Biomedical subjects

Bastiaan E de Galan

Publications and source records attributed to Bastiaan E de Galan.

8 recordsLinked to original sources

PubMed2026

Factors Associated With Progression From Level 1 to Level 2 Sensor-Detected Hypoglycaemia in People With Type 1 and Insulin-Treated Type 2 Diabetes: A Post Hoc Analysis From the Hypo-METRICS Study.

AIMS: We investigated the proportion of sensor-detected hypoglycaemic (SDH) events progressing to level 2, and associated variables. MATERIALS AND METHODS: We used data from Hypo-METRICS, which recruited people with type 1 (pwT1D) and insulin-treated type 2 diabetes (pwT2D) with ≥ 1 hypoglycaemic event in preceding 3 months, wearing blinded continuous glucose monitoring devices (CGM), additional to usual monitoring modality, and FitBits for 10 weeks. We defined: L1: SDH < 3.9 mmol/L for ≥ 15 min but ≥ 3.0 mmol/L; L2: SDH < 3.9 mmol/L with ≥ 15 min of sensor glucose < 3.0 mmol/L; L2 ratio = L2/(L1 + L2), restricted to participants with both event types during the study period. Associations of selected variables on L2 ratio was assessed using beta regression and purposeful variable selection. RESULTS: We analysed 23 768 SDH events from 212 pwT1D and 213 pwT2D. PwT1D were predominantly female (53% vs. 42% in T2D, p = 0.023) and younger (median age 49 vs. 62 years, p < 0.001), with a higher L2 ratio (16% vs. 14%, p = 0.03). Coefficient of variation (CV), OR = 1.07, 95% CI = 1.06-1.09 (p < 0.001), and mean sensor glucose, OR = 1.13, 95% CI = 1.08-1.18 (p < 0.001) were the principal predictors in T1D and T2D respectively; mean L1-SDH duration, weekly L1-SDH frequency, personal CGM usage, impaired awareness were not. Progression was higher during sleep than wakefulness (21% vs. 11%, p < 0.001); L2 ratios during sleep did not differ by awareness status. CONCLUSIONS: Approximately one sixth of SDH events progressed to L2, with a higher proportion in T1D than T2D. The principal determinants were CV in T1D and mean glucose in T2D. Awareness status was not associated with progression risk during sleep.

Humans↗

PubMed2026

Hypoglycaemia Was Not Associated With Depression, Anxiety, Diabetes Distress or Fear of Hypoglycaemia Scores in People With Type 1 or Insulin-Treated Type 2 Diabetes in the Hypo-METRICS Study.

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Letter↗

PubMed2026

Gold and Clarke Questionnaires Identify Different People With Insulin-Treated Diabetes and Impaired Awareness of Hypoglycaemia in Almost 60% of Cases: A Post Hoc Analysis From the Hypo-METRICS Study.

AIMS: Gold and Clarke questionnaires are used to identify impaired awareness of hypoglycaemia (IAH) and severe hypoglycaemic event (SHE) risk in people with diabetes (pwD). We explored their overlap, including Clarke's Hypoglycaemia Awareness Status (Clarke-HAS) subfactor, and subsection differences in SHE incidence (Gold, Clarke, overlap). MATERIALS AND METHODS: This post hoc analysis of the Hypo-METRICS study recruited pwD on insulin (type 1: T1D; type 2: T2D) with ≥ 1 hypoglycaemic event in the previous 3 months. IAH was defined as Gold ≥ 4, Clarke ≥ 4, Clarke-HAS ≥ 2. RESULTS: Gold and Clarke were completed by 232 pwT1D and 285 pwT2D (age: 47 vs. 62 years, p < 0.001; HbA1c: 56 mmol/mol (7.3%) vs. 57 mmol/mol (7.4%), p = 0.03). IAH prevalence in T1D vs. T2D was 21% vs. 26% (p = 0.1), 14% vs. 18% (p = 0.2), and 41% vs. 48% (p = 0.2) according to Gold, Clarke and Clarke-HAS. The overlap between Gold ≥ 4, Clarke ≥ 4 was 40% (T1D: 45%; T2D: 37%); between Gold ≥ 4, Clarke-HAS ≥ 2 it was 45% (T1D: 43%; T2D: 47%). The overlap between Gold ≥ 4, Clarke ≥ 4 was 41% vs. 39% in CGM vs. non-CGM users (T1D: 50% vs. 35%; T2D: 32% vs. 40%); between Gold ≥ 4, Clarke-HAS ≥ 2 it was 39% vs. 53% (T1D: 38% vs. 54%; T2D: 40% vs. 53%). In the IAH sample, SHE rate was lower in people found with IAH by Gold vs. Clarke, 9% vs. 53%, and in those assessed by Gold-Clarke overlap vs. Clarke, 20% vs. 53% (all p < 0.001). CONCLUSIONS: Gold and Clarke show moderate consistency (37%-54%) in identifying IAH in insulin-treated diabetes, with/without CGM use, each associated with different SHE rates, indicating the two questionnaires measure different, independent aspects of IAH.

Humans↗

PubMed2006

Effect of sex on the cardiovascular response to adrenaline in humans.

Cardiovascular responsiveness to stress conditions differs between men and women. It is not known to what extent this observation is explained by differences in the release of stress hormones like adrenaline, or by differences in the response to adrenaline. Therefore, we quantified the hemodynamic response to infusion of adrenaline (0.04, 0.06, and 0.08 microg x kg(-1) x min(-1) for 20 minutes each) in 8 healthy men and 8 healthy premenopausal women. Arterial plasma adrenaline levels were measured before and after infusion. Heart rate and intra-arterial blood pressure were monitored throughout the experiment. Arterial plasma adrenaline levels increased similarly in both sexes. There was a larger increase in systolic blood pressure in women compared with men (17.6 +/- 2.8 versus 5.1 +/- 3.1 mm Hg, P < 0.01). In contrast, men showed a larger increase in heart rate compared with women (20.3 +/- 1.4 versus 11.2 +/- 2.8 bpm, P < 0.01). In conclusion, these data suggest that the cardiovascular response to adrenaline is predominantly alpha-adrenergic in premenopausal women, and predominantly beta-adrenergic in age-matched men.

Adult↗

PubMed2003

Effect of 2 weeks of theophylline on glucose counterregulation in patients with type 1 diabetes and unawareness of hypoglycemia.

BACKGROUND AND OBJECTIVE: A single dose of theophylline improves hypoglycemia unawareness in type 1 diabetic patients. Prolonged theophylline use is, however, associated with emergence of tolerance. This study investigated whether prolonged use of theophylline retains efficacy for counterregulatory defects in patients with type 1 diabetes and hypoglycemia unawareness. METHODS: Experiments were performed with 12 subjects with type 1 diabetes and hypoglycemia unawareness. All subjects participated in a crossover study of 2 randomly scheduled 15-day study periods during which 250 mg theophylline twice daily or matching placebo was used. On the final day of each period, hyperinsulinemic (360 pmol x m(-2) x min(-1)) hypoglycemic (5.0, 3.5, 2.5 mmol x L(-1)) glucose clamps were used to assess counterregulatory and cardiovascular responses. RESULTS: Under normoglycemic conditions, there were no differences between theophylline and placebo. Under hypoglycemic conditions, theophylline enhanced responses of growth hormone, symptoms, heart rate, and pulse pressure (all P <.05), induced sweating at higher plasma glucose levels (P =.039), and reduced exogenous glucose requirements (P =.018). Hypoglycemia-induced responses of epinephrine, norepinephrine, and cortisol were not enhanced by theophylline. CONCLUSIONS: Prolonged use of theophylline has a sustained effect on cardiovascular, metabolic, and symptom responses to hypoglycemia in patients with type 1 diabetes and hypoglycemia unawareness. Whether these results translate into clinical benefit remains to be determined.

Adult↗

PubMed2003

Antecedent adrenaline attenuates the responsiveness to but not the release of counterregulatory hormones during subsequent hypoglycemia.

Hypoglycemia unawareness is thought to be the consequence of recurrent hypoglycemia, yet the underlying mechanism is still incompletely understood. The aim of the present study was to determine the role of antecedent elevated adrenaline in the pathogenesis of hypoglycemia unawareness. Sixteen healthy volunteers (eight of either sex) participated in two experiments, performed in random order and at least 3 wk apart. During the morning, three consecutive doses of 0.04, 0.06, and 0.08 microg.kg(-1).min(-1) of adrenaline or matching placebo (normal saline) were infused for the total duration of 1 h. Three hours later, a hyperinsulinemic (360 pmol.m(-2).min(-1)) two-step hypoglycemic (5.0-3.5-2.5 mmol.liter(-1)) clamp study was performed. During hypoglycemia, hypoglycemic symptoms, counterregulatory hormones, cardiovascular responses, and cognitive function were monitored. Hypoglycemia induced similar responses of autonomic and neuroglycopenic symptoms, counterregulatory hormones, and lengthening in reaction time on the choice reaction time task, irrespective of antecedent infusions. However, prior adrenaline was associated with higher exogenous glucose requirements at hypoglycemic nadir (10.1 +/- 1.3 vs. 7.3 +/- 1.3 micromol.kg(-1).min(-1), P = 0.017), an attenuated hypoglycemia-induced fall in blood pressure (mean arterial pressure, -13 +/- 2 vs. -8 +/- 2 mm Hg, P = 0.006), and preserved cognitive function as assessed by the symbol digit test during hypoglycemia, when compared with prior placebo. We conclude that elevated adrenaline attenuates the responsiveness to, but not the release of counterregulatory hormones during subsequent hypoglycemia. As such, adrenaline's role in the development of hypoglycemia unawareness is limited.

Adrenergic Agonists↗

PubMed2002

No vasodilator response to low-dose heparin in the forearm skeletal-muscle vascular bed.

OBJECTIVE: Recent reports show that heparin induces vasodilation. This heparin-induced vasodilation might interfere with the results of vascular studies using the perfused-forearm technique because the arterial catheter is often flushed with a heparin solution in those experiments. Therefore, we investigated the vascular effects of flushing an arterial catheter with a heparin solution compared with a placebo solution (NaCl 0.9%) in six healthy volunteers. METHODS: During the first half of each experiment, the arterial catheter was flushed several times with the placebo solution. In the second half, identical flushes were performed with a solution of heparin diluted in NaCl 0.9% (4U x ml(-1)). RESULTS: Forearm blood flow (venous occlusion plethysmography) response was similar with heparin and placebo after all flushes. CONCLUSION: We conclude that low-dose heparin in the solution to flush an arterial catheter has no short-term vasodilator effect in the human forearm vascular bed. Therefore, the results of studies using the perfused-forearm technique are not confounded by flushes with a low-dose heparin solution.

Adult↗

PubMed2002

Theophylline improves hypoglycemia unawareness in type 1 diabetes.

Iatrogenic hypoglycemias and the subsequent occurrence of hypoglycemia unawareness are well-known complications of intensive insulin therapy in type 1 diabetic patients that limit glycemic management. From a pharmacological point of view, the adenosine-receptor antagonist theophylline might be beneficial in the management of hypoglycemia unawareness. Theophylline stimulates the release of catecholamines and reduces cerebral blood flow, thereby facilitating stronger metabolic responses to and a prompter perception of decreasing glucose levels. To test the effect of theophylline on responses to hypoglycemia, we performed paired hyperinsulinemic-hypoglycemic clamp studies in 15 diabetic patients with hypoglycemia unawareness and 15 matched healthy control subjects. In random order, we concurrently infused either theophylline or placebo. Measurements included counterregulatory hormones, symptoms, hemodynamic parameters, and sweat detection using a dew-point electrode. Additionally, middle cerebral artery velocities (V(MCA)) using transcranial Doppler were monitored as an estimate of cerebral blood flow. When compared with placebo, theophylline significantly enhanced responses of plasma epinephrine, norepinephrine, and cortisol levels in both diabetic patients and control subjects. Because of the theophylline, sweat production started at approximately 0.3 mmol/l higher glucose levels in both groups (P < 0.01), and symptom scores in diabetic patients approached those in control subjects. Theophylline decreased V(MCA) in both groups (P < 0.001), but significantly greater in diabetic patients (P < 0.01), and prevented the hypoglycemia-induced increase of V(MCA) that occurred during the placebo studies. We conclude that theophylline improves counterregulatory responses to and perception of hypoglycemia in diabetic patients with impaired awareness of hypoglycemia.

Adult↗