REDUCED GLUCOSE EFFECTIVENESS AS A FEATURE OF GLUCOSE INTOLERANCE : EVIDENCE IN ELDERLY TYPE-2 DIABETIC SUBJECTS

One of the factors determining glucose tolerance is glucose disappearance independent from the dynamic insulin (glucose effectiveness); the debate on its role in the development of Type-2 diabetes is still open. The aim of the present study was to evaluate insulin delivery, insulin sensitivity (Sj), and glucose effectiveness (SG) in a group of elderly Type-2 diabetic patients (D, 4/6 F/M, age 67±2 years, 64±2 kg, BMI 23.8±0.5 kg/m2), compared to young controls (C, 4/6 F/M, 25±2 years, 72±4 kg, 23.7±1.1 kg/m2) and elderly controls (E, 2/4 F/M, 73±3 years, 63±4 kg, 23.1 ±0.5 kg/m2). We performed oral (OGTT) and intravenous (FSIGT) glucose tolerance tests. The OGTT showed that C and E were normotolerant, while D had a markedly reduced glucose tolerance. This was also confirmed in the FSIGT where the glucose tolerance index (KG) was 0.6±0.1% min−1 in D vs 1.8±0.2 in C and 1.5±0.2 in E (p<0.0002). Total insulin area of D and the overall insulin delivery were not different from those of the control groups. The early phase area was instead significantly reduced (0.19±0.02 mU min/mL vs 0.61±0.06 of C and 0.46±0.06 of E, p<0.001) given the reduction in the dynamic first-phase insulin delivery (0.86±0.17 min(μU/mL)/(mg/dL) vs 3.95±0.61 in C (p<0.005) and 2.61 ±0.66 (p<0.001) in E). S1 of D was 3.4±0.4 10−4min−1/(μU/mL), not different from that of C (4.7±0.6) and E (3.5±0.2). This study showed a marked difference between SG of D and that of both control groups [0.010±0.001 min−1 vs 0.026±0.004 (p<0.001) of C and 0.020±0.003 (p<0.002) of E], mostly due to the zero-insulin component GEZI which was 0.006±0.001 in D vs 0.021±0.004 in C and 0.016±0.003 in E (p<0.003). In the elderly groups, when taken together, SG exhibited a positive correlation with the area under insulin concentration during the early phase and with KG (r=0.69, p=0.0032 and r=0.90, p=0.0001, respectively), demonstrating the importance of the first-phase insulin delivery in modulating glucose effectiveness and glucose tolerance.