HLA-DQA1 and -DQB1 are strongly associated with type 1 diabetes (T1D), and DQ8.1 and DQ2.5 are major risk haplotypes. Next generation targeted sequencing of HLA-DQA1 and -DQB1 in Swedish newly diagnosed 1-18 year-old patients (n=962) and controls (n=636) was used to construct abbreviated DQ haplotypes, converted into amino acid (AA) residues, and assessed for their associations with T1D. A hierarchically-organized haplotype (HOH) association analysis, allowed 45 unique DQ haplotypes to be categorized into seven clusters. The DQ8/9 cluster included two DQ8.1 risk and the DQ9 resistant haplotypes, and the DQ2 cluster, included the DQ2.5 risk and DQ2.2 resistant haplotypes. Within each cluster, HOH found residues α44Q (OR 3.29, p=2.38*10^-85 ) and β57A (OR 3.44, p=3.80*10^-84) to be associated with T1D in the DQ8/9 cluster representing all ten residues (α22, α23, α44, α49, α51, α53, α54, α73, α184, β57) due to complete linkage-disequilibrium (LD) of α44 with eight such residues. Within the DQ2 cluster and due to LD, HOH analysis found α44C and β135D to share the risk for T1D (OR 2.10, p=1.96*10^-20). The motif "QAD" of α44, β57, and β135 captured the T1D risk association of DQ8.1 (OR 3.44, p=3.80*10^-84), the corresponding motif "CAD" captured the risk association of DQ2.5 (OR 2.10, p=1.96*10^-20). Two risk associations were related to GADA and IA-2A, but in opposite directions. "CAD" was positively associated with GADA (OR 1.56; p=6.35*10^-8) but negatively with IA-2A (OR 0.59, p= 6.55*10^-11). "QAD" was negatively associated with GADA (OR 0.88; p= 3.70*10^-3) but positively with IA-2A (OR 1.64; p= 2.40*10^-14), despite a single difference at α44. The residues are found in and around anchor pockets 1 and 9, as potential TCR contacts, in the areas for CD4 binding and putative homodimer formation. The identification of three HLA-DQ AA (α44, β57, β135) conferring T1D risk should sharpen functional and translational studies.

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.

Luigi Fontana
Apr 1, 2007; 56:1010-1013
Metabolism

Elisabeth F.C. van Rossum
Oct 1, 2002; 51:3128-3134
Genetics

Members Event

Event participants

Michelle Bachelet, United Nations High Commissioner for Human Rights

Chair: Ruma Mandal, Head, International Law Programme, Chatham House

Invitation Only Research Event

Event participants

Christopher Davis, Professorial Fellow, Institute of Population Ageing, University of Oxford
Samuel Greene, Director, King's Russia Institute; Reader of Russian Politics, King’s College London
Nikolai Petrov, Senior Research Fellow, Russia and Eurasia Programme, Chatham House
Natalia Zubarevich, Director, Regional Programme, Independent Institute for Social Policy

Invitation Only Research Event

Event participants

Iryna Brunova-Kalisetska, Independent Researcher, Trainer and Dialogue Facilitator
Maxim Ieligulashvili, Independent Researcher, Trainer and Dialogue Facilitator
Volodymyr Lupatsy, Co-founder, National Platform on Dialogue for Peace and Secure Reintegration; Board Member, Centre for Security and Development Research, Ukraine
Orysia Lutsevych, Research Fellow and Manager, Ukraine Forum, Chatham House

LOCAL MUSICIAN Janine JKUHL’s two-month-long immersive creative residency programme in Bali, Indonesia, has been extended indefinitely, or at least until the world has the COVID-19 spread under control and international airports open up to...

LOS ANGELES (AP) — It’s been over a decade since reggae king Buju Banton and R&B star John Legend collaborated on a song, and the Grammy winners have reunited for a new track. Banton and Legend released the easygoing love song...

Active maintenance of β-cell identity through fine-tuned regulation of key transcription factors ensures β-cell function. Tacrolimus, a widely used immunosuppressant, accelerates onset of diabetes after organ transplantation, but underlying molecular mechanisms are unclear. Here we show that tacrolimus induces loss of human β-cell maturity and β-cell failure through activation of the BMP/SMAD signaling pathway when administered under mild metabolic stress conditions. Tacrolimus-induced phosphorylated SMAD1/5 acts in synergy with metabolic stress–activated FOXO1 through formation of a complex. This interaction is associated with reduced expression of the key β-cell transcription factor MAFA and abolished insulin secretion, both in vitro in primary human islets and in vivo in human islets transplanted into high-fat diet–fed mice. Pharmacological inhibition of BMP signaling protects human β-cells from tacrolimus-induced β-cell dysfunction in vitro. Furthermore, we confirm that BMP/SMAD signaling is activated in protocol pancreas allograft biopsies from recipients on tacrolimus. To conclude, we propose a novel mechanism underlying the diabetogenicity of tacrolimus in primary human β-cells. This insight could lead to new treatment strategies for new-onset diabetes and may have implications for other forms of diabetes.

It could be argued that Ender Inciarte stands as the X-factor in regard to the Braves' bid to defend last year's National League East crown and experience a successful postseason.

The reality is setting in for Astros star second baseman Jose Altuve, who's shared a clubhouse with close friend Marwin Gonzalez for the previous seven springs. They became confidants on and off the field, which is what makes this spring so strange.

KINGSTON COLLEGE (KC) principal Dave Myrie has refuted claims that St Jago High School sprint hurdler Vashaun Vascianna will be joining the school this September. The Gleaner understands that Vascianna, who broke the Class Two boys’ 110m hurdles...

We talk about financial conflicts of interest a lot atThe BMJ - and have take taken the decision that our educational content should be without them. We also talk a lot about non-financial conflicts of interest, but the choppy waters of those are much more difficult to navigate. In this podcast, we discuss whether we should, or if we could even...

Non-medical interventions are increasingly being proposed to address wider determinants of health and to help patients improve health behaviours and better manage their conditions - this is known as social prescribing. In England, the NHS Long Term Plan states that nearly one million people will qualify for referral to social prescribing schemes...

A UK general election has been called - polling day is on the 12th of December, and from now until then we’re going to be bringing you a weekly election-themed podcast. We want to help you make sense of the promises and pledges, claims and counter-claims, that are being made around healthcare and the NHS out on the campaign trail. This week...

If you read the Christmas BMJ in the last few weeks, you might have noticed a lot around art and health - the way in which engagement in arts can help in prevention and treatment, but can also affect those more nebulous things which really matter to patients - loneliness, self expression, being connected to the wider community. That obviously...

Last week the BMJ published it’s first special edition into Racism in Medicine. The issues tacked ranged from differential attainment in medical school, to the physiological effects that experiencing everyday discrimination has. The issue was guest edited by Victor Adebowale, the Chief Executive of the social care enterprise Turning Point, and...

There is no doubt that anxiety levels that clinicians are feeling during this pandemic are high. One military medic believes the current situation is comparable to his experience when posted during British campaigns in Afghanistan and Iraq. Cormac Doyle offers advice on how to deal with high-stress conditions, both in a work and at home, as...

Samar I. Itani
Jul 1, 2002; 51:2005-2011
Rapid Publications

ME Griffin
Jun 1, 1999; 48:1270-1274
Articles

Many taxi and bus operators in sections of Kingston and St Andrew are seemingly adhering to social-distancing guidelines outlined by the Government for the sector, in terms of the number of passengers they are allowed to transport at a time. These...

THE EDITOR, Madam May is Child Month, and we, as parents, would show love and appreciation by taking out our kids for recreation, but instead, we have to keep them indoors because of a bush tiger called coronavirus. Every year at this time, I...

THE EDITOR, Madam: The right to education, decent work, an adequate standard of living, and housing all fall within the realm of economic, social, and cultural rights (ESCRs) guaranteed under the International Covenant on Economic, Social and...

The number of people in Germany infected with covid-19, could be 10 times higher than official government estimates, according to a new study by University of Bonn researchers.1The Heinsberg study is...

4 November 2019

The third Social Innovation for Refugee Inclusion conference in Brussels, co-organized by MPI Europe with the U.S. and Canadian Missions to the European Union and the European Economic and Social Committee, explored how innovations in living situations for refugees can promote community-driven inclusion, overcome divisions, facilitate economic opportunities, and foster a sense of "home."

Una llamada en español que analiza las dinámicas cambiantes y las cuestiones políticas relacionadas con la migración a través de México a los Estados Unidos.

Durante este seminario, ponentes presentaron hallazgos de un reciente informe que utiliza datos de agencias gubernamentales mexicanas, entrevistas con funcionarios clave y relatos de la sociedad civil para examinar el marco legal para la protección de menores no acompañados y su aplicación, al igual que las brechas entre este marco y su aplicación durante los procesos de detención, interrogación y alojamiento. El presidente de MPI, Andrew Selee, también expuso cómo el cambio en la dinámica política en Estados Unidos puede afectar las cuestiones migratorias con México, así como los efectos en la relación bilateral en medio de tensiones sobre el muro fronterizo, la renegociación del acuerdo del TLCAN y una cifra significativa de repatriaciones de migrantes mexicanos.

Social Distancing (date: 5/9/2020 - Rank: 6)

Edward A. Chow
Jul 1, 2012; 30:130-133
Diabetes Advocacy

OBJECTIVE

This study investigates two-phase growth patterns in early life and their association with development of islet autoimmunity (IA) and type 1 diabetes (T1D).

OBJECTIVE

This study aimed to understand the longitudinal relationship between financial, psychosocial, and neighborhood social determinants and glycemic control (HbA_1c) in older adults with diabetes.

OBJECTIVE

To analyze the differences in health care costs according to glycemic control in people with type 2 diabetes.

OBJECTIVE

To assess the contemporaneous prevalence of diabetic peripheral neuropathy (DPN) in people with type 1 diabetes (T1D) in Scotland and study its cross-sectional association with risk factors and other diabetic complications.

Boris P. Kovatchev
Jul 1, 2013; 36:1851-1858
Diabetes Care Symposium

Richard R Rubin
Nov 1, 1992; 15:1640-1657
Behavioral Diabetes Series

Korey K. Hood
Jun 1, 2006; 29:1389-1389
BR Epidemiology/Health Services/Psychosocial Research