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  • 1.
    Hallberg, Pär
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Nagy, Julia
    Karawajczyk, Malgorzata
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Nordang, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Islander, Gunilla
    Norling, Pia
    Johansson, Hans-Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kämpe, Mary
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lung- allergi- och sömnforskning.
    Hugosson, Svante
    Yue, Qun-Ying
    Wadelius, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Comparison of Clinical Factors Between Patients With Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema and Cough2017Inngår i: The Annals of Pharmacotherapy, ISSN 1060-0280, E-ISSN 1542-6270, Vol. 51, nr 4, s. 293-300Artikkel i tidsskrift (Fagfellevurdert)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Persson, Matilda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Axelsson, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Cavalli, Marco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Norling, Pia
    Sickla Hlth Ctr, Nacka, Sweden..
    Johansson, Hans-Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Eriksson, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Wadelius, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Genetic variants associated with angiotensin-converting enzyme inhibitor-induced cough: a genome-wide association study in a Swedish population2017Inngår i: Pharmacogenomics (London), ISSN 1462-2416, E-ISSN 1744-8042, Vol. 18, nr 3, s. 201-213Artikkel i tidsskrift (Fagfellevurdert)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism. Falun Cent Hosp, Dept Surg, Bariatr Clin, Falun, Sweden.
    Nilsen, Inger
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap. Mora Hosp, Dept Surg, Mora, Sweden.
    Johansson, Hans-Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. 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 diabetes2018Inngår i: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 14, nr 5, s. 576-582Artikkel i tidsskrift (Fagfellevurdert)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    The Impact of Bariatric Surgery on Obesity related Metabolic Traits with Specific Emphasis on Glucose, Insulin and Proinsulin2010Doktoravhandling, med artikler (Annet vitenskapelig)
    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.

    Delarbeid
    1. Gastric bypass alters the dynamics and metabolic effects of insulin and proinsulin secretion
    Åpne denne publikasjonen i ny fane eller vindu >>Gastric bypass alters the dynamics and metabolic effects of insulin and proinsulin secretion
    Vise andre…
    2007 (engelsk)Inngår i: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 24, nr 11, s. 1213-1220Artikkel i tidsskrift (Fagfellevurdert) 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.

    Emneord
    Gastric by-pass, Insulin, Obesity, Proinsulin
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-11731 (URN)10.1111/j.1464-5491.2007.02240.x (DOI)000250297500006 ()17894830 (PubMedID)
    Tilgjengelig fra: 2007-10-15 Laget: 2007-10-15 Sist oppdatert: 2017-12-11bibliografisk kontrollert
    2. Bileopancreatic Diversion with Duodenal Switch lowers both Early and Late Phases of Glucose, Insulin and Proinsulin responses after Meal
    Åpne denne publikasjonen i ny fane eller vindu >>Bileopancreatic Diversion with Duodenal Switch lowers both Early and Late Phases of Glucose, Insulin and Proinsulin responses after Meal
    Vise andre…
    2010 (engelsk)Inngår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 20, nr 5, s. 549-558Artikkel i tidsskrift (Fagfellevurdert) 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.

    Emneord
    Proinsulin; Insulin; Obesity; Bileopancreatic diversion with duodenal switch
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-111314 (URN)10.1007/s11695-010-0102-6 (DOI)000276470700003 ()20198453 (PubMedID)
    Tilgjengelig fra: 2009-12-09 Laget: 2009-12-09 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    3. Alterations in proinsulin and insulin dynamics, HDL Cholesterol and ALT after gastric bypass surgery: A 42-months follow-up study
    Åpne denne publikasjonen i ny fane eller vindu >>Alterations in proinsulin and insulin dynamics, HDL Cholesterol and ALT after gastric bypass surgery: A 42-months follow-up study
    Vise andre…
    2009 (engelsk)Inngår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 19, nr 5, s. 601-7Artikkel i tidsskrift (Fagfellevurdert) 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.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-110754 (URN)10.1007/s11695-009-9806-x (DOI)000266585500013 ()19229660 (PubMedID)
    Tilgjengelig fra: 2009-11-24 Laget: 2009-11-24 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    4. Serum Magnesium Status After Gastric Bypass Surgery in Obesity
    Åpne denne publikasjonen i ny fane eller vindu >>Serum Magnesium Status After Gastric Bypass Surgery in Obesity
    Vise andre…
    2009 (engelsk)Inngår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 19, nr 9, s. 1250-1255Artikkel i tidsskrift (Fagfellevurdert) 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.

    Emneord
    Morbid obesity, Gastric bypass surgery, Magnesium
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-17697 (URN)10.1007/s11695-008-9536-5 (DOI)000269153200009 ()18542850 (PubMedID)
    Tilgjengelig fra: 2008-08-15 Laget: 2008-08-15 Sist oppdatert: 2017-12-08bibliografisk kontrollert
  • 5.
    Johansson, Hans-Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Edholm, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Rosqvist, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Rudling, Mats
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Straniero, Sara
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Karlsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Energy restriction in obese women suggest linear reduction of hepatic fat content and time-dependent metabolic improvements2019Inngår i: Nutrition & Diabetes, ISSN 2044-4052, E-ISSN 2044-4052, Vol. 9, nr 1, artikkel-id 34Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Energy restriction reduces liver fat, improves hepatic insulin resistance and lipid metabolism. However, temporal data in which these metabolic improvements occur and their interplay is incomplete. By performing repeated MRI scans and blood analysis at day 0, 3, 7, 14 and 28 the temporal changes in liver fat and related metabolic factors were assessed at five times during a low-calorie diet (LCD, 800-1100 kcal/day) in ten obese non-diabetic women (BMI 41.7 ± 2.6 kg/m2) whereof 6 had NAFLD. Mean weight loss was 7.4 ± 1.2 kg (0.7 kg/day) and liver fat decreased by 51 ± 16%, resulting in only three subjects having NAFLD at day 28. Marked alteration of insulin, NEFA, ALT and 3-hydroxybuturate was evident 3 days after commencing LCD, whereas liver fat showed a moderate but a linear reduction across the 28 days. Other circulating-liver fat markers (e.g. triglycerides, adiponectin, stearoyl-CoA desaturase-1 index, fibroblast growth factor 21) demonstrated modest and variable changes. Marked elevations of NEFA, 3-hydroxybuturate and ALT concentrations occurred until day 14, likely reflecting increased tissue lipolysis, fat oxidation and upregulated hepatic fatty acid oxidation. In summary, these results suggest linear reduction in liver fat, time-specific changes in metabolic markers and insulin resistance in response to energy restriction.

  • 6.
    Johansson, Hans-Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Haenni, Arvo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Changes in Erythrocyte Sedimentation Rate, White Blood Cell Count, Liver Enzymes, and Magnesium after Gastric Bypass Surgery2011Inngår i: Journal of Obesity, ISSN 2090-0708, E-ISSN 2090-0716, Vol. 2011, s. 273105-Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 7.
    Johansson, Hans-Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Haenni, Arvo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Platelet counts and liver enzymes after bariatric surgery2013Inngår i: Journal of Obesity, ISSN 2090-0708, E-ISSN 2090-0716, Vol. 2013, s. 567984-Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 8.
    Johansson, Hans-Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hänni, Arvo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Karlsson, F. Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Edén-Engström, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Öhrvall, Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Bileopancreatic Diversion with Duodenal Switch lowers both Early and Late Phases of Glucose, Insulin and Proinsulin responses after Meal2010Inngår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 20, nr 5, s. 549-558Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 9.
    Johansson, Hans-Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Falu Lasarett, Dept Surg, Uppsala, Sweden.
    Platelet Counts and Liver Enzymes After Gastric Bypass Surgery2018Inngår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 28, nr 6, s. 1526-1531Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 10.
    Johansson, Hans-Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Öhrvall, Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Haenni, Arvo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Serum Magnesium Status After Gastric Bypass Surgery in Obesity2009Inngår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 19, nr 9, s. 1250-1255Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 11.
    Wahlen, Anna
    et al.
    Ostervala Primary Hlth Care Ctr, Ostervala, Sweden..
    Haenni, Arvo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Outpatient Clin Obes Care, Skonvikt, Sater, Sweden..
    Johansson, Hans-Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. 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?2017Inngår i: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, ISSN 1178-7007, E-ISSN 1178-7007, Vol. 10, s. 151-154Artikkel i tidsskrift (Fagfellevurdert)
    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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