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

Martine J. Wellens; Charlotte E. Vollenbrock; Pim Dekker; Lianne S. M. Boesten; Petronella H. Geelhoed-Duijvestijn; Martine M. C. de Vries-Velraeds; Giesje Nefs; Bruce H. R. Wolffenbuttel; Henk-Jan Aanstoot; Peter R. van Dijk

doi:10.1136/bmjdrc-2021-002288

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

Martine J. Wellens, Charlotte E. Vollenbrock, Pim Dekker, Lianne S. M. Boesten, Petronella H. Geelhoed-Duijvestijn, Martine M. C. de Vries-Velraeds, Giesje Nefs, Bruce H. R. Wolffenbuttel^*, Henk-Jan Aanstoot, Peter R. van Dijk

^*Corresponding author for this work

Medical and Clinical Psychology

Research output: Contribution to journal › Article › Scientific › peer-review

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Abstract

Introduction

This 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 methods

We 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.

Results

In 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.

Conclusions

Higher 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.

Original language	English
Article number	002288
Number of pages	8
Journal	BMJ Open Diabetes Research & Care
Volume	9
Issue number	1
DOIs	https://doi.org/10.1136/bmjdrc-2021-002288
Publication status	Published - 2021

Keywords

awareness
C-peptide
hypoglycemia
age of onset
IMPAIRED AWARENESS
ADULTS
UNAWARENESS
IMPACT
COMPLICATIONS
MECHANISMS
FREQUENCY
ONSET
CARE
AGE

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MCP Nefs residual C peptide secretion BMJ ODR&C 2021Final published version, 597 KBLicence: CC BY

Cite this

Wellens, M. J., Vollenbrock, C. E., Dekker, P., Boesten, L. S. M., Geelhoed-Duijvestijn, P. H., de Vries-Velraeds, M. M. C., Nefs, G., Wolffenbuttel, B. H. R., Aanstoot, H.-J., & van Dijk, P. R. (2021). Residual C-peptide secretion and hypoglycemia awareness in people with type 1 diabetes. BMJ Open Diabetes Research & Care, 9(1), Article 002288. https://doi.org/10.1136/bmjdrc-2021-002288

@article{8878b504021140718bee3fb796ea0a3b,

title = "Residual C-peptide secretion and hypoglycemia awareness in people with type 1 diabetes",

abstract = "Introduction This 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 methods We 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. Results In 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. Conclusions Higher 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.",

keywords = "awareness, C-peptide, hypoglycemia, age of onset, IMPAIRED AWARENESS, ADULTS, UNAWARENESS, IMPACT, COMPLICATIONS, MECHANISMS, FREQUENCY, ONSET, CARE, AGE",

author = "Wellens, {Martine J.} and Vollenbrock, {Charlotte E.} and Pim Dekker and Boesten, {Lianne S. M.} and Geelhoed-Duijvestijn, {Petronella H.} and {de Vries-Velraeds}, {Martine M. C.} and Giesje Nefs and Wolffenbuttel, {Bruce H. R.} and Henk-Jan Aanstoot and {van Dijk}, {Peter R.}",

note = "Funding This study was supported by the Juvenile Diabetes Research Foundation (JDRF), grant no. 3-SRA-2014-291-M-R, and the Dutch Diabetes Research Foundation, project 2015.16.1856, for which we are very grateful. ",

year = "2021",

doi = "10.1136/bmjdrc-2021-002288",

language = "English",

volume = "9",

journal = "BMJ Open Diabetes Research & Care",

issn = "2052-4897",

publisher = "BMJ Publishing Group",

number = "1",

}

TY - JOUR

T1 - Residual C-peptide secretion and hypoglycemia awareness in people with type 1 diabetes

AU - Wellens, Martine J.

AU - Vollenbrock, Charlotte E.

AU - Dekker, Pim

AU - Boesten, Lianne S. M.

AU - Geelhoed-Duijvestijn, Petronella H.

AU - de Vries-Velraeds, Martine M. C.

AU - Nefs, Giesje

AU - Wolffenbuttel, Bruce H. R.

AU - Aanstoot, Henk-Jan

AU - van Dijk, Peter R.

N1 - Funding This study was supported by the Juvenile Diabetes Research Foundation (JDRF), grant no. 3-SRA-2014-291-M-R, and the Dutch Diabetes Research Foundation, project 2015.16.1856, for which we are very grateful.

PY - 2021

Y1 - 2021

N2 - Introduction This 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 methods We 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. Results In 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. Conclusions Higher 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.

AB - Introduction This 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 methods We 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. Results In 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. Conclusions Higher 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.

KW - awareness

KW - C-peptide

KW - hypoglycemia

KW - age of onset

KW - IMPAIRED AWARENESS

KW - ADULTS

KW - UNAWARENESS

KW - IMPACT

KW - COMPLICATIONS

KW - MECHANISMS

KW - FREQUENCY

KW - ONSET

KW - CARE

KW - AGE

U2 - 10.1136/bmjdrc-2021-002288

DO - 10.1136/bmjdrc-2021-002288

M3 - Article

SN - 2052-4897

VL - 9

JO - BMJ Open Diabetes Research & Care

JF - BMJ Open Diabetes Research & Care

IS - 1

M1 - 002288

ER -

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

Abstract

Keywords

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