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The Impact of Bariatric Surgery on Obesity related Metabolic Traits with Specific Emphasis on Glucose, Insulin and Proinsulin
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hyperproinsulinemia is associated with type 2 diabetes (T2DM) and obesity and is a predictor for future coronary heart disease. This thesis examines the effect of bariatric surgery on glucometabolic status including insulin and proinsulin responses after meal. Further we explored longitudinally the effects of bariatric surgery on glucose, insulin and proinsulin secretion as well as lipids, liver enzymes and magnesium concentrations.

We explored by a standardised meal test the postprandial dynamics of proinsulin and insulin and effects on glucose and lipids in patients treated with gastric bypass (RYGBP) surgery and in patients treated with bileopancreatic diversion with duodenal switch surgery (BPD-DS). Comparisons were made to morbidly obese patients and normal weight controls (NW). RYGBP surgery markedly lowers fasting and postprandial proinsulin concentrations although BMI was higher compared to NW-controls. BPD-DS surgery induces a large weight loss and normalises postprandial responses of glucose, proinsulin and insulin and markedly lowers triglycerides.

We evaluated non-diabetic morbidly obese patients who underwent bariatric surgery followed-up for up to four years after surgery. Long-term follow-up showed that RYGBP surgery is not only characterized by markedly and sustained lowered BMI but also lowered concentrations of proinsulin, insulin, ALT and increased HDL-C possibly via reduced hepatic insulin resistance.

We also examined how magnesium status is affected by bariatric surgery as magnesium has been shown to be inversely related to glucose and to insulin resistance. The serum magnesium concentrations increased by 6% after RYGBP and 10% after BPD-DS.

In summary, RYGBP and BPD-DS surgery results in marked weight loss, alterations in insulin and proinsulin dynamics, lowered fasting and postprandial proinsulin concentrations and improved glucometabolic and magnesium status.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2010. , p. 78
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 511
Keywords [en]
Proinsulin, insulin, glucose, obesity, bariatric surgery
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-111316ISBN: 978-91-554-7695-3 (print)OAI: oai:DiVA.org:uu-111316DiVA, id: diva2:280451
Public defence
2010-02-10, Universitetshuset, sal IV, Universitetshuset Uppsala Universitet 740 10 Uppsala, Uppsala, 09:30 (Swedish)
Opponent
Supervisors
Available from: 2010-01-19 Created: 2009-12-09 Last updated: 2010-01-19Bibliographically approved
List of papers
1. Gastric bypass alters the dynamics and metabolic effects of insulin and proinsulin secretion
Open this publication in new window or tab >>Gastric bypass alters the dynamics and metabolic effects of insulin and proinsulin secretion
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2007 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 24, no 11, p. 1213-1220Article in journal (Refereed) Published
Abstract [en]

Aims Hyperproinsulinaemia is associated with obesity and is a risk factor for Type 2 diabetes. We explored the dynamics of proinsulin and insulin and postprandial effects on glucose and lipids in subjects who had undergone gastric bypass (GBP) surgery compared with morbidly obese (MO) subjects and normal weight control subjects (NW). Methods Subjects free from diabetes were recruited: 10 previously MO subjects [body mass index (BMI) ± SD, 34.8 ± 6.2 kg/m2] who had undergone GBP surgery, 10 MO subjects (BMI 44 ± 3.1 kg/m2) and 12 NW control subjects (BMI 23.2 ± 2.4 kg/m2). After an overnight fast, a standard meal (2400 kJ) was ingested and glucose, proinsulin, insulin free fatty acids and triglycerides were determined up to 180 min. Results Fasting proinsulin was similar in the GBP group and NW control subjects, but threefold increased in MO subjects (P < 0.05). Postprandial AUC for glucose was similar in the three groups and AUC for proinsulin was high in MO, intermediate in the GBP group and lowest in NW control subjects (P for trend = 0.020). Postprandial proinsulin at 60 min was similar in the GBP group and MO subjects and twofold higher than in NW control subjects. Postprandial proinsulin at 180 min was normal in the GBP group, but fivefold increased in MO subjects (P = 0.008). Insulin increased rapidly at 30 min in the GBP group and was normal at 90 min, whereas insulin was still increased at 90-180 min in the MO subjects (P < 0.001). Conclusions MO subjects, free from diabetes, have elevated proinsulin concentrations in the fasting as well as the postprandial phase. After GBP surgery markedly lower fasting and postprandial proinsulin concentrations were observed, although BMI was higher compared with NW control subjects.

Keywords
Gastric by-pass, Insulin, Obesity, Proinsulin
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-11731 (URN)10.1111/j.1464-5491.2007.02240.x (DOI)000250297500006 ()17894830 (PubMedID)
Available from: 2007-10-15 Created: 2007-10-15 Last updated: 2017-12-11Bibliographically approved
2. Bileopancreatic Diversion with Duodenal Switch lowers both Early and Late Phases of Glucose, Insulin and Proinsulin responses after Meal
Open this publication in new window or tab >>Bileopancreatic Diversion with Duodenal Switch lowers both Early and Late Phases of Glucose, Insulin and Proinsulin responses after Meal
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2010 (English)In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 20, no 5, p. 549-558Article in journal (Refereed) Published
Abstract [en]

Hyperproinsulinemia is associated with obesity and type 2 diabetes. We explored the after-meal dynamics of proinsulin and insulin and postprandial effects on glucose and lipids in patients treated with bileopancreatic diversion with duodenal switch (BPD-DS) surgery compared with normal-weight controls [body mass index (BMI)+/- SD, 23.2 +/- 2.4 kg/m(2)].

Ten previously morbidly obese (BMI +/- SD, 53.5 +/- 3.8 kg/m(2)) patients free from diabetes who had undergone BPD-DS (BMI +/- SD, 29.0 +/- 5.2 kg/m(2)) 2 years earlier were recruited. A standardised meal (2400 kJ) was ingested, and glucose, proinsulin, insulin, free fatty acids and triglycerides (TGs) were determined during 180 min. Follow-up characteristics yearly on glucose, lipids, creatinine and uric acid over 3 years after BPD-DS are presented.

Fasting glucose and insulin were lower, 0.4 mmol/L and 4.6 pmol/L, respectively, in the BPD-DS group despite higher BMI. Fasting proinsulin was similar in both groups. Postprandial area under the curve (AUC) for glucose, proinsulin and insulin did not differ between the two groups (p = 0.106-734). Postprandial changes in glucose, proinsulin and insulin were essentially similar but absolute concentrations of proinsulin and insulin were lower in the later phases in the BPD-DS group (p = 0.052-0.001). Postprandial AUC for TGs was lower in the BPD-DS group (p = 0.005). Postprandial changes in TGs were lowered in the intermediate phase (p = 0.07-0.08) and in the late phase (0.002). Follow-up data showed markedly lowered creatinine and uric acid after BPD-DS.

BPD-DS surgery induces a large weight loss and lowers, close to normal, postprandial responses of glucose, proinsulin and insulin but with marked lowering of TGs.

Keywords
Proinsulin; Insulin; Obesity; Bileopancreatic diversion with duodenal switch
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-111314 (URN)10.1007/s11695-010-0102-6 (DOI)000276470700003 ()20198453 (PubMedID)
Available from: 2009-12-09 Created: 2009-12-09 Last updated: 2017-12-12Bibliographically approved
3. Alterations in proinsulin and insulin dynamics, HDL Cholesterol and ALT after gastric bypass surgery: A 42-months follow-up study
Open this publication in new window or tab >>Alterations in proinsulin and insulin dynamics, HDL Cholesterol and ALT after gastric bypass surgery: A 42-months follow-up study
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2009 (English)In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 19, no 5, p. 601-7Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) powerfully reduces type 2 diabetes (T2DM) incidence. Proinsulin predicts development of T2DM. Adjustable gastric banding is associated with lowered proinsulin but after RYGBP information is scant. METHODS: Twenty-one non-diabetic morbidly obese patients who underwent RYGBP surgery were evaluated before (baseline), at 12 months (first follow-up), and at 42 months, range 36-50 (second follow-up), after surgery and compared to a control group, matched at baseline regarding fasting glucose, insulin, proinsulin, alanine aminotransferase (ALT), high-density lipoprotein (HDL) cholesterol, and body mass index (BMI). RESULTS: In the RYGBP group, fasting serum proinsulin concentrations were markedly lowered from 13.5 to 3.5 pmol/l at first follow-up and to 4.9 pmol/l at second follow-up (p < 0.001, respectively). Fasting insulin concentrations were reduced from 83.4 to 24.6 pmol/l at first follow-up (p < 0.001) and to 36.4 pmol/l at second follow-up (p < 0.01). ALT was lowered from 0.62 to 0.34 mukatal/l at first follow-up and continued to lower to 0.24 mukatal/l at second follow-up (p < 0.001, respectively). The further decrease between first and second follow-up was also significant (p = 0.002). HDL cholesterol increased from 1.16 to 1.45 mmol/l at the first follow-up and continued to increase at second follow-up to 1.58 mmol/l (p < 0.001, respectively). The further increase between first and second follow-up was also significant (p = 0.006). The differences between groups at first follow-up were significant for BMI, proinsulin, insulin, ALT, and HDL cholesterol (p = 0.04-0.001). CONCLUSION: RYGBP surgery in morbidly obese patients is not only characterized by markedly and sustained lowered BMI but also lowered concentrations of proinsulin, insulin, and ALT and increased HDL cholesterol.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-110754 (URN)10.1007/s11695-009-9806-x (DOI)000266585500013 ()19229660 (PubMedID)
Available from: 2009-11-24 Created: 2009-11-24 Last updated: 2017-12-12Bibliographically approved
4. Serum Magnesium Status After Gastric Bypass Surgery in Obesity
Open this publication in new window or tab >>Serum Magnesium Status After Gastric Bypass Surgery in Obesity
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2009 (English)In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 19, no 9, p. 1250-1255Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) has become a common surgical procedure to treat morbid obesity. Furthermore, it strongly reduces the incidence of type 2 diabetes and mortality. However, there is scant information on how magnesium status is affected by RYGBP surgery. Previous bariatric surgery methods, like jejunoileal bypass, are associated with hypomagnesemia. METHODS: Twenty-one non-diabetic morbidly obese patients who underwent RYGBP were evaluated before and 1 year after surgery and compared to a matched morbidly obese control group regarding serum magnesium. Groups were matched regarding weight, BMI, abdominal sagittal diameter and fasting glucose, blood pressure, and serum magnesium concentrations before surgery in the RYGBP group. RESULTS: The serum magnesium concentrations increased by 6% from 0.80 to 0.85 mmol/l (p = 0.019) in the RYGBP group while a decrease by 4% (p = 0.132) was observed in the control group. The increase in magnesium concentration at the 1-year follow-up in the RYGBP group was accompanied by a decreased abdominal sagittal diameter (r (2) = 0.32, p = 0.009), a lowered BMI (r (2) = 0.28, p = 0.0214), a lowered glucose concentration (r (2) = 0.28, p = 0.027) but not by a lowered insulin concentration (p = 0.242), a lowered systolic (p = 0.789) or a lowered diastolic (p = 0.785) blood pressure. CONCLUSION: RYGBP surgery in morbidly obese subjects is characterized by reduced visceral adiposity, lowered plasma glucose, and increased circulating magnesium concentrations. The inverse association between lowered central obesity, lowered plasma glucose and increased magnesium concentrations, needs further detailed studies to identify underlying mechanisms.

Keywords
Morbid obesity, Gastric bypass surgery, Magnesium
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-17697 (URN)10.1007/s11695-008-9536-5 (DOI)000269153200009 ()18542850 (PubMedID)
Available from: 2008-08-15 Created: 2008-08-15 Last updated: 2017-12-08Bibliographically approved

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