PMID- 30612138 OWN - NLM STAT- MEDLINE DCOM- 20200218 LR - 20200218 IS - 1432-0428 (Electronic) IS - 0012-186X (Linking) VI - 62 IP - 4 DP - 2019 Apr TI - Inappropriate glucagon and GLP-1 secretion in individuals with long-standing type 1 diabetes: effects of residual C-peptide. PG - 593-597 LID - 10.1007/s00125-018-4804-y [doi] AB - AIMS/HYPOTHESIS: Recent studies have demonstrated that residual beta cells may be present in some people with long-standing type 1 diabetes, but little is known about the potential impact of this finding on alpha cell function and incretin levels. This study aimed to evaluate whether insulin microsecretion could modulate glucagon and glucagon-like peptide-1 (GLP-1) responses to a mixed meal tolerance test (MMTT). METHODS: Adults with type 1 diabetes onset after the age of 15 years (n = 29) underwent a liquid MMTT after an overnight fast. Insulin microsecretion was defined when peak C-peptide levels were >30 pmol/l using an ultrasensitive assay. Four individuals with recent-onset type 1 diabetes were included as controls. Glucagon and GLP-1 responses were analysed according to C-peptide patterns. RESULTS: We found comparable peak values, Delta(0-max) levels and AUCs of glucagon and GLP-1 responses in C-peptide-positive participants (n = 9) and C-peptide-negative participants (n = 16) with long-standing diabetes and in participants with recent-onset diabetes (n = 4). Mean glucagon levels, however, differed (p = 0.01). Mean GLP-1 responses were significantly lower according to C-peptide positivity (p < 0.001, ANOVA). Interestingly, GLP-1 levels correlated to glucagon values in C-peptide-positive participants with long-standing diabetes (Pearson's r = 0.915, p = 0.004) and in participants with recent-onset diabetes (p < 0.001) but not in C-peptide-negative participants. CONCLUSIONS/INTERPRETATION: The glucagon response to an MMTT in people with long-standing type 1 diabetes is not reduced by the presence of residual beta cells. The reduction of GLP-1 responses according to residual C-peptide levels suggests specific regulatory pathways. FAU - Thivolet, Charles AU - Thivolet C AD - Department of Endocrinology and Diabetes, Lyon-Sud Hospital, Hospices Civils de Lyon, 69310, Pierre-Benite, France. charles.thivolet@chu-lyon.fr. AD - UnivLyon, Inserm, INRA, INSA Lyon, Universite Claude Bernard Lyon 1, Oullins, France. charles.thivolet@chu-lyon.fr. FAU - Marchand, Lucien AU - Marchand L AD - Department of Endocrinology and Diabetes, Lyon-Sud Hospital, Hospices Civils de Lyon, 69310, Pierre-Benite, France. AD - UnivLyon, Inserm, INRA, INSA Lyon, Universite Claude Bernard Lyon 1, Oullins, France. FAU - Chikh, Karim AU - Chikh K AD - UnivLyon, Inserm, INRA, INSA Lyon, Universite Claude Bernard Lyon 1, Oullins, France. AD - Department of Biochemistry, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre-Benite, France. LA - eng PT - Journal Article DEP - 20190106 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Blood Glucose) RN - 0 (C-Peptide) RN - 0 (Incretins) RN - 0 (Insulin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9007-92-5 (Glucagon) SB - IM MH - Adult MH - Area Under Curve MH - Blood Glucose/metabolism MH - C-Peptide/*blood MH - Diabetes Mellitus, Type 1/*blood/*metabolism MH - Female MH - Glucagon/*blood MH - Glucagon-Like Peptide 1/*blood MH - Glucagon-Secreting Cells/metabolism MH - Glucose Tolerance Test MH - Humans MH - Incretins/metabolism MH - Insulin/metabolism MH - Insulin-Secreting Cells/metabolism MH - Male MH - Young Adult OTO - NOTNLM OT - Incretins OT - Insulin microsecretion OT - Pancreatic alpha cells OT - Type 1 diabetes EDAT- 2019/01/07 06:00 MHDA- 2020/02/19 06:00 CRDT- 2019/01/07 06:00 PHST- 2018/10/31 00:00 [received] PHST- 2018/12/03 00:00 [accepted] PHST- 2019/01/07 06:00 [pubmed] PHST- 2020/02/19 06:00 [medline] PHST- 2019/01/07 06:00 [entrez] AID - 10.1007/s00125-018-4804-y [pii] AID - 10.1007/s00125-018-4804-y [doi] PST - ppublish SO - Diabetologia. 2019 Apr;62(4):593-597. doi: 10.1007/s00125-018-4804-y. Epub 2019 Jan 6.