the range 4–7 mmol/l [area under the curve (AUC) = 0.58] or 7–10 mmol (AUC = 0.60) was not strong enough to be a useful clinical predictor of neonatal hypoglycaemia. HbA1c in the second trimester of pregnancy (P = 0.02, OR 1.42) and percentage time spent in BGL range of 7–10 mmol/l (P = 0.001, OR 1.02) were both associated with a risk of neonatal hypoglycaemia in a logistic regression model. HbA1c in the third trimester (P = 0.07, OR 1.28) approached, but did not reach, significance. Conclusions These data support a BGL range of 4–7 mmol/l as an intrapartum target. Glycaemic control in the second trimester is associated with neonatal hypoglycaemia. Improvement in ante- and intrapartum glycaemic control may reduce neonatal hypoglycaemia in women with pre-existing diabetes.

OBJECTIVE Peptide YY3–36 (PYY3–36), a Y2 receptor agonist, and oxyntomodulin, a glucagon-like peptide 1 (GLP-1) receptor agonist, are cosecreted by intestinal L-cells after each meal. Separately each hormone acts as an endogenous satiety signal and reduces appetite in humans when infused intravenously. The aim of the current study was to investigate whether the anorectic effects of PYY3–36 and oxyntomodulin can be additive. RESEARCH DESIGN AND METHODS Twelve overweight or obese human volunteers underwent a randomized, double-blinded, placebo-controlled study. An ad libitum test meal was used to measure energy intake during intravenous infusions of either PYY3–36 or oxyntomodulin or combined PYY3–36/oxyntomodulin. RESULTS Energy intake during coadministration of PYY3–36 and oxyntomodulin was reduced by 42.7% in comparison with the saline control and was significantly lower than that during infusions of either hormone alone. CONCLUSIONS The anorectic effects of PYY3–36 and oxyntomodulin can be additive in overweight and obese humans. Coadministration of Y2 receptor agonists and GLP-1 receptor agonists may be a useful treatment strategy for obesity.

Oxyntomodulin has recently been found to decrease body-weight in obese humans and may be a potential anti-obesity therapy.To determine whether oxyntomodulin alters energy expenditure, in addition to reducing energy intake, in 'free-living' overweight and obese volunteers.Randomized double-blind controlled cross-over trial.Community and hospital-based.Fifteen healthy overweight and obese men and women (age: 23-49 years, BMI: 25.1-39.0 kg/m(2)). All volunteers completed the study protocol.Four-day subcutaneous self-administration of pre-prandial oxyntomodulin, three times daily. Participants were advised to maintain their normal dietary and exercise regimen.(1) Energy expenditure, measured by indirect calorimetry and combined heart rate and movement monitoring; (2) energy intake, measured during a study meal.Oxyntomodulin administration reduced energy intake at the study meal by 128+/-29 kcal (P=0.0006) or 17.3+/-5.5% (P=0.0071), with no change in meal palatability. Oxyntomodulin did not alter resting energy expenditure; but increased activity-related energy expenditure by 143+/-109 kcal/day or 26.2+/-9.9% (P=0.0221); total energy expenditure by 9.4+/-4.8% (P=0.0454) and physical activity level by 9.5+/-4.6% (P=0.0495). A reduction in body weight of 0.5+/-0.2% was observed during the oxyntomodulin administration period (P=0.0232).Oxyntomodulin increases energy expenditure while reducing energy intake resulting in negative energy balance. This data supports the role of oxyntomodulin as a potential anti-obesity therapy.

The responses of the gut hormone peptide YY (PYY) to food were investigated in 20 normal-weight and 20 obese humans in response to six test meals of varying calorie content. Human volunteers had a graded rise in plasma PYY (R2 = 0.96; P0.001) during increasing calorific meals, but the obese subjects had a lower endogenous PYY response at each meal size (P0.05 at all levels). The ratio of plasma PYY(1-36) to PYY(3-36) was similar in normal-weight and obese subjects. The effect on food intake and satiety of graded doses of exogenous PYY(3-36) was also evaluated in 12 human volunteers. Stepwise increasing doses of exogenous PYY(3-36) in humans caused a graded reduction in food intake (R2 = 0.38; P0.001). In high-fat-fed (HF) mice that became obese and low-fat-fed mice that remained normal weight, we measured plasma PYY, tissue PYY, and PYY mRNA levels and assessed the effect of exogenous administered PYY(3-36) on food intake in HF mice. HF mice remained sensitive to the anorectic effects of exogenous ip PYY(3-36). Compared with low-fat-fed fed mice, the HF mice had lower endogenous plasma PYY and higher tissue PYY but similar PYY mRNA levels, suggesting a possible reduction of PYY release. Thus, fasting and postprandial endogenous plasma PYY levels were attenuated in obese humans and rodents. The PYY(3-36) infusion study showed that the degree of plasma PYY reduction in obese subjects were likely associated with decreased satiety and relatively increased food intake. We conclude that obese subjects have a PYY deficiency that would reduce satiety and could thus reinforce their obesity.

Our knowledge of the physiological systems controlling energy homeostasis has increased dramatically over the last decade. The roles of peripheral signals from adipose tissue, pancreas, and the gastrointestinal tract reflecting short- and long-term nutritional status are now being described. Such signals influence central circuits in the hypothalamus, brain stem, and limbic system to modulate neuropeptide release and hence food intake and energy expenditure. This review discusses the peripheral hormones and central neuronal pathways that contribute to control of appetite.

This study investigated the effect of subcutaneously administered oxyntomodulin on body weight in healthy overweight and obese volunteers. Participants self-administered saline or oxyntomodulin subcutaneously in a randomized, double-blind, parallel-group protocol. Injections were self-administered for 4 weeks, three times daily, 30 min before each meal. The volunteers were asked to maintain their regular diet and level of physical exercise during the study period. Subjects’ body weight, energy intake, and levels of adipose hormones were assessed at the start and end of the study. Body weight was reduced by 2.3 ± 0.4 kg in the treatment group over the study period compared with 0.5 ± 0.5 kg in the control group (P = 0.0106). On average, the treatment group had an additional 0.45-kg weight loss per week. The treatment group demonstrated a reduction in leptin and an increase in adiponectin. Energy intake by the treatment group was significantly reduced by 170 ± 37 kcal (25 ± 5%) at the initial study meal (P = 0.0007) and by 250 ± 63 kcal (35 ± 9%) at the final study meal (P = 0.0023), with no change in subjective food palatability. Oxyntomodulin treatment resulted in weight loss and a change in the levels of adipose hormones consistent with a loss of adipose tissue. The anorectic effect was maintained over the 4-week period. Oxyntomodulin represents a potential therapy for obesity.

Anorexia and malnutrition confer significant morbidity and mortality to patients with end-stage kidney disease but are resistant to therapy. The aim of this study was to determine whether subcutaneous administration of ghrelin, an appetite-stimulating gut hormone, could enhance food intake in patients who are receiving maintenance peritoneal dialysis and have evidence of malnutrition. The principal outcome measure was energy intake during a measured study meal. Secondary outcome measures were BP and heart rate and 3-d food intake after intervention. Nine peritoneal dialysis patients with mild to moderate malnutrition (mean serum albumin 28.6 +/- 5.0 g/L, total cholesterol 4.4 +/- 0.6 mmol/L, subjective global assessment score of 5.7 +/- 1.7) were given subcutaneous ghrelin (3.6 nmol/kg) and saline placebo in a randomized, double-blind, crossover protocol. Administration of subcutaneous ghrelin significantly increased the group mean absolute energy intake, compared with placebo, during the study meal (690 +/- 190 versus 440 +/- 250 kcal; P = 0.0062). When expressed as proportional energy increase for each individual, ghrelin administration resulted in immediate doubling of energy intake (204 +/- 120 versus 100%; P = 0.0319). Administration of ghrelin maintained a nonsignificant increase in energy intake over 24 h after intervention (2009 +/- 669 versus 1579 +/- 330 kcal) and was not followed by subsequent underswing (1790 +/- 370 versus 1670 +/- 530 and 1880 +/- 390 versus 1830 +/- 530 kcal on days 2 and 3, respectively). Ghrelin administration resulted in a significant fall in mean arterial BP (P = 0.0030 by ANOVA). There were no significant adverse events during the study. Subcutaneous ghrelin administration enhances short-term food intake in dialysis patients with mild to moderate malnutrition.

Signals generated by the gastrointestinal tract are able to regulate appetite and influence body weight. Ghrelin is an orexigenic peptide produced by the stomach. Satiety signals derived from the intestine and pancreas include peptide YY, pancreatic polypeptide, glucagon-like peptide 1, oxyntomodulin, and cholecystokinin. Signals from the gut and adipose tissue are integrated in the central nervous system to provide energy homeostasis. Knowledge of the body's control of appetite is important because we strive to combat obesity in man.

A woman aged 67 years was referred with pituitary enlargement identified on CT scan. Imaging was performed to investigate a progressive, incapacitating, 12-month history of nausea, vertigo, gait disturbance and recurrent falls. Her presentation included chronic occipitofrontal headaches, which had increased in severity and were exacerbated by upright posture. She had a history of lumboperitoneal (LP) shunting for idiopathic intracranial hypertension, systemic hypertension, ischaemic heart disease and pulmonary disease secondary to cigarette smoking. Physical examination demonstrated normal cranial nerves, bilateral upper motor neuron signs in both upper and lower limbs and severe gait instability. Her anterior pituitary function testing showed mildly …

The current obesity epidemic is fuelled by the availability of highly palatable, calorie-dense food, and the low requirement for physical activity in our modern environment. If energy intake exceeds energy use, the excess calories are stored as body fat. Although the body has mechanisms that act to maintain body weight over time, they primarily defend against starvation and are less robust in preventing the development of obesity. Knowledge of this homeostatic system that controls body weight has increased exponentially over the last decade and has revealed new possibilities for the treatment of obesity and its associated comorbidities. One therapeutic target is the development of agents based on the gastrointestinal hormones that control appetite. This review discusses the hormones oxyntomodulin, peptide YY, glucagon-like peptide 1, pancreatic polypeptide, and ghrelin and their emerging potential as anti-obesity treatments.

Oxyntomodulin and peptide tyrosine-tyrosine (PYY) are released from intestinal enteroendocrine cells in response to a meal. These circulating hormones are considered to be satiety signals, as they have been found to decrease food intake, body weight and adiposity in rodents. Their effect on energy homeostasis is mediated by the hypothalamus and brainstem, and several studies have demonstrated alterations in neuropeptide signaling within the arcuate nucleus. The weight loss that has been observed in animal models after repeated administration of oxyntomodulin and PYY has led to interest in developing these peptides as antiobesity therapies in humans. Indeed, preliminary studies have found that oxyntomodulin or PYY administration reduces food intake and body weight effectively in overweight human volunteers. This research suggests that modulation of these gut hormones could prove to be effective long-term therapies in the quest to combat the obesity epidemic.

The worsening global epidemic of obesity has increased the urgency of research aimed at understanding the mechanisms of appetite regulation. An important aspect of the complex pathways involved in modulating energy intake is the interaction between hormonal signals of energy status released from the gut in response to a meal, and appetite centres in the brain and brainstem. In particular, the gut peptides cholecystokinin, peptide YY, glucagon-like peptide 1, oxyntomodulin and pancreatic polypeptide have been implicated in signaling satiety post-prandially. The ultimate goal of work in this field is the development of effective treatments for obesity, and manipulation of these gut-brain axes offers potentially useful strategies for the conquest of this significant cause of morbidity and mortality and future burden on healthcare systems worldwide.

Many peptides are synthesized and released from the gastrointestinal tract and pancreas, including pancreatic polypeptide (PP) and the products of the gastrointestinal L cells, glucagon-like peptide 1 (GLP-1), oxyntomodulin, and peptide YY (PYY). Whereas their roles in regulation of gastrointestinal function have been known for some time, it is now evident that they also influence eating behavior. This review considers the anorectic peptides PYY, PP, GLP-1, and oxyntomodulin, which decrease appetite and promote satiety in both animal models and humans.

Malnutrition is a common complication in patients on dialysis and is strongly associated with poor prognosis. Effective therapy could substantially improve morbidity and mortality, but neither enteral nor parenteral supplementation provide long-term benefit because of the strong appetite suppression seen in such patients. We performed a double-blinded randomized crossover study of a week-long treatment with daily subcutaneous ghrelin, a gut hormone that regulates hunger through the hypothalamus, in a group of 12 malnourished dialysis patients. Ghrelin administration increased ghrelin levels in circulation, modestly reduced blood pressure for up to 2 h, and immediately and significantly increased appetite, with an increase in energy intake noted at the first study meal. Persistence of this effect throughout the week was confirmed with food diaries and final study meals. Energy expenditure, measured with free-living pulse and motion monitors, was unchanged by ghrelin. Our study shows that daily treatment with ghrelin achieves a sustained positive change in energy balance in malnourished dialysis patients. Direct manipulation of appetite with ghrelin or its analogs represents an attractive and promising therapeutic strategy for this difficult clinical problem.