Comment on: Nathan DM, Buse JB, Davidson MB et al. (2006) Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 49: 1711–1721

Abstract

Glucose-responsive insulin secretion is frequently impaired prior to the onset of type 2 diabetes [1]. In addition, considering the reduced pancreatic beta cell mass in patients with type 2 diabetes [2], defects in insulin secretion appear heterogeneous in this patient group. In some patients, only postprandial insulin secretion appears impaired, whilst in others, basal insulin secretion is also affected. However, postprandial insulin secretion is impaired in almost all patients with type 2 diabetes. In the recently published consensus statement from the American Diabetes Association [3] and the European Association for the Study of Diabetes [4] concerning the initiation and adjustment of therapy for managing hyperglycaemia in type 2 diabetes, initial insulin therapy is aimed at increasing basal insulin supply with intermediateor long-acting insulins. Such a regimen cannot completely mimic a physiological pattern of insulin secretion. Consequently, postprandial glycaemic control tends to be inadequate, and a risk exists of fasting hypoglycaemia. Furthermore, the postprandial hyperglycaemia observed in patients with early-stage or mild type 2 diabetes increased the risk of microangiopathy or arteriosclerosis in two largescale clinical studies of type 2 diabetes, the United Kingdom Prospective Diabetes Study [5] and the DECODE study [6]. It has also been suggested that therapy focused on lowering postprandial glucose, rather than fasting glucose, may be superior for lowering HbA1c [7] and glucose variability (spike) [8]. Insulin preparations have been developed to provide insulin replacement that more closely reflects physiological insulin secretion; the introduction of rapid-acting insulin analogues and long-acting soluble insulin analogues has been a further step in this direction. Rapid-acting insulin analogues have been particularly effective at targeting postprandial hyperglycaemia [8]. They can, therefore, effectively reduce postprandial plasma glucose, even if administered immediately before a meal, and also minimise the risk of hypoglycaemia prior to the next meal [8]. The exact contribution of postprandial and fasting glucose increments to overall hyperglycaemia remains controversial. Monnier et al. reported that postprandial glucose excursion contributes up to ∼70% of the glucose load in patients with diabetes whose HbA1c levels are <7.3%, whereas the contribution of fasting hyperglycaemia increases gradually as diabetes worsens [9]. However, even in patients whose glycaemic control is poor, studies have demonstrated that treatment targeting postprandial hyperglycaemia, which improves glucose-responsive insulin secretion in patients with glucose desensitisation, improves both postprandial and also morning fasting plasma glucose (FPG) in such patients [10–12]. We hypothesised that mealtime dosing with rapid-acting insulin analogues strictly controls postprandial and daytime plasma glucose levels, and thereby improves glucose desensitisation and glucose-responsive insulin secretion. To test these hypotheses, we recently evaluated the effect of a mealtime, rapid-acting insulin analogue on the minimum early morning FPG levels (nadir FPG) in 40 Japanese Diabetologia (2007) 50:229–230 DOI 10.1007/s00125-006-0524-9