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dc.contributor.advisorPaulssen, Eyvind Jakob
dc.contributor.authorIsaksen, Victoria Therese
dc.date.accessioned2023-10-30T13:33:56Z
dc.date.available2023-10-30T13:33:56Z
dc.date.issued2023-11-15
dc.description.abstract<p><i>Background:</i> Evidence suggests that the link between obesity and chronic lifestyle disease is chronic, low-grade inflammation. Leptin and adiponectin play principal roles in inducing inflammation and promoting insulin resistance, resulting in metabolic syndrome. Our study aimed to find clinically feasible biologic markers to identify metabolically dysregulated obese individuals and to study these markers’ improvement with modest weight loss. <p><i>Methods:</i> We included participants with either BMI ≥ 30 kg/m2 or moderately elevated liver enzymes for liver ultrasonography and calculated their hepatorenal index (HRI). We measured fasting and postprandial triglycerides, insulin, glucose, leptin, adiponectin, and resting energy expenditure (REE) at baseline and after weight loss in participants with obesity. We used ROC analyses to assess test properties of HRI and L:A ratio for predicting other conditions of metabolic dysregulation. We assessed improvements in the above-mentioned variables after a weight loss of ≥ 5% using repeated measures analyses. <p><i>Results:</i> HRI ≥ 1.17 could predict HOMA-IR ≥ 2.3 with 94% sensitivity and 70% specificity in obese participants. HRI ≥ 1.42 demonstrated low sensitivity and high specificity in all participants. L:A ratio ≥ 3.65 predicted delayed triglyceride clearance with PPV 0.86 and NPV 0.48 in obese participants. L:A ratio ≥ 1.88 was suitable for detecting 2/3 of insulin resistance, leptin resistance and delayed triglyceride clearance. HOMA-IR (-23.1%), REE:leptin ratio (+80.1%) and L:A ratio (-45.7%) improved in participants with weight loss ≥ 5%. Postprandial triglycerides did not improve with weight loss. <p><i>Conclusion:</i> HRI and L:A ratio are feasible markers for detecting underlying metabolic disturbances and are feasible for monitoring the improvement of metabolic health during weight loss, whereas postprandial triglyceride measurements are not.en_US
dc.description.abstract<p><i>Bakgrunn:</i> Overvekt og kjente følgetilstander er relatert gjennom kronisk, lavgradig betennelse. Leptin og adiponektin spiller sentrale roller i å fremme betennelse. Dette bidrar til insulinresistens og metabolsk syndrom. Formålet med studien var å finne enkle markører som kan skille mellom metabolsk syke og friske overvektige. Videre ønsket vi å undersøke endring med vektreduksjon. <p><i>Metoder:</i> Vi rekrutterte deltakere med BMI ≥ 30 kg/m2 og/eller lett forhøyede leverprøver, gjennomførte ultralyd av lever og kalkulerte hepatorenal indeks (HRI). Vi brukte dette til å predikere insulinresistens (forhøyet HOMA-IR). Dernest målte vi insulin, glukose, triglyserider, hvileforbrenning, leptin og adiponektin fastende og etter måltid hos deltakere med fedme ved start og etter konservativ behandling for vektreduksjon. <p><i>Resultater:</i> HRI ≥ 1,17 kunne predikere insulinresistens med 94% sensitivitet og 70% spesifisitet hos personer med fedme. HRI-grensa ≥ 1,42 hadde lav sensitivitet men høy spesifisitet for å predikere insulinresistens. L:A ratio ≥ 3,65 kunne predikere forsinket triglyseridfall etter måltid, og L:A ratio ≥ 1,88 kunne predikere forstyrrelser i to av de tre ovennevnte markørene. HOMA-IR (-23,1%), REE:leptin ratio (+80,1%) og L:A ratio (-45,7%) bedret seg med vektreduksjon ≥ 5%. Forsinket triglyseridfall etter måltid bedret seg ikke med vektreduksjon. <p><i>Konklusjon:</i> HRI og L:A ratio kan brukes for å oppdage underliggende metabolske forstyrrelser ved fedme. L:A ratio, men ikke triglyserider etter måltid, kan brukes til å følge metabolsk bedring ved vektreduksjon.en_US
dc.description.doctoraltypeph.d.en_US
dc.description.popularabstractObesity and lifestyle-related diseases such as heart attack, stroke, diabetes, cancer and autoimmune disease are related through chronic, low-grade inflammation. Leptin and adiponectin are two hormones produced in fatty tissue that play important roles in inducing inflammation, thus promoting metabolic disturbances in the body. Our study aimed to find simple biological markers to identify early metabolic disturbances in obese individuals and to study these markers’ improvement with modest weight loss. Methods: We included participants for liver ultrasound to compare the grayscale of the liver and kidney in order to calculate their hepatorenal index (HRI, grade of fatty liver disease). We measured resting energy expenditure, triglycerides, insulin, glucose, leptin and adiponectin before and after meals, and performed these tests before and after weight loss treatment for participants with obesity. Results: Detecting mild-grade fatty liver disease (HRI ≥1.17) in ultrasound could predict insulin resistance in obese participants reasonably well for a screening test. Using a stricter limit for fatty liver disease (HRI ≥1.42) we could better rule out false positive predictions of insulin resistance. Leptin to adiponectin (L:A) ratio ≥3.65 predicted delayed triglyceride clearance after a fatty meal reasonably well in obese participants. L:A ratio ≥1.88 was suitable for detecting 2/3 of insulin resistance, leptin resistance and delayed triglyceride clearance. All of the above-mentioned conditions, except triglycerides after a fatty meal, improved substantially with modest weight loss of ≥5%. Conclusion: The biological markers in our study can be useful for detecting and monitoring early metabolic disturbances in individuals with obesity, and also metabolic improvement with weight loss of as little as 5%. Furthermore, they can help us prioritize which patients to help in a healthcare system with limited resources.en_US
dc.description.sponsorshipForskerlinjen medisin for stud.med Victoria Therese Isaksen 2011 og Maria Arlen Larsen 2009en_US
dc.identifier.urihttps://hdl.handle.net/10037/31647
dc.language.isoengen_US
dc.publisherUiT The Arctic University of Norwayen_US
dc.publisherUiT Norges arktiske universiteten_US
dc.relation.haspart<p>Paper I: Isaksen, V.T., Larsen, M.A., Goll, R., Florholmen, J.R. & Paulssen, E.J. (2016). Hepatic Steatosis, detected by hepatorenal index in ultrasonography as a predictor of insulin resistance in obese subjects. <i>BMC Obesity, 3</i>, 39. Also available in Munin at <a href=https://hdl.handle.net/10037/10693>https://hdl.handle.net/10037/10693</a>. <p>Paper II: Larsen, M.A., Isaksen, V.T., Moen, O.S., Wilsgaard, L., Remijn, M., Paulssen, E.J., Florholmen, J. & Goll, R. (2018). Leptin to adiponectin ratio – a surrogate biomarker for early detection of metabolic disturbances in obesity. <i>Nutrition, Metabolism and Cardiovascular Diseases, 28</i>(11), 1114-1121. Also available at <a href=https://doi.org/10.1016/j.numecd.2018.06.020>https://doi.org/10.1016/j.numecd.2018.06.020</a>. <p>Paper III: Isaksen, V.T., Larsen, M.A., Goll, R., Paulssen, E.J. & Florholmen, J.R. (2023). Correlations between modest weight loss and leptin to adiponectin ratio, insulin and leptin resensitization in a small cohort of Norwegian individuals with obesity. <i>Endocrine and Metabolic Science, 12</i>, 100134. Also available in Munin at <a href=https://hdl.handle.net/10037/30040>https://hdl.handle.net/10037/30040</a>en_US
dc.relation.isbasedonIsaksen, V.T., Larsen, M.A., Goll, R., Paulssen, E.J. & Florholmen, J. (2019). Replication data for: Correlations between modest weight loss and leptin to adiponectin ratio, insulin and leptin resensitization in a small cohort of Norwegian individuals with obesity. DataverseNO, V1, <a href=https://doi.org/10.18710/KRYLXN> https://doi.org/10.18710/KRYLXN</a>.en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2023 The Author(s)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Gasteroenterologi: 773en_US
dc.subjectAdipokinesen_US
dc.subjectInsulin resistanceen_US
dc.subjectLeptin resistanceen_US
dc.subjectLeptin to adiponectin ratioen_US
dc.subjectMetabolic syndromeen_US
dc.subjectNon-alcoholic fatty liver diseaseen_US
dc.subjectObesityen_US
dc.subjectUltrasonographyen_US
dc.subjectWeight lossen_US
dc.titleEarly Markers of Metabolic Dysregulation in Obese Individuals - Identification at Baseline and Effect of Modest Weight Lossen_US
dc.typeDoctoral thesisen_US
dc.typeDoktorgradsavhandlingen_US


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