Latent Autoimmune Diabetes in Adults (LADA) is a metabolic disorder at the crossroad between type 1 (T1DM) and type 2 diabetes (T2DM). Aim of our study was to carefully assess beta cell function and insulin sensitivity in patients with LADA, in comparison to patients with either type 2 diabetes clinically undistinguishable from LADA or typical type 2 diabetes. In 35 (M/F=19/16) patients (mean±SEM: age 57.4±1.6 years, BMI 27.5±0.9 kg/m2) with newly diagnosed LADA were compared to 35 patients with newly diagnosed T2DM matched for age, gender, BMI and HbA1c (LADA-like). The latter group was extracted from the database of the Verona Newly Diagnosed Type 2 diabetes (VNDS; N=589 GADA-negative patients) The rest of VNDS patients herein represent typical T2DM. LADA patients were further divided in two groups according to GADA levels (median 4 kU/L): low GAD-LADA (GADA < 4kU/L) and high GAD-LADA (GADA > 4 kU/L). In all patients we performed on separate days: 1. prolonged (5-hours) frequently sampled OGTT to assess derivative control (DC) and proportional control (PC) of beta cell function by state of art mathematical modeling of glucose and C-peptide curves; 2. standard euglycemic insulin clamp to assess insulin sensitivity (SI). SI was not statistically different (p<0.12) in LADA-like and in LADA patients, but in the latter was higher (+28%) than in VNDS (812±SEM vs 635±SEM µmol.min-1.m-2 BSA, respectively; p=0.01). The DC of beta cell function was impaired in LADA compared to LADA-like (p<0.01) and to VNDS (p<0.05). The PC in LADA was similar to LADA-like (p=0.42), but it was reduced when compared to VNDS (p<0.03). High GAD- and low GAD-LADA had similar SI, but the former had worse PC of beta cell function than the latter (p<0.01). In conclusion, patients with newly diagnosed LADA display more severe defects in beta cell function even when compared to LADA-like patients with newly diagnosed T2DM; furthermore, the higher the GADA titer, the worse is beta cell dysfunction. These data may be of help in optimizing metabolic therapy and in refining metabolic prognosis of these patients.
"Presence and titer of GAD antibodies are determinants of beta cell function in patients with newly diagnosed type 2 diabetes mellitus: further insights in the metabolic phenotype of LADA patients"
TROMBETTA, Maddalena;BOSELLI, Maria Linda;BRANGANI, Corinna;ZARDI, Federica;NEGRI, Carlo;STOICO, Vincenzo;BONORA, Enzo;BONADONNA, Riccardo
2014-01-01
Abstract
Latent Autoimmune Diabetes in Adults (LADA) is a metabolic disorder at the crossroad between type 1 (T1DM) and type 2 diabetes (T2DM). Aim of our study was to carefully assess beta cell function and insulin sensitivity in patients with LADA, in comparison to patients with either type 2 diabetes clinically undistinguishable from LADA or typical type 2 diabetes. In 35 (M/F=19/16) patients (mean±SEM: age 57.4±1.6 years, BMI 27.5±0.9 kg/m2) with newly diagnosed LADA were compared to 35 patients with newly diagnosed T2DM matched for age, gender, BMI and HbA1c (LADA-like). The latter group was extracted from the database of the Verona Newly Diagnosed Type 2 diabetes (VNDS; N=589 GADA-negative patients) The rest of VNDS patients herein represent typical T2DM. LADA patients were further divided in two groups according to GADA levels (median 4 kU/L): low GAD-LADA (GADA < 4kU/L) and high GAD-LADA (GADA > 4 kU/L). In all patients we performed on separate days: 1. prolonged (5-hours) frequently sampled OGTT to assess derivative control (DC) and proportional control (PC) of beta cell function by state of art mathematical modeling of glucose and C-peptide curves; 2. standard euglycemic insulin clamp to assess insulin sensitivity (SI). SI was not statistically different (p<0.12) in LADA-like and in LADA patients, but in the latter was higher (+28%) than in VNDS (812±SEM vs 635±SEM µmol.min-1.m-2 BSA, respectively; p=0.01). The DC of beta cell function was impaired in LADA compared to LADA-like (p<0.01) and to VNDS (p<0.05). The PC in LADA was similar to LADA-like (p=0.42), but it was reduced when compared to VNDS (p<0.03). High GAD- and low GAD-LADA had similar SI, but the former had worse PC of beta cell function than the latter (p<0.01). In conclusion, patients with newly diagnosed LADA display more severe defects in beta cell function even when compared to LADA-like patients with newly diagnosed T2DM; furthermore, the higher the GADA titer, the worse is beta cell dysfunction. These data may be of help in optimizing metabolic therapy and in refining metabolic prognosis of these patients.
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