Lessons From the Mixed-Meal Tolerance Test

Besser, Rachel E.J.; Shields, Beverley M.; Casas, Rosaura; Hattersley, Andrew T.; Ludvigsson, Johnny

doi:10.2337/dc12-0836

Cited by 91Diabetes Management and ResearchDiabetes and associated disordersPancreatic function and diabetes

Lessons From the Mixed-Meal Tolerance Test

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Besser, Rachel E.J., Shields, Beverley M., Casas, Rosaura, Hattersley, Andrew T., Ludvigsson, Johnny·2013·Diabetes Care

DOI 10.2337/dc12-0836PMC PMC3554273

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Abstract

OBJECTIVE: Mixed-meal tolerance test (MMTT) area under the curve C-peptide (AUC CP) is the gold-standard measure of endogenous insulin secretion in type 1 diabetes but is intensive and invasive to perform. The 90-min MMTT-stimulated CP ≥0.2 nmol/L (90CP) is related to improved clinical outcomes, and CP ≥0.1 nmol/L is the equivalent fasting measure (FCP). We assessed whether 90CP or FCP are alternatives to a full MMTT. RESEARCH DESIGN AND METHODS: CP was measured during 1,334 MMTTs in 421 type 1 diabetes patients aged <18 years at 3, 9, 18, 48, and 72 months duration. We assessed: 1) correlation between mean AUC CP and 90CP or FCP; 2) sensitivity and specificity of 90CP ≥0.2 nmol/L and FCP ≥ 0.1 nmol/L to detect peak CP ≥0.2 nmol/L and the equivalent AUC CP; and 3) how the time taken to reach the CP peak varied with age of diagnosis and diabetes duration. RESULTS: AUC CP was highly correlated to 90CP (rs = 0.96; P < 0.0001) and strongly correlated to FCP (rs = 0.84; P < 0.0001). AUC CP ≥23 nmol/L/150 min was the equivalent cutoff for peak CP ≥0.2 nmol/L (98% sensitivity/97% specificity). A 90CP ≥0.2 nmol/L correctly classified 96% patients using AUC or peak CP, whereas FCP ≥0.1 nmol/L classified 83 and 85% patients, respectively. There was only a small difference seen between peak and 90CP (median 0.02 nmol/L). The CP peak occurred earlier in patients with longer diabetes duration (6.1 min each 1-year increase in duration) and younger age (2.5 min each 1-year increase). CONCLUSIONS: 90CP is a highly sensitive and specific measure of AUC and peak CP in children and adolescents with type 1 diabetes and offers a practical alternative to a full MMTT.

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The relationship between age at diagnosis and C-peptide levels may be explained by age at diagnosis reflecting the strength and intensity of the underlying autoimmune process.
“This may explain the relationship seen in our data and numerous other studies(3; 18; 19).”
From Most people with long-duration type 1 diabetes in a large population-based study are insulin microsecretors (2015) · cites this paper as [18]

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Lessons From theMixed-Meal Tolerance Test Use of 90-minute and fasting C-peptide in pediatric diabetes
Besser, R. E. J., Shields, B. M., Casas, R., Hattersley, A. T., Shields, B. M., Casas, R., & Shields, B. M. (2015)
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Comment on: Besser et al. Lessons From the Mixed-Meal Tolerance Test: Use of 90-Minute and Fasting C-Peptide in Pediatric Diabetes. Diabetes Care 2013;36:195–201
CHAUDHARY, S. K., Thukral, A., Kataria, M., Ghosh, S. K., Mukherjee, S., & Chowdhury, S. (2013) · Diabetes Care · doi:10.2337/dc13-0369 · Cited by 2 · see citing works
Urine C-peptide creatinine ratio is a noninvasive alternative to the mixed-meal tolerance test in children and adults with type 1 diabetes
Besser, R. E. J., Ludvigsson, J., Jones, A. G., McDonald, T. J., Shields, B. M., Knight, B. A., & Hattersley, A. T. (2011) · Diabetes Care · doi:10.2337/dc10-2114 · Cited by 82 · see citing works
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Evaluating the role of spot urine C-peptide creatinine ratio (UCPCR) in the diagnosis and management of diabetes in children and young adults
Besser, R. E. J. (2012) · OpenGrey (Institut de l'Information Scientifique et Technique)
Self-citation
Surrogate markers and predictors of endogenous insulin secretion in children and adolescents with type 1 diabetes
Yuan, J., Zhang, J., Cutfield, W. S., Dong, G., Jiang, Y., Wu, W., Huang, K., Chen, X., Zheng, Y., Liu, B., et al. (2021) · World Journal of Pediatrics · doi:10.1007/s12519-020-00382-0 · Cited by 2 · see citing works

Authors: Besser, R. E. J., Shields, B. M., Casas, R., Hattersley, A. T., & Ludvigsson, J.
Affiliations: University of Exeter (GB)
Linköping University (SE)
Corresponding author: Besser, Rachel E.J.
ORCID: Besser, Rachel E.J.
Shields, Beverley M.
Casas, Rosaura
Hattersley, Andrew T.
Ludvigsson, Johnny
Venue: Diabetes Care
Publisher: American Diabetes Association
Published: 2013-01-17
Volume: 36
Issue: 2
Pages: 195-201
ISSN: 0149-5992 (ISSN-L)
1935-5548
DOI: 10.2337/dc12-0836
PMC: PMC3554273
OpenAlex: W2170019319
Cited by: 91
References: 37
Citations by year: 2026: 10 · 2025: 8 · 2024: 5 · 2023: 7 · 2022: 9 · 2021: 13 · 2020: 7 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 5 · 2014: 5 · 2013: 7
FWCI: 4.36
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
creativecommons.org/licenses/by-nc-nd/3.0/ (vor, 3149 d)
Locations: Diabetes Care (publishedVersion, cc-by-nc-nd)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
Funders: National Institute for Health and Care Research (NF-SI-0611-10219)
Diabetes UK
Vetenskapsrådet
Barndiabetesfonden
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords: mixed meal tolerance test, C-peptide, type 1 diabetes, endogenous insulin secretion, fasting C-peptide, diagnostic thresholds, diabetes duration, age at diagnosis, children and adolescents
MeSH terms: Adolescent, C-Peptide, Child, Diabetes Mellitus, Type 1, Fasting, Female, Humans, Male, Postprandial Period

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