Preserved Sensitivity to β2-Adrenergic Receptor Agonists in Patients with Type 1 Diabetes Mellitus and Hypoglycemia Unawareness

Galan, Bastiaan E. De; Mol, Pieter de; Wennekes, Lianne; Schouwenberg, B.J.J.W.; Smits, Paul

doi:10.1210/jc.2006-0528

Cited by 23 publications

(9 citation statements)

References 24 publications

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“…Data from healthy volunteers have partly been reported before (8) but were reanalyzed for this study. Patients with T1DM were excluded if they had a history of repeated severe hypoglycemia, a severe hypoglycemic incident in the past 6 months, or evidence of hypoglycemia unawareness on the Clarke’s questionnaire (9,10). Patients with signs of autonomic neuropathy, peripheral neuropathy, proliferative retinopathy, or micro- or macroalbuminuria by review of medical records or physical examination were also excluded from participating.…”

Section: Methodsmentioning

confidence: 99%

Steady-State Brain Glucose Concentrations During Hypoglycemia in Healthy Humans and Patients With Type 1 Diabetes

et al. 2012

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The objective of this study was to investigate the relationship between plasma and brain glucose levels during euglycemia and hypoglycemia in healthy subjects and patients with type 1 diabetes mellitus (T1DM). Hyperinsulinemic euglycemic (5 mmol/L) and hypoglycemic (3 mmol/L) [1-13C]glucose clamps were performed in eight healthy subjects and nine patients with uncomplicated T1DM (HbA1c 7.7 ± 1.4%). Brain glucose levels were measured by 13C magnetic resonance spectroscopy. Linear regression analysis was used to fit the relationship between plasma and brain glucose levels and calculate reversible Michaelis-Menten (MM) kinetic parameters. Brain glucose values during euglycemia (1.1 ± 0.4 μmol/g vs. 1.1 ± 0.3 μmol/g; P = 0.95) and hypoglycemia (0.5 ± 0.2 μmol/g vs. 0.6 ± 0.3 μmol/g; P = 0.52) were comparable between healthy subjects and T1DM patients. MM kinetic parameters of combined data were calculated to be maximum transport rate/cerebral metabolic rate of glucose (Tmax/CMRglc) = 2.25 ± 0.32 and substrate concentration at half maximal transport (Kt) = 1.53 ± 0.88 mmol/L, which is in line with previously published data obtained under hyperglycemic conditions. In conclusion, the linear MM relationship between plasma and brain glucose can be extended to low plasma glucose levels. We found no evidence that the plasma to brain glucose relationship or the kinetics describing glucose transport over the blood–brain barrier differ between healthy subjects and patients with uncomplicated, reasonably well-controlled T1DM.

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Section: Methodsmentioning

confidence: 99%

Steady-State Brain Glucose Concentrations During Hypoglycemia in Healthy Humans and Patients With Type 1 Diabetes

et al. 2012

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“…Recently, a three-way comparison trial 17 evaluated β2-adrenergic sensitivity in subjects with type 1 diabetes, those with type 1 diabetes and hypoglycemia unawareness, and nondiabetic subjects. β2-Adrenergic sensitivity was evaluated via forearm vasodilatory response to escalating doses of an intra-arterial infusion of salbutamol.…”

Section: The Contribution Of Medications To Hypoglycemia Unawarenessmentioning

confidence: 99%

The Contribution of Medications to Hypoglycemia Unawareness

White¹

2007

Diabetes Spectrum

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“…After cannulations, a 30-min equilibration period was allowed to pass before baseline variables were obtained. Subsequently, 5-min infusions of saline and incremental doses of salbutamol (Ventolin; GlaxoSmithKline, Zeist, the Netherlands) diluted in a saline vehicle (0.003, 0.01, 0.03, 0.1, 0.3, 1.0 μg/min per 100 ml of forearm tissue) were administered intra-arterially [24]. Forearm blood flow (FBF) was measured during the final 2 min of each dosing step in both arms, using ECG-triggered mercury-in-silastic strain gauge venous occlusion plethysmography as described previously [25].…”

Section: Methodsmentioning

confidence: 99%

The effect of antecedent hypoglycaemia on β2-adrenergic sensitivity in healthy participants with the Arg16Gly polymorphism of the β2-adrenergic receptor

et al. 2011

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Aims/hypothesisHomozygosity for glycine at codon 16 (GlyGly) of the β2-adrenergic receptor may alter receptor sensitivity upon chronic stimulation and has been implicated in the pathogenesis of hypoglycaemia unawareness. We compared the effect of antecedent hypoglycaemia on β2-adrenergic receptor sensitivity between GlyGly participants and those with arginine 16 homozygosity (ArgArg) for the β2-adrenergic receptor.MethodsWe enrolled 16 healthy participants, who were either GlyGly (n = 8) or ArgArg (n = 8). They participated randomly in two 2 day experiments. Day 1 consisted of two 2-h hyperinsulinaemic hypoglycaemic (2.8 mmol/l) or euglycaemic (4.8 mmol/l) glucose clamps. On day 2, we measured the forearm vasodilator response to the β2-adrenergic receptor agonist salbutamol and the dose of isoprenaline required to increase the heart rate by 25 bpm (IC25).ResultsThe vasodilator response to salbutamol tended to be greater after antecedent hypoglycaemia than after euglycaemia (p = 0.078), consistent with increased β2-adrenergic receptor sensitivity. This effect was driven by a significant increase in β2-adrenergic receptor sensitivity following hypoglycaemia compared with euglycaemia in ArgArg participants (p = 0.019), whereas no such effect was observed in the GlyGly participants. Antecedent hypoglycaemia tended to decrease the IC25 in ArgArg participants, whereas the reverse occurred in the GlyGly participants (GlyGly vs ArgArg group p = 0.047).Conclusion/interpretationAntecedent hypoglycaemia did not affect β2-adrenergic receptor sensitivity in healthy GlyGly participants, but increased it in ArgArg participants. If these results also hold for participants with type 1 diabetes, such an increase in β2-adrenergic receptor sensitivity may potentially reduce the risk of repeated hypoglycaemia and the subsequent development of hypoglycaemia unawareness in ArgArg diabetic participants.Trial registrationClinicalTrials.gov NCT00160056FundingRadboud University Nijmegen Medical Centre.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-011-2062-3) contains supplementary material, which is available to authorised users.

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Preserved Sensitivity to β2-Adrenergic Receptor Agonists in Patients with Type 1 Diabetes Mellitus and Hypoglycemia Unawareness

Abstract: Sensitivity to beta(2)-adrenergic receptor agonist stimulation is preserved in type 1 diabetic patients with hypoglycemia unawareness.

Cited by 23 publications

References 24 publications

Steady-State Brain Glucose Concentrations During Hypoglycemia in Healthy Humans and Patients With Type 1 Diabetes

Steady-State Brain Glucose Concentrations During Hypoglycemia in Healthy Humans and Patients With Type 1 Diabetes

The Contribution of Medications to Hypoglycemia Unawareness

The effect of antecedent hypoglycaemia on β2-adrenergic sensitivity in healthy participants with the Arg16Gly polymorphism of the β2-adrenergic receptor

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