Residual β cell function in long-term type 1 diabetes associates with reduced incidence of hypoglycemia

DCCT/EDIC Research Group

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND. We investigated residual β cell function in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study participants with an average 35-year duration of type 1 diabetes mellitus (T1DM). METHODS. Serum C-peptide was measured during a 4-hour mixed-meal tolerance test. Associations with metabolic outcomes and complications were explored among nonresponders (all C-peptide values after meal <0.003 nmol/L) and 3 categories of responders, classified by peak C-peptide concentration (nmol/L) as high (>0.2), intermediate (>0.03 to ≤0.2), and low (≥ 0.003 to ≤0.03). RESULTS. Of the 944 participants, 117 (12.4%) were classified as responders. Residual C-peptide concentrations were associated with higher DCCT baseline concentrations of stimulated C-peptide (P value for trend = 0.0001). Residual C-peptide secretion was not associated with current or mean HbA1c, HLA high-risk haplotypes for T1DM, or the current presence of T1DM autoantibodies. The proportion of subjects with a history of severe hypoglycemia was lower with high (27%) and intermediate (48%) residual C-peptide concentrations than with low (74%) and no (70%) residual C-peptide concentrations (P value for trend = 0.0001). Responders and nonresponders demonstrated similar rates of advanced microvascular complications. CONCLUSION. β Cell function can persist in long-duration T1DM. With a peak C-peptide concentration of >0.03 nmol/L, we observed clinically meaningful reductions in the prevalence of severe hypoglycemia. TRIAL REGISTRATION. ClinicalTrials.gov NCT00360815 and NCT00360893.

Original languageEnglish (US)
Article numbere143011
JournalJournal of Clinical Investigation
Volume131
Issue number3
DOIs
StatePublished - Feb 1 2021

Bibliographical note

Funding Information:
See Supplemental Acknowledgments for DCCT/EDIC Research Group details. EDIC is funded by a NIH cooperative agreement (U01), a support mechanism that entails substantial involvement from NIH scientific staff. RAGK and BHB are the guarantors of this work and, as such, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. RAGK had final responsibility for the decision to submit for publication. Industry contributors have had no role in the conduct of the DCCT/EDIC study but have provided free or discounted supplies or equipment to support participants’ adherence to the study protocols; these contributors include Abbott Diabetes Care, Animas, Bayer Diabetes Care, BD, Eli Lilly, Extend Nutrition, Insulet Corporation, LifeScan, Medtronic Diabetes, Nipro Home Diagnostics, Nova Diabetes Care, Omron, Perrigo Diabetes Care, Roche Diabetes Care, and Sanofi-Aventis. DCCT/ EDIC has been supported by cooperative agreement grants (1982– 1993, 2012–2017, 2017–2022) and contracts (1982–2012) with the Division of Diabetes, Endocrinology, and Metabolic Diseases of the NIDDK (U01 DK094176 and U01 DK094157) as well as by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program (1993–2007), and Clinical Translational Science Center Program, Bethesda, Maryland, USA (2006 to present). Additional support for this DCCT/EDIC collaborative study was provided by the NIH through the NIDDK grant 1-DP3-DK104438.

Funding Information:
Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (DP3-DK104438, U01 DK094176, and U01 DK094157). See Supplemental Acknowledgments for DCCT/EDIC Research Group details. EDIC is funded by a NIH cooperative agreement (U01), a support mechanism that entails substantial involvement from NIH scientific staff. RAGK and BHB are the guarantors of this work and, as such, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. RAGK had final responsibility for the decision to submit for publication. Industry contributors have had no role in the conduct of the DCCT/EDIC study but have provided free or discounted supplies or equipment to support participants' adherence to the study protocols; these contributors include Abbott Diabetes Care, Animas, Bayer Diabetes Care, BD, Eli Lilly, Extend Nutrition, Insulet Corporation, LifeScan, Medtronic Diabetes, Nipro Home Diagnostics, Nova Diabetes Care, Omron, Perrigo Diabetes Care, Roche Diabetes Care, and Sanofi-Aventis. DCCT/ EDIC has been supported by cooperative agreement grants (1982-1993, 2012-2017, 2017-2022) and contracts (1982-2012) with the Division of Diabetes, Endocrinology, and Metabolic Diseases of the NIDDK (U01 DK094176 and U01 DK094157) as well as by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program (1993-2007), and Clinical Translational Science Center Program, Bethesda, Maryland, USA (2006 to present). Additional support for this DCCT/EDIC collaborative study was provided by the NIH through the NIDDK grant 1-DP3-DK104438.

PubMed: MeSH publication types

  • Journal Article

Fingerprint Dive into the research topics of 'Residual β cell function in long-term type 1 diabetes associates with reduced incidence of hypoglycemia'. Together they form a unique fingerprint.

Cite this