title: C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop, 21-22 October 2001.
abstract: The underlying cause of type 1 diabetes, loss of beta-cell function, has become the therapeutic target for a number of interventions in patients with type 1 diabetes. Even though insulin therapies continue to improve, it remains difficult to achieve normal glycemic control in type 1 diabetes, especially long term. The associated risks of hypoglycemia and end-organ diabetic complications remain. Retention of beta-cell function in patients with type 1 diabetes is known to result in improved glycemic control and reduced hypoglycemia, retinopathy, and nephropathy. To facilitate the development of therapies aimed at altering the type 1 diabetes disease process, an American Diabetes Association workshop was convened to identify appropriate efficacy outcome measures in type 1 diabetes clinical trials. The following consensus emerged: While measurements of immune responses to islet cells are important in elucidating pathogenesis, none of these measures have directly correlated with the decline in endogenous insulin secretion. HbA(1c) is a highly valuable clinical measure of glycemic control, but it is an insensitive measure of beta-cell function, particularly with the currently accepted standard of near-normal glycemic control. Rates of severe hypoglycemia and diabetic complications ultimately will be improved by therapies that are effective at preserving beta-cell function but as primary outcomes require inordinately large and protracted trials. Endogenous insulin secretion is assessed best by measurement of C-peptide, which is cosecreted with insulin in a one-to-one molar ratio but unlike insulin experiences little first pass clearance by the liver. Measurement of C-peptide under standardized conditions provides a sensitive, well accepted, and clinically validated assessment of beta-cell function. C-peptide measurement is the most suitable primary outcome for clinical trials of therapies aimed at preserving or improving endogenous insulin secretion in type 1 diabetes patients. Available data demonstrate that even relatively modest treatment effects on C-peptide will result in clinically meaningful benefits. The development of therapies for addressing this important unmet clinical need will be facilitated by trials that are carefully designed with beta-cell function as determined by C-peptide measurement as the primary efficacy outcome.
authors.affiliation: Department of Medicine, University of Washington,and DVA Puget Sound Health Care System, Seattle, Washington 98108, USA. jpp@u.washington.edu
authors.forename: Jerry P
authors.initials: JP
authors.lastname: Palmer
authors.forename: G Alexander
authors.initials: GA
authors.lastname: Fleming
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Jansa
authors.forename: Hubert
authors.initials: H
authors.lastname: Kolb
authors.forename: John M
authors.initials: JM
authors.lastname: Lachin
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Polonsky
authors.forename: Paolo
authors.initials: P
authors.lastname: Pozzilli
authors.forename: Jay S
authors.initials: JS
authors.lastname: Skyler
authors.forename: Michael W
authors.initials: MW
authors.lastname: Steffes
mesh_terms: D002096:C-Peptide / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000628:therapy; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D016896:Treatment Outcome
chemical_list: D002096:C-Peptide