title: The rise and fall of insulin secretion in type 1 diabetes mellitus.
abstract: An understanding of the natural history of beta cell responses is an essential prerequisite for interventional studies designed to prevent or treat type 1 diabetes. Here we review published data on changes in insulin responses in humans with type 1 diabetes. We also describe a new analysis of C-peptide responses in subjects who are at risk of type 1 diabetes and enrolled in the Diabetes Prevention Trial-1 (DPT-1). C-peptide responses to a mixed meal increase during childhood and through adolescence, but show no significant change during adult life; responses are lower in adults who progress to diabetes than in those who do not. The age-related increase in C-peptide responses may account for the higher levels of C-peptide observed in adults with newly diagnosed type 1 diabetes compared with those in children and adolescents. Based on these findings, we propose a revised model of the natural history of the disease, in which an age-related increase in functional beta cell responses before the onset of autoimmune beta cell damage is an important determinant of the clinical features of the disease.
authors.affiliation: Division of Endocrinology and Naomi Berrie Diabetes Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Tsai
authors.forename: N A
authors.initials: NA
authors.lastname: Sherry
authors.forename: J P
authors.initials: JP
authors.lastname: Palmer
authors.forename: K C
authors.initials: KC
authors.lastname: Herold
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging; D015551:Autoimmunity; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000473:pathology / Q000502:physiology; D011236:Prediabetic State
chemical_list: D002096:C-Peptide; D007328:Insulin