Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans

Background: Exogenous use of the intestinal hormone glucagon-like peptide 1 (GLP-1) lowers glycaemia by stimulation of insulin, inhibition of glucagon, and delay of gastric emptying.Aims: To assess the effects of endogenous GLP-1 on endocrine pancreatic secretion and antro-pyloro-duodenal motility by utilising the GLP-1 receptor antagonist exendin(9-39)amide (ex(9-39)NH2).Methods: Nine healthy volunteers underwent four experiments each. In two experiments with and without intravenous infusion of ex(9-39)NH2 300 pmol/kg/min, a fasting period was followed by intraduodenal glucose perfusion at 1 and 2.5 kcal/min, with the higher dose stimulating GLP-1 release. Antro-pyloro-duodenal motility was measured by perfusion manometry. To calculate the incretin effect (that is, the proportion of plasma insulin stimulated by intestinal hormones) the glycaemia observed during the luminal glucose experiments was mimicked using intravenous glucose in two further experiments.Results: Ex(9-39)NH2 significantly increased glycaemia during fasting and duodenal glucose. It diminished plasma insulin during duodenal glucose and significantly reduced the incretin effect by approximately 50%. Ex(9-39)NH2 raised plasma glucagon during fasting and abolished the decrease in glucagon at the high duodenal glucose load. Ex(9-39)NH2 markedly stimulated antroduodenal contractility. At low duodenal glucose it reduced the stimulation of tonic and phasic pyloric motility. At the high duodenal glucose load it abolished pyloric stimulation.Conclusions: Endogenous GLP-1 stimulates postprandial insulin release. The pancreatic \textgreeka cell is under the tonic inhibitory control of GLP-1 thereby suppressing postprandial glucagon. GLP-1 tonically inhibits antroduodenal motility and mediates the postprandial inhibition of antral and stimulation of pyloric motility. We therefore suggest GLP-1 as a true incretin hormone and enterogastrone in humans

Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes

Peer reviewe

Health care cost of crusted scabies in Aboriginal communities in the Northern Territory, Australia.

BACKGROUND: Crusted scabies is a debilitating dermatological condition. Although still relatively rare in the urban areas of Australia, rates of crusted scabies in remote Aboriginal communities in the Northern Territory (NT) are reported to be among the highest in the world. OBJECTIVE: To estimate the health system costs associated with diagnosing, treating and managing crusted scabies. METHODS: A disease pathway model was developed to identify the major phases of managing crusted scabies. In recognition of the higher resource use required to treat more severe cases, the pathway differentiates between crusted scabies severity grades. The disease pathway model was populated with data from a clinical audit of 42 crusted scabies patients diagnosed in the Top-End of Australia's Northern Territory between July 1, 2016 and May 1, 2018. These data were combined with standard Australian unit costs to calculate the expected costs per patient over a 12-month period, as well as the overall population cost for treating crusted scabies. FINDINGS: The expected health care cost per patient diagnosed with crusted scabies is $35,418 Australian dollars (AUD) (95$27,000 to $43,800), resulting in an overall cost of$1,558,392AUD (95% CI: $1,188,000 to$1,927,200) for managing all patients diagnosed in the Northern Territory in a given year (2018). By far, the biggest component of the health care costs falls on the hospital system. DISCUSSION: This is the first cost-of-illness analysis for treating crusted scabies. Such analysis will be of value to policy makers and researchers by informing future evaluations of crusted scabies prevention programs and resource allocation decisions. Further research is needed on the wider costs of crusted scabies including non-financial impacts such as the loss in quality of life as well as the burden of care and loss of well-being for patients, families and communities

Impaired Hyperglycemia-Induced Delay in Gastric Emptying in Patients With Type 1 Diabetes Deficient for Islet Amyloid Polypeptide

OBJECTIVE—Slowing of gastric emptying by hyperglycemia, a physiological response to minimize postprandial hyperglycemia, may be impaired in patients with type 1 diabetes. The causes and consequences on glucose homeostasis are unknown

The impact of financial incentives on the implementation of asthma or diabetes self-management: A systematic review

Introduction: Financial incentives are utilised in healthcare systems in a number of countries to improve quality of care delivered to patients by rewarding practices or practitioners for achieving set targets. Objectives: To systematically review the evidence investigating the impact of financial incentives for implementation of supported self-management on quality of care including: organisational process outcomes, individual behavioural outcomes, and health outcomes for individuals with asthma or diabetes; both conditions with an extensive evidence base for self-management. Methods: We followed Cochrane methodology, using a PICOS search strategy to search eight databases in November 2015 (updated May 2017) including a broad range of implementation methodologies. Studies were weighted by robustness of methodology, number of participants and the quality score. We used narrative synthesis due to heterogeneity of studies. Results: We identified 2,541 articles; 12 met our inclusion criteria. The articles were from the US (n = 7), UK (n = 4) and Canada (n = 1). Measured outcomes were HbA1c tests undertaken and/or the level achieved (n = 10), written action plans for asthma (n = 1) and hospital/emergency department visits (n = 1). Three of the studies were part of a larger incentive scheme including many conditions; one focused on asthma; eight focussed on diabetes. In asthma, the proportion receiving ‘perfect care’ (including providing a written action plan) increased from 4% to 88% in one study, and there were fewer hospitalisations/emergency department visits in another study. Across the diabetes studies, quality-of-care/GP performance scores improved in three, were unchanged in six and deteriorated in one. Conclusions: Results for the impact of financial incentives for the implementation of self-management were mixed. The evidence in diabetes suggests no consistent impact on diabetic control. There was evidence from a single study of improved process and health outcomes in asthma. Further research is needed to confirm these findings and understand the process by which financial incentives may impact (or not) on care

Understanding diabetes in patients with HIV/AIDS

This paper reviews the incidence, pathogenetic mechanisms and management strategies of diabetes mellitus in patients with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). It classifies patients based on the aetiopathogenetic mechanisms, and proposes rational methods of management of the condition, based on aetiopathogenesis and concomitant pharmacotherapy

Safety, tolerability and effects on cardiometabolic risk factors of empagliflozin monotherapy in drug-naïve patients with type 2 diabetes: a double-blind extension of a Phase III randomized controlled trial

BACKGROUND: To investigate the long-term efficacy and safety of empagliflozin monotherapy compared with placebo and sitagliptin in drug-naïve patients with type 2 diabetes mellitus. METHODS: Of 899 patients randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, placebo, or sitagliptin 100 mg once daily for 24 weeks, 615 continued in a double-blind extension trial for ≥52 weeks. Exploratory endpoints included changes from baseline in HbA1c, weight and blood pressure at week 76. RESULTS: Compared with placebo, adjusted mean changes from baseline in HbA1c at week 76 were −0.78 % (95 % CI −0.94, −0.63; p < 0.001) and −0.89 % (95 % CI −1.04, −0.73; p < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Compared with placebo, adjusted mean changes from baseline in weight at week 76 were −1.8 kg (95 % CI −2.4, −1.3; p < 0.001) and −2.0 kg (95 % CI −2.6, −1.5; p < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Empagliflozin led to reductions in systolic blood pressure (SBP) compared with placebo in the primary analysis but not in sensitivity analyses. Compared with sitagliptin, empagliflozin 25 mg reduced HbA1c and both empagliflozin doses reduced weight and SBP. Adverse events (AEs) were reported in 76.8, 78.0, 76.4 and 72.2 % of patients on empagliflozin 10 mg, empagliflozin 25 mg, placebo and sitagliptin, respectively. Confirmed hypoglycaemic AEs (glucose ≤3.9 mmol/l and/or requiring assistance) were reported in two patients (0.9 %) per treatment group. CONCLUSIONS: Empagliflozin monotherapy for ≥76 weeks was well tolerated and led to sustained reductions in HbA1c and weight compared with placebo

Effect of blood glucose level on standardized uptake value (SUV) in F-18- FDG PET-scan : a systematic review and meta-analysis of 20,807 individual SUV measurements

Objectives To evaluate the effect of pre-scan blood glucose levels (BGL) on standardized uptake value (SUV) in F-18-FDG-PET scan. Methods A literature review was performed in the MEDLINE, Embase, and Cochrane library databases. Multivariate regression analysis was performed on individual datum to investigate the correlation of BGL with SUVmax and SUVmean adjusting for sex, age, body mass index (BMI), diabetes mellitus diagnosis, F-18-FDG injected dose, and time interval. The ANOVA test was done to evaluate differences in SUVmax or SUVmean among five different BGL groups (200 mg/dl). Results Individual data for a total of 20,807 SUVmax and SUVmean measurements from 29 studies with 8380 patients was included in the analysis. Increased BGL is significantly correlated with decreased SUVmax and SUVmean in brain (p <0.001, p <0.001,) and muscle (p <0.001, p <0.001) and increased SUVmax and SUVmean in liver (p = 0.001, p = 0004) and blood pool (p=0.008, p200 mg/dl had significantly lower SUVmax. Conclusion If BGL is lower than 200mg/dl no interventions are needed for lowering BGL, unless the liver is the organ of interest. Future studies are needed to evaluate sensitivity and specificity of FDG-PET scan in diagnosis of malignant lesions in hyperglycemia.Peer reviewe

Efficacy and safety of linagliptin in persons with Type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24-week randomized study1

Aims To examine the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in persons with Type 2 diabetes mellitus inadequately controlled [HbA1c 53–86 mmol/mol (7.0–10.0%)] by metformin and sulphonylurea combination treatment. Methods A multi-centre, 24-week, randomized, double-blind, parallel-group study in 1058 patients comparing linagliptin (5 mg once daily) and placebo when added to metformin plus sulphonylurea. The primary endpoint was the change in HbA1c after 24 weeks. Results At week 24, the linagliptin placebo-corrected HbA1c adjusted mean change from baseline was −7 mmol/mol (−0.62%) [95% CI −8 to −6 mmol/mol (−0.73 to −0.50%); P < 0.0001]. More participants with baseline HbA1c≥ 53 mmol/mol (≥ 7.0%) achieved an HbA1c < 53 mmol/mol (< 7.0%) with linagliptin compared with placebo (29.2% vs. 8.1%, P < 0.0001). Fasting plasma glucose was reduced with linagliptin relative to placebo (−0.7 mmol/l, 95% CI −1.0 to −0.4; P < 0.0001). Improvements in homeostasis model assessment of β-cell function were seen with linagliptin (P < 0.001). The proportion of patients who reported a severe adverse event was low in both groups (linagliptin 2.4%; placebo 1.5%). Symptomatic hypoglycaemia occurred in 16.7 and 10.3% of the linagliptin and placebo groups, respectively. Hypoglycaemia was generally mild or moderate; severe hypoglycaemia was reported in 2.7 and 4.8% of the participants experiencing hypoglycaemic episodes in the linagliptin and placebo groups, respectively. No significant weight changes were noted. Conclusions In patients with Type 2 diabetes, adding linagliptin to metformin given in combination with a sulphonylurea significantly improved glycaemic control and this was well tolerated. Linagliptin could provide a valuable treatment option for individuals with inadequate glycaemic control despite ongoing combination therapy with metformin and a sulphonylurea