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On the Impact of Bariatric Surgery on Glucose Homeostasis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Endokrin och Diabetes, prof Jan Eriksson)
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
Keyword [en]
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: urn:nbn:se:uu:diva-276381ISBN: 978-91-554-9480-3OAI: diva2:902735
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
List of papers
1. Gastric Bypass Surgery Elevates NT-ProBNP Levels
Open this publication in new window or tab >>Gastric Bypass Surgery Elevates NT-ProBNP Levels
2013 (English)In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 23, no 9, 1421-1426 p.Article in journal (Refereed) Published
Abstract [en]


Brain natriuretic peptide (BNP) is produced in the heart in response to stretching of the myocardium. BNP levels are negatively correlated to obesity, and in obese subjects, a reduced BNP responsiveness has been described. Diet-induced weight loss has been found to lower or to have no effect on BNP levels, whereas gastric banding and gastric bypass have reported divergent results. We studied obese patients undergoing gastric bypass (GBP) surgery during follow-up of 1 year.


Twenty patients, 18 women, mean 41 (SD 9.5) years old, with a mean preoperative BMI of 44.6 (SD 5.5) kg/m2 were examined. N-terminal pro-brain natriuretic peptide (NT-ProBNP), glucose and insulin were measured preoperatively, at day 6 and months 1, 6 and 12. In 14 of the patients, samples were also taken at days 1, 2 and 4.


The NT-ProBNP levels showed a marked increase during the postoperative week (from 54 pg/mL preop to 359 pg/mL on day 2 and fell to 155 on day 6). At 1 year, NT-ProBNP was 122 pg/mL (125 % increase, p = 0.01). Glucose, insulin and HOMA indices decreased shortly after surgery without correlation to NT-ProBNP change. Mean BMI was reduced from 44.6 to 30.5 kg/m2 at 1 year and was not related to NT-ProBNP change.


The data indicate that GBP surgery rapidly alters the tone of BNP release, by a mechanism not related to weight loss or to changes in glucometabolic parameters. The GBP-induced conversion of obese subjects, from low to high NT-ProBNP responders, is likely to influence the evaluation of cardiac function in GBP operated individuals.

National Category
Medical and Health Sciences
urn:nbn:se:uu:diva-199870 (URN)10.1007/s11695-013-0889-z (DOI)000322494800011 ()23456799 (PubMedID)
Available from: 2013-05-17 Created: 2013-05-17 Last updated: 2016-03-11Bibliographically approved
2. GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery: a potential new indication?
Open this publication in new window or tab >>GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery: a potential new indication?
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.

National Category
Medical and Health Sciences
urn:nbn:se:uu:diva-213465 (URN)10.1530/EJE-13-0504 (DOI)000327539100021 ()
Available from: 2014-01-02 Created: 2013-12-23 Last updated: 2016-03-11Bibliographically approved
3. Hypoglycemia in everyday life after gastric bypass and duodenal switch
Open this publication in new window or tab >>Hypoglycemia in everyday life after gastric bypass and duodenal switch
2015 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 173, no 1, 91-100 p.Article in journal (Refereed) Published
Abstract [en]

Design: Gastric bypass (GBP) and duodenal switch (DS) in morbid obesity are accompanied by marked metabolic improvements, particularly in glucose control. In recent years, episodes of severe late postprandial hypoglycemia have been increasingly described in GBP patients; data in DS patients are scarce. We recruited three groups of subjects; 15 GBP, 15 DS, and 15 non-operated overweight controls to examine to what extent hypoglycemia occurs in daily life. Methods: Continuous glucose monitoring (CGM) was used during 3 days of normal activity. The glycemic variability was measured by mean amplitude of glycemic excursion and continuous overall net glycemic action. Fasting blood samples were drawn, and the patients kept a food and symptom log throughout the study. Results: The GBP group displayed highly variable CGM curves, and 2.9% of their time was spent in hypoglycemia (< 3.3 mmol/l, or 60 mg/dl). The DS group had twice as much time in hypoglycemia (5.9%) and displayed CGM curves with little variation as well as lower HbA1c levels (29.3 vs 35.9 mmol/mol, P < 0.05). Out of a total of 72 hypoglycemic episodes registered over the 3-day period, 70 (97%) occurred in the postprandial state and only about one-fifth of the hypoglycemic episodes in the GBP and DS groups were accompanied by symptoms. No hypoglycemias were seen in controls during the 3-day period. Conclusion: Both types of bariatric surgery induce marked, but different, changes in glucose balance accompanied by frequent, but mainly unnoticed, hypoglycemic episodes. The impact and mechanism of hypoglycemic unawareness after weight-reduction surgery deserves to be clarified.

National Category
Endocrinology and Diabetes
urn:nbn:se:uu:diva-261313 (URN)10.1530/EJE-14-0821 (DOI)000358947700018 ()25899582 (PubMedID)
Available from: 2015-09-03 Created: 2015-09-01 Last updated: 2016-03-11Bibliographically approved
4. Gastric bypass reduces symptoms and hormonal responses to hypoglycemia
Open this publication in new window or tab >>Gastric bypass reduces symptoms and hormonal responses to hypoglycemia
Show others...
2016 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, no 9, 2667-2675 p.Article in journal (Refereed) Published
Abstract [en]

Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.

Gastric bypass, hypoglycemia
National Category
Endocrinology and Diabetes
urn:nbn:se:uu:diva-276380 (URN)10.2337/db16-0341 (DOI)000382099800021 ()27313315 (PubMedID)
Swedish Diabetes Association
Available from: 2016-02-12 Created: 2016-02-12 Last updated: 2016-10-05Bibliographically approved

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