Pathophysiological characteristics in patients with latent autoimmune diabetes in adults using clamp tests: evidence of a continuous disease spectrum of diabetes.

Abstract

This study aimed to assess islet insulin secretion and insulin resistance in Chinese patients with latent autoimmune diabetes in adults (LADA). Twelve patients with LADA, 10 with type 1 diabetes mellitus (T1DM), 10 with type 2 diabetes mellitus (T2DM), and 10 nondiabetic healthy controls (HCs) were included. Patients with LADA were subtyped according to the glutamic acid decarboxylase antibody (GADA) titer (LADA1, GADA titer ≥ 180 U/mL; LADA2, GADA titer 18-180 U/mL). Insulin secretion and sensitivity were assessed using hyperglycemic and hyperinsulinemic-euglycemic clamp tests, respectively. The first-phase insulin secretion gradually increased in patients with T1DM, LADA1, LADA2, and T2DM to HCs (29.32 ± 6.00mU/L vs. 68.71 ± 4.50mU/L vs. 87.60 ± 11.60mU/L vs. 138.27 ± 13.18mU/L vs. 248.49 ± 21.97mU/L; P < 0.05). The second-phase insulin secretion (2ph) and maximum insulin secretion (MIS) were significantly lower in patients with LADA2 and T2DM than in HCs, but higher in those with LADA1 and T1DM. No significant differences in 2ph and MIS were observed between patients with LADA1 and T1DM, and between those with LADA2 and T2DM. The levels of insulin sensitivity index (ISI) during hyperinsulinemic-euglycemic clamps were lower in patients with LADA and T2DM than in those with T1DM. Patients with T1DM displayed lower ISI compared with HCs. Chinese patients with LADA and T1DM had impaired insulin sensitivity and β-cell function. Furthermore, the hypothesis that diabetes is a continuous spectrum from T1DM, LADA1, LADA2 to T2DM was confirmed in this study.