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Demonstration of an Intrinsic Relationship Between Endogenous C-Peptide Concentration and Determinants of Glycemic Control in Type 1 Diabetes Following Islet Transplantation

Lookup NU author(s): Dr Augustin Brooks, Emeritus Professor Philip Home, Dr Nick Steen, Professor James Shaw

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Abstract

OBJECTIVEMaintenance of endogenous pancreatic beta-cell function could be an important goal in the management of type 1 diabetes. However, the impact of stimulated C-peptide level on overall glycemic control is unknown. The relationship between C-peptide and parameters of glucose control was therefore characterized in a cohort with rapidly changing beta-cell function following islet transplantation.RESEARCH DESIGN AND METHODSStandardized mixed-meal tolerance test was undertaken in 12 consecutive islet recipients at 1-6-month intervals, with graft function determined by 90-min stimulated C-peptide. Continuous glucose monitoring was undertaken in the week preceding each assessment and the relationship between C-peptide and glucose control evaluated by mixed Poisson regression.RESULTSRecipients completed 5 (1-14) [median (range)] clinical assessments over 18 (1-51) months posttransplant encompassing a wide range of stimulated C-peptide levels (7-2,622 pmol/L). Increasing beta-cell function across predefined C-peptide groups was associated with reduced insulin dose, HbA(1c), mean glucose (low [<200 pmol/L] 10.7 vs. excellent [>1,000 pmol/L] 7.5 mmol/L), and glucose SD (low, 4.4 vs. excellent, 1.4 mmol/L). Highly statistically significant continuous associations between stimulated C-peptide and mean interstitial glucose (lower by 2.5% [95% CI 1.5-3.5%] per 100 pmol/L higher C-peptide), glucose SD, time outside glucose target range, and measures of hyper-/hypoglycemia risk were confirmed.CONCLUSIONSRepeated assessment of islet transplant recipients has enabled modeling of the relationship between endogenous beta-cell function and measures of glycemic control providing quantitative estimates of likely impact of an acute change in beta-cell function in individuals with type 1 diabetes.

Publication metadata

Author(s): Brooks AM, Oram R, Home P, Steen N, Shaw JAM

Publication type: Article

Publication status: Published

Journal: Diabetes Care

Year: 2015

Volume: 38

Issue: 1

Pages: 105-112

Print publication date: 01/01/2015

Acceptance date: 09/10/2014

ISSN (print): 0149-5992

ISSN (electronic): 1935-5548

Publisher: American Diabetes Association

URL: http://dx.doi.org/10.2337/dc14-1656

DOI: 10.2337/dc14-1656

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