Rarity of a Marked “Dawn Phenomenon” in Diabetic Subjects Treated by Continuous Subcutaneous Insulin Infusion

Abstract

We assessed the quality of overnight glycemic control and the frequency of the "dawn phenomenon" (nadir-0800 h glycemic increase) in 41 insulin-dependent diabetic patients treated by continuous subcutaneous insulin infusion (CSII). Mean plasma glucose levels were near-normal during the 24 h and, in particular, constant throughout the night. In a subset of six patients overnight plasma free insulin concentrations were also constant during CSII. The majority of profiles (88%) showed a glucose nadir from 2.0 to 5.9 mmol/L (most frequently at 0600 h) and had an 0800 h value from 2.0 to 6.9 mmol/L (92%). A large proportion (46%) of profiles showed a zero or negative nadir-0800 h glycemic increase. In 22 patients with three or more profiles recorded at the same basal insulin infusion rate, only one of 103 profiles had a fasting glycemic increase greater than an arbitrary value of 5.0 mmol/L (5.3), although many patients exhibited small dawn glycemic increases (e.g., 14 of 22 had a mean increase of from 0 to 2 mmol/L). In 12 subjects a 15% reduction in basal insulin infusion rate increased the mean +/- SEM dawn glycemic increase from 0.58 +/- 0.25 mmol/L to 2.7 +/- 0.76 mmol/L (P less than 0.025) as well as significantly increasing the nocturnal nadir and 0800 h plasma glucose concentrations. Thus, a marked dawn phenomenon is rare when a single but adequate basal infusion rate is used for CSII, and this questions the need in the majority of patients for preprogrammable pumps with nocturnal infusion rate changes.

Early posthypoglycemic insulin resistance in man is mainly an effect of beta-adrenergic stimulation.

“…This is similar to our recent study ofthe effect of infused catecholamine on glucose metabolism (28). In this context, it is important to point out that the insulin levels used in the present study during the clamps are clinically relevant as corresponding levels are frequently seen in patients with type I diabetes during both conventional insulin therapy and continuous subcutaneous insulin infusion (29,30).…”

The Relevance of Glucose Counterregulatory Systems to Patients with Insulin-Dependent Diabetes Mellitus*

“…Morning hyperglycemia can be overcome by increasing insulin doses, but only at the expense of lower nighttime glucose levels (65). Bolli et al (34) demonstrated that posthypoglycemic hyperglycemia is the result of both dissipation of injected insulin and activation of counterregulatory systems, principally adrenomedullary epinephrine secretion (20), perhaps coupled with GH secretion, in patients with IDDM.…”

“…It should be emphasized that the nighttime to morning increase in plasma glucose is variable in a given patient (64) and absent or rather minor in many patients (65,66) with IDDM. Morning hyperglycemia can be overcome by increasing insulin doses, but only at the expense of lower nighttime glucose levels (65).…”

Adrenergic mechanisms contribute to the late phase of hypoglycemic glucose counterregulation in humans by stimulating lipolysis.

“…In the first set ofexperiments (study I), to induce moderate hypoglycemia, insulin (Actrapid HM U-40; Novo Research Institute, Copenhagen, Denmark), diluted to 1 U/ml in 100 ml of0.9% NaCl containing 2 ml of the subject's blood, was intravenously infused at the rate of 0.30 mU* kg-' * min' from 0 to 180 min and 0.40 mU -kg-' -min' from 180 to 480 min with a syringe pump (Harvard Apparatus Co., Inc., The Ealing Corp., South Natick, MA). This intravenous rate ofinsulin infusion was chosen to reproduce the mild hyperinsulinemia observed in previous studies during subcutaneous insulin infusion in normal man (1)(2)(3)(4)(5)(6), and to simulate the type of hypoglycemia that may develop in diabetic patients undergoing intensive insulin therapy (8,9,(22)(23)(24)(25).…”