OBJECTIVE -Chronic hyperglycemia is known to increase tissue glycation and diabetic complications, but controversy exists regarding the independent role of increased postprandial glucose excursions. To address this question, we have studied the effect of postprandial glycemic excursions (PPGEs) on levels of methylglyoxal (MG) and 3-deoxyglucosone (3-DG), two highly reactive precursors of advanced glycation end products (AGEs).RESEARCH DESIGN AND METHODS -We performed 4-month crossover studies on 21 subjects with type 1 diabetes and compared the effect of premeal insulin lispro or regular insulin on PPGEs and MG/3-DG excursions. PPGE was determined after standard test meal (STMs) and by frequent postprandial glucose monitoring. HbA 1c and postprandial MG and D-lactate were measured by HPLC, whereas 3-DG was determined by gas chromatography/mass spectroscopy.RESULTS -Treatment with insulin lispro resulted in a highly significant reduction in PPGEs relative to the regular insulin-treated group (P ϭ 0.0005). However, HbA 1c levels were similar in the two groups, and no relationship was observed between HbA 1c and PPGE (P ϭ 0.93). Significant postprandial increases in MG, 3-DG, and D-lactate occurred after the STM. Excursions of MG and 3-DG were highly correlated with levels of PPGE (R ϭ 0.55, P ϭ 0.0002 and R ϭ 0.61, P ϭ 0.0004; respectively), whereas a significant inverse relationship was seen between PPGE and D-lactate excursions (R ϭ 0.40, P ϭ 0.01). Conversely, no correlation was observed between HbA1c and postprandial MG, 3-DG, or D-lactate levels.CONCLUSIONS -Increased production of MG and 3-DG occur with greater PPGE, whereas HbA1c does not reflect these differences. Reduced PPGE also leads to increased production of D-lactate, indicating a role for increased detoxification in reducing MG levels. The higher postprandial levels of MG and 3-DG observed with greater PPGE may provide a partial explanation for the adverse effects of glycemic lability and support the value of agents that reduce glucose excursions. Diabetes Care 24:726 -732, 2001

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