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Casey M Rebholz, Bing Yu, Zihe Zheng, Patrick Chang, Adrienne Tin, Anna Köttgen, Lynne E Wagenknecht, Josef Coresh, Eric Boerwinkle, Elizabeth Selvin
AIMS/HYPOTHESIS: Metabolomic profiling offers the potential to reveal metabolic pathways relevant to the pathophysiology of diabetes and improve diabetes risk prediction. METHODS: We prospectively analysed known metabolites using an untargeted approach in serum specimens from baseline (1987-1989) and incident diabetes through to 31 December 2015 in a subset of 2939 Atherosclerosis Risk in Communities (ARIC) study participants with metabolomics data and without prevalent diabetes...
March 20, 2018: Diabetologia
Thomas Laeger, Teresa Castaño-Martinez, Martin W Werno, Lukasz Japtok, Christian Baumeier, Wenke Jonas, Burkhard Kleuser, Annette Schürmann
AIMS/HYPOTHESIS: Low-protein diets are well known to improve glucose tolerance and increase energy expenditure. Increases in circulating fibroblast growth factor 21 (FGF21) have been implicated as a potential underlying mechanism. METHODS: We aimed to test whether low-protein diets in the context of a high-carbohydrate or high-fat regimen would also protect against type 2 diabetes in New Zealand Obese (NZO) mice used as a model of polygenetic obesity and type 2 diabetes...
March 17, 2018: Diabetologia
Sherly X Li, Fumiaki Imamura, Matthias B Schulze, Jusheng Zheng, Zheng Ye, Antonio Agudo, Eva Ardanaz, Dagfinn Aune, Heiner Boeing, Miren Dorronsoro, Courtney Dow, Guy Fagherazzi, Sara Grioni, Marc J Gunter, José María Huerta, Daniel B Ibsen, Marianne Uhre Jakobsen, Rudolf Kaaks, Timothy J Key, Kay-Tee Khaw, Cecilie Kyrø, Francesca Romana Mancini, Elena Molina-Portillo, Neil Murphy, Peter M Nilsson, N Charlotte Onland-Moret, Domenico Palli, Salvatore Panico, Alaitz Poveda, J Ramón Quirós, Fulvio Ricceri, Ivonne Sluijs, Annemieke M W Spijkerman, Anne Tjonneland, Rosario Tumino, Anna Winkvist, Claudia Langenberg, Stephen J Sharp, Elio Riboli, Robert A Scott, Nita G Forouhi, Nicholas J Wareham
AIMS/HYPOTHESIS: Gene-macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes. METHODS: We investigated the influence of interactions between genetic risk scores (GRSs) for type 2 diabetes, insulin resistance and BMI and macronutrient intake on the development of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a prospective case-cohort study across eight European countries (N = 21,900 with 9742 incident type 2 diabetes cases)...
March 17, 2018: Diabetologia
Camilla Sortsø, Anastasija Komkova, Annelli Sandbæk, Simon J Griffin, Martha Emneus, Torsten Lauritzen, Rebecca K Simmons
AIMS/HYPOTHESIS: Trials have not demonstrated benefits to the population of screening for type 2 diabetes. However, there may be cost savings for those found to have diabetes. We therefore aimed to compare healthcare costs among individuals with incident type 2 diabetes in a screened group with those in an unscreened group. METHODS: In this register-based, non-randomised controlled trial, eligible individuals were men and women aged 40-69 years without known diabetes who were registered with a general practice in Denmark (n = 1,912,392)...
March 16, 2018: Diabetologia
Mika Hilvo, Tuire Salonurmi, Aki S Havulinna, Dimple Kauhanen, Eva Ringdal Pedersen, Grethe S Tell, Klaus Meyer, Anna-Maria Teeriniemi, Tiina Laatikainen, Pekka Jousilahti, Markku J Savolainen, Ottar Nygård, Veikko Salomaa, Reijo Laaksonen
AIMS/HYPOTHESIS: Ceramide lipids have a role in the development of insulin resistance, diabetes and risk of cardiovascular disease. Here we investigated four ceramides and their ratios to find the best predictors of incident diabetes. METHODS: A validated mass-spectrometric method was applied to measure Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1) from serum or plasma samples. These ceramides were analysed in a population-based risk factor study (FINRISK 2002, n = 8045), in a cohort of participants undergoing elective coronary angiography for suspected stable angina pectoris (Western Norway Coronary Angiography Cohort [WECAC], n = 3344) and in an intervention trial investigating improved methods of lifestyle modification for individuals at high risk of the metabolic syndrome (Prevent Metabolic Syndrome [PrevMetSyn], n = 371)...
March 15, 2018: Diabetologia
Yulin Chen, Jie Wu, Jiajia Wang, Wenjing Zhang, Bohui Xu, Xiaojun Xu, Li Zong
AIMS/HYPOTHESIS: The intestinal immune system is an ideal target to induce immune tolerance physiologically. However, the efficiency of oral protein antigen delivery is limited by degradation of the antigen in the gastrointestinal tract and poor uptake by antigen-presenting cells. Gut dendritic cells (DCs) are professional antigen-presenting cells that are prone to inducing antigen-specific immune tolerance. In this study, we delivered the antigen heat shock protein 65-6×P277 (H6P) directly to the gut DCs of NOD mice through oral vaccination with H6P-loaded targeting nanoparticles (NPs), and investigated the ability of this antigen to induce immune tolerance to prevent autoimmune diabetes in NOD mice...
March 15, 2018: Diabetologia
Anna E Long, Isabel V Wilson, Dorothy J Becker, Ingrid M Libman, Vincent C Arena, F Susan Wong, Andrea K Steck, Marian J Rewers, Liping Yu, Peter Achenbach, Rosaura Casas, Johnny Ludvigsson, Alistair J K Williams, Kathleen M Gillespie
AIMS/HYPOTHESIS: Multiple islet autoimmunity increases risk of diabetes, but not all individuals positive for two or more islet autoantibodies progress to disease within a decade. Major islet autoantibodies recognise insulin (IAA), GAD (GADA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A). Here we describe the baseline characteristics of a unique cohort of 'slow progressors' (n = 132) who were positive for multiple islet autoantibodies (IAA, GADA, IA-2A or ZnT8A) but did not progress to diabetes within 10 years...
March 12, 2018: Diabetologia
Helen M Colhoun, M Loredana Marcovecchio
Diabetic kidney disease (DKD) remains one of the leading causes of reduced lifespan in diabetes. The quest for both prognostic and surrogate endpoint biomarkers for advanced DKD and end-stage renal disease has received major investment and interest in recent years. However, at present no novel biomarkers are in routine use in the clinic or in trials. This review focuses on the current status of prognostic biomarkers. First, we emphasise that albuminuria and eGFR, with other routine clinical data, show at least modest prediction of future renal status if properly used...
March 8, 2018: Diabetologia
Jannie Nielsen, Adam Hulman, Daniel R Witte
AIMS/HYPOTHESIS: In the UK, more than one million people have undiagnosed diabetes and an additional five million are at high risk of developing the disease. Given that early identification of these people is key for both primary and secondary prevention, new screening approaches are needed. Since spouses resemble each other in cardiometabolic risk factors related to type 2 diabetes, we aimed to investigate whether diabetes and cardiometabolic risk factors in one spouse can be used as an indicator of incident type 2 diabetes in the other spouse...
March 8, 2018: Diabetologia
Lorenzo Piemonti, Eelco J P de Koning, Thierry Berney, Jon S Odorico, James F Markmann, Peter G Stock, Michael R Rickels
Defined outcomes for beta cell replacement therapy in the treatment of diabetes are critically needed. Progress towards the clinical acceptance of pancreas and islet transplantation has been hampered by the lack of clear definitions of functional and efficacy outcomes, as well as a lack of consistently applied glycaemic control metrics, together with poor alignment with the field of artificial insulin delivery/artificial pancreas development. To address this problem, the International Pancreas & Islet Transplant Association (IPITA) collaborated with the European Pancreas and Islet Transplant Association (EPITA) to develop a consensus for a joint statement on the definition of function and failure of beta cell replacement therapies, which is summarised in this commentary...
March 6, 2018: Diabetologia
Adam Hulman, Dorte Vistisen, Charlotte Glümer, Michael Bergman, Daniel R Witte, Kristine Færch
No abstract text is available yet for this article.
March 4, 2018: Diabetologia
Aafke W F Janssen, Saeed Katiraei, Barbara Bartosinska, Daniel Eberhard, Ko Willems van Dijk, Sander Kersten
AIMS/HYPOTHESIS: Angiopoietin-like 4 (ANGPTL4) is an important regulator of triacylglycerol metabolism, carrying out this role by inhibiting the enzymes lipoprotein lipase and pancreatic lipase. ANGPTL4 is a potential target for ameliorating cardiometabolic diseases. Although ANGPTL4 has been implicated in obesity, the study of the direct role of ANGPTL4 in diet-induced obesity and related metabolic dysfunction is hampered by the massive acute-phase response and development of lethal chylous ascites and peritonitis in Angptl4-/- mice fed a standard high-fat diet...
March 3, 2018: Diabetologia
Isabel González-Mariscal, Rodrigo A Montoro, Máire E Doyle, Qing-Rong Liu, Michael Rouse, Jennifer F O'Connell, Sara Santa-Cruz Calvo, Susan M Krzysik-Walker, Soumita Ghosh, Olga D Carlson, Elin Lehrmann, Yongqing Zhang, Kevin G Becker, Chee W Chia, Paritosh Ghosh, Josephine M Egan
AIMS/HYPOTHESIS: The cannabinoid 1 receptor (CB1R) regulates insulin sensitivity and glucose metabolism in peripheral tissues. CB1R is expressed on pancreatic beta cells and is coupled to the G protein Gαi, suggesting a negative regulation of endogenous signalling in the beta cell. Deciphering the exact function of CB1R in beta cells has been confounded by the expression of this receptor on multiple tissues involved in regulating metabolism. Thus, in models of global genetic or pharmacological CB1R blockade, it is difficult to distinguish the indirect effects of improved insulin sensitivity in peripheral tissues from the direct effects of inhibiting CB1R in beta cells per se...
March 1, 2018: Diabetologia
Daniel F Vatner, Leigh Goedeke, Joao-Paulo G Camporez, Kun Lyu, Ali R Nasiri, Dongyan Zhang, Sanjay Bhanot, Susan F Murray, Christopher D Still, Glenn S Gerhard, Gerald I Shulman, Varman T Samuel
AIMS/HYPOTHESIS: Targeting regulators of adipose tissue lipoprotein lipase could enhance adipose lipid clearance, prevent ectopic lipid accumulation and consequently ameliorate insulin resistance and type 2 diabetes. Angiopoietin-like 8 (ANGPTL8) is an insulin-regulated lipoprotein lipase inhibitor strongly expressed in murine adipose tissue. However, Angptl8 knockout mice do not have improved insulin resistance. We hypothesised that pharmacological inhibition, using a second-generation antisense oligonucleotide (ASO) against Angptl8 in adult high-fat-fed rodents, would prevent ectopic lipid accumulation and insulin resistance by promoting adipose lipid uptake...
March 1, 2018: Diabetologia
Nurah M Hammoud, Gerard H A Visser, Lenie van Rossem, Douwe H Biesma, Jan M Wit, Harold W de Valk
AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is reported to be associated with childhood obesity, however the magnitude of this association and relation to intrauterine growth is uncertain. We, therefore, aimed to assess whether the growth trajectories of large for gestational age (LGA) and non-LGA offspring of mothers with GDM (OGDM) are different until early adolescence. We also aimed to explore whether growth trajectories of OGDM differ from those of offspring of mothers with type 1 or 2 diabetes (ODM1, ODM2)...
February 28, 2018: Diabetologia
Caroline Honsek, Stefan Kabisch, Margrit Kemper, Christiana Gerbracht, Ayman M Arafat, Andreas L Birkenfeld, Ulrike Dambeck, Martin A Osterhoff, Martin O Weickert, Andreas F H Pfeiffer
AIMS/HYPOTHESIS: Insoluble cereal fibres have been shown in large prospective cohort studies to be highly effective in preventing type 2 diabetes, but there is a lack of interventional data. Our 2 year randomised double-blind prospective intervention study compared the effect of an insoluble oat fibre extract with that of placebo on glucose metabolism and incidence of diabetes. METHODS: A total of 180 participants with impaired glucose tolerance underwent a modified version of the 1 year lifestyle training programme PREvention of DIAbetes Self-management (PREDIAS) and were randomised to receive a fibre supplement (n = 89; 7...
February 28, 2018: Diabetologia
Veroniqa Lundbäck, Agne Kulyte, Rona J Strawbridge, Mikael Ryden, Peter Arner, Claude Marcus, Ingrid Dahlman
AIMS/HYPOTHESIS: By genome-wide association meta-analysis, 17 genetic loci associated with fasting serum insulin (FSI), a marker of systemic insulin resistance, have been identified. To define potential culprit genes in these loci, in a cross-sectional study we analysed white adipose tissue (WAT) expression of 120 genes in these loci in relation to systemic and adipose tissue variables, and functionally evaluated genes demonstrating genotype-specific expression in WAT (eQTLs). METHODS: Abdominal subcutaneous adipose tissue biopsies were obtained from 114 women...
February 27, 2018: Diabetologia
(no author information available yet)
No abstract text is available yet for this article.
February 27, 2018: Diabetologia
Andrea Tura, Gaetano Chemello, Julia Szendroedi, Christian Göbl, Kristine Færch, Jana Vrbíková, Giovanni Pacini, Ele Ferrannini, Michael Roden
AIMS/HYPOTHESIS: The euglycaemic-hyperinsulinaemic clamp is the gold-standard method for measuring insulin sensitivity, but is less suitable for large clinical trials. Thus, several indices have been developed for evaluating insulin sensitivity from the oral glucose tolerance test (OGTT). However, most of them yield values different from those obtained by the clamp method. The aim of this study was to develop a new index to predict clamp-derived insulin sensitivity (M value) from the OGTT-derived oral glucose insulin sensitivity index (OGIS)...
February 26, 2018: Diabetologia
Mandy Stadion, Kristin Schwerbel, Antonia Graja, Christian Baumeier, Maria Rödiger, Wenke Jonas, Christian Wolfrum, Harald Staiger, Andreas Fritsche, Hans-Ulrich Häring, Nora Klöting, Matthias Blüher, Pamela Fischer-Posovszky, Tim J Schulz, Hans-Georg Joost, Heike Vogel, Annette Schürmann
AIMS/HYPOTHESIS: Obesity results from a constant and complex interplay between environmental stimuli and predisposing genes. Recently, we identified the IFN-activated gene Ifi202b as the most likely gene responsible for the obesity quantitative trait locus Nob3 (New Zealand Obese [NZO] obesity 3). The aim of this study was to evaluate the effects of Ifi202b on body weight and adipose tissue biology, and to clarify the functional role of its human orthologue IFI16. METHODS: The impact of Ifi202b and its human orthologue IFI16 on adipogenesis was investigated by modulating their respective expression in murine 3T3-L1 and human Simpson-Golabi-Behmel syndrome (SGBS) pre-adipocytes...
February 24, 2018: Diabetologia
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