TY - JOUR
T1 - Residual insulin secretion in individuals with type 1 diabetes in Finland
T2 - longitudinal and cross-sectional analyses
AU - Harsunen, Minna
AU - Haukka, Jani
AU - Harjutsalo, Valma
AU - Mars, Nina
AU - Syreeni, Anna
AU - Härkönen, Taina
AU - Käräjämäki, Annemari
AU - Ilonen, Jorma
AU - Knip, Mikael
AU - Sandholm, Niina
AU - Miettinen, Päivi Johanna
AU - Groop, Per Henrik
AU - Tuomi, Tiinamaija
N1 - Funding Information:
The study has been financially supported by grants from Folkhälsan Research Foundation; the Academy of Finland (grants number 312072 and 336826 to TT, 331671 to NM, and 316664 to PHG); University of Helsinki; Medical Society of Finland (Finska Läkaresällskapet); Wilhelm and Else Stockmann Foundation; “Liv och Hälsa” Society; Sigrid Juselius Foundation; Novo Nordisk Foundation (NNF OC0013659), Helsinki University Central Hospital Research Funds (TYH2018207 and TYH 2020305); State Research Funding via the Helsinki University Hospital, the Vasa Hospital District, the Turku University Hospital, Vasa Central Hospital, Jakobstadsnejdens Heart Foundation, and the Medical Foundation of Vaasa. The skillful assistance of the Direva study Group and research assistants Paula Kokko and Susanna Saarinen is gratefully acknowledged. We acknowledge the participants and investigators of FinnGen study, which was used for the polygenic risk score analysis (acknowledgments and funding in the appendix p 3 ). The FPDR has been supported by the Academy of Finland (grant number 292538 to MK), the Sigrid Juselius Foundation, Medical Society of Finland (Finska Läkaresällskapet), and the “Liv and Hälsa“ Society. We acknowledge the physicians and nurses at each FinnDiane centre participating in the collection of the patient data ( appendix p 5 ). We are indebted to the late Carol Forsblom (1964–2022), the international coordinator of the FinnDiane study group, for his considerable contribution. The contribution of the FinnDiane study group ( appendix p 5 ) and the skillful assistance of the research nurses Anna Sandelin, Jaana Tuomikangas, and Mira Korolainen is gratefully acknowledged.
Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/7
Y1 - 2023/7
N2 - Background: Contrary to the presumption that type 1 diabetes leads to an absolute insulin deficiency, many individuals with type 1 diabetes have circulating C-peptide years after the diagnosis. We studied factors affecting random serum C-peptide concentration in individuals with type 1 diabetes and the association with diabetic complications. Methods: Our longitudinal analysis included individuals newly diagnosed with type 1 diabetes from Helsinki University Hospital (Helsinki, Finland) with repeated random serum C-peptide and concomitant glucose measurements from within 3 months of diagnosis and at least once later. The long-term cross-sectional analysis included data from participants from 57 centres in Finland who had type 1 diabetes diagnosed after 5 years of age, initiation of insulin treatment within 1 year from diagnosis, and a C-peptide concentration of less than 1·0 nmol/L (FinnDiane study) and patients with type 1 diabetes from the DIREVA study. We tested the association of random serum C-peptide concentrations and polygenic risk scores with one-way ANOVA, and association of random serum C-peptide concentrations, polygenic risk scores, and clinical factors with logistic regression. Findings: The longitudinal analysis included 847 participants younger than 16 years and 110 aged 16 years or older. In the longitudinal analysis, age at diagnosis strongly correlated with the decline in C-peptide secretion. The cross-sectional analysis included 3984 participants from FinnDiane and 645 from DIREVA. In the cross-sectional analysis, at a median duration of 21·6 years (IQR 12·5−31·2), 776 (19·4%) of 3984 FinnDiane participants had residual random serum C-peptide secretion (>0·02 nmol/L), which was associated with lower type 1 diabetes polygenic risk compared with participants without random serum C-peptide (p<0·0001). Random serum C-peptide was inversely associated with hypertension, HbA1c, and cholesterol, but also independently with microvascular complications (adjusted OR 0·61 [95% CI 0·38–0·96], p=0·033, for nephropathy; 0·55 [0·34–0·89], p=0·014, for retinopathy). Interpretation: Although children with multiple autoantibodies and HLA risk genotypes progressed to absolute insulin deficiency rapidly, many adolescents and adults had residual random serum C-peptide decades after the diagnosis. Polygenic risk of type 1 and type 2 diabetes affected residual random serum C-peptide. Even low residual random serum C-peptide concentrations seemed to be associated with a beneficial complications profile. Funding: Folkhälsan Research Foundation; Academy of Finland; University of Helsinki and Helsinki University Hospital; Medical Society of Finland; the Sigrid Juselius Foundation; the “Liv and Hälsa“ Society; Novo Nordisk Foundation; and State Research Funding via the Helsinki University Hospital, the Vasa Hospital District, Turku University Hospital, Vasa Central Hospital, Jakobstadsnejdens Heart Foundation, and the Medical Foundation of Vaasa.
AB - Background: Contrary to the presumption that type 1 diabetes leads to an absolute insulin deficiency, many individuals with type 1 diabetes have circulating C-peptide years after the diagnosis. We studied factors affecting random serum C-peptide concentration in individuals with type 1 diabetes and the association with diabetic complications. Methods: Our longitudinal analysis included individuals newly diagnosed with type 1 diabetes from Helsinki University Hospital (Helsinki, Finland) with repeated random serum C-peptide and concomitant glucose measurements from within 3 months of diagnosis and at least once later. The long-term cross-sectional analysis included data from participants from 57 centres in Finland who had type 1 diabetes diagnosed after 5 years of age, initiation of insulin treatment within 1 year from diagnosis, and a C-peptide concentration of less than 1·0 nmol/L (FinnDiane study) and patients with type 1 diabetes from the DIREVA study. We tested the association of random serum C-peptide concentrations and polygenic risk scores with one-way ANOVA, and association of random serum C-peptide concentrations, polygenic risk scores, and clinical factors with logistic regression. Findings: The longitudinal analysis included 847 participants younger than 16 years and 110 aged 16 years or older. In the longitudinal analysis, age at diagnosis strongly correlated with the decline in C-peptide secretion. The cross-sectional analysis included 3984 participants from FinnDiane and 645 from DIREVA. In the cross-sectional analysis, at a median duration of 21·6 years (IQR 12·5−31·2), 776 (19·4%) of 3984 FinnDiane participants had residual random serum C-peptide secretion (>0·02 nmol/L), which was associated with lower type 1 diabetes polygenic risk compared with participants without random serum C-peptide (p<0·0001). Random serum C-peptide was inversely associated with hypertension, HbA1c, and cholesterol, but also independently with microvascular complications (adjusted OR 0·61 [95% CI 0·38–0·96], p=0·033, for nephropathy; 0·55 [0·34–0·89], p=0·014, for retinopathy). Interpretation: Although children with multiple autoantibodies and HLA risk genotypes progressed to absolute insulin deficiency rapidly, many adolescents and adults had residual random serum C-peptide decades after the diagnosis. Polygenic risk of type 1 and type 2 diabetes affected residual random serum C-peptide. Even low residual random serum C-peptide concentrations seemed to be associated with a beneficial complications profile. Funding: Folkhälsan Research Foundation; Academy of Finland; University of Helsinki and Helsinki University Hospital; Medical Society of Finland; the Sigrid Juselius Foundation; the “Liv and Hälsa“ Society; Novo Nordisk Foundation; and State Research Funding via the Helsinki University Hospital, the Vasa Hospital District, Turku University Hospital, Vasa Central Hospital, Jakobstadsnejdens Heart Foundation, and the Medical Foundation of Vaasa.
U2 - 10.1016/S2213-8587(23)00123-7
DO - 10.1016/S2213-8587(23)00123-7
M3 - Article
C2 - 37290465
AN - SCOPUS:85162877125
SN - 2213-8587
VL - 11
SP - 465
EP - 473
JO - The Lancet Diabetes and Endocrinology
JF - The Lancet Diabetes and Endocrinology
IS - 7
ER -
