Assessment of β Cell Mass and Function by AIRmax and Intravenous Glucose in High-Risk Subjects for Type 1 Diabetes.

Abstract

There is little information regarding β cell mass in individuals at early stages of type 1 diabetes (T1D). To investigate both acute insulin response to arginine at hyperglycemia (AIRmax), as a correlate of β cell mass, and β cell function by the intravenous glucose tolerance test (IVGTT) in subjects at early stages of T1D. Forty subjects were enrolled: (1) low-risk group: relatives of patients with T1D with 0 to 1 antibody (n = 21) and (2) high-risk group: relatives with ≥2 antibodies (n = 19). Acute insulin and C-peptide responses to IVGTT and to AIRmax. Participants underwent two IVGTT and AIRmax procedures on different days. AIRmax was reproducible, well tolerated, and correlated to first-phase insulin response (FPIR) from IVGTT (r = 0.779). The high-risk group had greater impaired β cell function compared with the low-risk group, determined both by lower mean FPIR and a greater number of subjects below an established threshold for abnormal function [10 of 19 (52.6%) versus 4 of 21 (19%)]. There was a heterogeneous AIRmax response in these subjects with low FPIR, ranging from 38 to 250 μU/mL. There is significant variation in insulin secretory reserve as assessed by AIRmax in family members with low β cell function assessed by FPIR. As AIRmax is a functional measure of β cell mass, these data suggest heterogeneity in disease pathogenesis in which mass is preserved in relation to function in some individuals. The tolerability and reproducibility of AIRmax suggest it could be a useful stratification measure in clinical trials of disease-modifying therapy.