Dilys J. Freeman
May 1, 2002; 51:1596-1600
Complications

EJ Kurth-Kraczek
Aug 1, 1999; 48:1667-1671
Articles

Joseph G. Yu
Oct 1, 2002; 51:2968-2974
Obesity Studies

Alan R Saltiel
Dec 1, 1996; 45:1661-1669
Perspectives in Diabetes

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

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

Franz M Matschinsky
Feb 1, 1996; 45:223-241
Banting Lecture 1995

Charles M. Alexander
May 1, 2003; 52:1210-1214
Complications

Tatsuya Hayashi
Aug 1, 1998; 47:1369-1373
Rapid Publications

T Inoguchi
Nov 1, 2000; 49:1939-1945
Articles

D A Pan
Jun 1, 1997; 46:983-988
Original Article

Richard S Surwit
Sep 1, 1988; 37:1163-1167
Original Article

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

G Xu
Dec 1, 1999; 48:2270-2276
Articles

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

Norikazu Maeda
Sep 1, 2001; 50:2094-2099
Pathophysiology

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

BM Spiegelman
Apr 1, 1998; 47:507-514
Articles

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

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

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

Lipodystrophies are a group of disorders characterized by absence or loss of adipose tissue and abnormal fat distribution, commonly accompanied by metabolic dysregulation. Although considered rare disorders, their prevalence in the general population is not well understood. We aimed to evaluate the clinical and genetic prevalence of lipodystrophy disorders in a large clinical care cohort. We interrogated the electronic health record (EHR) information of >1.3 million adults from the Geisinger Health System for lipodystrophy diagnostic codes. We estimate a clinical prevalence of disease of 1 in 20,000 individuals. We performed genetic analyses in individuals with available genomic data to identify variants associated with inherited lipodystrophies and examined their EHR for comorbidities associated with lipodystrophy. We identified 16 individuals carrying the p.R482Q pathogenic variant in LMNA associated with Dunnigan familial partial lipodystrophy. Four had a clinical diagnosis of lipodystrophy, whereas the remaining had no documented clinical diagnosis despite having accompanying metabolic abnormalities. We observed a lipodystrophy-associated variant carrier frequency of 1 in 3,082 individuals in our cohort with substantial burden of metabolic dysregulation. We estimate a genetic prevalence of disease of ~1 in 7,000 in the general population. Partial lipodystrophy is an underdiagnosed condition. and its prevalence, as defined molecularly, is higher than previously reported. Genetically guided stratification of patients with common metabolic disorders, like diabetes and dyslipidemia, is an important step toward precision medicine.

This study aims to model genetic, immunologic, metabolomics, and proteomic biomarkers for development of islet autoimmunity (IA) and progression to type 1 diabetes in a prospective high-risk cohort. We studied 67 children: 42 who developed IA (20 of 42 progressed to diabetes) and 25 control subjects matched for sex and age. Biomarkers were assessed at four time points: earliest available sample, just prior to IA, just after IA, and just prior to diabetes onset. Predictors of IA and progression to diabetes were identified across disparate sources using an integrative machine learning algorithm and optimization-based feature selection. Our integrative approach was predictive of IA (area under the receiver operating characteristic curve [AUC] 0.91) and progression to diabetes (AUC 0.92) based on standard cross-validation (CV). Among the strongest predictors of IA were change in serum ascorbate, 3-methyl-oxobutyrate, and the PTPN22 (rs2476601) polymorphism. Serum glucose, ADP fibrinogen, and mannose were among the strongest predictors of progression to diabetes. This proof-of-principle analysis is the first study to integrate large, diverse biomarker data sets into a limited number of features, highlighting differences in pathways leading to IA from those predicting progression to diabetes. Integrated models, if validated in independent populations, could provide novel clues concerning the pathways leading to IA and type 1 diabetes.

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.

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...

Tears flowed yesterday down the face of Donaree Anderson, cousin of 15-year-old Nyron Taylor, one of two children shot dead in west Kingston hours apart on Wednesday. Eight-year-old Toya Brown was the other child killed just days into the month...

Latoya Rose used the last $3,000 she had to invest in 26 baby chicks and feed with the hope of turning a profit after they matured. Last Friday, as the Spaldings resident went to her coop to feed the chickens, they were all gone. “When I don’t see...

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...

Sandra Ferguson resides with her children and grandchildren in a concrete dwelling that is sectioned into four living quarters in the Fort George Road area of Annotto Bay. With 10 of them sharing kitchen and bathroom facilities, Ferguson said...

Edmond Campbell/Senior Parliamentary Reporter Conceding that healthcare workers in the public sector are burnt out as they combat COVID-19, Health and Wellness Minister Dr Christopher Tufton says the Government is taking steps to boost its...

The Senate on Friday paid tribute to distinguished consultant psychiatrist, Frederick Hickling, for his tremendous contribution to persons with intellectual disabilities. Hickling died on Thursday. Senator Dr Saphire Longmore remembered Professor...

PORT OF SPAIN, Trinidad, CMC – Thirty three Trinidad and Tobago nationals who have been stranded in Barbados since March 23 are scheduled to return home on Tuesday. It’s reported that early Tuesday, National Security Minister...

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...

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...

Director of the Pan American Health Organization (PAHO), Carissa Etienne, today urged for vaccination programmes to continue during the COVID-19 pandemic. “If we fall behind on routine immunisations, particularly for children, we risk...

Glucagon-like peptide 1 (GLP-1) mimetics are effective drugs for treatment of type 2 diabetes, and there is consequently extensive interest in increasing endogenous GLP-1 secretion and L-cell abundance. Here we identify G-protein–coupled bile acid receptor 1 (GPBAR1) as a selective regulator of intestinal L-cell differentiation. Lithocholic acid and the synthetic GPBAR1 agonist, L3740, selectively increased L-cell density in mouse and human intestinal organoids and elevated GLP-1 secretory capacity. L3740 induced expression of Gcg and transcription factors Ngn3 and NeuroD1. L3740 also increased the L-cell number and GLP-1 levels and improved glucose tolerance in vivo. Further mechanistic examination revealed that the effect of L3740 on L cells required intact GLP-1 receptor and serotonin 5-hydroxytryptamine receptor 4 (5-HT4) signaling. Importantly, serotonin signaling through 5-HT4 mimicked the effects of L3740, acting downstream of GLP-1. Thus, GPBAR1 agonists and other powerful GLP-1 secretagogues facilitate L-cell differentiation through a paracrine GLP-1–dependent and serotonin-mediated mechanism.

Led by vice president of home clubhouse operations Rick Stowe, who began working for the club in 1981 and became head of the clubhouse in 1997, the Reds have a well-oiled machine with regard to packing up and moving out.

Reds Spring Training in Goodyear, Ariz., will feature a new manager in David Bell, a new coaching staff and several new players. Here is what you need to know about 2019 camp.

Frank Robinson is considered one of the greatest players to ever wear a Cincinnati Reds uniform. His talent and success brought dynamic change to the Reds and to our City.

One of the best catchers in baseball was available all winter in J.T. Realmuto, and the Reds were very much one of the teams in hot pursuit in trade talks with the Marlins. But on Thursday, it was the Phillies who acquired Realmuto from Miami.

Plenty of teams say they will make roster moves in the offseason to improve and then often underwhelm. No one could say that this winter about the Reds, who were arguably the busiest team during the Hot Stove season.

Here's an early look at how the Reds' 25-man roster could shape up on Opening Day.

The Reds made their signing of reliever Zach Duke official on Monday, announcing that they've signed the veteran left-hander to a one-year contract.

It wasn't just that there were new faces when Reds camp opened Tuesday with the reporting of pitchers and catchers for physicals, there was a different vibe that could be felt in the hallways and clubhouse.