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.

OBJECTIVE -The exact contributions of postprandial and fasting glucose increments to overall hyperglycemia remain controversial. The discrepancies between the data published previously might be caused by the interference of several factors. To test the effect of overall glycemic control itself, we analyzed the diurnal glycemic profiles of type 2 diabetic patients investigated at different levels of HbA 1c .RESEARCH DESIGN AND METHODS -In 290 non-insulin-and non-acarboseusing patients with type 2 diabetes, plasma glucose (PG) concentrations were determined at fasting (8:00 A.M.) and during postprandial and postabsorptive periods (at 11:00 A.M., 2:00 P.M., and 5:00 P.M.). The areas under the curve above fasting PG concentrations (AUC 1 ) and Ͼ6.1 mmol/l (AUC 2 ) were calculated for further evaluation of the relative contributions of postprandial (AUC 1 /AUC 2 , %) and fasting [(AUC 2 Ϫ AUC 1 )/AUC 2 , %] PG increments to the overall diurnal hyperglycemia. The data were compared over quintiles of HbA 1c .RESULTS -The relative contribution of postprandial glucose decreased progressively from the lowest (69.7%) to the highest quintile of HbA 1c (30.5%, P Ͻ 0.001), whereas the relative contribution of fasting glucose increased gradually with increasing levels of HbA 1c : 30.3% in the lowest vs. 69.5% in the highest quintile (P Ͻ 0.001).CONCLUSIONS -The relative contribution of postprandial glucose excursions is predominant in fairly controlled patients, whereas the contribution of fasting hyperglycemia increases gradually with diabetes worsening. These results could therefore provide a unifying explanation for the discrepancies as observed in previous studies. Diabetes Care 26:881-885, 2003

Glycaemic variability is an integral component of glucose homoeostasis. Although it has not yet been definitively confirmed as an independent risk factor for diabetes complications, glycaemic variability can represent the presence of excess glycaemic excursions and, consequently, the risk of hyperglycaemia or hypoglycaemia. Glycaemic variability is currently defined by a large and increasing number of metrics, representing either short-term (within-day and between-day variability) or long-term glycaemic variability, which is usually based on serial measurements of HbA or other measures of glycaemia over a longer period of time. In this Review, we discuss recent evidence examining the association between glycaemic variability and diabetes-related complications, as well as non-pharmacological and pharmacological strategies currently available to address this challenging aspect of diabetes management.

OBJECTIVE -The aim of the study was to determine whether the loss of fasting and postprandial glycemic control occurs in parallel or sequentially in the evolution of type 2 diabetes.RESEARCH DESIGN AND METHODS -In 130 type 2 diabetic patients, 24-h glucose profiles were obtained using a continuous glucose monitoring system. The individuals with type 2 diabetes were divided into five groups according to A1C levels: 1 (Ͻ6.5%, n ϭ 30), 2 (6.5-6.9%, n ϭ 17), 3 (7-7.9%, n ϭ 32), 4 (8 -8.9%, n ϭ 25), and 5 (Ն9%, n ϭ 26). The glucose profiles between the groups were compared. The overall glucose concentrations for the diurnal, nocturnal, and morning periods, which represent the postprandial, fasting, and the dawn phenomenon states, respectively, were also compared.RESULTS -Glucose concentrations increased steadily from group 1 to 5 in a stepwise manner. The initial differences in mean glucose concentrations reaching statistical significance occurred 1) between groups 1 and 2 (6.4 vs. 7.7 mmol/l, P ϭ 0.0004) for daytime postprandial periods, followed by differences; 2) between groups 2 and 3 (7.5 vs. 9.3 mmol/l, P ϭ 0.0003) for the morning periods (dawn phenomenon); and finally 3) between groups 3 and 4 (6.3 vs. 8.4 mmol/l, P Ͻ 0.0001) for nocturnal fasting periods.CONCLUSIONS -The deterioration of glucose homeostasis in individuals with type 2 diabetes progressed from postprandial to fasting hyperglycemia following a three-step process. The first step related to the three diurnal postmeal periods considered as a whole, the second step occurred during the morning period, and the third and final step corresponded to sustained hyperglycemia over the nocturnal fasting periods. Such a description of the key stages in the evolution of type 2 diabetes may be of interest for implementing antidiabetes treatment. Diabetes Care 30:263-269, 2007T he steady decline in the quality of glucose homeostasis (1) as observed in type 2 diabetes results from an increasing defect (2) in both insulin sensitivity and secretion (3). The data from the UK Prospective Diabetes Study indicate that the gradual increase in both A1C levels and fasting glucose concentrations is mainly due to a relentless linear deterioration in ␤-cell function from the time of diagnosis. In contrast, the years that precede the development of type 2 diabetes are characterized by a progressive decline in both insulin action and defects in the early phase of the insulin secretion (4,5). Such abnormalities lead to a progressive transition from normal glucose tolerance to impaired glucose tolerance and finally to frank type 2 diabetes. As impaired glucose tolerance is acknowledged as a prediabetic stage, it has been postulated that losses of postprandial glucose control occur before deterioration in fasting glucose concentration (4,6,7). In a previous study (8), we have demonstrated that postprandial glucose increments are predominant contributors to the overall hyperglycemia in patients with an A1C Ͻ7.3%, while fasting increments represent the major contributor to worsenin...