Changes in the hormone producing pancreatic islet cells are culprits in the development of diabetes, and these changes are often reflected by changes in expression of key genes. Analysis of such changes require advanced bioinformatics tools that can translate the process into simple visible information.To achieve these goals we have developed a tool called Islet Gene View (IGW), that aims to make information on gene expression in human pancreatic islets from organ donors easily accessible to the scientific community. Islet Gene View currently consists of information on islets from 188 donors where data on RNA expression of more than 15 000 genes can be related to phenotypic information (gender, age, BMI, HbA1c, insulin and glucagon secretion etc.). Also this information can be related to expression other genes and how gene expression is regulated by genetic variants(so called eQTLs, expression Quantitative Traits) The data will be accessible thorugh the easy-to-use Islet Gene View web application.2 Significance StatementWe present Islet Gene View (IGW), a web resource that aims to make information on gene expression in human pancreatic islets from organ donors easily accessible to the scientific community. In IGW, we leveraged global RNA expression data from 191 donor-islets to understand their relationship with islet phenotypes such as gender, age, BMI, HbA1c, insulin and glucagon secretion as well as with islet hormones coding genes. GWAS based on European studies have shown that 403 genetic variants associate with T2D risk however the target genes and function in islets are largely unknown. We linked T2D risk variants to gene expression in islets and further functionally report if their expression is modulated in relation to T2D status and other related features.3

Characterization of gene expression in pancreatic islets and its alteration in type 2 diabetes (T2D) are vital in understanding islet function and T2D pathogenesis. We leveraged RNA sequencing and genome-wide genotyping in islets from 188 donors to create the Islet Gene View (IGW) platform to make this information easily accessible to the scientific community. Expression data were related to islet phenotypes, diabetes status, other islet-expressed genes, islet hormone-encoding genes and for expression in insulin target tissues. The IGW web application produces output graphs for a particular gene of interest. In IGW, 284 differentially expressed genes (DEGs) were identified in T2D donor islets compared with controls. Forty percent of DEGs showed cell-type enrichment and a large proportion significantly co-expressed with islet hormone-encoding genes; glucagon (GCG, 56%), amylin (IAPP, 52%), insulin (INS, 44%), and somatostatin (SST, 24%). Inhibition of two DEGs, UNC5D and SERPINE2, impaired glucose-stimulated insulin secretion and impacted cell survival in a human β-cell model. The exploratory use of IGW could help designing more comprehensive functional follow-up studies and serve to identify therapeutic targets in T2D.

Background Middle Eastern immigrants to Europe represent a high risk population for type 2 diabetes. We compared prevalence of novel subgroups and assessed risk of diabetic macro‐ and microvascular complications between diabetes patients of Middle Eastern and European origin. Methods This study included newly diagnosed diabetes patients born in Sweden (N = 10641) or Iraq (N = 286), previously included in the All New Diabetes in Scania cohort. The study was conducted between January 2008 and August 2016. Patients were followed to April 2017. Incidence rates in diabetic macro‐ and microvascular complications were assessed using cox‐regression adjusting for the confounding effect of age at onset, sex, anthropometrics, glomerular filtration rate (eGFR) and HbA1c. Findings In Iraqi immigrants versus native Swedes, severe insulin‐deficient diabetes was almost twice as common (27.9 vs. 16.2% p < 0.001) but severe insulin‐resistant diabetes was less prevalent. Patients born in Iraq had higher risk of coronary events (hazard ratio [HR] 1.84, 95% CI 1.06–3.12) but considerably lower risk of chronic kidney disease (CKD) than Swedes (HR 0.19; 0.05–0.76). The lower risk in Iraqi immigrants was partially attributed to better eGFR. Genetic risk scores (GRS) showed more genetic variants associated with poor insulin secretion but lower risk of insulin resistance in the Iraqi than native Swedish group. Interpretation People with diabetes, born in the Middle East present with a more insulin‐deficient phenotype and genotype than native Swedes. They have a higher risk of coronary events but lower risk of CKD. Ethnic differences should be considered in the preventive work towards diabetes and its complications.

Diabetes increases the risk of bacterial infections. We investigated whether common genetic variants associate with infection susceptibility in Finnish diabetic individuals. We performed genome-wide association studies and pathway analysis for bacterial infection frequency in Finnish adult diabetic individuals (FinnDiane Study; N = 5092, Diabetes Registry Vaasa; N = 4247) using national register data on antibiotic prescription purchases. Replication analyses were performed in a Swedish diabetic population (ANDIS; N = 9602) and in a Finnish non-diabetic population (FinnGen; N = 159,166). Genome-wide data indicated moderate but significant narrow-sense heritability for infection susceptibility (h2 = 16%, P = 0.02). Variants on chromosome 2 were associated with reduced infection susceptibility (rs62192851, P = 2.23 × 10–7). Homozygotic carriers of the rs62192851 effect allele (N = 44) had a 37% lower median annual antibiotic purchase rate, compared to homozygotic carriers of the reference allele (N = 4231): 0.38 [IQR 0.22–0.90] and 0.60 [0.30–1.20] respectively, P = 0.01). Variants rs6727834 and rs10188087, in linkage disequilibrium with rs62192851, replicated in the FinnGen-cohort (P < 0.05), but no variants replicated in the ANDIS-cohort. Pathway analysis suggested the IRAK1 mediated NF-κB activation through IKK complex recruitment-pathway to be a mediator of the phenotype. Common genetic variants on chromosome 2 may associate with reduced risk of bacterial infections in Finnish individuals with diabetes.