Effects of obesity and hyperglycemia on postprandial insulin-mediated and non-insulin-mediated glucose disposal

Objective. To evaluate total, insulin-mediated, and non-insulin-mediated glucose disposal (TGD, IMGD, NIMGD) after ingesting glucose in people with obesity and different glycemic status.

Research Design and Methods. We developed and validated a new glucose tracer model in conjunction with an oral glucose tolerance test (OGTT) to determine IMGD, NIMGD, and TGD (sum of IMGD and NIMGD) after glucose ingestion in four groups of people: i) lean with normal glucose tolerance (NGT); ii) obese with insulin resistance and NGT due to hyperinsulinemia (Ob-NGT group); iii) obese with insulin resistance and impaired glucose tolerance (IGT) due to inadequate hyperinsulinemia (Ob-IGT group); and iv) obese with insulin resistance and type 2 diabetes due to marked insulin insufficiency (Ob-T2D group). In addition, we evaluated the effect of intensive lifestyle therapy (ILT) that caused ~15% weight loss on IMGD and NIMGD in people with obesity and T2D.

Results. IMGD progressively decreased and NIMGD progressively increased from Lean to Ob-NGT to Ob-IGT to Ob-T2D. IMGD accounted for about 70%, 65%, 50% and 20% of TGD and NIMGD accounted for ~40%, 35%, 50%, and 80% of TGD in Lean, Ob-NGT, Ob-IGT and Ob-T2D, respectively. Although NIMGD was ~2-fold and ~3-fold higher in Ob-IGT and Ob-T2D compared with Ob-NGT, NIMGD only partially compensated for markedly impaired IMGD in the Ob-IGT and Ob-T2D. ILT in people with obesity and T2D increased IMGD and decreased NIMGD.

Conclusion. NIMGD is a major mechanism of postprandial TGD in people with insulin resistance and inadequate insulin secretion.