| 1. |
- Särnblad, Stefan, 1963-
(författare)
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Body Composition in Adolescents with Type 1 Diabetes : Aspects of Glycaemic Control and Insulin Sensitivity
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Excessive weight gain has frequently been reported in adolescents with type 1 diabetes, especially in girls. In general, puberty is associated with reduced insulin sensitivity that is further diminished by overweight. The causes and consequences of excessive weight gain in adolescents with type 1 diabetes are not fully understood. The studies described in this thesis addressed body composition in adolescents with type 1 diabetes and the relationships between physical activity, energy intake and changes in body composition. Furthermore, the effect of metformin as additional therapy on glycaemic control and insulin sensitivity was examined in a randomised placebo-controlled study. Body mass index (BMI) and percentage body fat (%BF) were significantly higher in girls with type 1 diabetes compared to healthy control girls. Mean HbA1c during puberty, but not mean insulin dose, was positively related to BMI at the age of 18 in girls with diabetes. A centralised fat distribution was associated with poor glycaemic control, increased daily dosage of insulin and elevated cholesterol and triglyceride levels. Neither total physical activity nor total energy intake differed between adolescent girls with type 1 diabetes and healthy age-matched control girls. A high dietary fat intake was positively related to gain in %BF in girls with type 1 diabetes. Additional therapy with metformin for three months improved glycaemic control and peripheral insulin sensitivity in adolescents with poorly controlled type 1 diabetes. The improvement in glycaemic control was related to insulin sensitivity at baseline, implying that the most insulin resistant subjects benefited most from the metformin therapy. It is concluded that the excessive weight gain observed in girls with type 1 diabetes is mainly attributable to an increased fat mass and that dietary fat intake is of importance for this gain in body fat. Additional treatment with metformin improves glycaemic control in adolescents with poorly controlled type 1 diabetes.
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| 2. |
- Allbrand, Marianne, 1958-
(författare)
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Gene expression of inflammatory markers and growth factors in placenta in relation to maternal obesity and foetal and postnatal growth
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Maternal obesity is a growing health problem, that contributes to obstetrical complications in pregnancy, as well as neonatal morbidity and mortality. The placenta serves for gas and nutrient exchange between the mother and the foetus, and obesity may influence and modify placental growth and function. The aims of this thesis were to investigate associations between maternal obesity without associated morbidity and gene expression of inflammatory markers and growth factors in the placenta, as well as offspring birth weight and postnatal growth. Study I and III were designed as matched case-control studies including 32 obese women with an early pregnancy body mass index (BMI) ≥ 35.0 kg/m2, study II was an experimental study examining twelve placentas of normal weight women, and study IV was a cohort study including 109 obese women with a BMI ≥ 34.5 kg/m2. In studies I-IV analyses of gene expression were performed and in study III additionally cord blood concentrations were determined. No difference was found in the occurrence of placental gene expression of inflammatory markers or growth factors between obese and normal weight women, nor did the sampling site in placentas of normal weight women influence gene expression of these markers, except for leptin gene (LEP) and insulin receptor gene (INSR) expression. Ghrelin gene (GHRL) and LEP expression, as well as cord blood ghrelin and adiponectin levels, was not altered in maternal obesity, and a negatively U-shaped relationship between LEP expression and infant birth weight (BW) z-scores was observed in the placentas of obese women.In conclusion, no statistically significant difference in gene expressions of inflammatory markers and growth factors in the placenta between severely obese and normal weight women was found. These results are in contrast with earlier studies and could be due to the fact that we examined mainly healthy obese women. The correlations we found between gene expression of leptin in the placenta and the birth weight of the infants warrants further studies.
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| 3. |
- Lindström, Caisa, 1955-
(författare)
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Burnout in parents of chronically ill children
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Parents of children with a chronic disease are usually highly involved in their child’s treatment and may be affected by the heavy demands and constant stress. This can increase the risk of developing burnout, which is an individual reaction to long-term stress consisting of symptoms associated with emotional exhaustion, as well as physical and cognitive fatigue. The overall aim was to estimate the prevalence of burnout in parents of children with Type 1 Diabetes Mellitus (T1DM) and inflammatory bowel disease (IBD) (paper I), identify the risk factors associated with parenting a child with T1DM (paper II), explore how mothers suffering from burnout describe their mothering of a child with diabetes, with special focus on their need for control and Performance-based self-esteem (PBSE) (paper IV), and to evaluate the effect of a group intervention aimed at reducing stress-related symptoms (paper III). A total of 251 parents of children with T1DM, 38 parents of children with IBD and 124 parents of healthy children participated in a population-based study (I, II). The validated Shirom-Melamed Burnout Questionnaire (SMBQ) was used to assess burnout. 16 parents (SMBQ ≥3.75) participated in a group intervention and were evaluated for changes in SMBQ and PBSE (III). A total of 21 mothers of children with T1DM who scored for clinical burnout (SMBQ) participated in a qualitative study. Semi-structured interviews were conducted and Inductive content analysis was used (IV). In the study group 36.0% parents of children with a chronic disease scored for clinical burnout (SMBQ ≥3.75) compared to 20.2% of the reference parents (p=0.001) with a preponderance of mothers compared to fathers, 42% vs. 20.5% (p=0.001), respectively (I). Less support from the social network, sleep disturbances and lack of personal leisure time and recovery seem to be important risk factors for clinical burnout in parents of children with T1DM, especially mothers (II). Mothers’ experiences of mothering a child with T1DM were interpreted as one theme; Mission impossible, illustrating the extremely difficult circumstances under which they bring up the child with diabetes to adulthood (IV). Parents’ subjective evaluation of the intervention group was mainly positive and SMBQ (p=0.01) and PBSE scale (p= 0.04) measurements were significantly reduced 6 months after completion of the intervention (III). It is important to pay attention to how parents and especially mothers experience their daily life in order to support those who are at risk of developing burnout.
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| 4. |
- Lodefalk, Maria, 1968-
(författare)
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Adolescent type 1 diabetes : Eating and gastrointestinal function
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Adolescents with type 1 diabetes (T1DM) are given nutritional education, but the knowledge about their adherence to the food recommendations and associations between dietary intake and metabolic control is poor. Gastrointestinal symptoms are more prevalent in adults with T1DM than in healthy controls, which may be due to disturbed gastrointestinal motility. The meal content affects the gastric emptying rate and the postprandial glycaemia in healthy adults and adults with type 2 diabetes. Meal ingestion also elicits several postprandial hormonal changes of importance for gastrointestinal motility and glycaemia. Eating disorders are more prevalent in young females with T1DM than in healthy females, and are associated with poor metabolic control. The prevalence of eating disorders in adolescent boys with T1DM is not known. This thesis focuses on eating and gastrointestinal function in adolescents with T1DM. Three population-based, cross-sectional studies demonstrated that adolescents with T1DM consume healthy foods more often and have a more regular meal pattern than age- and sex-matched controls. Yet both boys and girls are heavier than controls. The intake of saturated fat is higher and the intake of fibre is lower than recommended in adolescents with T1DM. Patients with poor metabolic control consume more fat and less carbohydrates than patients with better metabolic control. Gastrointestinal symptoms are common in adolescents with T1DM, but the prevalence is not increased compared with controls. Gastrointestinal symptoms in patients are associated with female gender, daily cigarette smoking, long duration of diabetes, poor metabolic control during the past year, and an irregular meal pattern. Adolescent boys with T1DM are heavier and have higher drive for thinness than healthy boys, but do not differ from them in scales measuring psychopathology associated with eating disorders. In a randomized, cross-over study, we found that a meal with a high fat and energy content reduces the initial (0–2 hours) postprandial glycaemic response and delays gastric emptying in adolescents with T1DM given a fixed prandial insulin dose compared with a low-fat meal. The glycaemic response is significantly associated with the gastric emptying rate. Both a high- and a low-fat meal increase the postprandial concentrations of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) and suppress the postprandial ghrelin levels in adolescents with T1DM. The postprandial changes of these hormones are more pronounced after the high-fat meal. Insulin-like growth factor binding-protein (IGFBP) –1 concentrations decrease after insulin administration irrespective of meal ingestion. The GLP-1 response is negatively associated with the gastric emptying rate. The fasting ghrelin levels are negatively associated with the postprandial glycaemic response, and the fasting IGFBP-1 levels are positively associated with the fasting glucose levels. We conclude that nutritional education to adolescents with T1DM should focus more on energy intake and expenditure to prevent and treat weight gain. It should also focus on fat quality and fibre intake to reduce the risk of macrovascular complications and improve glycaemia. Gastrointestinal symptoms in adolescents with T1DM should be investigated and treated as in other people irrespective of having diabetes. However, adolescents with long duration of diabetes, poor metabolic control, and symptoms from the upper gut should have their gastric emptying rate examined during euglycaemia. There may be an increased risk for development of eating disorders in adolescent males with T1DM since they are heavier than healthy boys and have higher drive for thinness. This should be investigated in future, larger studies. For the first time, we showed that a fat-rich meal delays gastric emptying and reduces the initial glycaemic response in patients with T1DM. The action profile of the prandial insulin dose to a fat-rich meal may need to be postponed and prolonged compared with the profile to a low-fat meal to reach postprandial normoglycaemia. Circulating insulin levels affect postprandial GIP, GLP-1, and ghrelin, but not IGFBP-1, responses less than the meal content. The pronounced GIP-response to a fat- and energy-rich meal may promote adiposity, since GIP stimulates lipogenesis. Such an effect would be disadvantageous for adolescents with T1DM since they already have increased body fat mass and higher weights compared with healthy adolescents. Adolescents with T1DM may have subnormal postprandial ghrelin suppression, which may be due to their increased insulin resistance or elevated growth hormone levels. This needs to be investigated in future, controlled studies.
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| 5. |
- Schölin, Anna
(författare)
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Diabetes in Young Adults : Remission, β-cell function and markers of inflammation
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 1 diabetes is caused by immuno-mediated β-cell destruction leading to insulin deficiency and hyperglycaemia. The decline in β-cell function and the clinical course after diagnosis vary. Whether the process of destruction of the β-cells is associated with markers of a non-specific inflammatory response is unknown. The aims of these studies were to identify factors of importance for clinical remission (low insulin need and normoglycaemia) and long-term β-cell function and estimate the degree of non-inflammatory response in type 1 diabetes in young adults. Clinical remission and β-cell function eight years after diagnosis were assessed and related to clinical, biochemical and immunological variables at diagnosis, including islet autoantibodies [ICA, GADA, IA-2A]. Markers of low-grade inflammation in plasma [CRP and IL-6] were estimated and the concentrations were related β-cell function [plasma C-peptide], glycaemic control and autoimmunity at diagnosis and the first year thereafter. The results showed that clinical remission occurred in about half of the patients with newly diagnosed type 1 diabetes. Preserved β-cell function eight years after diagnosis was observed in 16% of the patients classified at diagnosis as having autoimmune type 1 diabetes. Duration of remission was dependent on BMI, degree of metabolic derangement and presence of GADA at diagnosis. BMI at diagnosis was also of importance for preserved β-cell function after eight years of the disease, as were the amount of islet antibodies and presence of ICA. Elevated CRP levels were noted in the majority of cases at diagnosis and both CRP and IL-6 concentrations were stable the first year after clinical diagnosis. High concentrations of CRP and IL-6 did not relate to β-cell destruction or the degree of autoimmunity. CRP concentrations were higher in islet antibody negative than in positive patients. CRP also correlated positively to BMI, C-peptide at 12 months and to increasing HbA1c between six and 12 months. In general, females had shorter remissions, lower concentrations of serum bicarbonate and higher levels and prevalence of GADA at diagnosis, compared to males. Females also had higher HbA1c and CRP values the first year after diagnosis. In summary, BMI at diagnosis is a strong predictor of duration of remission and preservation of β-cell function. Elevated CRP concentrations are correlated to factors linked rather to insulin resistance than to β-cell destruction. Females appear to have a more acute onset and a more severe course of the disease than males.
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| 6. |
- Söderström, Ulf, 1947-
(författare)
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Type 1 diabetes in children with non-Swedish background : epidemiology and clinical outcome
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sweden holds third place of diabetes incidence in young people after Finland and Sardinia. One fifth of the population is nowadays of foreign descent. We have a substantial number of immigrants from countries where the risk for T1D is considerably lower. Migration as a natural experiment is a concept to assess the risk for diabetes in offspring of immigrant parents and assess the interaction between genetics (genotype) and the impact of environment (phenotype).Aims: To study the risk of incurring diabetes for children of immigrant parents living in Sweden (I) and further study the risk if the child is born in Sweden or not (II); to specifically study and evaluate if children from East Africa have increased risk to develop T1D (III). To investigate if clinical and sociodemographic status at T1D onset differs between immigrant children compared to their Swedish indigenous peers (IV). Finally to study the clinical outcome and the impact of socio-demographic factors at diabetes onset after three years of treatment (V).Methods: All five studies are observational, nationwide and population based, on prospectively collected data. Statistics mainly by logistic and linear regressions.Results: Parental country of origin is a strong determinant for diabetes in the offspring. Children born to immigrant parents seem to keep their low risk compared to their Swedish peers (I). When adding the factor of being born in Sweden, the pattern changed; there was a significantly (p < 0.001) increased risk for T1D if the child was born in Sweden (II). East Africans have a substantial risk for T1D and especially if the children are born in Sweden (III). Immigrant children and adolescents have worse metabolic start at T1D onset compared to their indigenous Swedish peers (IV). After 3 years of treatment, the immigrant children had a sustained higher median HbA1c, compared to their Swedish peers (V).Conclusions: Genotype and influences during fetal life or early infancy have an important impact for the risk of T1D pointing towards epigenetics playing a substantial role. Children with an origin in East Africa have a high risk of incurring T1D. Immigrant children have worse metabolic start at T1D onset, which sustains after three years of treatment
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| 7. |
- Åman, Jan E., 1948-
(författare)
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Symbolic computer calculations in general relativity
- 1982
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This report describes programs for symbolic computer calculations in General Relativity and results obtained by such programs. A perturbation calculation to obtain an approximate geometry from a given physically acceptable distribution of matter is presented. A program for classifying solutions of Einstein's field equations is presented. A number of such solutions have been classified. New results have been obtained this way.
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| 8. |
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