Regulation of intestinal metabolism in obesity and diabetes : studies using positron emission tomography

The global epidemic of obesity is a challenge to healthcare systems due to the increase in the incidence of type 2 diabetes (T2D) and its associated morbidities. Although the small intestine is the first absorptive organ to encounter the ingested and digesting nutrients, it has gained little attention in the research of T2D and obesity. In the present study, multimodality imaging by Positron emission tomography (PET) combined with magnetic resonance imaging (MRI) or computed tomography (CT) modalities were utilized to study intestinal blood flow and metabolic substrate uptake in healthy normal-weight controls and obese patients with T2D before and after surgical or medical treatments. In the PET imaging, we focused on intestinal blood flow and volume, fatty acid, glucose uptake using 15O-water, 15O-labeled carbon monoxide, palmitate analogue 14(RS)-[18F]fluoro-6-thia-heptadecanoic acid, ([18F]FTHA) and 2-[18F]fluoro- 2-deoxy-D-glucose ([18F]FDG), respectively. Morbidly obese subjects (mean BMI 41±4.5kg/m2) with T2D had similar blood flow in the intestine even after bariatric surgery when compared to healthy controls. The bariatric surgery was either Roux-en Y gastric bypass (n=13) or Sleeve gastrectomy (n=20). Postprandially, nutrient contact with the small intestine and infusion of glucose dependent insulinotrophic polypeptide (GIP) stimulated blood flow in the small intestine of all groups. These findings suggest that despite the adaptation changes after bariatric surgery of the intestine, postprandial blood flow regulation in the small intestine remains intact in T2D and obese individuals. Intestinal fatty acid (FA) uptake was higher in obese subjects compared to healthy counterparts and unexpectedly this increased after bariatric surgery. The FA extraction rate in the small intestine also increased after bariatric surgery and this phenomenon suggests that intestinal energy expenditure relies on high FFA-to-glucose ratio in obese patients, which persists even after weight loss. Glucose uptake in the small intestines of metformin treated study subjects with T2D was increased compared to baseline and reached the level observed in healthy study subjects in previous studies. Taken together, the data of the present study provide novel insight on the role of the small intestine in the multiorgan metabolic derangements associated with T2D. It is not known whether these changes are part of the adaptation mechanism, due to improved glycaemic control and insulin resistance breakdown or due to the fundamental pathophysiology behind T2D. The actual mechanism behind these changes should be addressed in future research.Suoliston aineenvaihdunnan säätely lihavuudessa ja diabeteksessa : positroniemissiotomografiaa käyttäen tehtyjä tutkimuksia Lihavuus on huomattavasti yleistynyt viime vuosikymmeninä ja kuormittaa terveydenhuoltoamme lisäten tyypin 2 diabeteksen ilmaantuvuutta ja yleistä sairastavuutta.Lihavuuden ja tyypin 2 diabeteksen tutkimuksessa on aiemmin keskitytty suoliston aineenvaihduntaan varsin vähän, vaikka suolisto ensimmäisenä elimenä käsittelee elimistöön tulevan ravinnon ja ruoansulatuskanavasta erittyvillä hormoneilla säätelee sokeriaineenvaihduntaa. Tutkimuksessa verrattiin suoliston verenvirtauksen ja ravintoaineiden soluunottokyvyn muutoksia ylipainoisilla tyypin 2 diabeetikoilla ja terveillä normaalipainoisilla verrokeilla käyttäen positroniemissiotomografiaa (PET) yhdistettynä rakenteelliseen magneetti- ja tietokonetomografia kuvantamiseen. Tutkittavat osallistuivat kliinisen hoitokäytännön mukaan lihavuusleikkaukseen tai käyttivät tutkimuslääkettä protokollan mukaan. PET-kuvantamisella tutkittiin suoliston verenvirtauksen ja verimäärän muutoksia sekä rasvahappojen ja sokerin soluunottokykyä käyttäen 15O-vettä, 15Oleimattua hiilimonoksidia, palmitaattianalogi 14(RS)-[18F]fluoro-6-thia-heptadekanoidi happoa ([18F]FTHA) ja 2-[18F]fluoro-2-deoxy-D-glukoosia ([18F]FDG). Sairaalloisen ylipainoisilla diabeetikoilla suoliston verenvirtaus ei poikennut terveistä kontrolleista edes lihavuusleikkauksen jälkeen. Ryhmien välisiä eroja veren virtauksessa ei todettu syömisen ja glukoosista riippuvaisen insuliinin eritystä lisäävän hormonin (GIP) annostelun jälkeen. Havainnot viittaavat siihen, että aterian jälkeinen verenvirtauksen säätely ei ole muuttunut lihavilla diabeetikoilla edes lihavuuskirurgian jälkeen, vaikka suolisto muuten sopeutuu kirurgian aiheuttamiin anatomisiin muutoksiin. Ylipainoisilla tyypin 2 diabetesta sairastavilla tutkittavilla suoliston rasvahappojen soluunottokyky todettiin lisääntyneeksi verrattuna terveisiin kontrollihenkilöihin ja odottamatta lihavuuskirurgia lisäsi kyseistä muutosta. Rasvahappojen soluunottokyvyn lisääntyminen verenkierrosta vielä lihavuuskirurgian jälkeen, osoittaa suoliston energiankäytön riippuvan korkeasta rasvahappo-sokerin käyttösuhteesta vielä laihtumisen jälkeenkin. Metformiini-lääkitys lisäsi suoliston sokerin käyttöä ja vähensi suoliston insuliiniresistenssiä, jopa normaalistaen sen terveiden tasolle. Tämä väitöskirjatutkimus osoittaa, että suolistossa tapahtuu merkittäviä aineenvaihdunnallisia muutoksia tyypin 2 diabeteksessa, ylipainossa ja lihavuusleikkauksen jälkeen. Avoimeksi jää säätelevätkö lihavuuskirurgian ja lääkehoitojen myötä lisääntyneet suoliston rasvahappojen ja sokerin käyttö koko elimistö aineenvaihduntaa vai ovatko ne seurausta suoliston sopeutumisesta muuttuneeseen energia-aineenvaihduntaan. Koska lihavuuskirurgia johtaa usein merkittävään painonlaskuun ja tyypin 2 diabeteksen paranemiseen tulisi suoliston energia-aineenvaihdunnan tutkimusta jatkaa kyseisten tautien syntymekanismin ymmärtämiseksi

Penkin suunnittelu Mum´sille

Opinnäytetyön tavoitteena oli suunnitella penkki toimeksiantajayritys Mum ́sille. Mum ́s valmistaa tuotteita reilun kaupan periaatteiden mukaisesti pääosin Afrikassa. Tavoitteena oli, että penkissä huomioitaisiin Mum ́sin tuotantotavat ja osa penkistä valmistettaisiin Suomessa. Suunnitelman ohella tavoitteena oli tuottaa toimeksiantajayritykselle tutkimustietoa ja ideoita sekä luonnoksia heidän tarjontaansa sopivasta tuotteesta, sekä valmistaa osien hahmomalleja tai penkin prototyyppi. Tavoitteeseen pääsemiseksi selvitettiin penkin käsitettä ja ominaisuuksia, sekä kartoitettiin markkinoilla olevia penkkejä dokumenttiaineistosta. Penkin sijoittumista nykyaikaisiin koteihin sekä asiakkaiden ostopäätökseen vaikuttavia seikkoja selvitettiin haastattelemalla kuutta sisustusalan ammattilaista. Toimeksiantajan toiveet, mahdollisuudet ja toimintamallit kartoitettiin haastattelemalla yrityksen omistajaa. Mum ́sin olemassaolevia tuotteita analysoimalla selvitettiin asiakkaan tuotevalikoiman ominaisuuksia. Dokumenttiaineistolla pyrittiin selvittämään myös skandinaavista tyyliä. Lähdeaineistoista ja haastatteluista ilmeni, että suurin osa markkinoilla olevista penkeistä on visuaalisesti massiivisia, joten sirommalle vaihtoehdolle olisi kysyntää. Penkin yleisin sijoituskohde asunnossa on eteinen. Mum ́sin tuotteita yhdestää leikkimielisyys, graafisuus ja valmistustavan sekä materiaalin korostuminen. Skandinaavinen tyyli suosii luonnonmukaisia materiaaleja, vaaleaa yleisilmettä sekä funktionaalisia, mutta pehmeälinjaisia muotoja. Näiden tietojen perusteella suunniteltiin Mum’sin tuotevalikoimaan penkki.The aim of this thesis was to design a bench for the client company Mum ́s. Mum ́s manufactures products by the principles of fair trade, mainly in Africa. In addition to the design, the aim was to produce a product appropriate to their product range through a background research, ideas and sketches and to manufacture character models from the parts of the design or prototype of the bench. To achieve the target of this thesis, research was done from the concept and features of the average bench, including mapping types of commercially available benches from documentary materials. Information about the placement of benches in modern homes, in addition to the factors affecting customers' purchasing decisions were clarified by interviewing six interior design professionals. Interviewing the owner of the company identified the client’s wishes, possibilities and approaches for the product. Mum ́s ́ existing products were studied by analyzing the client's product range. Documented material was explored to identify the Scandinavian style. The source material and interviews revealed that most of the benches on the market are visually massive, thus a slender option would be in demand. The most common place for a bench is the hallway. The factors that combine Mum's' products are playfulness, the use of patterns and emphasis of the manufacturing method and material. The Scandinavian style favours natural materials, a bright overall look and functionality, but with curved forms. Based on these findings a bench was designed to accompany Mum's' existing product range.Työstä on valmistettu 1:1 prototyypp

Masentuneen potilaan hoito videoavusteisella lyhytpsykoterapialla

VideoTalk-menetelmässä psykoterapiaa tehostetaan potilaan kotona itsestään ottamilla videoilla. Terapiatunnilla potilas tekee havaintoja itsestään videolta. Hän voi oivaltaa, miten kielteinen puhe itsestä aiheuttaa välittömästi huonovointisuuteen liittyviä kehollisia muutoksia, kuten ryhdin lysähtämisen ja kasvojen ilmeettömyyden. Masennuksesta kärsivän potilaamme toipumisessa merkittävää oli se, että video auttoi häntä tarkastelemaan itseään etäämpää, mikä aktivoi aiemmin piilossa olleita tunteita.</p

Combining biological therapies in patients with inflammatory bowel disease : a Finnish multi-centre study

Background and aims Therapy with two concomitant biologicals targeting different inflammatory pathways has emerged as a new therapy option for treatment refractory inflammatory bowel disease (IBD). Data on the efficacy and safety of dual biological therapy (DBT) are scarce and are investigated in this study. Materials and methods Data on all patients treated with a combination of two biologicals in four Finnish tertiary centres were collected and analysed. Remission was assessed by a physician on the basis of biomarkers, endoscopic evaluation and alleviation of symptoms. Results A total of 16 patients with 22 trials of DBT were included. Fifteen patients had Crohn's disease. The most common combination of DBT was adalimumab (ADA) and ustekinumab (USTE; 36%) with median follow-up of nine months (range 2-31). Altogether seven (32%) patients were in remission at the end of follow-up and in two trials response to DBT was assessed to be partial with the relief of patient symptoms. In a total of four trials DBT reduced the need for corticosteroids. The majority of patients achieving a response to DBT were treated with the combination of ADA and USTE (56%). At the end of follow-up all nine (41%) patients responding to DBT continued treatment. Infection complications occurred in three patients (19%). Conclusion DBT is a promising alternative treatment for refractory IBD, and half of our patients benefitted from it. More data on the efficacy and safety of DBT are needed especially in long-term follow up.Peer reviewe

Predictive Markers of Crohn's Disease in Small Bowel Capsule Endoscopy: A Retrospective Study of Small Bowel Capsule Endoscopy

To distinguish between functional gastrointestinal disorders like irritable bowel syndrome (IBS) and mild small bowel Crohn's disease (CD) can be a burden. The diagnosis of CD often requires small bowel capsule endoscopy (SBCE). The main goal of this research was to find predictive markers to rule out clinically significant small bowel CD without SBCE. A retrospective study of 374 patients who underwent SBCE for suspected small bowel CD in Turku University Hospital in 2012-2020 was conducted. We gathered the patient's laboratory, imaging and endoscopic findings at the time of SBCE. SBCE findings were graded along CECDAI (Capsule Endoscopy Crohn's Disease Activity Index)-scoring system. Fecal calprotectin (FC), serum albumin and ESR were significantly different with patients diagnosed with CD and those with not. Hb and CRP had no significant differences between the two groups. Sensitivity, specificity, PPV and NPV for FC < 50 ug/g were 96.4%, 19.6%, 34.6% and 92.5% and for CECDAI (cut-off value 3) 98.2%, 90.3%, 81.1% and 99.1%, respectively. A CECDAI-score of 3 would be a reasonable cut-off value for small bowel CD. Small bowel CD is possible with FC < 100 ug/g. Our results suggest a follow-up with FC before SBCE for patients with no endoscopic ileitis, negative imaging results and FC < 50 ug/g before SBCE

Partial restoration of normal intestinal microbiota in morbidly obese women six months after bariatric surgery

We studied the impact of bariatric surgery on the intestinal microbiota of morbidly obese study subjects. A total of 13 morbidly obese women (five of which had type 2 diabetes) and 14 healthy age- and gender-matched controls were recruited and the microbiota composition of fecal samples were determined by using a phylogenetic microarray. Sampling of the patients took place just one month before and 6 months after the operation. Within six months after bariatric surgery, the obese subjects had lost on average a quarter of their weight whereas four of the five of the diabetic subjects were in remission. Bariatric surgery was associated with an increased microbial community richness and Bacteroidetes/Firmicutes ratio. In addition, we observed an increased relative abundance of facultative anaerobes, such as Streptococcus spp., and a reduction in specific butyrate-producing Firmicutes. The observed postoperative alterations in intestinal microbiota reflect adaptation to the changing conditions in the gastrointestinal tract, such as energy restriction and the inability to process fiber-rich foods after bariatric surgery.Peer reviewe

Facilitating psychotherapy with patient-made videos: A qualitative study of patient experiences

We have developed a method utilizing video material to facilitate the psychotherapeutic process we call VideoTalk. In this method, which uses schema therapy as a theoretical framework, patients make videos at home in various emotional situations following the therapist’s detailed instructions. They then watch the videos together with the therapist making observations about the patient and how they speak about themselves and other people. The aim of this article is to describe five patients’ personal experiences of psychotherapy consisting of 15 video-assisted sessions. We used mixed methods methodology consisting of material-based content analysis of patient interviews done after the therapy and changes in symptoms measured by psychological symptom scales. Based on the symptom scales, this outcome study found that all participants benefited from the VideoTalk therapy. ‘Gaining bodily self-awareness and insight’, ‘Thinking more clearly and with self-compassion’, and ‘Challenges associated with the technology and practicalities of video work’ were found to be the main categories in the content analysis. After some minor technical difficulties, the patients found the video method workable. The results showed a wide range of self-observations, which began to be positively integrated into the patients’ lives and to increase their overall wellbeing. In the course of VideoTalk therapy, patients face painful emotions and may begin to create a new kind of connection between their own insulated internal world and the surrounding world.</p

Patient-Made Videos as a Tool of Self-Observation Enhancing Self-Reflection in Psychotherapy: Description of the Method and a Clinical Case

Photographs have been used in psychotherapy from the late 1970s, but patient-made videos have not been used directly as an integral part in individual psychotherapeutic treatment. We now propose a new approach, VideoTalk, using visual material as an aid in the psychotherapy process with a schema therapy framework as an example. VideoTalk builds on life-review method, providing information about the patient’s social relations, coping skills, affect/emotion regulation and schemas. This information is used as a platform for focused patient-made videos, i.e. self-talk at home in a typical problematic situation for the patient. The VideoTalk method enables documentation of the expression of mind states and dysfunctional schemas in a natural environment and related to an everyday emotional context. Subsequently, this video material is watched step by step together with the therapist. In this report, we describe the flow and functionality of the VideoTalk method through the case of a 24-year-old female patient suffering from depression and social phobia. The self-mirroring from the video facilitates self-observations of the patient’s own facial expressions, voice and body posture. We hypothesize that this new information gradually changes emotional processing, leads to better self-awareness and strengthens more functional schemas.</p

Morbid obesity and type 2 diabetes alter intestinal fatty acid uptake and blood flow

Aims: Bariatric surgery is the most effective treatment to tackle morbid obesity and type 2 diabetes, but the mechanisms of action are still unclear. The objective of this study was to investigate the effects of bariatric surgery on intestinal fatty acid (FA) uptake and blood flow. Materials and Methods: We recruited 27 morbidly obese subjects, of whom 10 had type 2 diabetes and 15 were healthy age-matched controls. Intestinal blood flow and fatty acid uptake from circulation were measured during fasting state using positron emission tomography (PET). Obese subjects were re-studied 6 months after bariatric surgery. The mucosal location of intestinal FA retention was verified in insulin resistant mice with autoradiography. Results: Compared to lean subjects, morbidly obese subjects had higher duodenal and jejunal FA uptake (P </p

Partial restoration of normal intestinal microbiota in morbidly obese women six months after bariatric surgery

We studied the impact of bariatric surgery on the intestinal microbiota of morbidly obese study subjects. A total of 13 morbidly obese women (five of which had type 2 diabetes) and 14 healthy age- and gender-matched controls were recruited and the microbiota composition of fecal samples were determined by using a phylogenetic microarray. Sampling of the patients took place just one month before and 6 months after the operation. Within six months after bariatric surgery, the obese subjects had lost on average a quarter of their weight whereas four of the five of the diabetic subjects were in remission. Bariatric surgery was associated with an increased microbial community richness and Bacteroidetes/Firmicutes ratio. In addition, we observed an increased relative abundance of facultative anaerobes, such as Streptococcus spp., and a reduction in specific butyrate-producing Firmicutes. The observed postoperative alterations in intestinal microbiota reflect adaptation to the changing conditions in the gastrointestinal tract, such as energy restriction and the inability to process fiber-rich foods after bariatric surgery