Nocturnal spikes of growth hormone secretion cause the dawn phenomenon in Type 1 (insulin-dependent) diabetes mellitus by decreasing hepatic (and extrahepatic) sensitivity to insulin in the absence of insulin waning

Abstract

The aim of the present studies was to test the hypothesis that the dawn phenomenon in Type 1 (insulin-dependent) diabetes mellitus is due to a decrease in insulin sensitivity caused by nocturnal spikes of growth hormone. Twelve subjects with Type 1 diabetes were studied on two different occasions, from 24.00 to 02.00 hours, and from 06.00 to 08.00 hours with the euglycaemic clamp technique at two plasma free insulin levels (approximately 25 mU/l, n = 7; approximately 80 mU/l, n = 5). To eliminate the confounding factor of insulin waning of previous Biostator studies, prior to clamp experiments the diabetic subjects were infused with i.v. insulin by means of a syringe pump according to their minute-to-minute insulin requirements. Insulin sensitivity decreased at dawn as compared to the early night hours (approximately 30% increase in the rate of hepatic glucose production, approximately 25% decrease in the rate of peripheral glucose utilisation). Plasma insulin clearance did not change overnight. In seven Type 1 diabetic subjects, suppression of nocturnal spikes of growth hormone secretion by somatostatin during basal glucagon and growth hormone replacement resulted in complete abolition of the increased rate of hepatic glucose production at dawn. Replacement of nocturnal spikes of growth hormone faithfully reproduced the increase in hepatic glucose production at dawn of the control study.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin Detemir Is Associated With More Predictable Glycemic Control and Reduced Risk of Hypoglycemia Than NPH Insulin in Patients With Type 1 Diabetes on a Basal-Bolus Regimen With Premeal Insulin Aspart

“…The effect of insulin detemir was most pronounced during the early morning hours, reflected in the lower FPG levels with insulin detemir compared with NPH insulin. The optimal effect of insulin detemir coincided with the "dawn phenomenon" between 0500 and 0800, where blood glucose tends to rise because of decreased insulin sensitivity and secretion of growth hormone (27).…”

Insulin analogues and their potential in the management of diabetes mellitus

“…Patients with Type I diabetes have variable insulin requirements at night, i. e. less need for insulin between midnight and approximately 0300 hours and about 30 % greater insu- . In these double-blind studies, human regular and aspart insulins were both injected at mealtime lin requirements between 0400 and 0700 hours [114], primarily because of decreased insulin sensitivity in the liver [115]. An ideal long-acting insulin preparation injected s. c. should therefore provide variable insulin delivery, i. e. less insulin in the first than second part of the night.…”

Substitution of night-time continuous subcutaneous insulin infusion therapy for bedtime NPH insulin in a multiple injection regimen improves counterregulatory hormonal responses and warning symptoms of hypoglycaemia in IDDM

“…depot insulins, which have a highly variable absorption rate from the subcutaneous tissue [13±15] and a peak insulin activity at a time when insulin requirements are declining [16]. Meticulous prevention of hypoglycaemia has been shown to improve the counterregulatory hormonal responses and warning symptoms of hypoglycaemia [17].…”