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Diabetologia

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https://www.readbyqxmd.com/read/28646275/up-front
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June 23, 2017: Diabetologia
https://www.readbyqxmd.com/read/28642969/diverse-metabolic-effects-of-o-glcnacylation-in-the-pancreas-but-limited-effects-in-insulin-sensitive-organs-in-mice
#2
Shogo Ida, Katsutaro Morino, Osamu Sekine, Natsuko Ohashi, Shinji Kume, Tokuhiro Chano, Kanako Iwasaki, Norio Harada, Nobuya Inagaki, Satoshi Ugi, Hiroshi Maegawa
AIMS/HYPOTHESIS: O-GlcNAcylation is characterised by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (OGT) and serves in sensing intracellular nutrients by modulating various cellular processes. Although it has been speculated that O-GlcNAcylation is associated with glucose metabolism, its exact role in whole body glucose metabolism has not been fully elucidated. Here, we investigated whether loss of O-GlcNAcylation globally and in specific organs affected glucose metabolism in mammals under physiological conditions...
June 22, 2017: Diabetologia
https://www.readbyqxmd.com/read/28623387/retinal-vascular-geometry-and-6%C3%A2-year-incidence-and-progression-of-diabetic-retinopathy
#3
Carol Yim-Lui Cheung, Charumathi Sabanayagam, Antony Kwan-Pui Law, Neelam Kumari, Daniel Shu-Wei Ting, Gavin Tan, Paul Mitchell, Ching Yu Cheng, Tien Yin Wong
AIMS/HYPOTHESIS: We aimed to examine prospectively the association between a range of retinal vascular geometric variables measured from retinal photographs and the 6 year incidence and progression of diabetic retinopathy. METHODS: We conducted a prospective, population-based cohort study of Asian Malay individuals aged 40-80 years at baseline (n = 3280) who returned for a 6 year follow-up. Retinal vascular geometric variables (tortuosity, branching, fractal dimension, calibre) were measured from baseline retinal photographs using a computer-assisted program (Singapore I Vessel Assessment)...
June 16, 2017: Diabetologia
https://www.readbyqxmd.com/read/28620823/the-vegf-a-inhibitor-sflt-1-improves-renal-function-by-reducing-endothelial-activation-and-inflammation-in-a-mouse-model-of-type-1-diabetes
#4
Pascal Bus, Marion Scharpfenecker, Priscilla Van Der Wilk, Ron Wolterbeek, Jan A Bruijn, Hans J Baelde
AIMS/HYPOTHESIS: Animal models of diabetic nephropathy show increased levels of glomerular vascular endothelial growth factor (VEGF)-A, and several studies have shown that inhibiting VEGF-A in animal models of diabetes can prevent albuminuria and glomerular hypertrophy. However, in those studies, treatment was initiated before the onset of kidney damage. Therefore, the aim of this study was to investigate whether transfecting mice with the VEGF-A inhibitor sFlt-1 (encoding soluble fms-related tyrosine kinase 1) can reverse pre-existing kidney damage in a mouse model of type 1 diabetes...
June 15, 2017: Diabetologia
https://www.readbyqxmd.com/read/28612106/the-kynurenine-tryptophan-ratio-as-a-predictor-of-incident-type-2-diabetes-mellitus-in-individuals-with-coronary-artery-disease
#5
Eirik W Rebnord, Elin Strand, Øivind Midttun, Gard F T Svingen, Monika H E Christensen, Per M Ueland, Gunnar Mellgren, Pål R Njølstad, Grethe S Tell, Ottar K Nygård, Eva R Pedersen
AIMS/HYPOTHESIS: The tryptophan metabolite kynurenine has potent immune modulatory and vasoactive properties. Experimental data implicate kynurenine in obesity-related morbidities. Epidemiological studies are, however, sparse. We evaluated associations of the plasma and urine kynurenine:tryptophan ratio (KTR) to incident type 2 diabetes. METHODS: We followed 2519 individuals with coronary artery disease (CAD; 73.1% men) without diabetes at baseline for a median of 7...
June 13, 2017: Diabetologia
https://www.readbyqxmd.com/read/28608285/the-glp-1-analogue-lixisenatide-decreases-atherosclerosis-in-insulin-resistant-mice-by-modulating-macrophage-phenotype
#6
Ángela Vinué, Jorge Navarro, Andrea Herrero-Cervera, Marta García-Cubas, Irene Andrés-Blasco, Sergio Martínez-Hervás, José T Real, Juan F Ascaso, Herminia González-Navarro
AIMS/HYPOTHESIS: Recent clinical studies indicate that glucagon-like peptide-1 (GLP-1) analogues prevent acute cardiovascular events in type 2 diabetes mellitus but their mechanisms remain unknown. In the present study, the impact of GLP-1 analogues and their potential underlying molecular mechanisms in insulin resistance and atherosclerosis are investigated. METHODS: Atherosclerosis development was evaluated in Apoe (-/-) Irs2 (+/-) mice, a mouse model of insulin resistance, the metabolic syndrome and atherosclerosis, treated with the GLP-1 analogues lixisenatide or liraglutide...
June 12, 2017: Diabetologia
https://www.readbyqxmd.com/read/28601906/unravelling-the-regulation-of-insulin-transport-across-the-brain-endothelial-cell
#7
Sarah M Gray, Kevin W Aylor, Eugene J Barrett
AIMS/HYPOTHESIS: For circulating insulin to act on the brain it must cross the blood-brain barrier (BBB). Remarkably little is known about how circulating insulin crosses the BBB's highly restrictive brain endothelial cells (BECs). Therefore, we examined potential mechanisms regulating BEC insulin uptake, signalling and degradation during BEC transcytosis, and how transport is affected by a high-fat diet (HFD) and by astrocyte activity. METHODS: (125)I-TyrA14-insulin uptake and transcytosis, and the effects of insulin receptor (IR) blockade, inhibition of insulin signalling, astrocyte stimulation and an HFD were tested using purified isolated BECs (iBECs) in monoculture and co-cultured with astrocytes...
June 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/28601908/urinary-liver-type-fatty-acid-binding-protein-is-an-independent-predictor-of-stroke-and-mortality-in-individuals-with-type-1-diabetes
#8
Nicolae M Panduru, Carol Forsblom, Markku Saraheimo, Lena M Thorn, Daniel Gordin, Nina Elonen, Valma Harjusalo, Angelika Bierhaus, Per M Humpert, Per-Henrik Groop
AIMS/HYPOTHESIS: In type 1 diabetes, cardiovascular disease (CVD) and diabetic nephropathy progress in parallel, thereby potentiating the risk of premature death during their development. Since urinary liver-type fatty acid binding protein (L-FABP) predicts the progression of diabetic nephropathy, the aim of this study was to investigate whether urinary L-FABP also predicts cardiovascular outcomes and mortality. METHODS: We tested our hypothesis in a Finnish cohort of 2329 individuals with type 1 diabetes and a median follow-up of 14...
June 10, 2017: Diabetologia
https://www.readbyqxmd.com/read/28601907/high-glucose-increases-the-formation-and-pro-oxidative-activity-of-endothelial-microparticles
#9
Dylan Burger, Maddison Turner, Fengxia Xiao, Mercedes N Munkonda, Shareef Akbari, Kevin D Burns
AIMS/HYPOTHESIS: Individuals with diabetes exhibit increases in circulating endothelial microparticles (eMPs, also referred to as endothelial microvesicles), which are associated with endothelial dysfunction and a heightened risk of cardiovascular complications. We have shown that eMPs are markers and mediators of vascular injury although their role in diabetes is unclear. We hypothesised that the composition and biological activity of eMPs are altered in response to high glucose exposure...
June 10, 2017: Diabetologia
https://www.readbyqxmd.com/read/28597075/improved-pregnancy-outcomes-in-women-with-type-1-and-type-2-diabetes-but-substantial-clinic-to-clinic-variations-a-prospective-nationwide-study
#10
Helen R Murphy, Ruth Bell, Cher Cartwright, Paula Curnow, Michael Maresh, Margery Morgan, Catherine Sylvester, Bob Young, Nick Lewis-Barned
AIMS/HYPOTHESIS: The aim of this prospective nationwide study was to examine antenatal pregnancy care and pregnancy outcomes in women with type 1 and type 2 diabetes, and to describe changes since 2002/2003. METHODS: This national population-based cohort included 3036 pregnant women with diabetes from 155 maternity clinics in England and Wales who delivered during 2015. The main outcome measures were maternal glycaemic control, preterm delivery (before 37 weeks), infant large for gestational age (LGA), and rates of congenital anomaly, stillbirth and neonatal death...
June 8, 2017: Diabetologia
https://www.readbyqxmd.com/read/28597074/early-metabolic-markers-identify-potential-targets-for-the-prevention-of-type-2-diabetes
#11
Gopal Peddinti, Jeff Cobb, Loic Yengo, Philippe Froguel, Jasmina Kravić, Beverley Balkau, Tiinamaija Tuomi, Tero Aittokallio, Leif Groop
AIMS/HYPOTHESIS: The aims of this study were to evaluate systematically the predictive power of comprehensive metabolomics profiles in predicting the future risk of type 2 diabetes, and to identify a panel of the most predictive metabolic markers. METHODS: We applied an unbiased systems medicine approach to mine metabolite combinations that provide added value in predicting the future incidence of type 2 diabetes beyond known risk factors. We performed mass spectrometry-based targeted, as well as global untargeted, metabolomics, measuring a total of 568 metabolites, in a Finnish cohort of 543 non-diabetic individuals from the Botnia Prospective Study, which included 146 individuals who progressed to type 2 diabetes by the end of a 10 year follow-up period...
June 8, 2017: Diabetologia
https://www.readbyqxmd.com/read/28597073/beta-cell-heterogeneity-an-evolving-concept
#12
REVIEW
Dana Avrahami, Agnes Klochendler, Yuval Dor, Benjamin Glaser
Beta cells are primarily defined by their ability to produce insulin and secrete it in response to appropriate stimuli. It has been known for some time, however, that beta cells are not functionally identical to each other and that the rates of insulin synthesis and release differ from cell to cell, although the functional significance of this variability remains unclear. Recent studies have used heterogeneous gene expression to isolate and evaluate different subpopulations of beta cells and to demonstrate alterations in these subpopulations in diabetes...
June 8, 2017: Diabetologia
https://www.readbyqxmd.com/read/28593353/diabetic-ketoacidosis-and-diabetes-associated-with-antipsychotic-exposure-among-a-previously-diabetes-naive-population-with-schizophrenia-a-nationwide-nested-case-control-study
#13
Christoffer Polcwiartek, Kristian Kragholm, Christopher Rohde, Nasseh Hashemi, Torkel Vang, Jimmi Nielsen
AIMS/HYPOTHESIS: Diabetic ketoacidosis (DKA) is a potentially fatal metabolic emergency of both type 1 and type 2 diabetes. Although there is a reduced risk of type 1 diabetes in schizophrenia, the incidence of DKA is tenfold higher than that of the general population. Thus, we aimed to investigate associations between exposure to antipsychotic medication (within 3 months prior to event) and DKA, type 1 diabetes and type 2 diabetes. We also reported related, clinically relevant outcomes...
June 7, 2017: Diabetologia
https://www.readbyqxmd.com/read/28580535/metabolically-inactive-insulin-friend-or-foe-in-the-prevention-of-autoimmune-diabetes
#14
EDITORIAL
Mikael Knip
About 20 years ago an American study suggested that daily subcutaneous injections of a metabolically inactive insulin analogue with a single amino acid substitution (aspartic acid instead of phenylalanine) at position 25 of the B chain was as effective as intact insulin in preventing autoimmune diabetes in NOD mice. In this issue of Diabetologia Grönholm et al (DOI: 10.1007/s00125-017-4276-5 ) report that parenteral administration of the same insulin analogue has no preventive effect whatsoever on the development of diabetes in NOD mice; in fact, high doses of the metabolically inactive insulin accelerated disease development...
June 3, 2017: Diabetologia
https://www.readbyqxmd.com/read/28577176/complement-c5a-induces-mesenchymal-stem-cell-apoptosis-during-the-progression-of-chronic-diabetic-complications
#15
Ming Zhu, Xiao He, Xiao-Hui Wang, Wei Qiu, Wei Xing, Wei Guo, Tian-Chen An, Luo-Quan Ao, Xue-Ting Hu, Zhan Li, Xiao-Ping Liu, Nan Xiao, Jian Yu, Hong Huang, Xiang Xu
AIMS/HYPOTHESIS: Regeneration and repair mediated by mesenchymal stem cells (MSCs) are key self-protection mechanisms against diabetic complications, a reflection of diabetes-related cell/tissue damage and dysfunction. MSC abnormalities have been reported during the progression of diabetic complications, but little is known about whether a deficiency in these cells plays a role in the pathogenesis of this disease. In addition to MSC resident sites, peripheral circulation is a major source of MSCs that participate in the regeneration and repair of damaged tissue...
June 3, 2017: Diabetologia
https://www.readbyqxmd.com/read/28573394/cancer-risk-among-insulin-users-comparing-analogues-with-human-insulin-in-the-caring-five-country-cohort-study
#16
Anna But, Marie L De Bruin, Marloes T Bazelier, Vidar Hjellvik, Morten Andersen, Anssi Auvinen, Jakob Starup-Linde, Marjanka K Schmidt, Kari Furu, Frank de Vries, Øystein Karlstad, Nils Ekström, Jari Haukka
AIMS/HYPOTHESIS: The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies. METHODS: National Health Registries from Denmark (1996-2010), Finland (1996-2011), Norway (2005-2010) and Sweden (2007-2012) and the UK Clinical Practice Research Datalink database (1987-2013) were used to conduct a cohort study on new insulin users (N = 327,112)...
June 1, 2017: Diabetologia
https://www.readbyqxmd.com/read/28573393/genetic-risk-scores-in-the-prediction-of-plasma-glucose-impaired-insulin-secretion-insulin-resistance-and-incident-type-2-diabetes-in-the-metsim-study
#17
Alena Stančáková, Teemu Kuulasmaa, Johanna Kuusisto, Karen L Mohlke, Francis S Collins, Michael Boehnke, Markku Laakso
AIMS/HYPOTHESIS: Many SNPs have been associated with glycaemic traits and type 2 diabetes, but their joint effects on glycaemic traits and the underlying mechanisms leading to hyperglycaemia over time are largely unknown. We aimed to investigate the association of six genetic risk scores (GRSs) with changes in plasma glucose, insulin sensitivity, insulin secretion and incident type 2 diabetes in the prospective METabolic Syndrome In Men (METSIM) study. METHODS: We generated weighted GRSs for fasting plasma glucose ([FPG] GRSFPG, 35 SNPs), 2 h plasma glucose ([2hPG] GRS2hPG, 9 SNPs), insulin secretion (GRSIS, 17 SNPs), insulin resistance (GRSIR, 9 SNPs) and BMI (GRSBMI, 95 SNPs) and a non-weighted GRS for type 2 diabetes (GRST2D, 76 SNPs) in up to 8749 non-diabetic Finnish men...
June 1, 2017: Diabetologia
https://www.readbyqxmd.com/read/28567513/age-dependent-insulin-resistance-in-male-mice-with-null-deletion-of-the-carcinoembryonic-antigen-related-cell-adhesion-molecule-2-gene
#18
Simona S Ghanem, Harrison T Muturi, Anthony M DeAngelis, Jiang Hu, Rohit N Kulkarni, Garrett Heinrich, Sonia M Najjar
AIMS/HYPOTHESIS: Cc2 (-/-) mice lacking the gene encoding the carcinoembryonic-antigen-related cell adhesion molecule 2 (Cc2 [also known as Ceacam2]) exhibit hyperphagia that leads to obesity and insulin resistance. This starts at 2 months of age in female mice. Male mutants maintain normal body weight and insulin sensitivity until the last age previously examined (7-8 months), owing to increased sympathetic tone to white adipose tissue and energy expenditure. The current study investigates whether insulin resistance develops in mutant male mice at a later age and whether this is accompanied by changes in insulin homeostasis...
May 31, 2017: Diabetologia
https://www.readbyqxmd.com/read/28551699/the-role-of-somatostatin-in-glp-1-induced-inhibition-of-glucagon-secretion-in-mice
#19
Anne Ørgaard, Jens J Holst
AIMS/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) receptor agonists are currently used for the treatment of type 2 diabetes. Their main mechanism of action is enhancement of glucose-induced insulin secretion (from increased beta cell glucose sensitivity) and inhibition of glucagon secretion. The latter has been demonstrated to account for about half of their blood glucose-lowering activity. Whereas the effect of GLP-1 on insulin secretion is clearly dependent on ambient glucose concentrations and has been described in detail, the mechanism responsible for the inhibitory effect of GLP-1 on glucagon secretion is heavily debated...
May 27, 2017: Diabetologia
https://www.readbyqxmd.com/read/28551698/glucose-metabolism-during-rotational-shift-work-in-healthcare-workers
#20
Anu Sharma, Marcello C Laurenti, Chiara Dalla Man, Ron T Varghese, Claudio Cobelli, Robert A Rizza, Aleksey Matveyenko, Adrian Vella
AIMS/HYPOTHESIS: Shift-work is associated with circadian rhythm disruption and an increased risk of obesity and type 2 diabetes. We sought to determine the effect of rotational shift-work on glucose metabolism in humans. METHODS: We studied 12 otherwise healthy nurses performing rotational shift-work using a randomised crossover study design. On each occasion, participants underwent an isotope-labelled mixed meal test during a simulated day shift and a simulated night shift, enabling simultaneous measurement of glucose flux and beta cell function using the oral minimal model...
May 27, 2017: Diabetologia
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