We all know we should be doing more exercise, and one way to do that is by active commuting - journeying to work on foot or by bike. One thing preventing people from taking up cycling is the fear of being involved in road traffic accidents, and that the risk isn't worth the benefit of the extra exercise. It’s even more confusing when air...

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give...

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...

A new podcast from The BMJ, to help GP's feel more connected, heard, and supported. Subscribe on; Apple podcasts - https://bit.ly/applepodsDBI Spotify - https://bit.ly/spotifyDBI Google podcasts - https://bit.ly/googlepodsDBI This week, our topic is fear: we try to get a better understanding of fear, how it affects all of us as clinicians for...

A new podcast from The BMJ, to help GP's feel more connected, heard, and supported. Subscribe on; Apple podcasts - https://bit.ly/applepodsDBI Spotify - https://bit.ly/spotifyDBI Google podcasts - https://bit.ly/googlepodsDBI In our first episode, we discuss the highs and lows of video consultations, and how coronavirus has altered the landscape...

In this week’s episode, we discuss bystander guilt, convergence, brain hacks and “how you can sneeze on someone’s brain from anywhere in the world”. How can GPs cope with the myriad worries around treating patients during the current pandemic, both on the frontline and in general practice? How do we recognise and break unhelpful anxious behaviour...

We are more than six weeks into the lockdown and if you were to gauge the mood of the nation, it would be one of fatigue. It started as an all-hands-on-deck emergency situation, but it now transpires that the current work situation for healthcare professionals is not going to change any time soon. This is a marathon rather than a sprint. So how...

Mariano J Garcia
Feb 1, 1974; 23:105-111
Original Contribution

Masayuki Saito
Jul 1, 2009; 58:1526-1531
Metabolism

Cindy J.M. Loomans
Jan 1, 2004; 53:195-199
Complications

Marc Prentki
Mar 1, 1996; 45:273-283
Original Article

Christophe Bonny
Jan 1, 2001; 50:77-82
Islet Studies

Joachim Spranger
Mar 1, 2003; 52:812-817
Pathophysiology

Miriam Cnop
Dec 1, 2005; 54:S97-S107
Section III: Inflammation and beta-Cell Death

Gökhan S Hotamisligil
Nov 1, 1994; 43:1271-1278
Perspectives in Diabetes

D Dabelea
Dec 1, 2000; 49:2208-2211
Articles

Ralph A. DeFronzo
Apr 1, 2009; 58:773-795
Banting Lecture

Roger H Unger
Aug 1, 1995; 44:863-870
Perspectives in Diabetes

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

Andreas Festa
Apr 1, 2002; 51:1131-1137
Complications

David E. Cummings
Aug 1, 2001; 50:1714-1719
Rapid Publications

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

Steven E Kahn
Nov 1, 1993; 42:1663-1672
Original Article

David E. Kelley
Oct 1, 2002; 51:2944-2950
Metabolism and Signal Transduction

HE Hohmeier
Mar 1, 2000; 49:424-430
Articles

Patrice D. Cani
Jun 1, 2008; 57:1470-1481
Metabolism

Patrice D. Cani
Jul 1, 2007; 56:1761-1772
Obesity Studies

National Diabetes Data Group
Dec 1, 1979; 28:1039-1057
Articles

Alexandra E. Butler
Jan 1, 2003; 52:102-110
Islet Studies

The placenta participates in maternal insulin sensitivity changes during pregnancy; however, mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort. All women underwent 75-g oral glucose tolerance tests at ~26 weeks of gestation; we used glucose and insulin measures to estimate insulin sensitivity (Matsuda index). At delivery, we collected samples from placenta (fetal side) and measured DNA methylation using Illumina EPIC arrays. Using linear regression models to quantify associations at 720,077 cytosine-guanine dinucleotides (CpGs), with adjustment for maternal age, gravidity, smoking, BMI, child sex, and gestational age at delivery, we identified 188 CpG sites where placental DNA methylation was associated with Matsuda index (P < 6.94 x 10^–8). Among genes annotated to these 188 CpGs, we found enrichment in targets for miRNAs, in histone modifications, and in parent-of-origin DNA methylation including the H19/MIR675 locus (paternally imprinted). We identified 12 known placenta imprinted genes, including KCNQ1. Mendelian randomization analyses revealed five loci where placenta DNA methylation may causally influence maternal insulin sensitivity, including the maternally imprinted gene DLGAP2. Our results suggest that placental DNA methylation is fundamentally linked to the regulation of maternal insulin sensitivity in pregnancy.

Children at increased genetic risk for type 1 diabetes (T1D) after environmental exposures may develop pancreatic islet autoantibodies (IA) at a very young age. Metabolic profile changes over time may imply responses to exposures and signal development of the first IA. Our present research in The Environmental Determinants of Diabetes in the Young (TEDDY) study aimed to identify metabolome-wide signals preceding the first IA against GAD (GADA-first) or against insulin (IAA-first). We profiled metabolomes by mass spectrometry from children’s plasma at 3-month intervals after birth until appearance of the first IA. A trajectory analysis discovered each first IA preceded by reduced amino acid proline and branched-chain amino acids (BCAAs), respectively. With independent time point analysis following birth, we discovered dehydroascorbic acid (DHAA) contributing to the risk of each first IA, and -aminobutyric acid (GABAs) associated with the first autoantibody against insulin (IAA-first). Methionine and alanine, compounds produced in BCAA metabolism and fatty acids, also preceded IA at different time points. Unsaturated triglycerides and phosphatidylethanolamines decreased in abundance before appearance of either autoantibody. Our findings suggest that IAA-first and GADA-first are heralded by different patterns of DHAA, GABA, multiple amino acids, and fatty acids, which may be important to primary prevention of T1D.

The cardiovascular benefits of fibrates have been shown to be heterogeneous and to depend on the presence of atherogenic dyslipidemia. We investigated whether genetic variability in the PPARA gene, coding for the pharmacological target of fibrates (PPAR-α), could be used to improve the selection of patients with type 2 diabetes who may derive cardiovascular benefit from addition of this treatment to statins. We identified a common variant at the PPARA locus (rs6008845, C/T) displaying a study-wide significant influence on the effect of fenofibrate on major cardiovascular events (MACE) among 3,065 self-reported white subjects treated with simvastatin and randomized to fenofibrate or placebo in the ACCORD-Lipid trial. T/T homozygotes (36% of participants) experienced a 51% MACE reduction in response to fenofibrate (hazard ratio 0.49; 95% CI 0.34–0.72), whereas no benefit was observed for other genotypes (P_interaction = 3.7 x 10^–4). The rs6008845-by-fenofibrate interaction on MACE was replicated in African Americans from ACCORD (N = 585, P = 0.02) and in external cohorts (ACCORD-BP, ORIGIN, and TRIUMPH, total N = 3059, P = 0.005). Remarkably, rs6008845 T/T homozygotes experienced a cardiovascular benefit from fibrate even in the absence of atherogenic dyslipidemia. Among these individuals, but not among carriers of other genotypes, fenofibrate treatment was associated with lower circulating levels of CCL11—a proinflammatory and atherogenic chemokine also known as eotaxin (P for rs6008845-by-fenofibrate interaction = 0.003). The GTEx data set revealed regulatory functions of rs6008845 on PPARA expression in many tissues. In summary, we have found a common PPARA regulatory variant that influences the cardiovascular effects of fenofibrate and that could be used to identify patients with type 2 diabetes who would derive benefit from fenofibrate treatment, in addition to those with atherogenic dyslipidemia.

Western Bureau: Some displaced Iberostar employees in Rose Hall, St James, are angry with their employer, charging that they have been unable to benefit from the Government’s COVID-19 relief programme because of the hotel’s failure to pay over...

An application earlier this year by Mahoe Gaming Enterprises Limited (MGEL) has not benefited from any preferential treatment by the Betting, Gaming and Lotteries Commission (BGLC). That was the finding of ex-commissioner of the Integrity...

Days after The Gleaner reported a clarion call from Port Maria Mayor Richard Creary for the quarantine of St Mary communities owing to growing concerns about the spread of COVID-19 in the parish, the Government responded with the lockdown of three...

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...

DOVER, St Mary: Residents of Epsom and Dover in St Mary are on edge, but have accepted quarantine measures imposed by the Government to curtail the spread of the dreaded coronavirus in that parish. Security checkpoints at both ends of the parish...

The wet weather last Saturday (May 2) could not dampen the spirits of award-winning gospel artiste and ordained evangelist Kevin Downswell as he ventured into the St Catherine community of Central Village, where he spent some of his formative years...

WASHINGTON, CMC – The World Bank has predicted the sharpest decline of remittances to Latin America and the Caribbean, saying that global remittances on a whole are projected to fall by about 20 percent in 2020 due to the economic crisis...

PORT AU PRINCE, Haiti, CMC – The Government of Haiti has received funds amounting to US$16.1 million from the United States to help the country respond to the COVID-19 pandemic. The funds from the United States Agency for International...

KINGSTOWN, St Vincent, CMC – The St Vincent and the Grenadines Government has denied a United States-based airline permission to land, dashing hopes that an estimated 300 nationals employed with a US-based cruise line would have arrived home...

PORT AU PRINCE, Haiti, CMC – The Ministry of Public Health has confirmed that a 20-year-old man has become the seventh person in Haiti to die of the coronavirus (COVID-19). It is urging the population to follow restriction measures, including...

GEORGETOWN, Guyana, CMC – The Guyana government Friday confirmed that US$4.9 million had been deposited into the Natural Resources Fund as a result of the first royalty payment for the country’s crude oil. Finance Minister, Winston...

ROSEAU, Dominica, CMC –A senior education official Thursday said students would sit the Grade Six National Assessment examinations later this year, despite the disruption caused to the education system by the coronavirus (COVID-19). Dominica...

PORT OF SPAIN, Trinidad, CMC – The Trinidad-based Caribbean Public Health Agency (CARPHA) is urging people in the region to remember that despite the coronavirus (COVID-19) pandemic, they must be mindful that other public health threats still...