Emerging parameters of the insulin and glucose response on the oral glucose tolerance test: Reproducibility and implications for glucose homeostasis in individuals with and without diabetes

摘要

Aims: Recent studies have suggested that novel parameters of the insulin and glucose response on the oral glucose tolerance test (OGTT) can provide metabolic insight beyond glucose tolerance, but have not evaluated their reproducibility. Thus, our aim was to evaluate the reproducibility of these parameters and, if confirmed, characterize their clinical/pathophysiologic relevance in healthy and diabetic individuals. Methods: Thirty healthy adults each underwent 3 replicate OGTTs, enabling assessment of the reproducibility of the following 5 parameters: time to insulin peak, shape of the glucose curve, glucose nadir below baseline, 1-h post-challenge glucose, and time to glucose peak. The only reproducible parameter was then further evaluated in 63 patients with early type 2 diabetes (T2DM) before and after 4-weeks of intensive insulin therapy (IIT) designed to improve beta-cell function (measured by Insulin Secretion-Sensitivity-Index-2 (ISSI-2)). Results: Of the five parameters, only time to glucose peak displayed reliable reproducibility on replicate testing (κ=0.76). Over 80% of controls had their glucose peak at 30-min post-load, whereas all but one of the diabetic patients had their peak at 60-min or later. ISSI-2 was lower in T2DM patients with peak at ≥90-min than in those with peak at ≤60-min (P=0.012). In patients in whom IIT improved beta-cell function by ≥20% from baseline, 39.1% had glucose peak on the post-therapy OGTT shift to an earlier timepoint, as compared to 15.4% with similar shift in those without such improvement(P=0.03). Conclusion: Time to glucose peak is a reproducible characteristic on the OGTT and associated with beta-cell function in early T2DM.