Effectiveness of Liraglutide and Lixisenatide in the Treatment of Type 2 Diabetes: Real-World Evidence from The Health Improvement Network (THIN) Database in the United Kingdom.

INTRODUCTION: The glucagon-like peptide-1 receptor agonists liraglutide and lixisenatide are effective at reducing glycated hemoglobin (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM). Although liraglutide has demonstrated superior efficacy in head-to-head clinical trials, real-world evidence of comparative effectiveness is lacking. This observational study aimed to assess the effectiveness of liraglutide versus lixisenatide in UK clinical practice. METHODS: Electronic medical records from The Health Improvement Network (THIN) UK primary care database were analyzed. Patients aged ≥18 years, diagnosed with T2DM, and prescribed liraglutide or lixisenatide between 01 May 2013 and 31 December 2015 were included in the study. Adjusted linear regression models compared the difference in mean change in HbA1c, body mass index (BMI), and systolic blood pressure (SBP) after 12-month follow-up. The proportion of patients achieving glycemic control (HbA1c 1%; and weight reduction ≥3% within 12 months were determined. Cox proportional hazards modeling was used to evaluate the effect of treatment on time to achieving HbA1c and weight reduction targets. Healthcare resource use (HCRU) (GP, secondary care, hospitalizations) was compared using analysis of covariance. RESULTS: The primary outcome was assessed in 579 liraglutide and 213 lixisenatide new users. Fully adjusted linear regression indicated that liraglutide reduced HbA1c significantly more than lixisenatide (mean treatment difference -0.30; 95% CI -0.56, -0.04; p = 0.025). Compared to lixisenatide, liraglutide recipients were 2.5 times more likely to achieve HbA1c 1% HbA1c reduction (HR 1.29; p = 0.0002). BMI and SBP reductions were greater for the liraglutide group but results were not significant. HCRU was comparable between treatment groups. CONCLUSION: These results from the THIN database indicate that liraglutide treatment provided better outcomes related to glycemic control. FUNDING: Novo Nordisk

Regulering og prisdannelse i det norske frukt- og grøntmarkedet

Frukt- og grøntsektoren i Norge skiller seg fra øvrige landbrukssektorer ved at den ikke omfattes av en markedsregulator med mottaksplikt og reguleringsansvar. Dette innebærer at markedet i større grad er styrt av frivillige ordninger og kommersielle relasjoner. I en tid preget av økende geopolitisk uro og handelsbarrierer, er det økende behov for nasjonal matsikkerhet og en robust norsk produksjon. På bakgrunn av dette fremstår det som relevant å undersøke hvordan produsentprisene fastsettes i praksis. Studien har følgende problemstilling: Hvordan brukes kontrakter i frukt- og grøntsektoren, og hvordan påvirker dette produsentprisene? For å besvare problemstillingen er det gjennomført en kvalitativ casestudie basert på dybdeintervjuer med åtte informanter fra ulike ledd i verdikjeden for frukt og grønt. Fokuset har vært på verdikjeden knyttet til produsentorganisasjonen Gartnerhallen og grossistleddet Bama. Studien er avgrenset til den delen av markedet som leverer konsumvarer til dagligvareleddet. Bamas verdikjede er sammensatt og inkluderer både produsenter tilknyttet Gartnerhallen, uavhengige norske aktører og utenlandske leverandører. Produktene distribueres videre til blant annet NorgesGruppen og Rema, samt storkjøkken og industri gjennom Bamas øvrige forretningsområder. Selv om import utgjør en betydelig del av volumet, har denne studien fokusert på norskproduserte varer. Funnene viser at bruk av formelle kontrakter mellom produsent og grossist er begrenset. I stedet er samhandlingen organisert gjennom langsiktige avtaler mellom Bama og Gartnerhallen, mens produsentene forholder seg til medlemskap og produksjonsplaner i produsentorganisasjonene. Disse strukturene fungerer som rammeverk for produksjon og levering, mens produsentprisene blir fastsatt gjennom prisanbefalinger fra markedsmøtet som GPS avholder på Langhus.The fruit and vegetable sector in Norway differs from other agricultural sectors in that it is not subject to a market regulator with purchasing obligations and regulatory responsibility. As a result, the market is to a greater extent governed by voluntary arrangements and commercial relationships. In a time marked by increasing geopolitical instability and trade barriers, there is a growing need for national food security and a robust domestic production system. Against this backdrop, it is relevant to examine how producer prices are determined in practice. This study addresses the following research question: How are contracts used in the fruit and vegetable sector, and how does this affect producer prices? To answer this question, a qualitative case study was conducted based on in-depth interviews with eight informants representing various parts of the fruit and vegetable value chain. The study focuses on the segment connected to the producer organization Gartnerhallen and the wholesaler Bama, and is limited to products sold as fresh produce through the grocery retail market. Bama’s value chain is complex and includes producers affiliated with Gartnerhallen, independent Norwegian actors, and foreign suppliers. The products are distributed to, among others, NorgesGruppen and Rema 1000, as well as to the foodservice and processing industries through Bama’s other business units. Although imports constitute a significant share of the total volume, this study focuses on Norwegian-produced goods. The findings show that formal contracts between producers and wholesalers are limited. Instead, interactions are organized through long-term agreements between Bama and Gartnerhallen, while producers operate under membership terms and production plans issued by their producer organizations. These structures serve as a framework for production and delivery, while producer prices are determined through price recommendations established during the market meeting held by GPS at Langhus

The Association of Alcohol and Alcohol Metabolizing Gene Variants with Diabetes and Coronary Heart Disease Risk Factors in a White Population

BACKGROUND: Epidemiological studies have shown a J- or U-shaped relation between alcohol and type 2 diabetes and coronary heart disease (CHD). The underlying mechanisms are not clear. The aim was to examine the association between alcohol intake and diabetes and intermediate CHD risk factors in relation to selected ADH and ALDH gene variants. METHODOLOGY/PRINCIPAL FINDINGS: Cross-sectional study including 6,405 Northern European men and women aged 30-60 years from the general population of Copenhagen, Denmark. Data were collected with self-administered questionnaires, a physical examination, a 2 hour oral glucose tolerance test, and various blood tests. J shaped associations were observed between alcohol and diabetes, metabolic syndrome (MS), systolic and diastolic blood pressure, triglyceride, total cholesterol, and total homocysteine. Positive associations were observed with insulin sensitivity and HDL cholesterol, and a negative association with insulin release. Only a few of the selected ADH and ALDH gene variants was observed to have an effect. The ADH1c (rs1693482) fast metabolizing CC genotype was associated with an increased risk of impaired glucose tolerance (IGT)/diabetes compared to the CT and TT genotypes. Significant interactions were observed between alcohol and ADH1b (rs1229984) with respect to LDL and between alcohol and ALDH2 (rs886205) with respect to IGT/diabetes. CONCLUSIONS/SIGNIFICANCE: The selected ADH and ALDH gene variants had only minor effects, and did not seem to markedly modify the health effects of alcohol drinking. The observed statistical significant associations would not be significant, if corrected for multiple testing

Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits

The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Throug

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

This is the final version of the article. Available from the publisher via the DOI in this record.Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways

Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

Allosteric “beta-blocker” isolated from a DNA-encoded small molecule library

The present study reports the discovery of a small-molecule negative allosteric modulator for the β2-adrenergic receptor (β2AR) via in vitro affinity-based iterative selection of highly diverse DNA-encoded small-molecule libraries. Characterization of the compound demonstrates its selectivity for the β2AR and that it negatively modulates a wide range of receptor functions. More importantly, our findings establish a generally applicable, proof-of-concept strategy for screening DNA-encoded small-molecule libraries against purified G-protein–coupled receptors (GPCRs), which holds great potential for discovering therapeutic molecules

The prognosis for individuals on disability retirement An 18-year mortality follow-up study of 6887 men and women sampled from the general population

BACKGROUND: Several studies have shown a markedly higher mortality rate among disability pensioners than among non-retired. Since most disability pensions are granted because of non-fatal diseases the reason for the increased mortality therefore remains largely unknown. The aim of this study was to evaluate potential explanatory factors. METHODS: Data from five longitudinal cohort studies in Sweden, including 6,887 men and women less than 65 years old at baseline were linked to disability pension data, hospital admission data, and mortality data from 1971 until 2001. Mortality odds ratios were analyzed with Poisson regression and Cox's proportional hazards regression models. RESULTS: 1,683 (24.4%) subjects had a disability pension at baseline or received one during follow up. 525 (7.6%) subjects died during follow up. The subjects on disability pension had a higher mortality rate than the non-retired, the hazards ratio (HR) being 2.78 (95%CI 2.08–3.71) among women and 3.43 (95%CI 2.61–4.51) among men. HR was highest among individuals granted a disability pension at young ages (HR >7), and declined parallel to age at which the disability pension was granted. The higher mortality rate among the retired subjects was not explained by disability pension cause or underlying disease or differences in age, marital status, educational level, smoking habits or drug abuse. There was no significant association between reason for disability pension and cause of death. CONCLUSION: Subjects with a disability pension had increased mortality rates as compared with non-retired subjects, only modestly affected by adjustments for psycho-socio-economic factors, underlying disease, etcetera. It is unlikely that these factors were the causes of the unfavorable outcome. Other factors must be at work