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  • 1.
    Hallberg, Pär
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Nagy, Julia
    Karawajczyk, Malgorzata
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nordang, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Islander, Gunilla
    Norling, Pia
    Johansson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kämpe, Mary
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Hugosson, Svante
    Yue, Qun-Ying
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Comparison of Clinical Factors Between Patients With Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema and Cough2017In: The Annals of Pharmacotherapy, ISSN 1060-0280, E-ISSN 1542-6270, Vol. 51, no 4, p. 293-300Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Angioedema is a rare and serious adverse drug reaction (ADR) to angiotensin-converting enzyme (ACE) inhibitor treatment. Dry cough is a common side effect of ACE inhibitors and has been identified as a possible risk factor for angioedema.

    OBJECTIVE: We compared characteristics between patients with ACE inhibitor-induced angioedema and cough with the aim of identifying risk factors that differ between these adverse events.

    METHODS: Data on patients with angioedema or cough induced by ACE inhibitors were collected from the Swedish database of spontaneously reported ADRs or from collaborating clinicians. Wilcoxon rank sum test, Fisher's exact test, and odds ratios (ORs) with 95% CIs were used to test for between-group differences. The significance threshold was set to P <0.00128 to correct for multiple comparisons.

    RESULTS: Clinical characteristics were compared between 168 patients with angioedema and 121 with cough only. Smoking and concomitant selective calcium channel blocker treatment were more frequent among patients with angioedema than cough: OR = 4.3, 95% CI = 2.1-8.9, P = 2.2 × 10(-5), and OR = 3.7, 95% CI = 2.0-7.0, P = 1.7 × 10(-5). Angioedema cases were seen more often in male patients (OR = 2.2, 95% CI = 1.4-3.6, P = 1.3 × 10(-4)) and had longer time to onset and higher doses than those with cough ( P = 3.2 × 10(-10) and P = 2.6 × 10(-4)). A multiple model containing the variables smoking, concurrent calcium channel blocker treatment, male sex, and time to onset accounted for 26% of the variance between the groups.

    CONCLUSION: Smoking, comedication with selective calcium channel blockers, male sex, and longer treatment time were associated with ACE inhibitor-induced angioedema rather than cough.

  • 2.
    Hallberg, Pär
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Persson, Matilda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Cavalli, Marco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Norling, Pia
    Sickla Hlth Ctr, Nacka, Sweden..
    Johansson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Yue, Qun-Ying
    Med Prod Agcy, Uppsala, Sweden..
    Magnusson, Patrik K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Swedish Twin Registry, Stockholm, Sweden..
    Wadelius, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Genetic variants associated with angiotensin-converting enzyme inhibitor-induced cough: a genome-wide association study in a Swedish population2017In: Pharmacogenomics (London), ISSN 1462-2416, E-ISSN 1744-8042, Vol. 18, no 3, p. 201-213Article in journal (Refereed)
    Abstract [en]

    Aim: We conducted a genome-wide association study on angiotensin-converting enzyme inhibitor-induced cough and used our dataset to replicate candidate genes iden-tified in previous studies. Patients & methods: A total of 124 patients and 1345 treated controls were genotyped using Illumina arrays. The genome-wide significance level was set to p < 5 x 10(-8). Results: We identified nearly genome-wide significant associations in CLASP1, PDE11A, KCNMB2, TGFA, SLC38A6 and MMP16. The strongest association was with rs62151109 in CLASP1 (odds ratio: 3.97; p = 9.44 x 10(-8)). All top hits except two were located in intronic or noncoding DNA regions. None of the candidate genes were significantly associated in our study. Conclusion: Angiotensin-converting enzyme inhibitor-induced cough is potentially associated with genes that are independent of bradykinin pathways.

  • 3.
    Hänni, Arvo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Falun Cent Hosp, Dept Surg, Bariatr Clin, Falun, Sweden.
    Nilsen, Inger
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics. Mora Hosp, Dept Surg, Mora, Sweden.
    Johansson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Falun Cent Hosp, Dept Surg, Bariatr Clin, Falun, Sweden.
    Increased circulating magnesium concentrations after Roux-en-Y gastric bypass surgery in patients with type 2 diabetes2018In: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 14, no 5, p. 576-582Article in journal (Refereed)
    Abstract [en]

    Background: Low circulating magnesium concentrations predict cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D). Epidemiologic and clinical studies have indicated lower extra- and intracellular magnesium concentrations in patients with diabetes.

    Objective: We aimed to describe alterations, if any, in circulating magnesium concentrations after laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) in patients with obesity and T2D.

    Setting: Outpatient clinic of obesity and central hospital.

    Methods: Retrospective analysis of 1-year outcome of plasma magnesium (p-Mg) and glucometabolic status in all consecutive patients who underwent primary LRYGBP and who completed the follow-up visits, including biochemical test panels 6 and 12 months after surgery.

    Results: LRYGBP and complete follow-up visits were performed in 51 patients with T2D and 86 patients without T2D. All patients were given similar dietary advice and multivitamin and mineral supplementation after surgery. Before RYGB, the patients with T2D showed lower p-Mg compared with patients without T2D (.79 ± .06 mM and .82 ± .05 mM, respectively, P<.01). P-Mg was inversely correlated to fasting blood glucose and glycosylated hemoglobin levels. After surgery, mean p-Mg increased by 5.2% in the group with T2D compared with 1.4% in the patients without T2D (P<.01), ending at an equal level of .83 mM. The alterations in p-Mg were inversely related to the changes in fasting glucose and glycosylated hemoglobin concentrations.

    Conclusion: The lowered p-Mg associated with impaired glucometabolic status in patients with T2D was increased after LRYGBP, reaching similar concentrations as in patients without T2D.

  • 4.
    Johansson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    The Impact of Bariatric Surgery on Obesity related Metabolic Traits with Specific Emphasis on Glucose, Insulin and Proinsulin2010Doctoral 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.

    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
    Show others...
    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
    Show others...
    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
    Show others...
    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
  • 5.
    Johansson, Hans-Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Haenni, Arvo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Changes in Erythrocyte Sedimentation Rate, White Blood Cell Count, Liver Enzymes, and Magnesium after Gastric Bypass Surgery2011In: Journal of Obesity, ISSN 2090-0708, E-ISSN 2090-0716, Vol. 2011, p. 273105-Article in journal (Refereed)
    Abstract [en]

    Roux-en-Y gastric bypass (RYGBP) is an established method for treatment of obesity, a condition of chronic inflammation with liver steatosis, characterised by increased erythrocyte sedimentation rate (ESR), white blood cell count (WBC), liver enzymes, and decreased magnesium (Mg).We investigated alterations, if any, in ESR, WBC, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and Mg after RYGBP. Methods. 21 morbidly obese nondiabetic patients who underwent RYGBP surgery were evaluated preoperatively (baseline), then 1 year (1st followup) and 3.5 years (2nd followup) after RYGBP and compared to an untreated control group. Results. Body mass index, ESR, WBC, ALT, and GGT were all significantly reduced at 1 year in the RYGBP group (30%, 35%, 20%, 45%, and 57%, resp.) while Mg increased by 6%, compared to control group (P = 0.001 − 0.009). Conclusions. Obese patients treated by RYGBP show sustained reductions in ESR, WBC, ALT, and GGTpossibly due to reduced liver steatosis and increased Mg.

  • 6.
    Johansson, Hans-Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Haenni, Arvo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Platelet counts and liver enzymes after bariatric surgery2013In: Journal of Obesity, ISSN 2090-0708, E-ISSN 2090-0716, Vol. 2013, p. 567984-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Obesity is characterized by liver steatosis, chronic inflammation, and increased liver enzymes, that is, gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT), markers for nonalcoholic fatty liver disease (NAFLD) and liver fat content. Increased platelet counts (PCs) are associated with inflammatory conditions and are a valuable biomarker of the degree of fibrosis in NAFLD. We investigated alterations in PC, GGT, and ALT after biliopancreatic diversion with duodenal switch (BPD-DS) and Roux-en-Y gastric bypass (RYGBP).

    METHODS: Ten morbidly obese patients (body mass index, BMI: 53.5 ± 3.8 kg/m(2)) who underwent BPD-DS were evaluated preoperatively (baseline) and 1 year (1st followup) and 3 years (2nd followup) after surgery and compared with 21 morbidly obese patients (BMI: 42.3 ± 5.2 kg/m(2)) who underwent RYGBP.

    RESULTS: Over the 3 years of followup, changes in BPD-DS and RYGBP patients (BPD-DS/RYGBP) were as follows: BMI (-44%/-24%), GGT (-63%/-52%), and ALT (-48%/-62%). PC decreased (-21%) statistically significantly only in BPD-DS patients.

    CONCLUSIONS: Morbidly obese patients treated by RYGBP or BPD-DS show sustained reductions in BMI, ALT, and GGT. The decrease in PC and liver enzymes after BPD-DS may reflect a more pronounced decrease of liver-fat-content-related inflammation and, as a result, a lowered secondary thrombocytosis.

  • 7.
    Johansson, Hans-Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Hänni, Arvo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Karlsson, F. Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Edén-Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öhrvall, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Bileopancreatic Diversion with Duodenal Switch lowers both Early and Late Phases of Glucose, Insulin and Proinsulin responses after Meal2010In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 20, no 5, p. 549-558Article in journal (Refereed)
    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.

  • 8.
    Johansson, Hans-Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Östervala Primary Hlth Care Ctr, Abygrand 2, S-74046 Östervala, Sweden; Falu Lasarett, Dept Surg, Uppsala, Sweden.
    Wahlen, Anna
    Östervala Primary Hlth Care Ctr, Abygrand 2, S-74046 Östervala, Sweden.
    Aldenback, Erica
    Uppsala Univ, Fac Med, Uppsala, Sweden.
    Hänni, Arvo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Falu Lasarett, Dept Surg, Uppsala, Sweden.
    Platelet Counts and Liver Enzymes After Gastric Bypass Surgery2018In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 28, no 6, p. 1526-1531Article in journal (Refereed)
    Abstract [en]

    Obesity is associated with chronic inflammation, liver steatosis and increased liver enzymes such as gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT), markers for non-alcoholic fatty liver disease (NAFLD) and liver fat content. Increased platelet counts (PCs) are a biomarker reflecting inflammation and the degree of fibrosis in NAFLD. We investigated alterations in PCs, GGT, ALT, C-reactive protein (CRP) and ferritin after Roux-en-Y gastric bypass (RYGBP). One hundred twenty-four morbidly obese non-diabetic patients were evaluated before (baseline) and 12 months after (follow-up) RYGBP. Body mass index (BMI) was reduced from 43.5 kg/m(2) (baseline) to 31.1 kg/m(2) (follow-up), and p < 0.001 and weight declined from 126.2 to 89.0 kg. PCs decreased from 303 x 10(9) to 260 x 10(9)/l, p < 0.001. GGT was reduced from 0.63 to 0.38 mu kat/l, p < 0.001. ALT decreased from 0.69 to 0.59 mu kat/l, p = 0.006. CRP was lowered from 7.3 to 5.4 mg/l p < 0.001 and ferritin from 106 to 84 mu g/l p < 0.001. The alterations in PCs correlated with the changes in CRP (r = 0.38, p = 0.001), BMI (r = 0.25, p = 0.012), weight (r = 0.24, p = 0.015) and inversely correlated with ferritin (r = 21, p = 0.036). PCs, GGT and ALT (markers for NAFLD), and CRP and ferritin (markers for inflammation) decreased in morbidly obese after RYGBP. The decrease in PCs correlated with alterations in CRP, BMI, weight and ferritin. The lowering of liver enzymes may reflect a lowered liver fat content and decreased general inflammation.

  • 9.
    Johansson, Hans-Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Öhrvall, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Haenni, Arvo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Serum Magnesium Status After Gastric Bypass Surgery in Obesity2009In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 19, no 9, p. 1250-1255Article in journal (Refereed)
    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.

  • 10.
    Wahlen, Anna
    et al.
    Ostervala Primary Hlth Care Ctr, Ostervala, Sweden..
    Haenni, Arvo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Outpatient Clin Obes Care, Skonvikt, Sater, Sweden..
    Johansson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Ostervala Primary Hlth Care Ctr, Ostervala, Sweden.; Outpatient Clin Obes Care, Skonvikt, Sater, Sweden..
    Do we need to measure vitamin B12 and magnesium in morbidly obese patients with type 2 diabetes mellitus?2017In: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, ISSN 1178-7007, E-ISSN 1178-7007, Vol. 10, p. 151-154Article in journal (Refereed)
    Abstract [en]

    Objective: We aimed to investigate the prevalence of B12 deficiency in metformin-treated, morbidly obese, type 2 diabetes mellitus (T2DM) patients, compared to morbidly obese controls, as well as to evaluate the magnesium status. Design: Retrospective cross-sectional analysis of plasma vitamin B12, plasma magnesium, glucometabolic status and clinical measurements in all consecutive morbidly obese patients was conducted during 1 year. Setting: Outpatient Clinic of Obesity Care. Subjects: One hundred forty-seven patients were evaluated: 107 morbidly obese controls and 40 metformin-treated, morbidly obese patients with T2DM. Main outcome measures: Circulating plasma concentrations of vitamin B12 (cobalamin), magnesium, clinical measurements and metformin medication. Results: There were differences between the two groups regarding age, sagittal diameter, glucose parameters and magnesium concentrations. Longer diabetes duration was associated with lower magnesium. Metformin-treated T2DM patients had lower magnesium (0.76 +/- 0.07 mmol/L) than controls (0.82 +/- 0.07 mmol/L). A subgroup analysis of 26 non-metformin-treated T2DM patients showed a normal magnesium concentration compared to controls, that is, 0.81 +/- 0.06 mmol/L. We found no statistical difference in B12 concentrations between the two groups. Conclusion: To fully benefit from metformin medication, routine testing of B12 as well as magnesium in metformin-treated, morbidly obese patients should be performed, with consideration of substitution to avoid low levels.

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