Clinical trial NCT00694122
Conditions: Type 1 Diabetes Dawn Phenomenon
Keywords: glucose cortisol growth hormone glucagon insulin
Sponsor: Massachusetts General Hospital
Start date: 2005-06-01; Completion date: 2010-11-01
Enrollment: 27 participants; Allocation: NON_RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
1. To investigate the effect of insulin glargine (Lantus™) vs NPH insulin regarding glycemic control during the early AM (dawn phenomenon) in individuals with type 1 diabetes.
2. To measure hormones implicated in the pathogenesis of the dawn phenomenon in individuals with type 1 diabetes.

Detailed description:
Title: COMPARISON of LANTUS and NPH INSULIN IN THE DAWN PHENOMENON

I. Background and Significance

Diabetes mellitus affects greater than 6% of the population, with type 2 more prevalent than type 1. For individuals with type 1 diabetes, the challenge has been to replicate insulin secretion of the healthy pancreas to maintain blood glucose as close to the non-diabetic range as possible. Insulin regimes using insulins with varied activity profiles (multiple daily injections or MDI) and continuous subcutaneous insulin infusion (CSII) have been somewhat successful in "mimicking" normal pancreatic function (1, 2). For individuals with type 1 diabetes, the benefits of near-normal, long-term glycemic control in delaying the development and slowing the progression of long-term complications was demonstrated in the Diabetes Control and Complications Trial (3). Intensive insulin therapy to achieve near-normal glycemic control has been limited by a three-fold increase in episodes of hypoglycemia (3, 4). Insulin analogs that provide more stable physiologic insulin levels have led to the development of newer MDI regimes (5). Glargine (Lantus) is a long-acting recombinant human insulin analog demonstrated to provide a continuous, smooth supply of insulin with no pronounced peak over a 24-hour period (6).

An increase in blood glucose in type 1 and type 2 diabetics, and an increase in insulin secretion to maintain normoglycemia in non-diabetics, was documented in several studies in the 1980s (15-17). This physiological requirement for more insulin delivery (or secretion) in the early (4:00-6:00 AM) hours was termed the "dawn phenomenon". The mechanism for the dawn phenomenon was thought to be the overnight increase in growth hormone section, rather than diurnal glucocorticoids (16, 18, 19). Most intensive treatment regimens of the 1980-90's, with MDI or CSII, were designed to provide more insulin in the 4:00-7:00 AM period to cope with the dawn phenomenon which cannot be be achieved with glargine (20-21). Continuous monitoring of blood glucose has revealed that individuals treated with CSII had significantly better glycemic control than glargine treated individuals (22). Whether the dawn phenomenon, with increased area under the curve blood glucose levels during the dawn period is limiting the effectiveness of regimens with glargine is of crucial importance.

Arms: arm 1: Long acting insulin, glargine, that subject currently used as an outpatient. SC injections. Dose given at 22:00 is based on past week blood glucose data during evening overnight hours and AM glucose. 20.2 +/- 11.7 units glargine (mean +/- SD).

Glargine (Lantus): Sanolfi Aventis

Hourly blood glucose from 22:00 to 08:00 while receiving glargine (Lantus) insulin will be compared with the NPH insulin arm. arm 2: Long acting insulin, NPH, that participant was currently while an outpatient. SC injections. Dose (units) given at 22:00 is based on past week blood glucose during evening overnight period and AM glucose. 20.7 +/- 10.0 units NPH (mean +/- SD).

NPH: Eli Lilly

Hourly blood glucose from 22:00 to 08:00 while receiving glargine (Lantus) insulin will be compared with the glargine (Lantus) insulin arm.
Interventions: intervention 1: Lantus (glargine)
Intervention descriptions: intervention 1: Described in Arm Description

Protocol documents: