Year: 2020
Type: article
Study design: Observational Study
Abstract: BACKGROUNDResidual C-peptide is detected in many people for years following the diagnosis of type 1 diabetes; however, the physiologic significance of low levels of detectable C-peptide is not known.METHODSWe studied 63 adults with type 1 diabetes classified by peak mixed-meal tolerance test (MMTT) C-peptide as negative (<0.007 pmol/mL; n = 15), low (0.017-0.200; n = 16), intermediate (>0.200-0.400; n = 15), or high (>0.400; n = 17). We compared the groups' glycemia from continuous glucose monitoring (CGM), β cell secretory responses from a glucose-potentiated arginine (GPA) test, insulin sensitivity from a hyperinsulinemic-euglycemic (EU) clamp, and glucose counterregulatory responses from a subsequent hypoglycemic (HYPO) clamp.RESULTSLow and intermediate MMTT C-peptide groups did not exhibit β cell secretory responses to hyperglycemia, whereas the high C-peptide group showed increases in both C-peptide and proinsulin (P ≤ 0.01). All groups with detectable MMTT C-peptide demonstrated acute C-peptide and proinsulin responses to arginine that were positively correlated with peak MMTT C-peptide (P < 0.0001 for both analytes). During the EU-HYPO clamp, C-peptide levels were proportionately suppressed in the low, intermediate, and high C-peptide compared with the negative group (P ≤ 0.0001), whereas glucagon increased from EU to HYPO only in the high C-peptide group compared with negative (P = 0.01). CGM demonstrated lower mean glucose and more time in range for the high C-peptide group.CONCLUSIONThese results indicate that in adults with type 1 diabetes, β cell responsiveness to hyperglycemia and α cell responsiveness to hypoglycemia are observed only at high levels of residual C-peptide that likely contribute to glycemic control.FUNDINGFunding for this work was provided by the Leona M. and Harry B. Helmsley Charitable Trust, the National Center for Advancing Translational Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases.
DOI: 10.1172/jci134057
Institutions: University of Pennsylvania, Indiana University School of Medicine, Benaroya Research Institute, Children's Hospital Colorado, University of Colorado Anschutz, Children's Mercy Hospital, Yale University, Translational Research Institute for Metabolism and Diabetes, AdventHealth, University of Colorado Denver, Jaeb Center for Health Research
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: U.S. Department of Veterans Affairs, University of Pennsylvania, Leona M. and Harry B. Helmsley Charitable Trust, University of Washington, National Institutes of Health, Perelman School of Medicine, University of Pennsylvania, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: G1043879701, G106513794, G1074056680, G3374716125, The Next Generation of Innovative Cardiovascular Clinical/Translational Researchers, G3880418757, Mechanisms of Beta Cell Function in Health and Disease, University of Pennsylvania Diabetes Research Center, Institutional Clinical and Translational Science Award, Indiana Diabetes Research Center, Yale Clinical and Translational Science Award, Yale Diabetes Research Center
OpenAlex ID: W2998261787