scholarly journals One Repeated Transplantation of Allogeneic Umbilical Cord Mesenchymal Stromal Cells in Type 1 Diabetes: An Open Parallel Controlled Clinical Study

2020 ◽  
Author(s):  
Jing Lu ◽  
Shanmei Shen ◽  
Qing Ling ◽  
Wei Zhang ◽  
Duoduo Qu ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Cell Function ◽  
Treated Group ◽  
Control Group ◽  
Adult Onset ◽  
Juvenile Onset ◽  
C Peptide ◽  
B Cell Function

Abstract Background: The preservation or restoration of b-cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D. Methods: This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. 53 participants including 33 adult-onset (³18 years) and 20 juvenile-onset T1D were enrolled. 27 subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n=26) only received standard care based on intensive insulin therapy. Data at one-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses. Results: After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide was not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed. Conclusion: One repeated transplantation of allogeneic UC-MSCs is both safe and beneficial to preserve b-cell function for individuals with T1D. Trial registration: NCT 02763423. Registered on April 19, 2016 - Retrospectively registered, https://clinicaltrials.gov/

scholarly journals One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: an open parallel controlled clinical study

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Lu ◽  
Shan-mei Shen ◽  
Qing Ling ◽  
Bin Wang ◽  
Li-rong Li ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Stromal Cells ◽  
Treated Group ◽  
Control Group ◽  
Adult Onset ◽  
Β Cell ◽  
Juvenile Onset ◽  
C Peptide

Abstract Background The preservation or restoration of β cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D. Methods This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses. Results After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed. Conclusion One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet β cell preservation during the first year after diagnosis compared to standard treatment alone. Trial registration ChiCTR2100045434. Registered on April 15, 2021—retrospectively registered, http://www.chictr.org.cn/

C-Peptide Immunoreactivity (CPR): A New Method for Studying Infants of Insulin-Treated Diabetic Mothers

PEDIATRICS ◽  
1974 ◽  
Vol 53 (6) ◽  
pp. 923-928
Author(s):  
Marshall B. Block ◽  
Rosita S. Pildes ◽  
Nafessa A. Mossabhoy ◽  
Donald F. Steiner ◽  
Arthur H. Rubenstein
Keyword(s):  
B Cell ◽  
Cell Function ◽  
Gel Filtration ◽  
Newborn Infants ◽  
Diabetic Patients ◽  
Cell Secretion ◽  
Juvenile Onset ◽  
Intravenous Glucose ◽  
C Peptide ◽  
B Cell Function

Proinsulin is converted to insulin and C-peptide in the pancreatic islet cells; the latter two polypeptides are then secreted in equimolar concentration. Thus, measurement of C-peptide may provide an alternative means of studying B-cell function in pregnant, insulin-treated, diabetic patients and in their newborn infants (IDM). Using this approach, B-cell function was studied in eight normal, ten juvenile onset and five gestational diabetic patients at the time of delivery. Normal maternal and cord CPR (C-peptide immunoreactivity levels, mean ± SEM, were 1.5 ± 0.3 and 0.9 ± 0.1 ng/ml, respectively. In six of ten juvenile onset diabetics, CPR levels were undetectable, while in four CPR was elevated. Five gestational diabetic women had elevated CPR levels. Cord CPR levels were significantly higher in all IDM than in the normal controls. A prompt rise in CPR was seen following intravenous glucose load in four IDM. Gel filtration of selected sera demonstrated both C-peptide and proinsulin, the latter protein being bound to circulating insulin antibodies which have crossed the placenta. Thus, active B-cell secretion composed of proinsulin, C-peptide and presumably insulin is present during insulin therapy in gestational, in some juvenile-onset-diabetic, pregnant women and in their offspring.

Pathophysiological characteristics of preproinsulin-specific CD8+ T cells in subjects with juvenile-onset and adult-onset type 1 diabetes: A 1-year follow-up study

2017 ◽  
Vol 19 (1) ◽  
pp. 68-79 ◽  
Author(s):  
Mahinder Paul ◽  
Darshan Badal ◽  
Neenu Jacob ◽  
Devi Dayal ◽  
Rakesh Kumar ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Cd8 T Cells ◽  
Adult Onset ◽  
Juvenile Onset ◽  
Onset Type ◽  
Follow Up Study

The unfavorable impact of DR9/DR9 genotype on the frequency and quality of partial remission in type 1 diabetes

2021 ◽  
Author(s):  
Yan Chen ◽  
Ying Xia ◽  
Zhiguo Xie ◽  
Ting Zhong ◽  
Rong Tang ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Partial Remission ◽  
Cell Function ◽  
Age Of Onset ◽  
Human Leukocyte ◽  
Adult Onset ◽  
C Peptide ◽  
Β Cell Function ◽  
Remission Phase

Abstract Context Partial remission (PR) is a specific stage in type 1 diabetes (T1D). Although human leukocyte antigen (HLA) class II loci are the strongest genetic determinants in T1D, the relationship between PR and HLA remains unclear. Objective To investigate the association between PR status and HLA genotypes in T1D patients. Methods A total of 237 T1D patients were included. PR was defined according to C-peptide ≥300 pmol/L. The frequency of PR and peak C-peptide levels during remission phase were compared according to HLA status. Clinical characteristics including age of onset and diabetes autoantibodies were collected. All analyses were duplicated when subjects were divided into childhood- and adult-onset T1D. Results The median follow-up time was 24 months, 65.8% (156/237) of T1D patients went into PR. DR9/DR9 carriers had lower PR rate (44.2% vs. 70.6%, P=0.001) and less likely to enter PR (OR=0.218, 95% CI: 0.098-0.487, P<0.001) than the non-DR9/DR9 carriers, observed in both childhood- and adult-onset T1D. Besides, the peak C-peptide during PR phase was also lower in DR9/DR9 carriers, more notable in adult-onset T1D. When compared with non-DR9/DR9 carriers, T1D with DR9/DR9 genotype presented an older age of onset and a lower positivity of zinc transporter 8 antibody (ZnT8A), and the lower trend of ZnT8A was only found in adult-onset T1D (P=0.049). Conclusions T1D carrying susceptible DR9/DR9 are less prone to undergo PR. Additionally, the recovery extent of β-cell function during the PR phase tends to be lower in adults carrying DR9/DR9, which might be associated with ZnT8A.

Effect of 6-months’ vitamin D supplementation on residual beta cell function in children with type 1 diabetes: a case control interventional study

2016 ◽  
Vol 29 (4) ◽  
Author(s):  
Atindra Mishra ◽  
Devi Dayal ◽  
Naresh Sachdeva ◽  
Savita Verma Attri
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Beta Cell Function ◽  
Cell Function ◽  
Intervention Group ◽  
Vitamin D Supplementation ◽  
Control Group ◽  
Short Term ◽  
C Peptide

AbstractThe aim of this study was to evaluate the effect of short-term vitamin D supplementation on the decline of residual beta cell function (RBCF) in children with type 1 diabetes (T1D).The study involved an intervention group (cholecalciferol 2000 IU/day and calcium 25 mg/kg/day for 6 months) comprising 15 children aged 6–12 years and within 1–2 years of diagnosis of T1D. Fifteen age-matched T1D patients were followed up as controls. Stimulated C-peptide levels were estimated at baseline and 6 months.: The mean decrease in stimulated C-peptide levels in the intervention group was lower (–0.048±0.15 ng/mL) as compared with the controls (–0.107±0.23 ng/mL) but did not reach statistical significance (p=0.472). The percent decrease in stimulated C-peptide from baseline to endpoint (8.3% vs. 20.3%, p=0.357) and the monthly decrease (0.008 ng/mL vs. 0.017 ng/mL, p=0.22) were non-significantly lower in the intervention group compared with the control group. Three (20%) patients progressed to undetectable stimulated C-peptide (≤0.01 ng/mL) over the study period in the control group as compared with one (6%) in the intervention group (p-value 0.260).There was a trend towards lesser decline of RBCF with short term cholecalciferol supplementation in children with T1D. Further larger studies are urgently needed to explore the beneficial effects of the relatively inexpensive vitamin D supplementation on RBCF.

1917-P: Alpha-Cell Function in Patients with Type 1 Diabetes Is Compromised with Different Levels of Residual C-Peptide

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1917-P
Author(s):  
LINGYU ZHANG ◽  
YUWEN SHI ◽  
YITING HUANG ◽  
QIZHEN HU ◽  
YAO QIN ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Alpha Cell ◽  
C Peptide ◽  
Alpha Cell Function ◽  
Different Levels

scholarly journals Clinical and demographic features among patients with type 1 diabetes mellitus in Henan, China

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Liguo Yang ◽  
Guangxing Yang ◽  
Xialian Li
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Retinopathy ◽  
Blood Glucose Control ◽  
Disease Onset ◽  
Overweight And Obesity ◽  
Adult Onset ◽  
C Peptide ◽  
Young Onset ◽  
Onset Group

Abstract Background The hallmark of type 1 diabetes (T1D) is an absolute lack of insulin. However, many studies showed a tendency to heterogeneity in TID. We aimed to investigate the demographic and clinical characteristics in T1D and the differences in young-onset and adult-onset patients. Methods This retrospective study was conducted among 1943 patients with clinically diagnosed T1D. Medical records on patients’ demographics, anthropometric measurements, and clinical manifestation were collected. According to the age at onset, the newly diagnosed patients were divided into the young-onset group (< 18 years, 234 patients, mean age 11 years) and adult-onset group (≥ 18 years, 219 patients, mean age 27 years). Pancreatic β-cell function was assessed by fasting C-peptide (FCP) and 2-h C-peptide (2-h CP). Results The median age of patients at disease onset was 22 years. The median duration of patients was 3 years. The overall median glycated hemoglobin (HbA1c) value was 10.3 % [89(mmol/mol)]. The prevalence of diabetic retinopathy was 25.1 %. The overall rate of DKA at onset in the new-onset patients was 59.6 %. The frequency of overall dyslipidemia was 37.8 %. The most frequent dyslipidemia was low high-density lipoprotein-cholesterol (HDL) (29 %). The proportion of patients with anti-glutamic acid decarboxylase (GADA), insulin antibody (IAA) and islet cell antibody (ICA) were 28.1 %, 6.4 % and 21.6 %, respectively. The mean HbA1c showed a downward trend with age. Increasing or decreasing trends of overweight and obesity in this population during the period 2012 to 2018 was not found. Compared with young-onset T1D, adult-onset patients comprised better islet function (FCP: 0.4 vs. 0.3 ng/ml, P < 0.001; 2-h CP: 0.9 vs. 0.7 ng/ml P < 0.001, respectively) and glycemic control [12.9 % (117mmol/mol) vs. 11.7 % (104mmol/mol), P < 0.001], higher prevalence of diabetes condition in the male gender (64.4 % vs. 51.3 %, P = 0.006), higher proportion of obesity or overweight (24.6 % vs. 9.5 %, P = 0.002), higher frequency of GADA (33.7 % vs. 23.3 %, P = 0.025), and lower frequency of diabetic ketoacidosis at disease onset (64.5 % vs. 43.5 %, P < 0.001). Conclusions This population was characterized by poor overall blood glucose control, high prevalence of DKA, dyslipidemia and diabetic retinopathy, and low prevalence of islet-related antibodies, and overweight or obesity. Adult-onset patients with T1D were not uncommon and had better clinical manifestations than young-onset patients. Any findings related to body mass index (BMI) and autoantibodies should be considered strictly exploratory due to excessive missing data.

scholarly journals Continuous subcutaneous insulin infusion alters microRNA expression and glycaemic variability in children with type 1 diabetes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Emma S. Scott ◽  
Andrzej S. Januszewski ◽  
Luke M. Carroll ◽  
Gregory R. Fulcher ◽  
Mugdha V. Joglekar ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Continuous Subcutaneous Insulin Infusion ◽  
Insulin Infusion ◽  
Diabetes Diagnosis ◽  
Subcutaneous Insulin ◽  
Glycaemic Variability ◽  
Altered Expression ◽  
C Peptide

AbstractTo determine whether continuous subcutaneous insulin infusion (CSII) vs. multiple daily injections (MDI) therapy from near-diagnosis of type 1 diabetes is associated with reduced glycaemic variability (GV) and altered microRNA (miRNAs) expression. Adolescents (74% male) within 3-months of diabetes diagnosis (n = 27) were randomized to CSII (n = 12) or MDI. HbA1c, 1-5-Anhydroglucitol (1,5-AG), high sensitivity C-peptide and a custom TaqMan qPCR panel of 52 miRNAs were measured at baseline and follow-up (median (LQ-UQ); 535 (519–563) days). There were no significant differences between groups in baseline or follow-up HbA1c or C-peptide, nor baseline miRNAs. Mean ± SD 1,5-AG improved with CSII vs. MDI (3.1 ± 4.1 vs. − 2.2 ± − 7.0 mg/ml respectively, P = 0.029). On follow-up 11 miRNAs associated with diabetes vascular complications had altered expression in CSII-users. Early CSII vs. MDI use is associated with lower GV and less adverse vascular-related miRNAs. Relationships with future complications are of interest.

scholarly journals Insulin micro-secretion in Type 1 diabetes and related microRNA profiles

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrzej S. Januszewski ◽  
Yoon Hi Cho ◽  
Mugdha V. Joglekar ◽  
Ryan J. Farr ◽  
Emma S. Scott ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cross Sectional Study ◽  
Diabetes Duration ◽  
Adult Onset ◽  
Sectional Study ◽  
Childhood Onset ◽  
Cross Sectional ◽  
C Peptide ◽  
Adult Onset Diabetes

AbstractThe aim of this cross-sectional study was to compare plasma C-peptide presence and levels in people without diabetes (CON) and with Type 1 diabetes and relate C-peptide status to clinical factors. In a subset we evaluated 50 microRNAs (miRs) previously implicated in beta-cell death and associations with clinical status and C-peptide levels. Diabetes age of onset was stratified as adult (≥ 18 y.o) or childhood (< 18 y.o.), and diabetes duration was stratified as ≤ 10 years, 10–20 years and > 20 years. Plasma C-peptide was measured by ultrasensitive ELISA. Plasma miRs were quantified using TaqMan probe-primer mix on an OpenArray platform. C-peptide was detectable in 55.3% of (n = 349) people with diabetes, including 64.1% of adults and 34.0% of youth with diabetes, p < 0.0001 and in all (n = 253) participants without diabetes (CON). C-peptide levels, when detectable, were lower in the individuals with diabetes than in the CON group [median lower quartile (LQ)–upper quartile (UQ)] 5.0 (2.6–28.7) versus 650.9 (401.2–732.4) pmol/L respectively, p < 0.0001 and lower in childhood versus adult-onset diabetes [median (LQ–UQ) 4.2 (2.6–12.2) pmol/L vs. 8.0 (2.3–80.5) pmol/L, p = 0.02, respectively]. In the childhood-onset group more people with longer diabetes duration (> 20 years) had detectable C-peptide (60%) than in those with shorter diabetes duration (39%, p for trend < 0.05). Nine miRs significantly correlated with detectable C-peptide levels in people with diabetes and 16 miRs correlated with C-peptide levels in CON. Our cross-sectional study results are supportive of (a) greater beta-cell function loss in younger onset Type 1 diabetes; (b) persistent insulin secretion in adult-onset diabetes and possibly regenerative secretion in childhood-onset long diabetes duration; and (c) relationships of C-peptide levels with circulating miRs. Confirmatory clinical studies and related basic science studies are merited.

Sign in / Sign up

Export Citation Format

Share Document