The introduction of SMBG and of insulin analogues has made it possible for people with type 1 diabetes to manage blood glucose more effectively. Whereas the initial goal of therapy after the discovery of insulin was simply avoidance of ketoacidosis, by the 1980s and certainly after the report of the DCCT the new targets were meticulous glycemic control, avoidance of hypoglycemia, and improving the quality and duration of life so that ideally it was identical to those without diabetes.

The insulin regimens used in the “intensive therapy” group in the DCCT were the use of multiple daily injections (MDI) or CSII. These regimens, administering regular insulin with meals, at the time were the best mimics of normal insulin secretion. Also called “physiologic insulin replacement”, two types of insulin were provided. The first, “basal” insulin, is the background insulin required to modulate basal hepatic glucose production overnight and between meals. The other, “prandial” (also called “bolus” or simply “meal-time”) insulin replacement, provides enough insulin to dispose of glucose after eating. Physiologic insulin regimens with both basal and bolus insulin components provide flexibility not possible with older twice-daily NPH and regular regimens (figure 5). Unfortunately, more than a decade after the announcement of the results of the DCCT, many individuals both in the United States and around the world still use the older therapies which make it difficult if not impossible to attain meticulous control in type 1 diabetes. It should be pointed out that once- or twice-daily basal injections are sometimes adequate for newly diagnosed patients with type 1 diabetes or those with latent autoimmune diabetes mellitus of adults (LADA) who are still producing endogenous insulin. [LADA is the term used for a slowly progressive form of type 1 diabetes in adults. These individuals are positive for one of the immune markers of type 1 diabetes such as antibodies to glutamic acid decarboxylase (GAD) or insulin autoantibody 2 (IA-2) and are found to secrete endogenous insulin for several years after their diagnosis].

The main reason the twice daily regimens of NPH and regular are generally ineffective is due the fact the time-action profile of these two standard insulins do not readily allow for the clear separation of basal and prandial insulin action. Due to the overlapping pharmacokinetics and pharmacodynamics of these insulins, in the classic “split-mix” regimen each insulin component has both prandial and basal action rather than clear separation. Although the regular insulin components are nominally responsible for meal glucose disposal after breakfast and dinner, the effective duration of action of the morning regular insulin (approximately 6 to 8 hours) extends through lunch, making it a prandial insulin for that meal as well (figure 6), and letting it serve as a basal insulin between breakfast and lunch. At the same time, the morning NPH insulin, with an effective duration of 10-16 hours, functions as a basal insulin after absorption of breakfast and lunch, but because of its relatively rapid onset, also serves as part of the prandial insulin component at breakfast and as the primary prandial insulin at lunch. Compensating for the inherent variability of this overlapping action requires strict and consistent coordination as to the timing of injections and meals, especially in patients aiming for stringent glycemic control for whom delaying lunch or skipping a mid-morning snack may result in hypoglycemia.

A simpler conceptual approach – preferred by most patients with type 1 diabetes – is to use a distinct prandial insulin for each meal (e.g., regular insulin, insulin lispro, insulin aspart, or insulin glulisine) and a separate basal insulin (e.g., NPH, insulin glargine, or insulin detemir). Although these true basal-prandial regimens require more shots than conventional twice-daily regimens, they are considerably more flexible, allowing greater freedom to skip meals or change mealtimes. Moreover, use of the long-acting basal insulin analogues – insulin glargine or detemir – and the rapid-acting insulin analogues, – insulin lispro, insulin aspart, or insulin glulisine, – facilitates achievement of individual, defined blood glucose targets. Strategies used for attaining that control include changing the timing of insulin injections in relation to meals, changing the portions or content of food to be consumed, or adjusting insulin doses or supplements for premeal hyperglycemia.