Acute glucose fluctuations from peaks to nadirs include postprandial glucose (PPG) excursions that can be described by two components. The first is the duration of
postprandial excursions, and the second is the magnitude of postprandial rise. The first component, the duration of PPG increment, is a major contributor to sustained chronic hyperglycemia, while the magnitude is more a reflection of glucose variability. Calculating the PPG incremental area under curve above the preprandial glucose value can assess the entire phenomenon. By using this mode of calculation, we found that the absolute impact of PPG on hemoglobin A1c (percentage points of A1c) is constant and contributes approximately 1% in all patients with HbA1c levels above 6.5% (Figure 1).11
Although it is difficult to separate the contributions of the two components of the dysglycemia, it seems that both contribute to the two main mechanisms that lead to diabetes complications, namely, the excessive protein glycation and the activation of oxidative stress.12 As PPG excursions result in both acute and sustained hyperglycemia, it seems reasonable to think that PPG excursions and more generally acute glucose fluctuations activate the oxidative stress. For instance, the production of nitrotyrosine, a metabolite derived from nitrosamine stress, was significantly increased at fasting in patients with diabetes, but an additional increase was observed during postmeal periods. A reduction of the postmeal glucose excursions by using a premeal bolus of rapid insulin analog (Aspart) resulted in parallel decreases in glycemic and nitrotyrosine responses.13 Although PPG is usually the major contributor of glucose variability,
other fluctuations (especially downward fluctuations) must be taken into account.