scholarly journals Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications

2020 ◽  
Author(s):  
Anita Jeyam ◽  
Helen Colhoun ◽  
Stuart McGurnaghan ◽  
Luke Blackbourn ◽  
Timothy J McDonald ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Hospital Admission ◽  
Odds Ratio ◽  
Regression Models ◽  
Microvascular Complications ◽  
C Peptide ◽  
Peptide Secretion ◽  
The Relationship

<i>Objective: </i>To quantify the relationship of residual C-peptide secretion to glycemic outcomes and microvascular complications in type 1 diabetes. <p><i>Design and Methods: </i>C-peptide was measured in an untimed blood sample in the SDRNT1BIO cohort of 6076 people with type 1 diabetes followed for an average of 5.2 years. </p> <p><i>Results: </i>In regression models adjusted for age at onset and duration, effect sizes for C-peptide ≥200 versus <5 pmol/l were as follows: insulin dose at baseline 27% lower (p=2×10−39), HbA1c during follow-up 4.9 mmol/mol lower (p=3×10−13), hazard ratio for hospital admission for diabetic ketoacidosis during follow-up 0.44 (p=0.0001), odds ratio for incident retinopathy 0.51 (p=0.0003). Effects on risk of serious hypoglycemic episodes were detectable at lower levels of C-peptide, and the form of the relationship was continuous down to the limit of detection (3 pmol/l). In regression models contrasting C-peptide 30 to <200 with <5 pmol/l, the odds ratio for self-report of at least one serious hypoglycemic episode in the last year was 0.56 (p=6×10−8), and the hazard ratio for hospital admission for hypoglycemia during follow-up was 0.52 (p=0.03). </p> <p><i>Conclusion: </i>These results in a large representative cohort suggest that even minimal residual C-peptide secretion could have clinical benefit in type 1 diabetes, in contrast to a follow-up study of the DCCT intensively-treated cohort where an effect on hypoglycemia was seen only at C-peptide levels ≥130 pmol/l. This has obvious implications for design and evaluation of trials of interventions to preserve or restore pancreatic islet function in type 1 diabetes. </p>

scholarly journals Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications

2020 ◽  
Author(s):  
Anita Jeyam ◽  
Helen Colhoun ◽  
Stuart McGurnaghan ◽  
Luke Blackbourn ◽  
Timothy J McDonald ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Hospital Admission ◽  
Odds Ratio ◽  
Regression Models ◽  
Microvascular Complications ◽  
C Peptide ◽  
Peptide Secretion ◽  
The Relationship

<i>Objective: </i>To quantify the relationship of residual C-peptide secretion to glycemic outcomes and microvascular complications in type 1 diabetes. <p><i>Design and Methods: </i>C-peptide was measured in an untimed blood sample in the SDRNT1BIO cohort of 6076 people with type 1 diabetes followed for an average of 5.2 years. </p> <p><i>Results: </i>In regression models adjusted for age at onset and duration, effect sizes for C-peptide ≥200 versus <5 pmol/l were as follows: insulin dose at baseline 27% lower (p=2×10−39), HbA1c during follow-up 4.9 mmol/mol lower (p=3×10−13), hazard ratio for hospital admission for diabetic ketoacidosis during follow-up 0.44 (p=0.0001), odds ratio for incident retinopathy 0.51 (p=0.0003). Effects on risk of serious hypoglycemic episodes were detectable at lower levels of C-peptide, and the form of the relationship was continuous down to the limit of detection (3 pmol/l). In regression models contrasting C-peptide 30 to <200 with <5 pmol/l, the odds ratio for self-report of at least one serious hypoglycemic episode in the last year was 0.56 (p=6×10−8), and the hazard ratio for hospital admission for hypoglycemia during follow-up was 0.52 (p=0.03). </p> <p><i>Conclusion: </i>These results in a large representative cohort suggest that even minimal residual C-peptide secretion could have clinical benefit in type 1 diabetes, in contrast to a follow-up study of the DCCT intensively-treated cohort where an effect on hypoglycemia was seen only at C-peptide levels ≥130 pmol/l. This has obvious implications for design and evaluation of trials of interventions to preserve or restore pancreatic islet function in type 1 diabetes. </p>

scholarly journals Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications

Diabetes Care ◽  
2020 ◽  
pp. dc200567
Author(s):  
Anita Jeyam ◽  
Helen Colhoun ◽  
Stuart McGurnaghan ◽  
Luke Blackbourn ◽  
Timothy J. McDonald ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Microvascular Complications ◽  
Clinical Impact ◽  
C Peptide ◽  
Peptide Secretion

Erratum. Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications. Diabetes Care 2021;44:390–398

Diabetes Care ◽  
2021 ◽  
pp. dc21er04b
Author(s):  
Anita Jeyam ◽  
Helen Colhoun ◽  
Stuart McGurnaghan ◽  
Luke Blackbourn ◽  
Timothy J. McDonald ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetes Care ◽  
Microvascular Complications ◽  
Clinical Impact ◽  
C Peptide ◽  
Peptide Secretion

scholarly journals Residual C-peptide secretion and hypoglycemia awareness in people with type 1 diabetes

2021 ◽  
Vol 9 (1) ◽  
pp. e002288
Author(s):  
Martine J Wellens ◽  
Charlotte E Vollenbrock ◽  
Pim Dekker ◽  
Lianne S M Boesten ◽  
Petronella H Geelhoed-Duijvestijn ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Antihypertensive Drugs ◽  
Microvascular Complications ◽  
Severe Hypoglycemia ◽  
Diabetes Duration ◽  
Fasting Serum ◽  
C Peptide ◽  
Diabetes Onset ◽  
Peptide Secretion

IntroductionThis study aimed to assess the association between fasting serum C-peptide levels and the presence of impaired awareness of hypoglycemia (IAH) in people with type 1 diabetes.Research design and methodsWe performed a cross-sectional study among 509 individuals with type 1 diabetes (diabetes duration 5–65 years). Extensive clinical data and fasting serum C-peptide concentrations were collected and related to the presence or absence of IAH, which was evaluated using the validated Dutch version of the Clarke questionnaire. A multivariable logistic regression model was constructed to investigate the association of C-peptide and other clinical variables with IAH.ResultsIn 129 (25%) individuals, residual C-peptide secretion was detected, while 75 (15%) individuals reported IAH. The median (IQR) C-peptide concentration among all participants was 0.0 (0.0–3.9) pmol/L. The prevalence of severe hypoglycemia was lower in people with demonstrable C-peptide versus those with absent C-peptide (30% vs 41%, p=0.025). Individuals with IAH were older, had longer diabetes duration, more frequently had macrovascular and microvascular complications, and more often used antihypertensive drugs, antiplatelet agents and cholesterol-lowering medication. There was a strong association between IAH and having a severe hypoglycemia in the preceding year. In multivariable regression analysis, residual C-peptide, either continuously or dichotomous, was associated with lower prevalence of IAH (p=0.040–0.042), while age at diabetes onset (p=0.001), presence of microvascular complications (p=0.003) and body mass index (BMI) (p=0.003) were also independently associated with the presence of IAH.ConclusionsHigher BMI, the presence of microvascular complications and higher age at diabetes onset were independent risk factors for IAH in people with type 1 diabetes, while residual C-peptide secretion was associated with lower risk of this complication.

scholarly journals Erratum. Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications. Diabetes Care 2021;44:390–398

Diabetes Care ◽  
2021 ◽  
pp. dc21er04b
Author(s):  
Anita Jeyam ◽  
Helen Colhoun ◽  
Stuart McGurnaghan ◽  
Luke Blackbourn ◽  
Timothy J. McDonald ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetes Care ◽  
Microvascular Complications ◽  
Clinical Impact ◽  
C Peptide ◽  
Peptide Secretion

A Decade of Disparities in Diabetes Technology Use and HbA1c in Pediatric Type 1 Diabetes: A Trans-Atlantic Comparison

2020 ◽  
Author(s):  
Ananta Addala ◽  
Marie Auzanneau ◽  
Kellee Miller ◽  
Werner Maier ◽  
Nicole Foster ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Technology Use ◽  
Hemoglobin A1c ◽  
Diabetes Technology ◽  
Design And Methods ◽  
Relationship Of ◽  
The Relationship ◽  
Pediatric Type 1 Diabetes

<b>Objective:</b> As diabetes technology use in youth increases worldwide, inequalities in access may exacerbate disparities in hemoglobin A1c (HbA1c). We hypothesized an increasing gap in diabetes technology use by socioeconomic status (SES) would be associated with increased HbA1c disparities. <p> </p> <p><b>Research Design and Methods: </b>Participants aged <18 years with diabetes duration ≥1 year in the Type 1 Diabetes Exchange (T1DX, US, n=16,457) and Diabetes Prospective Follow-up (DPV, Germany, n=39,836) registries were categorized into lowest (Q1) to highest (Q5) SES quintiles. Multiple regression analyses compared the relationship of SES quintiles with diabetes technology use and HbA1c from 2010-2012 and 2016-2018. </p> <p> </p> <p><b>Results: </b>HbA1c was higher in participants with lower SES (in 2010-2012 & 2016-2018, respectively: 8.0% & 7.8% in Q1 and 7.6% & 7.5% in Q5 for DPV; and 9.0% & 9.3% in Q1 and 7.8% & 8.0% in Q5 for T1DX). For DPV, the association between SES and HbA1c did not change between the two time periods, whereas for T1DX, disparities in HbA1c by SES increased significantly (p<0.001). After adjusting for technology use, results for DPV did not change whereas the increase in T1DX was no longer significant.</p> <p> </p> <p><b>Conclusions: </b>Although causal conclusions cannot be drawn, diabetes technology use is lowest and HbA1c is highest in those of the lowest SES quintile in the T1DX and this difference for HbA1c broadened in the last decade. Associations of SES with technology use and HbA1c were weaker in the DPV registry. </p>

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/

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 Comparison of proinsulin and C-peptide secretion in healthy versus long-standing type 1 diabetes mellitus cohorts: A pilot study

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0207065 ◽  
Author(s):  
Catherine A. Sullivan ◽  
Jose M. Cacicedo ◽  
Iniya Rajendran ◽  
Devin W. Steenkamp
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Pilot Study ◽  
Type 1 Diabetes Mellitus ◽  
C Peptide ◽  
Peptide Secretion

scholarly journals Biological Activity of c-Peptide in Microvascular Complications of Type 1 Diabetes—Time for Translational Studies or Back to the Basics?

2020 ◽  
Vol 21 (24) ◽  
pp. 9723
Author(s):  
Aleksandra Ryk ◽  
Aleksandra Łosiewicz ◽  
Arkadiusz Michalak ◽  
Wojciech Fendler
Keyword(s):  
Type 1 Diabetes ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Negative Impact ◽  
Current Knowledge ◽  
Microvascular Complications ◽  
C Peptide ◽  
Increased Risk ◽  
The Impact

People with type 1 diabetes have an increased risk of developing microvascular complications, which have a negative impact on the quality of life and reduce life expectancy. Numerous studies in animals with experimental diabetes show that c-peptide supplementation exerts beneficial effects on diabetes-induced damage in peripheral nerves and kidneys. There is substantial evidence that c-peptide counteracts the detrimental changes caused by hyperglycemia at the cellular level, such as decreased activation of endothelial nitric oxide synthase and sodium potassium ATPase, and increase in formation of pro-inflammatory molecules mediated by nuclear factor kappa-light-chain-enhancer of activated B cells: cytokines, chemokines, cell adhesion molecules, vascular endothelial growth factor, and transforming growth factor beta. However, despite positive results from cell and animal studies, no successful c-peptide replacement therapies have been developed so far. Therefore, it is important to improve our understanding of the impact of c-peptide on the pathophysiology of microvascular complications to develop novel c-peptide-based treatments. This article aims to review current knowledge on the impact of c-peptide on diabetic neuro- and nephropathy and to evaluate its potential therapeutic role.

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