PMID- 30597609
OWN - NLM
STAT- Publisher
LR  - 20181231
IS  - 1464-5491 (Electronic)
IS  - 0742-3071 (Linking)
DP  - 2018 Dec 31
TI  - Prevention and reversal of Type 2 diabetes: highlights from a symposium at the
      2018 Diabetes UK Annual Professional Conference.
LID - 10.1111/dme.13892 [doi]
AB  - AIM: This symposium covers the gamut of Type 2 diabetes prevention, reversing
      established Type 2 diabetes, population-level delivery of weight loss programmes 
      and personal insights into achieving and retaining substantial weight loss.
      RESULTS: The NHS prevention programme was launched in 2016 with 49% accepting the
      invitation to participate and 52% of these completing the intervention. By March 
      2018, mean weight loss was 3.2 kg reflecting considerable health benefits.
      Established Type 2 diabetes is now known to be a reversible condition in the
      early years, and the underlying mechanism is the removal of the excess fat from
      within liver and pancreas in these susceptible individuals. The Diabetes
      Remission Clinical Trial has shown that around half of a primary care population 
      of people with Type 2 diabetes of less than 6 years' duration can be returned to 
      non-diabetic blood glucose control which lasts at least 12 months. This raises
      the question of population-level intervention to achieve weight loss. The success
      of some mass weight loss programmes requires to be recognized. Reframing mass
      provision of weight loss support should be a vital part of our clinical strategy 
      to prevent and treat Type 2 diabetes. However, the current obesogenic environment
      is a reality in which individuals must live. A personal account of achieving
      substantial and maintaining substantial weight loss provides an invaluable
      insight into practical problems encountered. All health professionals dealing
      with weight control should assimilate and reflect upon this understanding.
      CONCLUSIONS: Effective prevention and long term reversal of Type 2 diabetes is
      feasible. The impact upon the individual must be considered during delivery of
      advice and support. This article is protected by copyright. All rights reserved.
CI  - This article is protected by copyright. All rights reserved.
FAU - Taylor, R
AU  - Taylor R
AD  - Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle.
FAU - Valabhji, J
AU  - Valabhji J
AD  - Imperial College Healthcare NHS Trust, London.
FAU - Aveyard, P
AU  - Aveyard P
AD  - Nuffield Department of Primary Care Health Sciences, University of Oxford,
      Oxford.
FAU - Paul, D
AU  - Paul D
AD  - UK.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20181231
PL  - England
TA  - Diabet Med
JT  - Diabetic medicine : a journal of the British Diabetic Association
JID - 8500858
EDAT- 2019/01/01 06:00
MHDA- 2019/01/01 06:00
CRDT- 2019/01/01 06:00
PHST- 2019/01/01 06:00 [entrez]
PHST- 2019/01/01 06:00 [pubmed]
PHST- 2019/01/01 06:00 [medline]
AID - 10.1111/dme.13892 [doi]
PST - aheadofprint
SO  - Diabet Med. 2018 Dec 31. doi: 10.1111/dme.13892.

PMID- 30131391
OWN - NLM
STAT- MEDLINE
DCOM- 20181224
LR  - 20181224
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Linking)
VI  - 67
IP  - 11
DP  - 2018 Nov
TI  - Healthy Donor Polyclonal IgMs Diminish B-Lymphocyte Autoreactivity, Enhance
      Regulatory T-Cell Generation, and Reverse Type 1 Diabetes in NOD Mice.
PG  - 2349-2360
LID - 10.2337/db18-0456 [doi]
AB  - Autoimmune diseases such as type 1 diabetes (T1D) arise from unrestrained
      activation of effector lymphocytes that destroy target tissues. Many efforts have
      been made to eliminate these effector lymphocytes, but none has produced a
      long-term cure. An alternative to depletion therapy is to enhance endogenous
      immune regulation. Among these endogenous alternatives, naturally occurring Igs
      have been applied for inflammatory disorders but have lacked potency in
      antigen-specific autoimmunity. We hypothesized that naturally occurring
      polyclonal IgMs, which represent the majority of circulating, noninduced
      antibodies but are present only in low levels in therapeutic Ig preparations,
      possess the most potent capacity to restore immune homeostasis. Treatment of
      diabetes-prone NOD mice with purified IgM isolated from Swiss Webster (SW) mice
      (nIgMSW) reversed new-onset diabetes, eliminated autoreactive B lymphocytes, and 
      enhanced regulatory T-cell (Treg) numbers both centrally and peripherally.
      Conversely, IgM from prediabetic NOD mice could not restore this endogenous
      regulation, which represents an unrecognized component of T1D pathogenesis. Of
      note, IgM derived from healthy human donors was similarly able to expand human
      CD4 Tregs in humanized mice and produced permanent diabetes protection in treated
      NOD mice. Overall, these studies demonstrate that a potent, endogenous regulatory
      mechanism, nIgM, is a promising option for reversing autoimmune T1D in humans.
CI  - (c) 2018 by the American Diabetes Association.
FAU - Wilson, Christopher S
AU  - Wilson CS
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University
      Medical Center, Nashville, TN.
FAU - Chhabra, Preeti
AU  - Chhabra P
AD  - Department of Surgery, University of Virginia, Charlottesville, VA.
FAU - Marshall, Andrew F
AU  - Marshall AF
AD  - Department of Pediatrics, Ian Burr Division of Endocrinology and Diabetes,
      Vanderbilt University Medical Center, Nashville, TN.
FAU - Morr, Caleigh V
AU  - Morr CV
AD  - Department of Pediatrics, Ian Burr Division of Endocrinology and Diabetes,
      Vanderbilt University Medical Center, Nashville, TN.
FAU - Stocks, Blair T
AU  - Stocks BT
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University
      Medical Center, Nashville, TN.
FAU - Hoopes, Emilee M
AU  - Hoopes EM
AD  - Department of Pediatrics, Ian Burr Division of Endocrinology and Diabetes,
      Vanderbilt University Medical Center, Nashville, TN.
FAU - Bonami, Rachel H
AU  - Bonami RH
AD  - Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt
      University Medical Center, Nashville, TN.
FAU - Poffenberger, Greg
AU  - Poffenberger G
AD  - Department of Medicine, Division of Endocrinology, Vanderbilt University Medical 
      Center, Nashville, TN.
FAU - Brayman, Kenneth L
AU  - Brayman KL
AD  - Department of Surgery, University of Virginia, Charlottesville, VA.
FAU - Moore, Daniel J
AU  - Moore DJ
AUID- ORCID: 0000-0002-6889-9345
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University
      Medical Center, Nashville, TN daniel.moore@vanderbilt.edu.
AD  - Department of Pediatrics, Ian Burr Division of Endocrinology and Diabetes,
      Vanderbilt University Medical Center, Nashville, TN.
LA  - eng
GR  - F31 DK107321/DK/NIDDK NIH HHS/United States
GR  - P30 DK020593/DK/NIDDK NIH HHS/United States
GR  - P60 DK020593/DK/NIDDK NIH HHS/United States
GR  - R21 AI119224/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180821
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Immunoglobulin M)
SB  - AIM
SB  - IM
MH  - Animals
MH  - B-Lymphocytes/*immunology
MH  - Diabetes Mellitus, Type 1/*drug therapy/immunology
MH  - Immunoglobulin M/immunology/*therapeutic use
MH  - Mice
MH  - Mice, Inbred NOD
MH  - T-Lymphocytes, Regulatory/*immunology
PMC - PMC6198348
EDAT- 2018/08/23 06:00
MHDA- 2018/12/26 06:00
CRDT- 2018/08/23 06:00
PMCR- 2019/11/01 00:00
PHST- 2018/04/20 00:00 [received]
PHST- 2018/08/12 00:00 [accepted]
PHST- 2019/11/01 00:00 [pmc-release]
PHST- 2018/08/23 06:00 [pubmed]
PHST- 2018/12/26 06:00 [medline]
PHST- 2018/08/23 06:00 [entrez]
AID - db18-0456 [pii]
AID - 10.2337/db18-0456 [doi]
PST - ppublish
SO  - Diabetes. 2018 Nov;67(11):2349-2360. doi: 10.2337/db18-0456. Epub 2018 Aug 21.

PMID- 30115653
OWN - NLM
STAT- MEDLINE
DCOM- 20181224
LR  - 20181224
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Linking)
VI  - 67
IP  - 11
DP  - 2018 Nov
TI  - Whole-Organism Chemical Screening Identifies Modulators of Pancreatic beta-Cell
      Function.
PG  - 2268-2279
LID - 10.2337/db17-1223 [doi]
AB  - beta-Cell loss and dysfunction play a critical role in the progression of type 1 
      and type 2 diabetes. Identifying new molecules and/or molecular pathways that
      improve beta-cell function and/or increase beta-cell mass should significantly
      contribute to the development of new therapies for diabetes. Using the zebrafish 
      model, we screened 4,640 small molecules to identify modulators of beta-cell
      function. This in vivo strategy identified 84 stimulators of insulin expression, 
      which simultaneously reduced glucose levels. The insulin promoter activation
      kinetics for 32 of these stimulators were consistent with a direct mode of
      action. A subset of insulin stimulators, including the antidiabetic drug
      pioglitazone, induced the coordinated upregulation of gluconeogenic pck1
      expression, suggesting functional response to increased insulin action in
      peripheral tissues. Notably, Kv1.3 inhibitors increased beta-cell mass in larval 
      zebrafish and stimulated beta-cell function in adult zebrafish and in the
      streptozotocin-induced hyperglycemic mouse model. In addition, our data indicate 
      that cytoplasmic Kv1.3 regulates beta-cell function. Thus, using whole-organism
      screening, we have identified new small-molecule modulators of beta-cell function
      and glucose metabolism.
CI  - (c) 2018 by the American Diabetes Association.
FAU - Matsuda, Hiroki
AU  - Matsuda H
AD  - Department of Developmental Genetics, Max Planck Institute for Heart and Lung
      Research, Bad Nauheim, Germany hmatsud1@fc.ritsumei.ac.jp
      didier.stainier@mpi-bn.mpg.de.
FAU - Mullapudi, Sri Teja
AU  - Mullapudi ST
AD  - Department of Developmental Genetics, Max Planck Institute for Heart and Lung
      Research, Bad Nauheim, Germany.
FAU - Yang, Yu Hsuan Carol
AU  - Yang YHC
AD  - Department of Developmental Genetics, Max Planck Institute for Heart and Lung
      Research, Bad Nauheim, Germany.
FAU - Masaki, Hideki
AU  - Masaki H
AD  - Division of Stem Cell Therapy, The Institute of Medical Science, University of
      Tokyo, Tokyo, Japan.
FAU - Hesselson, Daniel
AU  - Hesselson D
AD  - Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney,
      New South Wales, Australia.
AD  - St Vincent's Clinical School, UNSW Sydney, Sydney, New South Wales, Australia.
FAU - Stainier, Didier Y R
AU  - Stainier DYR
AUID- ORCID: 0000-0002-0382-0026
AD  - Department of Developmental Genetics, Max Planck Institute for Heart and Lung
      Research, Bad Nauheim, Germany hmatsud1@fc.ritsumei.ac.jp
      didier.stainier@mpi-bn.mpg.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180816
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Insulin)
RN  - EC 4.1.1.32 (Phosphoenolpyruvate Carboxykinase (GTP))
RN  - X4OV71U42S (Pioglitazone)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Diabetes Mellitus, Experimental/genetics/metabolism
MH  - Gene Expression Profiling
MH  - Insulin/genetics/*metabolism
MH  - Insulin-Secreting Cells/drug effects/*metabolism
MH  - Mice
MH  - Phosphoenolpyruvate Carboxykinase (GTP)/genetics/metabolism
MH  - Pioglitazone/pharmacology
MH  - Promoter Regions, Genetic
MH  - Up-Regulation/drug effects
MH  - Zebrafish
EDAT- 2018/08/18 06:00
MHDA- 2018/12/26 06:00
CRDT- 2018/08/18 06:00
PHST- 2017/10/09 00:00 [received]
PHST- 2018/08/07 00:00 [accepted]
PHST- 2018/08/18 06:00 [pubmed]
PHST- 2018/12/26 06:00 [medline]
PHST- 2018/08/18 06:00 [entrez]
AID - db17-1223 [pii]
AID - 10.2337/db17-1223 [doi]
PST - ppublish
SO  - Diabetes. 2018 Nov;67(11):2268-2279. doi: 10.2337/db17-1223. Epub 2018 Aug 16.

PMID- 30291014
OWN - NLM
STAT- MEDLINE
DCOM- 20181227
LR  - 20181227
IS  - 1474-547X (Electronic)
IS  - 0140-6736 (Linking)
VI  - 392
IP  - 10157
DP  - 2018 Oct 27
TI  - HARMONY or discord in cardiovascular outcome trials of GLP-1 receptor agonists?
PG  - 1489-1490
LID - S0140-6736(18)32348-1 [pii]
LID - 10.1016/S0140-6736(18)32348-1 [doi]
FAU - Mafham, Marion
AU  - Mafham M
AD  - Medical Research Council Population Health Research Unit, Clinical Trial Service 
      Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, 
      University of Oxford, Oxford OX3 7LF, UK.
FAU - Preiss, David
AU  - Preiss D
AD  - Medical Research Council Population Health Research Unit, Clinical Trial Service 
      Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, 
      University of Oxford, Oxford OX3 7LF, UK. Electronic address:
      david.preiss@ndph.ox.ac.uk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Comment
DEP - 20181002
PL  - England
TA  - Lancet
JT  - Lancet (London, England)
JID - 2985213R
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 5E7U48495E (rGLP-1 protein)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
SB  - AIM
SB  - IM
CON - Lancet. 2018 Oct 27;392(10157):1519-1529. PMID: 30291013
MH  - Cardiovascular Diseases
MH  - *Diabetes Mellitus, Type 2
MH  - Double-Blind Method
MH  - Glucagon-Like Peptide 1/analogs & derivatives
MH  - *Glucagon-Like Peptide-1 Receptor
MH  - Humans
EDAT- 2018/10/07 06:00
MHDA- 2018/12/28 06:00
CRDT- 2018/10/07 06:00
PHST- 2018/09/18 00:00 [received]
PHST- 2018/09/19 00:00 [accepted]
PHST- 2018/10/07 06:00 [pubmed]
PHST- 2018/12/28 06:00 [medline]
PHST- 2018/10/07 06:00 [entrez]
AID - S0140-6736(18)32348-1 [pii]
AID - 10.1016/S0140-6736(18)32348-1 [doi]
PST - ppublish
SO  - Lancet. 2018 Oct 27;392(10157):1489-1490. doi: 10.1016/S0140-6736(18)32348-1.
      Epub 2018 Oct 2.