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1.
Diabet Med. 2018 Dec 31. doi: 10.1111/dme.13892. [Epub ahead of print]

Prevention and reversal of Type 2 diabetes: highlights from a symposium at the 2018 Diabetes UK Annual Professional Conference.

Author information

1
Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle.
2
Imperial College Healthcare NHS Trust, London.
3
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford.
4
UK.

Abstract

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.

PMID:
30597609
DOI:
10.1111/dme.13892
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Publication type

2.
Diabetes. 2018 Nov;67(11):2349-2360. doi: 10.2337/db18-0456. Epub 2018 Aug 21.

Healthy Donor Polyclonal IgMs Diminish B-Lymphocyte Autoreactivity, Enhance Regulatory T-Cell Generation, and Reverse Type 1 Diabetes in NOD Mice.

Author information

1
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN.
2
Department of Surgery, University of Virginia, Charlottesville, VA.
3
Department of Pediatrics, Ian Burr Division of Endocrinology and Diabetes, Vanderbilt University Medical Center, Nashville, TN.
4
Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, TN.
5
Department of Medicine, Division of Endocrinology, Vanderbilt University Medical Center, Nashville, TN.
6
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN daniel.moore@vanderbilt.edu.

Abstract

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.

PMID:
30131391
PMCID:
PMC6198348
[Available on 2019-11-01]
DOI:
10.2337/db18-0456
[Indexed for MEDLINE]
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3.
Diabetes. 2018 Nov;67(11):2268-2279. doi: 10.2337/db17-1223. Epub 2018 Aug 16.

Whole-Organism Chemical Screening Identifies Modulators of Pancreatic β-Cell Function.

Author information

1
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.
2
Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
3
Division of Stem Cell Therapy, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.
4
Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
5
St Vincent's Clinical School, UNSW Sydney, Sydney, New South Wales, Australia.

Abstract

β-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 β-cell function and/or increase β-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 β-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 β-cell mass in larval zebrafish and stimulated β-cell function in adult zebrafish and in the streptozotocin-induced hyperglycemic mouse model. In addition, our data indicate that cytoplasmic Kv1.3 regulates β-cell function. Thus, using whole-organism screening, we have identified new small-molecule modulators of β-cell function and glucose metabolism.

PMID:
30115653
DOI:
10.2337/db17-1223
[Indexed for MEDLINE]
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4.
Lancet. 2018 Oct 27;392(10157):1489-1490. doi: 10.1016/S0140-6736(18)32348-1. Epub 2018 Oct 2.

HARMONY or discord in cardiovascular outcome trials of GLP-1 receptor agonists?

Author information

1
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.
2
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.
PMID:
30291014
DOI:
10.1016/S0140-6736(18)32348-1
[Indexed for MEDLINE]
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