Duration of The Honeymoon Phase of Type 1 Diabetes: A Comparison of Insulins Detemir, Glargine and NPH

BACKGROUND: Type 1 diabetes (or insulin dependent diabetes mellitus (IDDM)) is a very common disorder affecting 1/400 persons by the age of 18 years and over 1 million people in the United States alone. An autoimmune disorder affecting the endocrine pancreas, it causes, in the untreated state, high blood glucose levels and ketosis. Over longer periods of time it can contribute to growth failure, malnutrition, and even death. It is responsible for a disproportionate percentage of the diabetes associated retinopathy and nephropathy seen in adults with diabetes (although type 1 diabetes only accounts for a small percentage of the total populace of patients with diabetes). Although insulin allows most children with this disease to grow and develop normally, it will not provide a permanent cure.

Many techniques have been studied to attempt to prevent the onset or progression of the autoimmune destruction of islets associated with type 1 diabetes, including a variety of immunomodulatory drugs, nicotinamide and small doses of insulin itself. Thus far nothing has proven completely successful. Some investigators have suggested that intensive control early in the disease process will slow the progression of the disease, but these results remain controversial. Ultimately, any treatment aimed at the prevention or cure of diabetes must have as its goal the preservation of the insulin secretory capacity of the pancreas.

In recent years, a number of insulin analogs have been developed which have different time-action profiles in humans. Currently, all children diagnosed with type 1 diabetes are placed on a combination of a long-acting insulin (such as insulins detemir or glargine) or a moderate-acting insulin (such as NPH), and a short acting insulin (such as lispro, aspart or regular insulin) as soon as they demonstrate they are able to resume a regular diet after their initial presentation. Each of the long- and moderate-acting insulins are given once or twice daily and the short-acting insulins at least twice and up to 4-5 times daily.

Normally, the pancreas secretes a basal level of insulin at rest, and then when challenged with a carbohydrate load, responds with an acute surge of insulin release. Intuitively, one might surmise that a pharmaceutical preparation that more closely mimics the normal physiological profile of the pancreas might be beneficial over the long term to pancreatic beta cell function. Levemir (insulin detemir) and Lantus (insulin glargine) are two relatively new insulin analogs known for their consistent and reproducible absorption profiles and steady time-action profiles. In comparison, insulin NPH is a product that had been the standard of care for children with diabetes for many years until the availability of the newer analogs, but is characterized by a peaking profile (with onset of action 2-4 hours after injection and peak effect 8-10 hours after injection). The combination of an insulin which mimics the basal insulin production of a pancreas at rest (i.e., glargine or detemir), together with a short-acting insulin with meals which mimics the bolus production of insulin generated in response to a carbohydrate load (regular, lispro or aspart), might allow for smoother blood glucose trends when compared to a combination of two "peaking" insulins (such as NPH and aspart).

In addition to the therapeutic benefit of better blood glucose control, we hypothesize that the maintenance of a steady baseline level of insulin with use of the newer insulin analogs may contribute to a longer period of pancreatic rest in the child newly diagnosed with diabetes. Many children with diabetes enter what is known as a "honeymoon phase" shortly after their diagnosis, which is characterized by relative ease of blood glucose control and relatively lower insulin requirements. This period represents a time during which the body is still able to make some insulin on its own.