Insulin Sensitive Patients With Impaired Glucose Tolerance: Physiologic and Metabolic Characterization ( <scp>STOP DIABETES</scp> )

AIMS: Insulin resistance is a key pathophysiologic defect in patients with impaired glucose tolerance (IGT) who progress to type 2 diabetes. However, some individuals progress to IGT despite normal total body insulin sensitivity (IS). In patients from the STOP DIABETES trial, physiologic and metabolic features were compared between IS patients manifesting IGT and insulin resistant (IR) patients with IGT. METHODS: From the STOP DIABETES trial population, we identified two groups of IGT subjects: (i) those who were insulin sensitive (IS) (n = 107) (> 25th percentile of patients with normal glucose tolerance) and (ii) those who were insulin resistant (IR) (n = 222) (≤ 25th percentile) using the Matsuda index. IS-IGT patients also were compared to insulin sensitive patients with NGT and 1-hour (1-h) plasma glucose < 155 mg/dL (n = 574). RESULTS: Compared to the IR-IGT group, IS IGT individuals had a higher plasma HDL, and lower BMI, plasma triglycerides, triglyceride/HDL ratio, hs-CRP (all p < 0.001) and normal blood pressure (p < 0.01). The IS-IGT group developed IGT with a higher disposition index, p < 0.0001, but the early insulinogenic index was significantly lower than in the IR group (p < 0.0001) (10.5 ± 0.4 vs. 21.4 ± 0.5, p < 0.0001). Compared with IS-NGT patients, the IS-IGT individuals manifested reduced beta cell function and increased insulin clearance. CONCLUSION: Approximately one third of patients from the STOP DIABETES study demonstrate impaired glucose tolerance despite having normal insulin sensitivity. This IS-IGT group had significantly less metabolic dyslipidaemia, less hypertension, better beta cell function and increased insulin clearance compared to insulin resistant IGT patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: number NCT03308773.