Abstract
Aims/hypothesisClassically, type 1 diabetes is thought to proceed to absolute insulin deficiency. Recently developed ultrasensitive assays capable of detecting C-peptide under 5 pmol/l now allow very low levels of C-peptide to be detected in patients with long-standing type 1 diabetes. It is not known whether this low-level endogenous insulin secretion responds to physiological stimuli. We aimed to assess how commonly low-level detectable C-peptide occurs in long-duration type 1 diabetes and whether it responds to a meal stimulus.MethodsWe performed a mixed-meal tolerance test in 74 volunteers with long-duration (>5 years) type 1 diabetes, i.e. with age at diagnosis 16 (9–23) years (median [interquartile range]) and diabetes duration of 30 (19–41) years. We assessed fasting and stimulated serum C-peptide levels using an electrochemiluminescence assay (detection limit 3.3 pmol/l), and also the urinary C-peptide:creatinine ratio (UCPCR).ResultsPost-stimulation serum C-peptide was detectable at very low levels (>3.3 pmol/l) in 54 of 74 (73%) patients. In all patients with detectable serum C-peptide, C-peptide either increased (n = 43, 80%) or stayed the same (n = 11) in response to a meal, with no indication of levels falling (p < 0.0001). With increasing disease duration, absolute C-peptide levels fell although the numbers with detectable C-peptide remained high (68%, i.e. 25 of 37 patients with >30 years duration). Similar results were obtained for UCPCR.Conclusions/interpretationMost patients with long-duration type 1 diabetes continue to secrete very low levels of endogenous insulin, which increase after meals. This is consistent with the presence of a small number of still functional beta cells and implies that beta cells are either escaping immune attack or undergoing regeneration.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-013-3067-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Highlights
Type 1 diabetes is defined as a disease of progressive autoimmune destruction of beta cells, leading to absolute insulin deficiency
C-peptide is detectable in most people with long-duration type 1 diabetes Serum C-peptide was detectable (>3.3 pmol/l ) in 54 of 74 (73%) patients with type 1 diabetes of more than 5 years duration when measured at 90 min post meal; in the fasted state it was detectable in 49 of 74 (66%) participants
We found persistent C-peptide secretion, which increased after a meal stimulus, in the majority of patients with type 1 diabetes and a disease duration of more than 5 years
Summary
Type 1 diabetes is defined as a disease of progressive autoimmune destruction of beta cells, leading to absolute insulin deficiency. The decline in insulin production in patients diagnosed with type 1 diabetes is variable. Most (92–97%) patients at more than 5 years from diagnosis have a stimulated serum C-peptide value
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