Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery

in European Journal of Endocrinology
Correspondence should be addressed to J W Eriksson; Email: jan.eriksson@medsci.uu.se

*(K E Almby and N Abrahamsson contributed equally to this work)

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Objectives

The aim of the study was to explore the role of GLP-1 receptor activation on the counter-regulation and symptoms of hypoglycemia in subjects who have undergone gastric bypass surgery (GBP).

Design

Experimental hyperinsulinemic–hypoglycemic clamp study.

Methods

Twelve post-GBP subjects participated in a randomized cross-over study with two hyperinsulinemic, hypoglycemic clamps (glucose nadir 2.7 mmol/L) performed on separate days with concomitant infusions of the GLP-1 analog exenatide or with saline, respectively. Continuous measurements of metabolites and counter-regulatory hormones as well as assessments of heart rate variability and symptoms of hypoglycemia were performed throughout the clamps.

Results

No effect of GLP-1 receptor activation on counter-regulatory hormones (glucagon, catecholamines, cortisol, GH) or glucose infusion rate was seen, but we found indications of a downregulation of the sympathetic relative to the parasympathetic nerve activity, as reflected in heart rate variability. No significant differences in symptom of hypoglycemia were observed.

Conclusions/interpretation

Short-term exposure to a GLP-1 receptor agonist does not seem to impact the counter-regulatory hormonal and metabolic responses in post-GBP subjects during hypoglycemic conditions, suggesting that the improvement in symptomatic hypoglycemia post-GBP seen following treatment with GLP-1 receptor agonists may be mediated by mechanism not directly involved in counter-regulation.

Downloadable materials

  • Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery
  • Supplementary Figure 1
  • Supplementary Table 1. Edinburgh Hypoglycemia Symptom Scale subdivisions and symptoms assessed. Subjects are asked to rate the follow symptoms on scales ranging from 1 (no symptoms) to 7 (maximal symptoms).
  • Supplementary Table 2: Hormone and metabolite concentrations

 

     European Society of Endocrinology

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Figures

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    Schematic overview of the hyperinsulinemic-hypoglycemic clamp.

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    Heart rate (A), systolic (B) and diastolic (C) blood pressure during hypoglycemic clamps. bpm, beats per minute. Data are mean and 95% confidence interval. *P<0.05 for exenatide vs saline.

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    Heart rate variability spectral components during hypoglycemic clamps for exenatide (solid lines) and saline (dashed lines). PLF, power of low frequency component (A); PHF, power of high frequency component (B); PLF/PHF, ratio (C). Values are ms2 (log) and the shaded areas indicate S.E.M. P values refer to differences between exenatide and saline during normoglycemia (0–60 min) and during hypoglycemia (90–165 min), respectively.

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    Levels of glucose (A), insulin (B), C-peptide (D), FFA (E) and glycerol (F) and GIR (C) during hypoglycemic clamps and concomitant infusion with exenatide and saline, respectively. GIR, glucose infusion rate. FFA, free fatty acids. Data are geometric mean and 95% confidence interval. *P < 0.05, **P < 0.01 and ***P < 0.001 for exenatide vs saline.

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    Hormone levels during hypoglycemic clamps and concomitant infusion with exenatide and saline, respectively. Glucagon (A), adrenaline (B), noradrenaline (C), cortisol (D), GH (E) and GIP (F). GH, growth hormone. GIP, glucose-dependent insulinotropic polypeptide. Data are geometric means and 95% confidence intervals. *P < 0.05, **P < 0.01 and ***P < 0.001 for exenatide vs saline.

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