Glucose fluctuations during postprandial periods and, more generally, during glucose swings exhibited a more specific triggering effect on oxidative stress than chronic sustained hyperglycemia. The present data suggest that interventional trials in type 2 diabetes should target not only hemoglobin A1c and mean glucose concentrations but also acute glucose swings.

As I noted in the cover story, Kantor loved ambiguity, "especially when he can hide it behind a cloud of facts." It seems he was successful. M. Therese Southgate, MD therese.southgate@jama-archives.orgTo the Editor: The study of activation of oxidative stress in patients with type 2 diabetes by Dr Monnier and colleagues 1 identifies an interesting association between glycemic variability and oxidative stress. However, it is important to highlight some limitations of the tools used in this study and the data reported.Continuous glucose monitoring systems (CGMSs) may be inaccurate or even intermittently fail to record. The authors report the accuracy of CGMSs for a single fasting time point but do not report whether a minimum accuracy criterion was applied prior to accepting a 24-hour glucose profile, such as a maximum permitted mean relative absolute difference between all concurrent CGMSs and capillary glucose measurements, or a maximum gap in the CGMS recording.The study examined only 1 marker of oxidative stress, urinary 8-iso prostaglandin F 2␣ (8-iso-PGF 2␣ ). Although most studies demonstrate elevated urinary 8-iso-PGF 2␣ in patients with diabetes, some studies have indicated normal values, even in the setting of type 1 diabetes, where glycemic variability is invariably high. 2 Little is known about the relationship between urinary excretion of 8-iso-PGF 2␣ and acute changes in blood glucose. It would be very helpful to know the day-to-day intraindividual variability of urinary 8-iso-PGF 2␣ excretion and whether urinary excretion responds acutely to improvement in glycemic control. If this is not the case, it raises questions about the significance of their data.While smoking is known to increase urinary 8-iso-PGF 2␣ , 3 the study does not report the number of smokers in the diabetes or control groups. Furthermore, urine albumin excretion rate was not reported. The association between urinary 8-iso-PGF 2␣ and urine albumin excretion rate has not been studied in the setting of diabetes, but microalbuminuria is associated with elevated oxidative stress. 4 Finally, the authors chose to measure glycemic variability over a 48-hour period using an average of day 1 and 2, even though the urine collection was only performed on day 1. It appears that no effort was made to standardize the patient's diet or physical activity during the study. Therefore, glucose variability may have differed substantially between the 24 hours of urinary 8-iso-PGF 2␣ collection and the second day. These data should be provided. LETTERS Louis Monnier, MD

Short-term calorie restriction in overweight or obese patients with type 2 diabetes resulted in dichotomous responses between interprandial and postprandial glycaemic excursions. The resistance of mid-morning glucose peaking to calorie restriction should result in additional dietary or pharmacological measures at breakfast.