© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION Inflammatory processes are thought to be involved in kidney function decline in individuals with type 2 diabetes. Glycosylation of immunoglobulin G (IgG) is an important post-translation process affecting the inflammatory potential of IgG. We investigated the prospective relationship between IgG N-glycosylation patterns and kidney function in type 2 diabetes. RESEARCH DESIGN AND METHODS In the DiaGene study, an all-lines-of-care case-control study (n=1886) with mean prospective follow-up of 7.0 years, the association between 58 IgG N-glycan profiles and estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) per year and during total follow-up was analyzed. Models were adjusted for clinical variables and multiple comparisons. RESULTS Eleven traits were significantly associated with eGFR change per year.  https://www.selleckchem.com/products/Gefitinib.html  Bisecting GlcNAc in fucosylated and fucosylated disialylated structures and monosialylation of fucosylated digalactosylated structures were associated with a faster decrease of eGFR. Fucosylation of neutral and monogalactosylated structures was associated with less eGFR decline per year. No significant associations between IgG glycans and ACR were found. CONCLUSIONS In type 2 diabetes, we found IgG N-glycosylation patterns associated with a faster decline of kidney function, reflecting a pro-inflammatory state of IgG. eGFR, but not ACR, was associated with IgG glycans, which suggests these associations may represent renal macroangiopathy rather than microvascular disease. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.Antimicrobial resistance (AMR) is a critical global health threat with a disproportionate impact on low-income and middle-income countries (LMICs) due to their higher burden of infections, reduced laboratory surveillance infrastructure and fewer regulations governing antimicrobial use among humans or animals. While there have been increasing descriptions of AMR within many LMICs in WHO's Western Pacific and South East Asian regions, there remains a paucity of data from Pacific Island countries and territories (PICTs). The PICTs represent 22 predominantly middle-income countries and territories with a combined population of 12 million people and 20 official languages, spread over hundreds of separate islands spanning an area corresponding to more than 15% of the earth's surface. Our paper outlines the present state of the evidence regarding AMR in PICTs-discussing the present estimates of AMR and their accompanying limitations, important drivers of AMR, as well as outlining key priorities and potential solutions for tackling AMR in this region. Significant areas for action include developing National Action Plans, strengthening laboratory surveillance systems and educational activities targeted at both healthcare workers and the wider community. Ensuring adequate funding for AMR activities in PICTs is challenging given competing health and environmental priorities, in this context global or regional funding initiatives such as the Fleming Fund can play a key role. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.Monogenic forms of obesity have been identified in ≤10% of severely obese European patients. However, the overall spectrum of deleterious variants (point mutations and structural variants) responsible for childhood severe obesity remains elusive. In this study, we genetically screened 225 severely obese children from consanguineous Pakistani families through a combination of techniques including an in-house developed augmented whole-exome sequencing (CoDE-seq) enabling simultaneous detection of whole exome copy number variations (CNVs) and of point mutations in coding regions. We identified 110 probands (49%) carrying 55 different pathogenic point mutations and CNVs in 13 genes/loci responsible for non-syndromic and syndromic monofactorial obesity. CoDE-seq also identified 28 rare or novel CNVs associated with intellectual disability in 22 additional obese subjects (10%). Additionally, we highlight variants in candidate genes for obesity warranting further investigation. Altogether, 59% of the studied cohort are likely to have a discrete genetic cause with 13% of these due to CNVs demonstrating a remarkably higher prevalence of monofactorial obesity than hitherto reported and a plausible over lapping of obesity and intellectual disabilities in several cases. Finally, inbred populations with high prevalence of obesity, provide a unique genetically enriched material in quest of new genes/variants influencing energy balance. © 2020 by the American Diabetes Association.We conducted a two-sample Mendelian randomisation study to investigate the causal associations of type 2 diabetes mellitus (T2DM) with risk of overall cancer and 22 site-specific cancers. Summary-level data for cancer were extracted from the Breast Cancer Association Consortium and UK Biobank. Genetic predisposition to T2DM was associated with higher odds of pancreatic, kidney, uterine and cervical cancer, lower odds of oesophageal cancer and melanoma, but not associated with 16 other site-specific cancers or overall cancer. The odds ratios (95% confidence interval) were 1.13 (1.04, 1.22), 1.08 (1.00, 1.17), 1.08 (1.01, 1.15), 1.07 (1.01, 1.15), 0.89 (0.81, 0.98), and 0.93 (0.89, 0.97) for pancreatic, kidney, uterine, cervical, and oesophageal cancer and melanoma, respectively. The association between T2DM and pancreatic cancer was also observed in a meta-analysis of this and a previous Mendelian randomisation study (odds ratio 1.08; 1.02, 1.14; p=0.009). There was limited evidence supporting causal associations between fasting glucose and cancer. Genetically predicted fasting insulin levels were positively associated with cancers of the uterus, kidney, pancreas and lung. The present study found causal detrimental effects of T2DM on several cancers. We suggested to reinforce the cancers screening in T2DM patients to enable the early detection of cancer. © 2020 by the American Diabetes Association.