Changing the landscape for type 1 diabetes: the first step to prevention

Dayan, Colin; Korah, Maria; Tatović, Danijela; Bundy, Brian N.; Herold, Kevan C.

doi:10.1016/s0140-6736(19)32127-0

Cited by 73 publications

(63 citation statements)

References 99 publications

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“…Participant characteristics Full characteristics are presented in Table 1, comparing those with low (<10 pmol/l) and preserved (10-200 pmol/l) C-peptide or micro-secretion of C-peptide (10-50 pmol/l). Median C-peptide was <4 pmol/l (<4 to <4) in the low group, 22 pmol/l (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) in the micro-secretion group and 32 pmol/l (19-67) in the preserved group. Cpeptide concentration was negatively correlated with duration of diabetes (r −0.362, p < 0.001) ( Fig.…”

Section: Resultsmentioning

confidence: 97%

“…C-peptide was not significantly correlated with plasma glucose at the time of C-peptide measurement (r 0.044, p = 0.460) or most recent HbA 1c (r 0.040, p = 0.450). In comparison with the other 2597 individuals with type 1 diabetes attending our centre, participants in this study had lower HbA 1c (58 [52-66] vs 63 [54-74] mmol/mol, p < 0.001) (7.5% [6.9%-8.2%] vs 7.9% [7.1%-8.9%]), were more likely to use CSII (28.3% vs 13.4%, p < 0.001), were younger (42 [31-53] vs 46 [31-59] years, p = 0.016) and had longer duration of diabetes (21 [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] vs 19 years, p = 0.007).…”

Section: Resultsmentioning

confidence: 99%

“…Given the apparent importance of persistent C-peptide secretion, every effort should be made to ensure early intensification of glycaemic control at diagnosis, as this is currently the only available intervention shown to preserve C-peptide secretion [6]. Moreover, studies of novel strategies to preserve C-peptide secretion, such as immunotherapies, should be supported and funded [24].…”

Section: Discussionmentioning

confidence: 99%

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Preserved C-peptide secretion is associated with fewer low-glucose events and lower glucose variability on flash glucose monitoring in adults with type 1 diabetes

et al. 2020

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Aims/hypothesis We aimed to assess whether persistence of C-peptide secretion is associated with less glucose variability and fewer low-glucose events in adults with type 1 diabetes who use flash monitoring. Methods We performed a cross-sectional study of 290 adults attending a university teaching hospital diabetes clinic, with type 1 diabetes, who use flash monitoring and in whom a random plasma C-peptide was available in the past 2 years. Variables relating to flash monitoring were compared between individuals with low C-peptide (<10 pmol/l) and those with persistent C-peptide (either 10-200 pmol/l or 10-50 pmol/l). In addition, the relationship between self-reported hypoglycaemia and C-peptide was assessed (n = 167). Data are median (interquartile range). Results Individuals with preserved C-peptide secretion (10-200 pmol/l) had shorter duration of diabetes (15 [9-24] vs 25 [15-34] years, p < 0.001) and older age at diagnosis (23 [14-28] vs 15 [9-25] years, p < 0.001), although current age did not differ in this cohort. Preserved C-peptide was associated with lower time with glucose <3.9 mmol/l (3% [2-6%] vs 5% [3-9%], p < 0.001), fewer low-glucose events per 2 week period (7 [4-10] vs 10 [5-16], p < 0.001), lower SD of glucose (3.8 [3.4-4.2] vs 4.1 [3.5-4.7] mmol/l, p = 0.017) and lower CV of glucose (38.0 [35.0-41.6] vs 41.8 [36.5-45.8], p < 0.001). These differences were also present in those with C-peptide 10-50 pmol/l and associations were independent of diabetes duration and estimated HbA 1c in logistic regression analysis. Preserved C-peptide was also associated with lower rates of self-reported asymptomatic hypoglycaemia (8.0% vs 22.8% in the past month, p = 0.028). Conclusions/interpretation Preserved C-peptide secretion is associated with fewer low-glucose events and lower glucose variability on flash monitoring. This suggests that individuals with preserved C-peptide may more safely achieve intensive glycaemic targets.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Preserved C-peptide secretion is associated with fewer low-glucose events and lower glucose variability on flash glucose monitoring in adults with type 1 diabetes

et al. 2020

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“…As the disease progresses, the functional β-cell mass has been severely impaired, leading to the inability to maintain normal metabolic function. Therefore, hyperglycaemia and typical clinical symptoms of diabetes (polyuria, polydipsia, and weight loss) occur and T1DM can be clinically diagnosed in stage 3 (symptomatic T1DM)[ 24 ]. At the time of diagnosis, there is approximately 80% to 90% of the original β-cell mass disrupted[ 25 ].…”

Section: Type 1 Diabetes Mellitusmentioning

confidence: 99%

“…From a few weeks to up to 20 years will be needed to progress from the presence of autoantibodies to clinical onset and this prediabetic phase facilitates to predict and prevent or delay T1DM[ 16 , 26 , 27 ]. For prevention of T1DM, similar to other autoimmune diseases, it is more effective during the early stages (stage 0, primary prevention or stage 1, secondary prevention) of disease progression[ 24 , 28 ]. However, compared to stages 2 and 3, prediction strategies performed in stages 0 and 1 show a lower accuracy[ 26 , 28 ].…”

Section: Type 1 Diabetes Mellitusmentioning

confidence: 99%

Type 1 diabetes mellitus and its oral tolerance therapy

Mao

Chen

Zhang

et al. 2020

WJD

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As a T cell-mediated autoimmune disease, type 1 diabetes mellitus (T1DM) is marked by insulin defect resulting from the destruction of pancreatic β-cells. The understanding of various aspects of T1DM, such as its epidemiology, pathobiology, pathogenesis, clinical manifestations, and complications, has been greatly promoted by valuable research performed during the past decades. However, these findings have not been translated into an effective treatment. The ideal treatment should safely repair the destroyed immune balance in a long-lasting manner, preventing or stopping the destruction of β-cells. As a type of immune hypo-responsiveness to the orally administrated antigen, oral tolerance may be induced by enhancement of regulatory T cells (Tregs) or by anergy/deletion of T cells, depending on the dosage of orally administrated antigen. Acting as an antigen-specific immunotherapy, oral tolerance therapy for T1DM has been mainly performed using animal models and some clinical trials have been completed or are still ongoing. Based on the review of the proposed mechanism of the development of T1DM and oral tolerance, we give a current overview of oral tolerance therapy for T1DM conducted in both animal models and clinical trials.

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Preferences and Insights for Participation in a Rheumatoid Arthritis Clinical Prevention Trial: A Mixed‐Methods Study

Fleischer

Bemis

Feser

et al. 2022

ACR Open Rheumatology

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Objective In rheumatoid arthritis (RA), anti–citrullinated protein antibodies (ACPA) can be elevated prior to inflammatory arthritis (IA). The potential to intervene in people with ACPA positivity underpins the development of prevention trials in RA. The Research Participation Influences Study examined factors influencing the decisions of individuals who are ACPA(+) to participate in a prevention trial using qualitative and quantitative methods. Methods Individuals with ACPA positivity without IA were provided information regarding their risk for future RA, were provided a description of a clinical prevention trial using hydroxychloroquine, and were asked if they would participate in the trial. After agreeing to or declining participation, they were surveyed on what influenced their decision using Likert scales and open‐response questions. Results Thirty‐nine individuals who agreed to trial participation (enrollees) and 31 individuals who declined (nonenrollees) completed surveys. Enrollees expressed greater perceived risk for RA and greater perception of benefit to themselves or others than nonenrollees. Nonenrollees expressed greater concern about medication effects and less personal or family experience with RA than enrollees. There was a higher proportion of first‐degree relatives (FDRs) of people with RA in enrollees versus nonenrollees (54% vs. 23%, P = 0.01). Conclusion Enrollees were more likely than nonenrollees to be FDRs, exhibit stronger concern for personal risk for RA, and have less concern about adverse effects. Further exploration is needed to determine why these differences were present, including exploration of symptoms and the role of family history. Understanding these issues will better inform researchers and individuals who are candidates for prevention.

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Changing the landscape for type 1 diabetes: the first step to prevention

Cited by 73 publications

References 99 publications

Preserved C-peptide secretion is associated with fewer low-glucose events and lower glucose variability on flash glucose monitoring in adults with type 1 diabetes

Preserved C-peptide secretion is associated with fewer low-glucose events and lower glucose variability on flash glucose monitoring in adults with type 1 diabetes

Type 1 diabetes mellitus and its oral tolerance therapy

Preferences and Insights for Participation in a Rheumatoid Arthritis Clinical Prevention Trial: A Mixed‐Methods Study

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