scispace - formally typeset
Search or ask a question

Showing papers by "Bastiaan E. de Galan published in 2013"


Journal ArticleDOI
TL;DR: The considerably more rapid insulin absorption after administration by jet injector translated to a significant if modest decrease in postprandial hyperglycemia in patients with type 1 and type 2 diabetes, and may specifically benefit patients who have difficulty in limiting postPRandial glucose excursions.
Abstract: OBJECTIVE Clamp studies have shown that the absorption and action of rapid-acting insulin are faster with injection by a jet injector than with administration by conventional pen. To determine whether these pharmacokinetic changes also exist in patients with diabetes and benefit postprandial glucose control, we compared the pharmacologic profiles of insulin administration by jet injection versus conventional insulin pen after a standardized meal in patients with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS In a randomized, double-blind, double-dummy crossover study, 12 patients with type 1 diabetes and 12 patients with type 2 diabetes received insulin aspart either by jet injection or by conventional pen, in both cases followed by a standardized meal. Blood was sampled for 6 h for determination of glucose and insulin levels to calculate pharmacologic profiles. RESULTS Insulin administration by jet injection resulted in shorter time until peak plasma insulin level (51.3 ± 6.4 vs. 91.9 ± 10.2 min; P = 0.003) and reduced hyperglycemic burden during the first hour (154.3 ± 20.8 vs. 196.3 ± 18.4 mmol · min · L −1 ; P = 0.041) compared with conventional administration. Jet injection did not, however, significantly reduce the hyperglycemic burden during the 5-h period thereafter. There was no indication that the jet injector performed differently in patients with type 1 and type 2 diabetes. CONCLUSIONS The considerably more rapid insulin absorption after administration by jet injector translated to a significant if modest decrease in postprandial hyperglycemia in patients with type 1 and type 2 diabetes. The improved early postprandial glucose control may specifically benefit patients who have difficulty in limiting postprandial glucose excursions.

36 citations


Journal ArticleDOI
TL;DR: The data suggest that the brains of patients with T1DM are better able to endure moderate hypoglycemia than those of subjects without diabetes.
Abstract: Patients with type 1 diabetes mellitus (T1DM) experience, on average, 2 to 3 hypoglycemic episodes per week. This study investigated the effect of hypoglycemia on cerebral glucose metabolism in patients with uncomplicated T1DM. For this purpose, hyperinsulinemic euglycemic and hypoglycemic glucose clamps were performed on separate days, using [1-13C]glucose infusion to increase plasma 13C enrichment. In vivo brain 13C magnetic resonance spectroscopy was used to measure the time course of 13C label incorporation into different metabolites and to calculate the tricarboxylic acid cycle flux (VTCA) by a one-compartment metabolic model. We found that cerebral glucose metabolism, as reflected by the VTCA, was not significantly different comparing euglycemic and hypoglycemic conditions in patients with T1DM. However, the VTCA was inversely related to the HbA1C and was, under hypoglycemic conditions, approximately 45% higher than that in a previously investigated group of healthy subjects. These data suggest that the brains of patients with T1DM are better able to endure moderate hypoglycemia than those of subjects without diabetes.

35 citations


Journal ArticleDOI
TL;DR: The clinical syndrome of severely impaired hypoglycemic awareness results from a vicious cycle of recurrent hypoglycemia and progressive counter-regulatory impairments, and patients with this syndrome are at a sixto ten-fold higher risk of severe hypoglyCEmia compared with those reporting normal hypogly glucose awareness.
Abstract: 281 ISSN 1758-1907 10.2217/DMT.13.25 © 2013 Future Medicine Ltd Diabetes Manage. (2013) 3(4), 281–283 Iatrogenic hypoglycemia is the most frequent acute complication of insulin therapy. Although the true incidence is difficult to ascertain, it is estimated that patients with Type 1 diabetes experience two to three hypoglycemic events per week and one severe event, requiring third-party assistance, once every 1–2 years [1]. There is substantial interand intra-individual variation in the incidence of hypoglycemic events, ranging from almost none to one or even multiple events per day. Hypo glycemia is considered to be the principal limiting factor to achieve optimal glycemic control in Type 1 diabetes because it is usually unavoidable in the pursuit of near-normal glucose levels [1]. Other factors impacting on the rate of hypoglycemia include (residual) b-cell function, the potency of glucose counter-regulatory function and hypo glycemic awareness. In addition, time of day (daytime versus nighttime), ambient temperature and other environmental factors (e.g., exercise or alcohol use) may play a role in the day-to-day variation. Approximately 25–30% of patients with Type 1 diabetes have severely impaired hypoglycemic awareness, meaning that hypoglycemia does not or only minimally elicits classical warning symptoms, such as sweating, pounding heart or trembling. In these patients, counter-regulatory hormone responses to hypoglycemia are often similarly impaired, meaning that glucose levels may fall more or less unimpeded. Since antecedent hypoglycemia exerts an attenuating effect on the counter-regulatory and symptom responses to subsequent hypoglycemia [2], impairments in both counter-regulatory function and hypoglycemic awareness are thought to result from habituation to recurrent hypoglycemia. The clinical syndrome of severely impaired hypoglycemic awareness thus results from a vicious cycle of recurrent hypoglycemia and progressive counter-regulatory impairments. Patients with this syndrome are at a sixto ten-fold higher risk of severe hypoglycemia compared with those reporting normal hypoglycemic awareness [3]. Severe hypoglycemic events are feared by many patients, relatives and care providers, mainly because of the associated loss of selfcontrol and its potential to cause direct or indirect harm. Extremely low blood glucose levels lasting for several hours may permanently damage the brain and occasionally be fatal. Although such events are extremely rare, a large survey of cause-specific mortality in the UK nevertheless attributed 4% of