Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Differential White Blood Cell Count and Type 2 Diabetes: Systematic Review and Meta-Analysis of Cross-Sectional and Prospective Studies

Objective: Biological evidence suggests that inflammation might induce type 2 diabetes (T2D), and epidemiological studies have shown an association between higher white blood cell count (WBC) and T2D. However, the association has not been systematically investigated.Research Design and Methods: Studies were identified through computer-based and manual searches. Previously unreported studies were sought through correspondence. 20 studies were identified (8,647 T2D cases and 85,040 non-cases). Estimates of the association of WBC with T2D were combined using random effects meta-analysis; sources of heterogeneity as well as presence of publication bias were explored.Results: The combined relative risk (RR) comparing the top to bottom tertile of the WBC count was 1.61 (95% CI: 1.45; 1.79, p = 1.5*10(-18)). Substantial heterogeneity was present (I-2 = 83%). For granulocytes the RR was 1.38 (95% CI: 1.17; 1.64, p = 1.5*10(-4)), for lymphocytes 1.26 (95% CI: 1.02; 1.56, p = 0.029), and for monocytes 0.93 (95% CI: 0.68; 1.28, p = 0.67) comparing top to bottom tertile. In cross-sectional studies, RR was 1.74 (95% CI: 1.49; 2.02, p = 7.7*10(-13)), while in cohort studies it was 1.48 (95% CI: 1.22; 1.79, p = 7.7*10(-5)). We assessed the impact of confounding in EPIC-Norfolk study and found that the age and sex adjusted HR of 2.19 (95% CI: 1.74; 2.75) was attenuated to 1.82 (95% CI: 1.45; 2.29) after further accounting for smoking, T2D family history, physical activity, education, BMI and waist circumference.Conclusions: A raised WBC is associated with higher risk of T2D. The presence of publication bias and failure to control for all potential confounders in all studies means the observed association is likely an overestimate

Basic Anthropometric Measures in Acute Myocardial Infarction Patients and Individually Sex- and Age-Matched Controls from the General Population

We compared weight, height, waist and hip circumferences (hip), body mass index (BMI), and waist-to-hip ratio in acute myocardial infarction (MI) patients and individually sex-and age-matched control subjects from the general population in the catchment area of the patients and predicted the risk of MI status by these basic anthropometric measures. The study cohort comprised 748 patients &lt;= 80 years of age with acute MI from a major Swedish cardiac center and their individually sex- and age-matched controls. The analyses were stratified for sex and age (&lt;= 65/&gt;= 66 years). Risk of MI was assessed by conditional logistic regression. A narrow hip in men &gt;66 years was the single strongest risk factor of MI among the anthropometric measures. The combination of hip and weight was particularly efficient in discriminating men &gt;= 66 years with MI from their controls (area under the receiver operating characteristic (AUROC) curve = 0.82). In men &lt;= 65 years, the best combination was hip, BMI, and height (AUROC = 0.79). In women &gt;= 66 years, the best discriminatory model contained only waist-to-hip ratio (AUROC = 0.67), whereas in women &lt;= 65 years, the best combination was hip and BMI (AUROC = 0.68). A narrow hip reasonably reflects small gluteal muscles. This finding might suggest an association between MI and sarcopenia, possibly related to deficiencies in physical activity and nutrition.Corrigendum in: Journal of Obesity, Volume 2018, Article ID 3126805, https://doi.org/10.1155/2018/3126805</p

Blockchain as enabler of organizational innovations

Blokķēdes tehnoloģija kļuva plaši pazīstama 2017.gada beigās kriptovalūtas Bitcoin cenas straujas kāpšanas dēļ. Taču vienprātības algoritmi, kas ir blokķēdes tehnoloģijas pamatā, jau ir samēra labi izpētīti vairākas desmitgades. Šie algoritmi ir domāti patiesības noteikšanai sadalītā sistēmā, kur dalībnieku integritāte nav ietverta. Ir jāatzīst, ka Bitcoin ir pirmais veiksmīgais šo ideju iemiesojums. Šis darbs pēta blokķēdes un to fundamentālās tehnoloģijas ar mērķi izprast, vai tās ir pietiekami revolucionāras, lai mainītu veidu, kā organizācijas reģistrē savus darījumus, izraisot inovāciju vilni, kad blokķēžu tehnoloģijas ieviešana kļūs par izdzīvošanas jautājumu.Blockchain technology became widely known at the end of 2017 thanks to the spike in the price of Bitcoin cryptocurrency. Consensus algorithms that form the foundation of blockchain technology were research topics for already several decades. Those algorithms are meant for truth determination in distributed systems where participants’ integrity is not guaranteed. It should be admitted though, that Bitcoin became the first widely known successful implementation of the blockchain technology. Current paper researches blockchain and its underlying technologies with the goal to understand whether they are revolutionary enough to change the way how organizational transactions are recorded, leading to destructive wave of innovation in organizations, where the question of implementing blockchain will become a question of survival

Long-term follow-up of a high- and a low-intensity smoking cessation intervention in a dental setting- a randomized trial

Background: Achieving lifelong tobacco abstinence is an important public health goal. Most studies use 1-year follow-ups, but little is known about how good these are as proxies for long-term and life-long abstinence. Also, intervention intensity is an important issue for development of efficient and cost-effective cessation treatment protocols. The study aims were to assess the long-term effectiveness of a high-and a low-intensity treatment (HIT and LIT) for smoking cessation and to analyze to what extent 12-month abstinence predicted long-term abstinence. Methods: 300 smokers attending dental or general health care were randomly assigned to HIT or LIT at the public dental clinic. Main outcome measures were self-reported point prevalence, continuous abstinence (&gt;= 6 months), and sustained abstinence. The study was a follow-up after 5-8 years of a previously performed 12-month follow-up, both by postal questionnaires. Results: Response rate was 85% (n=241) of those still alive and living in Sweden. Abstinence rates were 8% higher in both programs at the long-term than at the 12-month follow-up. The difference of 7% between HIT and LIT had not change, being 31% vs. 24% for point prevalence and 26% vs. 19% for 6-month continuous abstinence, respectively. Significantly more participants in HIT (12%) than in LIT (5%) had been sustained abstinent (p=0.03). Logistic regression analyses showed that abstinence at 12-month follow-up was a strong predictor for abstinence at long-term follow-up. Conclusions: Abstinence at 12-month follow-up is a good predictor for long-term abstinence. The difference in outcome between HIT and LIT for smoking cessation remains at least 5-8 years after the intervention

Genes encoding for AP-2 beta and the Serotonin Transporter are associated with the Personality Character Spiritual Acceptance

In several twin studies the relative contribution of genetic factors for personality traits has amounted to figures between 40 and 60%. In the present study we investigated to which degree polymorphisms in the 5-HTT and AP-2 beta genes are implicated in the neural processes involved in the formation of Temperament and Character traits, as estimated by Cloninger's TCI. Considering the background of previous reports, associations with the character Self-Transcendence and its sub-scale Spiritual Acceptance in particular, were of interest. A stratified random sample of 200 individuals (total population = 5173), matched for age, gender and risk behaviors, from volunteering 16- and 19-year-old adolescents students in Sweden was investigated. Cloninger's TCI inventory was used for investigation of temperament and character traits. Blood samples were used for analyses of a promoter serotonin transporter polymorphism (5-HTTLPR) and an intron 2 polymorphism in the transcription factor AP-2 beta gene. Among boys individuals with presence of the short 5-HTTLPR genotype showed lower scores, whereas individuals with presence of the short AP-2 beta genotype showed higher scores of personality character Self-Transcendence and its sub-scale Spiritual Acceptance. Among girls no effect of either genotype was found. Both among boys and girls, significant interactive effects were found between 5-HTTLPR and AP-2 beta genotypes, with regard to Self-Transcendence and Spiritual acceptance. Boys and girls with the combination of presence of the short 5-HTTLPR, and homozygosity for the long AP-2 beta genotype scored significantly lower on Self-Transcendence and Spiritual Acceptance. (c) 2006 Elsevier Ireland Ltd. All rights reserved