scholarly journals Zinc transporter 8 (ZnT8) autoantibody prevalence in black South African participants with type 1 diabetes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sureka Bhola ◽  
Eleanor M Cave ◽  
Sindeep Bhana ◽  
Nigel J Crowther ◽  
Carolyn J Padoa
Keyword(s):  
Type 1 Diabetes ◽  
South African ◽  
Disease Duration ◽  
Age At Diagnosis ◽  
Newly Diagnosed ◽  
Β Cell ◽  
Black South African ◽  
Younger Age ◽  
Znt8 Autoantibodies

Abstract Background Autoantibodies to β-cell specific antigens are markers of type 1 diabetes. The most recently identified autoantibodies are targeted to the zinc transporter 8 (ZnT8) protein located in the membrane of β-cell insulin secretory granules. The prevalence of ZnT8 autoantibodies in newly diagnosed participants with type 1 diabetes has been found to range from 33 to 80 %. Due to the lack of data on the immunological aetiology of type 1 diabetes in African populations, this study aimed to determine the prevalence of ZnT8 autoantibodies in black South Africans with type 1 diabetes and whether ZnT8 autoantibody positivity was associated with age at diagnosis and disease duration. Methods Participants with type 1 diabetes and controls were recruited from the greater Johannesburg area, South Africa. Positivity for ZnT8, GAD65 and IA2 autoantibodies was determined by ELISA. Results Participants with type 1 diabetes (n = 183) and controls (n = 49) were matched for age (29.1 ± 9.53 vs. 27.3 ± 7.29, respectively; p = 0.248). The mean age at diagnosis for participants with type 1 diabetes was 20.8 ± 8.46 years. The prevalence of ZnT8 autoantibody positivity was 17.5 % (32 of 183) in participants with type 1 diabetes with a median disease duration of 7.00 [2.00; 11.0] years. ZnT8 autoantibody prevalence in newly diagnosed participants (< 1 year duration) was 27.3 % (6 of 22). Logistic regression analysis found an association between ZnT8 autoantibody positivity and shorter disease duration (OR: 0.9 (0.81-1.00); p = 0.042). In addition, ZnT8 autoantibody positivity was significantly associated with an increased chance of being GAD65 (OR: 3.37 (1.10–10.3)) and IA2 (OR: 8.63 (2.82–26.4)) autoantibody positive. Multiple regression analysis found no association between ZnT8 autoantibody positivity and age at diagnosis. However, the presence of ≥ 2 autoantibodies was associated with a younger age at diagnosis of type 1 diabetes when compared to participants with ≤ 1 autoantibody (B = -5.270; p = 0.002). Conclusions The presence of ZnT8 autoantibodies was not related to a younger age at diagnosis in black South African patients with type 1 diabetes. However, the greater the numbers of autoantibodies present in an individual the earlier the age at diagnosis. ZnT8 autoantibodies decline with disease duration in the black South African population.

scholarly journals Systemic TNFα correlates with residual β-cell function in children and adolescents newly diagnosed with type 1 diabetes

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Anne Julie Overgaard ◽  
Jens Otto Broby Madsen ◽  
Flemming Pociot ◽  
Jesper Johannesen ◽  
Joachim Størling
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Disease Onset ◽  
Newly Diagnosed ◽  
Β Cell ◽  
Entire Study ◽  
C Peptide ◽  
Disease Remission ◽  
Β Cell Function

Abstract Background Type 1 diabetes (T1D) is caused by immune-mediated destruction of the β-cells. After initiation of insulin therapy many patients experience a period of improved residual β-cell function leading to partial disease remission. Cytokines are important immune-modulatory molecules and contribute to β-cell damage in T1D. The patterns of systemic circulating cytokines during T1D remission are not clear but may constitute biomarkers of disease status and progression. In this study, we investigated if the plasma levels of various pro- and anti-inflammatory cytokines around time of diagnosis were predictors of remission and residual β-cell function in children with T1D followed for one year after disease onset. Methods In a cohort of 63 newly diagnosed children (33% females) with T1D with a mean age of 11.3 years (3.3–17.7), ten cytokines were measured of which eight were detectable in plasma samples by Mesoscale Discovery multiplex technology at study start and after 6 and 12 months. Linear regression models were used to evaluate association of cytokines with stimulated C-peptide. Results Systemic levels of tumor necrosis factor (TNF)-α, interleukin (IL)-2 and IL-6 inversely correlated with stimulated C-peptide levels over the entire study (P < 0.05). The concentrations of TNFα and IL-10 at study start predicted stimulated C-peptide level at 6 months (P = 0.011 and P = 0.043, respectively, adjusted for sex, age, HbA1c and stage of puberty). Conclusions In recent-onset T1D, systemic cytokine levels, and in particular that of TNFα, correlate with residual β-cell function and may serve as prognostic biomarkers of disease remission and progression to optimize treatment strategies. Trial Registration The study was performed according to the criteria of the Helsinki II Declaration and was approved by the Danish Capital Region Ethics Committee on Biomedical Research Ethics (journal number H-3-2014-052). The parents of all participants gave written consent.

Prognosis for residual islet β‐cell secretion function in young patients with newly diagnosed type 1 diabetes

2019 ◽  
Vol 11 (10) ◽  
pp. 818-825 ◽  
Author(s):  
Haitao Miao ◽  
Juanjuan Zhang ◽  
Bin Gu ◽  
Aibo Gao ◽  
Jie Hong ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Young Patients ◽  
Newly Diagnosed ◽  
Cell Secretion ◽  
Β Cell

Younger age at diagnosis of type 1 diabetes mellitus in children of immigrated families born in Italy

2004 ◽  
Vol 27 (10) ◽  
pp. 913-918 ◽  
Author(s):  
F. Cadario ◽  
◽  
A. Vercellotti ◽  
M. Trada ◽  
M. Zaffaroni ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Age At Diagnosis ◽  
Younger Age

scholarly journals Genetic Composition and Autoantibody Titers Model the Probability of Detecting C-Peptide Following Type 1 Diabetes Diagnosis

2021 ◽  
Author(s):  
MacKenzie D. Williams ◽  
Rhonda Bacher ◽  
Daniel J. Perry ◽  
C. Ramsey Grace ◽  
Kieran M. McGrail ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Disease Duration ◽  
Cell Function ◽  
Age At Onset ◽  
Diabetes Diagnosis ◽  
Β Cell ◽  
C Peptide ◽  
Peptide Detection ◽  
Β Cell Function

We and others previously demonstrated that a type 1 diabetes genetic risk score (GRS) improves the ability to predict disease progression and onset in at-risk subjects with islet autoantibodies. Here, we hypothesized that GRS and islet autoantibodies, combined with age at onset and disease duration, could serve as markers of residual β-cell function following type 1 diabetes diagnosis. Generalized estimating equations were used to investigate whether GRS along with insulinoma-associated protein-2 autoantibody (IA-2A), zinc transporter 8 autoantibody (ZnT8A) and GAD autoantibody (GADA) titers were predictive of C-peptide detection in a largely cross-sectional cohort of 401 subjects with type 1 diabetes (duration median = 4.5 years, range 0-60). Indeed, a combined model incorporating disease duration, age at onset, GRS, and titers of IA-2A, ZnT8A and GADA provided superior capacity to predict C-peptide detection (QIC=334.6) compared with disease duration, age at onset, and GRS as the sole parameters (QIC=359.2). These findings support the need for longitudinal validation of our combinatorial model. The ability to project the rate and extent of decline in residual C-peptide production for individuals with type 1 diabetes could critically inform enrollment and benchmarking for clinical trials seeking to preserve or restore endogenous β-cell function.

Type 1 Diabetic Serum Interferes with Pancreatic β-cell Ca2+ -Handling

2007 ◽  
Vol 27 (6) ◽  
pp. 321-326 ◽  
Author(s):  
N. Dekki ◽  
R. Nilsson ◽  
S. Norgren ◽  
S. M. Rössner ◽  
I. Appelskog ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Ethnic Background ◽  
Diabetic Patients ◽  
Pancreatic Β Cell ◽  
Newly Diagnosed ◽  
Β Cells ◽  
Β Cell ◽  
First Degree Relatives ◽  
Type 1 Diabetic Patients

The aim of this study was to clarify the frequency of patients with type 1 diabetes that have serum that increases pancreatic β-cell cytoplasmic free Ca2+ concentration, [Ca2+]i, and if such an effect is also present in serum from first-degree relatives. We also studied a possible link between the serum effect and ethnic background as well as presence of autoantibodies. Sera obtained from three different countries were investigated as follows: 82 Swedish Caucasians with newly diagnosed type 1 diabetes, 56 Americans with different duration of type 1 diabetes, 117 American first-degree relatives of type 1 diabetic patients with a mixed ethnic background and 31 Caucasian Finnish children with newly diagnosed type 1 diabetes. Changes in [Ca2+]i, upon depolarization, were measured in β-cells incubated overnight with sera from type 1 diabetic patients, first-degree relatives or healthy controls. Our data show that there is a group constituting approximately 30% of type 1 diabetic patients of different gender, age, ethnic background and duration of the disease, as well as first-degree relatives of type 1 diabetic patients, that have sera that interfere with pancreatic β-cell Ca2+-handling. This effect on β-cell [Ca2+]i could not be correlated to the presence of autoantibodies. In a defined subgroup of patients with type 1 diabetes and first-degree relatives a defect Ca2+-handling may aggravate development of β-cell destruction.

Markers influencing the presence of partial clinical remission in patients with newly diagnosed type 1 diabetes

2017 ◽  
Vol 30 (11) ◽  
Author(s):  
Aleksandra Pyziak ◽  
Agnieszka Zmyslowska ◽  
Katarzyna Bobeff ◽  
Beata Malachowska ◽  
Wojciech Fendler ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Clinical Remission ◽  
Glycated Hemoglobin ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Insulin Requirement ◽  
Newly Diagnosed ◽  
Younger Age

AbstractBackground:The aim of the study was to compare the selected markers in children with and without partial clinical remission (CR) of newly diagnosed type 1 diabetes (T1D).Methods:The study group consisted of 186 patients (F/M; 87/99) at onset of T1D and 24 months of follow-up. Partial CR was defined as insulin requirement <0.5 IU/kg and glycated hemoglobin (HbAResults:Partial CR was observed in 115/186 (61.83%) of patients. At diagnosis body mass index standard deviation (BMI SDS) was higher among remitters than in non-remitters (p=0.0051) and remitters were younger (p=0.0029). In the follow-up a higher triglyceride concentration in non-remitters compared to remitters (p=0.0455) and a lower high density lipoprotein (HDL) cholesterol level (p=0.0119) were noticed.Conclusions:Younger age and higher BMI at diagnosis of T1D can predispose to partial CR in children. In patients with CR of T1D after 2 years of follow-up a lipid profile improvement is observed.

scholarly journals SKAP2, a candidate gene for type 1 diabetes, regulates β-cell apoptosis and glycaemic control in newly diagnosed patients

2020 ◽  
Author(s):  
Ada Admin ◽  
Tina Fløyel ◽  
Kira Meyerovich ◽  
Michala C. Prause ◽  
Simranjeet Kaur ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glycaemic Control ◽  
Candidate Gene ◽  
Cell Function ◽  
Human Islets ◽  
Newly Diagnosed ◽  
Β Cell ◽  
Functional Studies ◽  
Induced Apoptosis

The single nucleotide polymorphism rs7804356 located in the Src kinase-associated phosphoprotein 2<i> </i>(SKAP2) gene<i> </i>is associated with type 1 diabetes (T1D) suggesting <i>SKAP2</i> as a causal candidate gene. The objective of the study was to investigate if SKAP2 has a functional role in the β-cells in relation to T1D. In a cohort of children with newly diagnosed T1D, rs7804356 predicted glycaemic control and residual β-cell function during first year after diagnosis. In INS-1E cells and rat and human islets, pro-inflammatory cytokines reduced the content of SKAP2. Functional studies revealed that knockdown of SKAP2 aggravated cytokine-induced apoptosis in INS-1E cells and primary rat b-cells, suggesting an anti-apoptotic function of SKAP2. In support of this, overexpression of SKAP2 afforded protection against cytokine-induced apoptosis which correlated with reduced nuclear content of S536-phosphorylated NFκB subunit p65, lower nitric oxide production and diminished C/EBP-homologues protein (CHOP) expression indicative of decreased endoplasmic reticulum stress. Knockdown of CHOP partially counteracted the increase in cytokine-induced apoptosis caused by SKAP2 knockdown. In conclusion, our results suggest that SKAP2 controls β-cell sensitivity to cytokines possibly by affecting the NFκB-iNOS-ER stress pathway.

scholarly journals SKAP2, a candidate gene for type 1 diabetes, regulates β-cell apoptosis and glycaemic control in newly diagnosed patients

2020 ◽  
Author(s):  
Ada Admin ◽  
Tina Fløyel ◽  
Kira Meyerovich ◽  
Michala C. Prause ◽  
Simranjeet Kaur ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glycaemic Control ◽  
Candidate Gene ◽  
Cell Function ◽  
Human Islets ◽  
Newly Diagnosed ◽  
Β Cell ◽  
Functional Studies ◽  
Induced Apoptosis

The single nucleotide polymorphism rs7804356 located in the Src kinase-associated phosphoprotein 2<i> </i>(SKAP2) gene<i> </i>is associated with type 1 diabetes (T1D) suggesting <i>SKAP2</i> as a causal candidate gene. The objective of the study was to investigate if SKAP2 has a functional role in the β-cells in relation to T1D. In a cohort of children with newly diagnosed T1D, rs7804356 predicted glycaemic control and residual β-cell function during first year after diagnosis. In INS-1E cells and rat and human islets, pro-inflammatory cytokines reduced the content of SKAP2. Functional studies revealed that knockdown of SKAP2 aggravated cytokine-induced apoptosis in INS-1E cells and primary rat b-cells, suggesting an anti-apoptotic function of SKAP2. In support of this, overexpression of SKAP2 afforded protection against cytokine-induced apoptosis which correlated with reduced nuclear content of S536-phosphorylated NFκB subunit p65, lower nitric oxide production and diminished C/EBP-homologues protein (CHOP) expression indicative of decreased endoplasmic reticulum stress. Knockdown of CHOP partially counteracted the increase in cytokine-induced apoptosis caused by SKAP2 knockdown. In conclusion, our results suggest that SKAP2 controls β-cell sensitivity to cytokines possibly by affecting the NFκB-iNOS-ER stress pathway.

scholarly journals Evaluating the Effect of Prebiotics on the Gut Microbiome Profile and β-cell Function in Youth with Newly-Diagnosed Type 1 Diabetes

2020 ◽  
Author(s):  
Heba M. Ismail ◽  
Maria Spall ◽  
Carmella Evans-Molina ◽  
Linda A. DiMeglio
Keyword(s):  
Type 1 Diabetes ◽  
Gut Microbiome ◽  
Cell Function ◽  
Human Study ◽  
Newly Diagnosed ◽  
Β Cell ◽  
Microbiome Profile ◽  
Β Cell Function ◽  
Health Function

AbstractData show that disturbances in the gut microbiota play a role in glucose homeostasis, type 1 diabetes (T1D) risk and progression. The prebiotic high amylose maize starch (HAMS) alters the gut microbiome profile and metabolites favorably with an increase in bacteria producing short chain fatty acids (SCFAs) that have significant anti-inflammatory effects. HAMS also improves glycemia, insulin sensitivity and secretion in healthy non-diabetic adults. Additionally, a recent study testing an acetylated and butyrylated form of HAMS (HAMS-AB) that further increases SCFA production prevented T1D in a rodent model without adverse safety effects. The overall objective of this human study will be to assess how daily HAMS-AB consumption impacts the gut microbiome profile, SCFA production, β-cell heath, function and glycemia as well as immune responses in newly-diagnosed T1D youth. We hypothesize that HAMS-AB intake will improve the gut microbiome profile, increase SCFA production, improve β-cell health, function and glycemia as well as modulate the immune system. We describe here a pilot, randomized crossover trial of HAMS-AB in 12 newly-diagnosed T1D youth with residual β-cell function. In Aim 1, we will determine the effect of HAMS-AB on the gut microbiome profile and SCFA production; in Aim 2, we will determine the effect of HAMS-AB on β-cell health, function and glycemia; and in Aim 3, we will determine the peripheral blood effect of HAMS-AB on frequency, phenotype and function of specific T cell markers. We anticipate beneficial effects from a simple, inexpensive and safe dietary approach.

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