| 1. |
- Huus, Karina, 1968-
(författare)
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Weight gain in children : possible relation to the development of diabetes
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The prevalence of overweight and obesity among children has increased the last decades and is now defined as a global epidemic disease by the World Health Organization. Also the incidence of type 1 diabetes has increased and there are some hypothesises that argue there is a connection between overweight/obesity and type 1 diabetes.Aim: The general aim of this thesis was to study factors contributing to the development of overweight and obesity among children and to study possible relations to the development of diabetes.Method: All Babies in Southeast Sweden, ABIS, is a prospective cohort study. The study includes all babies who were born in southeast Sweden between Oct 1st 1997 until Oct1st 1999 and the design was to follow them up to school age in ABIS I and to follow them until 14 years in ABIS II, of the eligible 74 % entered the study. The families have answered questionnaires and biological samples were taken mainly from the children at the different time points: birth, 1 year, 2.5 years, 5 years and 8-9 years. In this thesis studies have been made including the whole cohort, but some studies have also been made involving only a part of the children.Results: The prevalence of overweight and obesity among children in the ABIS study was 12.9% overweight and 2.5 % obese at 5 years of age. One risk factor which appeared to have a great impact on the development of overweight and obesity at 5 years of age was the child’s own BMI at an early age and also the heredity for overweight/ obesity and the heredity for type 2 diabetes. If the father had a university degree, the child was less likely to be obese at 5 years of age. Other factors, such as the parents´ age, if the child had any siblings, and if the child lived with a single parent, did not show any significant correlation to the child’s BMI at 5 years of age.Early nutrition has been studied and no correlation could be found between breastfeeding less than 4 months and the development of overweight/obesity at 5 years of age. The parents answered questions about how frequent the child ate different food at 2.5 years and at 5 years. Intake of sweet lemonade was the only single food which was correlated to a higher BMI in 5 years old children. Porridge seemed to be protective against overweight/ obesity. In one of the studies the physical activity was measured by a step counter. The fewer steps the children were taking, the higher BMI and waist circumference they had. Low physical activity was also associated with a higher C-peptide value and decreased insulin sensitivity. Children who spent more time in front of TV/video had a higher fasting blood glucose value.Conclusions: A strong factor for the development of overweight and obesity among children is the child’s own BMI at an early age and also its heredity for overweight/ obesity and the heredity for type 2 diabetes. Early nutrition did not show any obvious correlations with overweight and obesity at 5 year old children. Low physical activity was associated with higher fasting C-peptide value and decreased insulin sensitivity. Low physical activity may cause β-cell stress which might contribute to an autoimmune process in individuals genetically predisposed to autoimmunity and, thereby, to the increasing incidence of Type 1 diabetes in children.
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| 2. |
- Röckert Tjernberg, Anna, 1975-
(författare)
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Celiac disease and Infections
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Celiac disease (CD) is a chronic immune-mediated enteropathy affecting about 1% of the population worldwide. CD is triggered by ingestion of gluten in genetically predisposed individuals but additional factors (e.g. infections) are required for the disease to develop. CD also seems to be associated with infectious complications.Aim: The main objective of this thesis was to increase the knowledge about the associations between CD and infections.Methods: Epidemiological and laboratory approaches. Studies I-III used a data set consisting of small intestinal biopsy reports. The biopsies were taken in 1969-2008 and collected in 2006-2008. A total of 29,096 individuals with CD, 13,306 with inflammation and 3,719 with potential CD were identified. Each individual was matched with up to 5 controls from the general population (n= 228,632). Through linkage of the data to the Patient Register study I examined the risk of hospital visits due to respiratory syncytial virus (RSV) in children <2 years prior to onset of CD. Study II used the Patient Register and Cause of Death Register to assess whether CD affects the outcome in sepsis. Study III linked the data to microbiological data bases and the Public Health Agency to estimate risk of invasive pneumococcal disease (IPD) in CD. In study IV children with CD and controls were recruited from Kalmar County Hospital. Complement activation (C3a and sC5b-9) in plasma were analysed after incubation with pneumococci.Results: Study I found that children with CD were more likely than controls to have attended hospital due to RSV infection prior to diagnosis (odds ratio 1.46; 95% confidence interval (CI)=1.02-2.07). CD did not seem to influence survival in sepsis (adjusted hazard ratio (HR) 1.10 95%CI=0.72-1.69) (study II). Study III indicated a 46% risk increase for individuals with CD to acquire IPD (HR 1.46; 95%CI=1.05-2.03) but study IV did not reveal any differences in complement response in regard to CD status (p=0.497and p=0.724), explaining this excess risk.Conclusion: This thesis supports associations between CD and infections preceding and complicating diagnosis. However, CD does not seem to influence the outcome in a severe infection like sepsis and altered complement function is unlikely to be responsible for the excess IPD risk in CD.
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| 3. |
- Samuelsson, John, 1981-
(författare)
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Metabolic Control, Morbidity and Mortality in Type 1 Diabetes with Onset in Childhood/Adolescence
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: The overall aim of this thesis was to study mortality in individuals with onset of type 1 diabetes (T1D) in childhood and adolescence in Sweden, related to clinical characteristics such as metabolic control in childhood/adolescence and comorbidity. Methods: All studies in this thesis were register-based observational studies using a nationwide and population-based quality register, the paediatric part of the Swe-dish National Diabetes Register (NDR), for identification and collection of clinical data of individuals with T1D diagnosed before 18 years of age. Study I included 8084 individuals between 2000 and 2014, and compared these during follow-up based on HbA1c at onset of T1D. In studies II and IV 16,537 individuals with T1D registered from 2000 to 2014 were identified. This population was merged with the Swedish Cause of Death register (CDR) to identify deceased individuals during the study period and retrieve causes of death. In study II, the study period was set between 2006 and 2014, including 12,652 individuals. Standardised mortality rates (SMRs) were calculated using data from the Swedish population register. Study III included 15,188 individuals with onset of T1D between 2000 and 2019. Five randomly selected control individuals from the Swedish population were matched to each individual with T1D. These cohorts were linked to the National Patient Register to retrieve ICD codes on autoimmune diseases (AIDs), and to the CDR to identify deceased individuals. Medical records were retrieved from treating clinics for all de-ceased individuals in study IV. Results: Individuals in the highest quintile of HbA1c at onset of T1D (>114 mmol/mol) had higher HbA1c during follow-up compared to the lowest quintile (<72 mmol/mol) at onset, but there was no significant correlation between individual HbA1c at onset and during follow-up. In study II, 68 individuals were identified as deceased, of which almost 40% died due to diabetes, mainly caused by acute complications. The overall SMR was 2.7 per 1000 person-year. Those who died due to diabetes had significantly elevated HbA1c in childhood compared to those who died from other causes or were still alive. In study III, almost 20% of individuals with T1D developed at least one other AID. Coeliac disease was the most common followed by thyroid disease. Individuals with an additional AID did not have worse outcome in terms of metabolic control or mortality risk. In study IV, after review, 72 individuals had information in the medical records which was possible to evaluate regarding cause of death. Hypoglycaemia was the cause of death in two individuals (2.8%) and ketoacidosis in eight individuals (11.1%). In 16 (22.2%) individuals with cause of death due to diabetes with coma, no conclusion on whether death was caused by hypoglycaemia or ketoacidosis could be drawn. HbA1c was significantly elevated both in childhood and in the last year before death in medical records in those deceased due to diabetes. Conclusions: High HbA1c at onset of T1D cannot be used as a predictor of future metabolic control in the individual child or adolescent. Children and adolescents with high HbA1c in childhood have an increased risk of premature mortality, mainly due to acute complications of T1D. Hypoglycaemia was uncommon as a cause of death, contributing for certain to only 2.8 % of the mortality. Individuals with T1D have a high risk of developing other AIDs from the onset of diabetes; however such comorbidity was not associated with worse outcome in terms of metabolic control or mortality risk.
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| 4. |
- Sundelin, Heléne E.K. 1965-
(författare)
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Comorbidity and complications in neurological diseases
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Neurological diseases are complex and many share etiology as well as comorbidities. Epilepsy, a brain disorder characterized by an enduring predisposition to generate epileptic seizures and autism spectrum disorder (ASD), are considered to be associated, but the connection is still not fully uncovered. Cerebral palsy (CP), a lifelong, nonspecific, non-progressive disorder of posture and movement control, and Ehlers-Danlos Syndrome (EDS), a connective tissue disorder, both have many consequences for health and wellbeing throughout life.Aims: The aim of this thesis was to explore the impact of comorbidity and complications in neurological diseases and EDS. The objective was to gain information on the nature of the connection between epilepsy and ASD, if EDS, ASD and CP have consequences for pregnancy outcome, and the risk of traffic accidents in individuals with epilepsy.Materials and methods: The studies are all historical observational population- based cohort studies with prospectively collected data from national registers. The risk of ASD was analysed in 85,201 individuals with epilepsy and compared with 425,760 controls as well as for their firstdegree relatives. In a cohort of 1,248,178 singleton births, 314 births to women with EDS, 2,072 births to women with ASD, and 770 births to women with CP, pregnancy outcome was explored. The risk of traffic accidents was estimated in 29,220 individuals with epilepsy and 267,637 matched controls.Results: There is an increased risk of; ASD in individuals with epilepsy and their relatives, moderately preterm birth and pre-eclampsia in maternal ASD, of preterm birth in maternal CP and transport accidents in individuals with epilepsy. There is no increased risk of adverse pregnancy outcome in women with EDS.Conclusions: This thesis found proofs of a bidirectional association between epilepsy and ASD, that ASD and CP have consequences for pregnancy outcome and epilepsy is a risk factor for traffic accidents.
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| 5. |
- Bozorg, Soran Rabin, 1993-
(författare)
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Various Aspects of Gastrointestinal Disease : Examining Validity and Health Economic Outcomes
- 2022
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Recent years have seen significant research advances within the gastroenterological field. Some of these consist of the recognition of serrated polyps as a precursor to colorectal cancer, and the realization of the health economic burden associated with gastrointestinal diseases.Aim: In this thesis, we aim to validate the specificity of serrated polyps in the ESPRESSO cohort (Paper I). We also aim to estimate work loss in patients with celiac disease, including the temporal relationship of work loss before and after diagnosis (Paper II).Method: By using the ESPRESSO cohort, we collected data on patients with serrated polyps and patients with celiac disease. In Paper I, the specificity of serrated polyps in the ESPRESSO cohort were validated by a structured retrospective review of patient chart. In Paper II, we estimated work loss in patients with celiac disease as compared withgeneral-population comparators matched on age, sex, county of residence and year of diagnosis.Result: The presence of a serrated polyp was confirmed in 101 out of 106 individuals identified through the ESPRESSO cohort, yielding a positive predictive value of 95% (95% confidence interval: 89-98%). Patients with celiac disase had 42.5 lost work days as compared to 28.6 days in comparators (mean difference, 14.7; 95% confidence interval, 13.2-16.2), corresponding to a relative increase of 49%. Excess work loss in patients with celiac disease was observed even 5 years before diagnosis and remained eleveated during the years after diagnosis this loss. Notebly, the excess work loss was concentrated to a small proportion while most celiac patients did not have any work loss before or after diagnosis. Conclusion: The ESPRESSO cohort has a high specificity for serrated polyps. Patients with celiac disease miss more work days than the general population even before diagnosis, and this loss persists after diagnosis.
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| 6. |
- Elfström, Peter, 1974-
(författare)
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Associated disorders in celiac disease
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Celiac disease (CD) is an autoimmune disorder that affects genetically susceptible individuals and is induced by dietary gluten. Treatment consists of a lifelong gluten-free diet. CD is common and affects about 1% of the general population. The classic symptoms include diarrhea and malabsorption, but many patients have only mild symptoms or no symptoms at all. The proportion of individuals presenting with atypical symptoms or discovered only when investigating an associated condition of CD is increasing. Aims: The aim of this thesis was to investigate the risk of possible associated disorders through Swedish population-based registers. The objective was to gain more information on the consequences of having CD and to identify high risk groups where screening may be considered. Materials and methods: We used the Swedish hospital discharge register to examine the risk of liver disease, autoimmune heart disease, Addison’s disease and thyroid disorders in a cohort of about 14,000 individuals with CD and an age and sex matched reference population of 70,000 individuals. In the last study we used all regional pathology registers and the cancer registry to examine the risk of hematopoietic cancer, including lymphoma in three different cohorts: I) 28,810 individuals with CD; II) 12,681 individuals with small intestinal mucosal inflammation but without villous atrophy; and III) 3552 individuals with latent CD (a positive serology test for CD with a normal small intestinal biopsy). Results: CD is statistically significantly associated with an increased risk of liver disease, Addison’s disease, thyroid disease and lymphoma. We also found an increased risk of lymphoma in individuals with small intestinal mucosal inflammation. There was no statistically significant association between autoimmune heart disease or leukemia and CD. Latent CD was not associated with any hematopoietic cancers. Conclusion: This thesis found a positive association between CD and a number of autoimmune and inflammatory disorders. Clinicians need to have a high awareness of this association and to test for these conditions when symptoms appear.
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| 7. |
- Emilsson, Louise, 1982-
(författare)
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Cardiac complications in celiac disease
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Celiac disease (CD) is an immune-mediated enteropathy induced by dietary gluten that affects about 1% of western populations. CD has been associated to an increased risk of cardiovascular mortality in some studies; however associations to cardiovascular diseases have not been broadly researched.Aim: The aim of this thesis was to examine the associations between CD and some cardiovascular diseases, namely; atrial fibrialltion, dilated cardiomyopathy and risk factors of ischemic heart disease.Methods: We used computerized data on all Swedish patients with biopsy-verified CD equal to villous atrophy from 1969 to 31st of December 2008. All CD patients were matched on age, sex, county and calendar year with up to five reference individuals. Altogether we had data on 29,096 CD patients and 144,522 reference individuals. Data were linked to different Swedish national registries and the Swedish quality and cardiac care registry SWEDEHEART. Main outcomes in the studies were: I: atrial fibrillation registered in the national patient registry or the cause of death registry, II: chart validated idiopathic dilated cardiomyopathy, III: different risk factors, clinical presentation and parameters in patients with first myocardial infarction (MI) registered in SWEDEHEART and IV: follow-up parameters, 6-10 weeks and one year after MI, registered in SWEDEHEART.Result: We showed a 34% increased risk of atrial fibrillation in CD and a 73% increased risk of dilated cardiomyopathy, the latter only of borderline significance, p=0.052. In the third study we showed that CD patients with MI had a more beneficial cardiovascular risk factor profile, better left ventricular ejection fraction and fewer stenoses on coronary angiography compared to reference individuals with MI. The fourth study showed that follow-up after MI does not differ from follow-up in reference individuals.Conclusion: This thesis supports an association of cardiovascular diseases in CD. Potential mechanisms include shared risk factors and chronic in-flammation.
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| 8. |
- Hagström, Hannes, et al.
(författare)
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Cardiovascular Outcomes in Patients With Biopsy-proven Alcohol-related Liver Disease
- 2023
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 21:7, s. 1841-1853.e12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Patients with alcohol-related liver disease (ALD) frequently have risk factors for cardiovascular disease (CVD), but their long-term risk of CVD is not well-known, especially considering the competing risk of death from liver-related causes. It is further unknown if any excess risk varies across histological subgroups.METHODS: We investigated the risk of CVD outcomes in 3488 persons with ALD and an available liver biopsy in Sweden between 1969 and 2016, compared with a matched reference population (n = 15,461). Administrative coding from national diagnostic and histopathology registers were used to define exposures and outcomes. Competing risk regression, taking non-CVD death into account and adjusting for potential confounders, was used to estimate subdistribution hazard ratios for incident CVD up until Dec 31, 2019.RESULTS: At baseline, patients with ALD had a median age of 58 years, 64% were men, and 2039 (58%) had cirrhosis on histology. The incidence rate of CVD was 35.6 per 1000 person-years in ALD compared with 19.0 per 1000 person-years in reference individuals. ALD was associated with a 2-fold increased short-term risk for CVD compared with matched reference individuals (subdistribution hazard ratio during the first year after diagnosis, 2.29; 95% confidence interval, 1.79-2.95), but this risk decreased with time. Incidence rates of CVD were comparable across histological subgroups (ranging from 27.4 CVD cases per 1000 person-years in those with normal histology to 39.2 cases per 1000 person-years in those with cirrhosis).CONCLUSIONS: Persons with biopsy-proven ALD have increased rates of CVD across histological subgroups compared with matched reference individuals, particularly just after ALD diagnosis. Active surveillance of modifiable CVD risk factors should be considered by clinicians treating patients with ALD.
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| 9. |
- Kaarme, Johan, 1973-
(författare)
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A world inside : Gastrointestinal microbiota in healthy Swedish children at day care centers and aspects on antibiotic resistance, enteric pathogens and transmission
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibiotic resistance is a growing threat to human health and is defined by the World Health Organization as a crisis that must be managed with the utmost urgency. Antibiotic resistant bacteria increase both mortality and morbidity and have a great impact on the global economy. Resistance is not confined to human health care, but is present also among animals and in our environment at large. Indeed, resistant bacterial strains have now been found in virtually all parts of the world, even in locations without direct human contact.The human gastrointestinal tract is populated by a complex, dynamic, diverse and highly interactive collection of microorganisms, including bacteria, archaea, fungi, yeasts and viruses, which constitutes our gastrointestinal microbiota. This microbiota is an important reservoir of resistance genes (our gastrointestinal resistome) and a “melting pot” for transfer of resistance genes between microbes, including potential pathogens.In this thesis I investigated the prevalences of two clinically important kinds of antibiotic resistance: extended-spectrum β-lactamases (ESBL) and vancomycin-resistant enterococci (VRE), as well as asymptomatic carriage of potential enteropathogens among healthy preschool children in Uppsala. Fecal samples from unidentified, individual diapers were collected in 2010 (125+313 samples) and in 2016 (334 samples). In addition, 204 environmental samples from the children’s preschools were collected in autumn 2016.A prevalence of 2.9% ESBL-producing Enterobactericeae was demonstrated in the first samples from 2010. No VRE were found and the occurrence of enteropathogens were reassuringly low. Results on ESBL prevalence in 2016 and transmission of resistance between children will be presented when the manuscript is published and at the dissertation.
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| 10. |
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