Anita Jeyam1, Helen Colhoun1, Stuart McGurnaghan1, Luke Blackbourn1, Timothy J McDonald2, Colin N A Palmer3, John A McKnight4, Mark W J Strachan4, Alan W Patrick5, John Chalmers6, Robert S Lindsay7, John R Petrie7, Sandeep Thekkepat8, Andrew Collier9, Sandra MacRury10, Paul M McKeigue. 1. Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital Campus, Edinburgh, U.K. 2. Medical School, University of Exeter, Exeter, U.K. 3. Medical School, University of Dundee, Dundee, U.K. 4. Metabolic Unit, Western General Hospital, Edinburgh, U.K. 5. Royal Infirmary of Edinburgh, Edinburgh, U.K. 6. Diabetes Centre, Victoria Hospital, Kirkaldy, U.K. 7. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, U.K. 8. David Matthews Diabetes Centre, Monklands Hospital, Airdrie, U.K. 9. Glasgow Caledonian University, Glasgow, U.K. 10. National Health Service Highland Diabetes Centre, Inverness, U.K.
Abstract
OBJECTIVE: To quantify the relationship of residual C-peptide secretion to glycemic outcomes and microvascular complications in type 1 diabetes. RESEARCH DESIGN AND METHODS: C-peptide was measured in an untimed blood sample in the Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) cohort of 6,076 people with type 1 diabetes monitored for an average of 5.2 years. RESULTS: In regression models adjusted for age at onset and duration, effect sizes for C-peptide ≥200 vs. <5 pmol/L were as follows: insulin dose at baseline, 27% lower (P = 2 × 10-39); HbA1c during follow-up, 4.9 mmol/mol lower (P = 3 × 10-13); hazard ratio for hospital admission for diabetic ketoacidosis during follow-up, 0.44 (P = 0.0001); odds ratio for incident retinopathy, 0.51 (P = 0.0003). Effects on the risk of serious hypoglycemic episodes were detectable at lower levels of C-peptide, and the form of the relationship was continuous down to the limit of detection (3 pmol/L). In regression models contrasting C-peptide 30 to <200 pmol/L with <5 pmol/L, the odds ratio for self-report of at least one serious hypoglycemic episode in the last year was 0.56 (P = 6 × 10-8), and the hazard ratio for hospital admission for hypoglycemia during follow-up was 0.52 (P = 0.03). CONCLUSIONS: These results in a large representative cohort suggest that even minimal residual C-peptide secretion could have clinical benefit in type 1 diabetes, in contrast to a follow-up study of the Diabetes Control and Complications Trial (DCCT) intensively treated cohort where an effect on hypoglycemia was seen only at C-peptide levels ≥130 pmol/L. This has obvious implications for the design and evaluation of trials of interventions to preserve or restore pancreatic islet function in type 1 diabetes.
OBJECTIVE: To quantify the relationship of residual C-peptide secretion to glycemic outcomes and microvascular complications in type 1 diabetes. RESEARCH DESIGN AND METHODS: C-peptide was measured in an untimed blood sample in the Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) cohort of 6,076 people with type 1 diabetes monitored for an average of 5.2 years. RESULTS: In regression models adjusted for age at onset and duration, effect sizes for C-peptide ≥200 vs. <5 pmol/L were as follows: insulin dose at baseline, 27% lower (P = 2 × 10-39); HbA1c during follow-up, 4.9 mmol/mol lower (P = 3 × 10-13); hazard ratio for hospital admission for diabetic ketoacidosis during follow-up, 0.44 (P = 0.0001); odds ratio for incident retinopathy, 0.51 (P = 0.0003). Effects on the risk of serious hypoglycemic episodes were detectable at lower levels of C-peptide, and the form of the relationship was continuous down to the limit of detection (3 pmol/L). In regression models contrasting C-peptide 30 to <200 pmol/L with <5 pmol/L, the odds ratio for self-report of at least one serious hypoglycemic episode in the last year was 0.56 (P = 6 × 10-8), and the hazard ratio for hospital admission for hypoglycemia during follow-up was 0.52 (P = 0.03). CONCLUSIONS: These results in a large representative cohort suggest that even minimal residual C-peptide secretion could have clinical benefit in type 1 diabetes, in contrast to a follow-up study of the Diabetes Control and Complications Trial (DCCT) intensively treated cohort where an effect on hypoglycemia was seen only at C-peptide levels ≥130 pmol/L. This has obvious implications for the design and evaluation of trials of interventions to preserve or restore pancreatic islet function in type 1 diabetes.
Authors: 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 Journal: BMJ Open Diabetes Res Care Date: 2021-09
Authors: Cyril P Landstra; Axel Andres; Mikael Chetboun; Caterina Conte; Yvonne Kelly; Thierry Berney; Eelco J P de Koning; Lorenzo Piemonti; Peter G Stock; François Pattou; Marie-Christine Vantyghem; Melena D Bellin; Michael R Rickels Journal: J Clin Endocrinol Metab Date: 2021-09-27 Impact factor: 6.134
Authors: Alice L J Carr; Richard A Oram; Shannon M Marren; Timothy J McDonald; Parth Narendran; Robert C Andrews Journal: J Endocr Soc Date: 2021-07-17
Authors: Guy S Taylor; Andy Shaw; Jadine H Scragg; Kieran Smith; Matthew D Campbell; Timothy J McDonald; James A Shaw; Mark D Ross; Daniel J West Journal: Front Endocrinol (Lausanne) Date: 2022-02-11 Impact factor: 5.555
Authors: Kitty de Leur; Charlotte Vollenbrock; Pim Dekker; Martine de Vries; Erwin Birnie; Dick Mul; Bruce H R Wolffenbuttel; Joost Groen; Henk-Jan Aanstoot; Lianne Boesten Journal: Diabet Med Date: 2022-01-17 Impact factor: 4.213