Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Jan;79(1):43-61.
doi: 10.1007/s40265-018-1035-y.

Disease-Modifying Therapies in Type 1 Diabetes: A Look into the Future of Diabetes Practice

Carla Greenbaum  1 , Dana VanBuecken  2 , Sandra Lord  3
Affiliations
Review

Disease-Modifying Therapies in Type 1 Diabetes: A Look into the Future of Diabetes Practice

Carla Greenbaum et al. Drugs. 2019 Jan.

Abstract

The novel understanding that the presence of multiple islet autoantibodies, indicating islet autoimmunity, inevitably leads to type 1 diabetes mellitus (T1DM) has necessitated the development of a new staging classification system for the condition. Coupled with an improved understanding of the disease course, the realization that T1DM appears to be more heterogeneous than previously thought has led to unique opportunities to develop more targeted therapies that may be applied even before the onset of dysglycemia or symptoms. To date, several therapies have been trialed to delay or halt disease progression in both presymptomatic and clinical T1DM, each demonstrating varying degrees of effectiveness, toxicity, and utility. Key research supports the eventual implementation of immunotherapy in autoimmune diabetes, potentially calling for a paradigm shift among care providers. It will likely be necessary to develop new approaches to trial design and to address potential barriers to progress before an effective treatment for the disease may be achieved.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest

Carla Greenbaum reports personal fees from Lilly, grants and personal fees from NovoNordisk, personal fees from Bristol Myers Squibb, grants and personal fees from Janssen, and personal fees from Pfizer.

Sandra Lord and Dana VanBuecken declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

Figures

Fig. 1a
Fig. 1a
DKA prevalence at diagnosis in monitoring programs vs. usual care [–, –51]
Fig. 1b
Fig. 1b
HbA1c at diagnosis in monitoring programs vs. usual care [–45, 50, 51]
Fig. 2
Fig. 2
the stages of type 1 diabetes. (From: “Type 1 Diabetes: Stage 3” from the TrialNet website. [Image on the Internet]. C2018. Available from https://www.trialnet.org/our-research/long-term-follow-up. Used with permission) [61]
Fig. 3
Fig. 3
Major pathways leading to beta cell destruction and potential mechanisms underlying the use of selected therapies. Figure used with permission from Endotext [69]
Fig. 4
Fig. 4
Stylized representation of selected new-onset clinical trial results with positive outcomes. Therapies generally delayed the fall in insulin secretion from ~8 to 12 months. Regardless of the therapy, the most pronounced effects were early after treatment. Figure used with permission from Endotext [69]
Fig. 5
Fig. 5
The positive results seen in both the rituximab (figure A) and abatacept (figure B) new-onset trials were driven by the response in the age < 18 cohorts. From Wherrett et al. [31].
See this image and copyright information in PMC

References

    1. Walsh D and McWilliams D, Mechanisms, impact and management of pain in rheumatoid arthritis. Nat Rev Rheumatol, 2014. 10: p. 581–592. - PubMed
    1. Firestein G, Ravinder N, and Romain P, Pathogenesis of rheumatoid arthritis. 2017, UpToDate.
    1. group D, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N. Engl. J. Med, 1993. 329(14): p. 977–986. - PubMed
    1. Group, E.o.D.I.a.C.E.R., Epidemiology of Diabetes Interventions and Complications (EDIC). Design, implementation, and preliminary results of a long-term follow- up of the Diabetes Control and Complications Trial cohort. Diabetes Care, 1999. 22(1): p. 99–111. - PMC - PubMed
    1. Secrest AM, Washington RE, and Orchard TJ, Mortality in Type 1 DIabetes, in Diabetes in America, 3rd Edition 2016, National Institutes of Health; p. 1–16.

MeSH terms