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GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery: a potential new indication?
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
2013 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 169, no 6, 885-889 p.Article in journal (Refereed) Published
Abstract [en]

Objective: The number of morbidly obese subjects submitted to bariatric surgery is rising worldwide. In a fraction of patients undergoing gastric bypass (GBP), episodes with late postprandial hypoglycemia (PPHG) develop 1-3 years after surgery. The pathogenesis of this phenomenon is not fully understood; meal-induced rapid and exaggerated increases of circulating incretins and insulin appear to be at least partially responsible. Current treatments include low-carbohydrate diets, inhibition of glucose intestinal uptake, reduction of insulin secretion with calcium channel blockers, somatostatin analogs, or diazoxide, a KATP channel opener. Even partial pancreatectomy has been advocated. In type 2 diabetes, GLP1 analogs have a well-documented effect of stabilizing glucose levels without causing hypoglycemia. Design: We explored GLP1 analogs as open treatment in five consecutive GBP cases seeking medical attention because of late postprandial hypoglycemic symptoms. Results: Glucose measured in connection with the episodes in four of the cases had been 2.7, 2.5, 1.8, and 1.6 mmol/l respectively. The patients consistently described that the analogs eliminated their symptoms, which relapsed in four of the five patients when treatment was reduced/discontinued. The drug effect was further documented in one case by repeated 24-h continuous glucose measurements. Conclusion: These open, uncontrolled observations suggest that GLP1 analogs might provide a new treatment option in patients with problems of late PPHG.

Place, publisher, year, edition, pages
2013. Vol. 169, no 6, 885-889 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-213465DOI: 10.1530/EJE-13-0504ISI: 000327539100021OAI: oai:DiVA.org:uu-213465DiVA: diva2:683209
Available from: 2014-01-02 Created: 2013-12-23 Last updated: 2016-03-11Bibliographically approved
In thesis
1. On the Impact of Bariatric Surgery on Glucose Homeostasis
Open this publication in new window or tab >>On the Impact of Bariatric Surgery on Glucose Homeostasis
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Obesity has grown to epidemic proportions, and in lack of efficient life-style and medical treatments, the bariatric surgeries are performed in rising numbers. The most common surgery is the Gastric Bypass (GBP) surgery, with the Biliopancreatic diversion with duodenal switch (DS) as an option for the most extreme cases with a BMI>50 kg/m2.

In paper I 20 GBP-patients were examined during the first post-operative year regarding the natriuretic peptide, NT-ProBNP, which is secreted from the cardiac ventricles. Levels of NT-ProBNP quickly increased during the first post-surgery week, and later established itself on a higher level than pre-surgery.

In paper II we report of 5 patient-cases after GBP-surgery with severe problems with postprandial hypoglycaemia that were successfully treated with GLP-1-analogs. The effect of treatment could be observed both symptomatically and in some cases using continuous glucose measuring systems (CGMS).

In paper III three groups of subjects; 15 post-GBP patients, 15 post-DS, and 15 obese controls were examined for three days using CGMS during everyday life. The post-GBP group had high glucose variability as measured by MAGE and CONGA, whereas the post-DS group had low variability. Both post-operative groups exhibited significant time in hypoglycaemia, about 40 and 80 minutes per day <3.3mmol/l and 20 and 40 minutes < 2.8mmol/l, respectively, longer time for DS-group. Remarkably, only about 20% of these hypoglycaemic episodes were accompanied with symptoms.

In Paper IV the hypoglycaemia counter regulatory system was investigated; 12 patients were examined before and after GBP-surgery with a stepped hypoglycaemic hyperinsulinemic clamp. The results show a downregulation of symptoms, counter regulatory hormones (glucagon, cortisol, epinephrine, norepinephrine, growth hormone), incretin hormones (GLP-1 and GIP), and sympathetic nervous response.

In conclusion patients post bariatric surgery exhibit a downregulated counter regulatory response to hypoglycaemia, accompanied by frequent asymptomatic hypoglycaemic episodes in everyday life. Patients suffering from severe hypoglycaemic episodes can often be treated successfully with GLP-1-analogues.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 73 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1181
Hypoglycaemia, Gastric Bypass surgery, Biliopancreatic diversion with duodenal switch (DS), NT-ProBNP, Continuous glucose measuring system (CGMS), GLP-1-analog, glucose variability, MAGE, CONGA, counter regulation, incretin, Heart Rate Variability
National Category
Endocrinology and Diabetes
Research subject
Endocrinology and Diabetology
urn:nbn:se:uu:diva-276381 (URN)978-91-554-9480-3 (ISBN)
Public defence
2016-04-08, Gunnesalen, ing 10, Akademiska Sjukhuset i Uppsala, Uppsala, 13:15 (English)
Available from: 2016-03-11 Created: 2016-02-12 Last updated: 2016-03-17Bibliographically approved

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Abrahamsson, NiclasEngström, Britt EdénSundbom, MagnusKarlsson, Anders F.
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