Proinsulin/C‐peptide ratio, glucagon and remission in new‐onset Type 1 diabetes mellitus in young adults

Schölin, Anna; Nyström, Lennarth; Arnqvist, Hans J.; Bolinder, Jan; Björk, Erik; Berne, Christian; Karlsson, F. Anders

doi:10.1111/j.1464-5491.2010.03191.x

Cited by 37 publications

(42 citation statements)

References 24 publications

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“…The detection of accelerated impairment in the b cell function in autoantibody-positive individuals would facilitate the identification of likely progressors suitable for secondary intervention trials. It might also help in the timing of immune interventions at a stage when the endogenous insulin production is higher than that seen at the time of diagnosis when ,30% of functioning b cells are left (24). There is also a need for a biomarker for monitoring the effects of interventions and helping in the assessment of residual b cell function and glycemic control both in children at increased risk for type 1 diabetes and in those with recently diagnosed type 1 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Th1/Th17 Plasticity Is a Marker of Advanced β Cell Autoimmunity and Impaired Glucose Tolerance in Humans

Reinert-Hartwall¹,

Honkanen²,

Salo³

et al. 2015

The Journal of Immunology

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Upregulation of IL-17 immunity and detrimental effects of IL-17 on human islets have been implicated in human type 1 diabetes. In animal models, the plasticity of Th1/Th17 cells contributes to the development of autoimmune diabetes. In this study, we demonstrate that the upregulation of the IL-17 pathway and Th1/Th17 plasticity in peripheral blood are markers of advanced β cell autoimmunity and impaired β cell function in human type 1 diabetes. Activated Th17 immunity was observed in the late stage of preclinical diabetes in children with β cell autoimmunity and impaired glucose tolerance, but not in children with early β cell autoimmunity. We found an increased ratio of IFN-γ/IL-17 expression in Th17 cells in children with advanced β cell autoimmunity, which correlated with HbA1c and plasma glucose concentrations in an oral glucose tolerance test, and thus impaired β cell function. Low expression of Helios was seen in Th17 cells, suggesting that Th1/Th17 cells are not converted thymus-derived regulatory T cells. Our results suggest that the development of Th1/Th17 plasticity may serve as a biomarker of disease progression from β cell autoantibody positivity to type 1 diabetes. These data in human type 1 diabetes emphasize the role of Th1/Th17 plasticity as a potential contributor to tissue destruction in autoimmune conditions.

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Section: Discussionmentioning

confidence: 99%

Th1/Th17 Plasticity Is a Marker of Advanced β Cell Autoimmunity and Impaired Glucose Tolerance in Humans

Reinert-Hartwall¹,

Honkanen²,

Salo³

et al. 2015

The Journal of Immunology

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“…Although C-peptide levels are typically increased in the months after diagnosis, this period has still been largely associated with a concomitant increase in proinsulin levels, with varying patterns in PI/C ratios during this partial remission or honeymoon period [21–24]. PI/C ratios at diagnosis are inversely correlated with length of the honeymoon period [21].…”

Section: Proinsulin/c-peptide Ratio As a Circulating Biomarker Of β-Cmentioning

confidence: 99%

Biomarkers of β-Cell Stress and Death in Type 1 Diabetes

et al. 2016

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The hallmark of type 1 diabetes (T1D) is a decline in functional β-cell mass arising as a result of autoimmunity. Immunomodulatory interventions at disease onset have resulted in partial stabilization of β-cell function, but full recovery of insulin secretion has remained elusive. Revised efforts have focused on disease prevention through interventions administered at earlier disease stages. To support this paradigm, there is a parallel effort ongoing to identify circulating biomarkers that have the potential to identify stress and death of the islet β-cells. Whereas no definitive biomarker(s) have been fully validated, several approaches hold promise that T1D can be reliably identified in the pre-symptomatic phase, such that either β-cell preservation or immunomodulatory agents might be employed in at-risk populations. This review summarizes the most promising protein- and nucleic acid-based biomarkers discovered to date and reviews the context in which they have been studied.

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“…On the other hand, some of the subjects with higher BMI at diagnosis may have increased insulin resistance which, in turn, is associated with worse metabolic control of diabetes, even despite preserved endogenous insulin secretion [21]. A positive relationship between BMI at onset of diabetes and the occurrence of remission was previously reported in adults [12,22] and in children [23]. In another study, low BMI at diagnosis of diabetes (BMI<20 kg/m 2 ) was associated with decreased possibility of entering remission and also with its shorter duration [24].…”

Section: Discussionmentioning

confidence: 92%

Factors associated with early beginning of partial remission in young adult patients with newly diagnosed type 1 diabetes

Piłaciński

Zozulińska‐Ziółkiewicz

Uruski

et al. 2015

Int J Diabetes Dev Ctries

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Clinical remission of type 1 diabetes reflects the transient recovery of β-cell function and improvement in insulin sensitivity, occurring after introduction of insulin therapy. The aim of the study was to identify factors associated with early beginning of partial remission phase in patients with newly diagnosed type 1 diabetes. One hundred and sixteen patients (41 women and 75 men), aged 18-34 (mean age 23.8±8.7 years), were included into the study. Mean hospitalization time was 7±2 days. Early remission was defined as reaching total daily insulin dose <0.3 U/kg with correct glycaemia in 24-h (7-point) glycaemic profile before discharge from the hospital, with random serum Cpeptide above 0.5 μg/l. In group entering early remission (74 patients), significantly lower HbA1c values (9.6±2.6 vs. 11.5±4.5 %, p<0.001), higher body mass index (BMI) (21.9 ± 2.9 vs. 20.8 ± 4.2 kg/m 2 , p < 0.05), less frequent ketonuria (45 vs. 79 %, p<0.01) and diabetic ketoacidosis (11 vs. 26 %, p = 0.06) were recorded at diagnosis. The results indicate that degree and duration of metabolic disturbances are associated with early beginning of partial remission in young adults with newly diagnosed type 1 diabetes. Early onset of remission is common in this age group.

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Proinsulin/C‐peptide ratio, glucagon and remission in new‐onset Type 1 diabetes mellitus in young adults

Cited by 37 publications

References 24 publications

Th1/Th17 Plasticity Is a Marker of Advanced β Cell Autoimmunity and Impaired Glucose Tolerance in Humans

Th1/Th17 Plasticity Is a Marker of Advanced β Cell Autoimmunity and Impaired Glucose Tolerance in Humans

Biomarkers of β-Cell Stress and Death in Type 1 Diabetes

Factors associated with early beginning of partial remission in young adult patients with newly diagnosed type 1 diabetes

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