Oxidative stress in type 2 diabetes: the role of fasting and postprandial glycaemia

Oxidative stress, through the production of reactive oxygen species (ROS), has been proposed as the root cause underlying the development of insulin resistance, β-cell dysfunction, impaired glucose tolerance and type 2 diabetes mellitus (T2DM). It has also been implicated in the progression of long-term diabetes complications, including microvascular and macrovascular dysfunction. Excess nourishment and a sedentary lifestyle leads to glucose and fatty acid overload, resulting in production of ROS. Additionally, reaction of glucose with plasma proteins forms advanced glycation end products, triggering production of ROS. These ROS initiate a chain reaction leading to reduced nitric oxide availability, increased markers of inflammation and chemical modification of lipoproteins, all of which may increase the risk of atherogenesis. With the postulation that hyperglycaemia and fluctuations in blood glucose lead to generation of ROS, it follows that aggressive treatment of fasting and postprandial hyperglycaemia is important for prevention of micro and macrovascular complications in T2DM

Contribution of fasting and postprandial plasma glucose to HbA1c

HbA1c has been regarded as the gold standard of glucose homeostasis assessment in diabetes, theoretically providing an indication of the time-weighted average of plasma glucose concentration over the preceding 6–8 weeks [1]. Reduction of HbA1c has been associated with a reduction of risk of both micro- and macrovascular diabetic complications by primary intervention studies [2]. However, HbA1c may not completely reflect glucose control, especially short-term postprandial glucose excursions [3–5], and acute increases in blood glucose appear to have a significant independent role in the pathogenesis of diabetic complications [3,6–8]. Accordingly, the relative contribution of fasting and postprandial glucose levels to the value of HbA1c has been discussed in recent medical literature [5,9–14]. We have developed a mathematical model of haemoglobin glycation to assist the clinical interpretation of this measurement [15]