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 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

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 Modification of the Association Between Severe Hypoglycemia and Ischemic Heart Disease by Surrogates of Vascular Damage Severity in Type 1 Diabetes During ∼30 Years of Follow-up in the DCCT/EDIC Study

2021 ◽  
Author(s):  
Elke R. Fahrmann ◽  
Laura Adkins ◽  
Henry K. Driscoll
Keyword(s):  
Type 1 Diabetes ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Severe Hypoglycemia ◽  
Vascular Damage ◽  
Diabetes Duration ◽  
Ischemic Heart

OBJECTIVE <p>Literature suggests that severe hypoglycemia (SH) may be linked to cardiovascular events only in older individuals with high cardiovascular risk score (CV-score). Whether a potential relationship between any-SH and cardiovascular disease exists and whether it is conditional on vascular damage severity in a young type 1 diabetes (T1D) cohort without apparent macro-vascular and no or mild-to-moderate micro-vascular complications at baseline is unknown.</p> <p>RESEARCH DESIGN AND METHODS</p> <p>We evaluated data of 1441 Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) volunteers (diabetes duration 1-15 years) followed for ~30 years. Time-dependent associations between any-SH, interactions of any-SH with surrogates of baseline micro-/macro- vascular damage severity (diabetes duration, Early Treatment Diabetic Retinopathy Study scale (ETDRS), Diabetes Complications Severity Index (DCSI), or CV-scores) and ischemic heart disease (IHD: death, silent/nonfatal myocardial infarct, revascularization, or confirmed angina) were analyzed.</p> <p>RESULTS</p> <p>Without interactions, in the minimal adjusted model controlling for confounding bias by age and HbA1c, SH was a significant IHD factor (p~0.003). SH remained a significant factor for IHD in fully adjusted models (p<0.05). In models with interactions, interactions between SH and surrogates of microvascular complications severity, but not between SH and CV-score, were significant. Hazard ratios for IHD based on SH increased 1.19-fold, 1.32-fold, and 2.21-fold for each additional year of diabetes duration, ETDRS-unit, and DCSI-unit, respectively. At time of IHD event, ~15% of 110 participants with SH had high CV-scores.</p> <p> </p> <p>CONCLUSION</p> <p>In a young T1D cohort with no baseline macrovascular complications, surrogates of baseline microvascular damage severity impact the effect of SH on IHD. Older age with high CV-score per se is not mandatory for an association of SH with IHD. However, the association is multifactorial.</p>

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 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 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 Modification of the Association Between Severe Hypoglycemia and Ischemic Heart Disease by Surrogates of Vascular Damage Severity in Type 1 Diabetes During ∼30 Years of Follow-up in the DCCT/EDIC Study

2021 ◽  
Author(s):  
Elke R. Fahrmann ◽  
Laura Adkins ◽  
Henry K. Driscoll
Keyword(s):  
Type 1 Diabetes ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Severe Hypoglycemia ◽  
Vascular Damage ◽  
Diabetes Duration ◽  
Ischemic Heart

OBJECTIVE <p>Literature suggests that severe hypoglycemia (SH) may be linked to cardiovascular events only in older individuals with high cardiovascular risk score (CV-score). Whether a potential relationship between any-SH and cardiovascular disease exists and whether it is conditional on vascular damage severity in a young type 1 diabetes (T1D) cohort without apparent macro-vascular and no or mild-to-moderate micro-vascular complications at baseline is unknown.</p> <p>RESEARCH DESIGN AND METHODS</p> <p>We evaluated data of 1441 Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) volunteers (diabetes duration 1-15 years) followed for ~30 years. Time-dependent associations between any-SH, interactions of any-SH with surrogates of baseline micro-/macro- vascular damage severity (diabetes duration, Early Treatment Diabetic Retinopathy Study scale (ETDRS), Diabetes Complications Severity Index (DCSI), or CV-scores) and ischemic heart disease (IHD: death, silent/nonfatal myocardial infarct, revascularization, or confirmed angina) were analyzed.</p> <p>RESULTS</p> <p>Without interactions, in the minimal adjusted model controlling for confounding bias by age and HbA1c, SH was a significant IHD factor (p~0.003). SH remained a significant factor for IHD in fully adjusted models (p<0.05). In models with interactions, interactions between SH and surrogates of microvascular complications severity, but not between SH and CV-score, were significant. Hazard ratios for IHD based on SH increased 1.19-fold, 1.32-fold, and 2.21-fold for each additional year of diabetes duration, ETDRS-unit, and DCSI-unit, respectively. At time of IHD event, ~15% of 110 participants with SH had high CV-scores.</p> <p> </p> <p>CONCLUSION</p> <p>In a young T1D cohort with no baseline macrovascular complications, surrogates of baseline microvascular damage severity impact the effect of SH on IHD. Older age with high CV-score per se is not mandatory for an association of SH with IHD. However, the association is multifactorial.</p>

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.

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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