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  • Toschke, Audré M., et al. (författare)
  • Paternal smoking is associated with a decreased prevalence of type 1 diabetes mellitus among offspring in two national British birth cohort studies (NCDS and BCS70)
  • 2007
  • Ingår i: Journal of Perinatal Medicine. - Berlin : Walter de Gruyter. - 0300-5577 .- 1619-3997. ; 35:1, s. 43-7
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>AB Aims: An association between paternal age and type 1 diabetes (IDDM) among their offspring was recently reported as well as transgenerational responses in humans. This paper aims to assess the association of markers for prenatal exposures with IDDM. Methods: We analysed data from two birth cohorts in Great Britain on 5214 cohort members from the National Child Development Study (NCDS) and 6068 members of the 1970 British Birth Cohort Study (BCS70) with full information on IDDM and explanatory variables using multivariate logistic regression. Results: IDDM prevalence was 0.7% (95% CI 0.5-1.0%; n = 38) in the NCDS and 0.4% (95% CI 0.3-0.6%; n = 27) in the BCS70 cohort. Paternal age was not associated with IDDM possibly due to lack of sample power. Unex-pectedly, a lowered prevalence of IDDM was observed among offspring of smoking fathers in both cohorts, with a combined odds ratio of 0.44 (95% CI 0.25-0.75). This association could not be explained by maternal smoking prior to, during or after pregnancy, number of siblings, parental social class, maternal and paternal age, or cohort. Maternal smoking in pregnancy did not alter the IDDM prevalence among offspring. Conclusions: This unexpected finding may be explained by germ-line mutations or other mechanisms associated with paternal smoking. This phenomenon should be investigated and these results should not be used as a justification for smoking. Paternal exposures may be important in determining IDDM risk.</p>
  • Pourhamidi, Kaveh, 1985-, et al. (författare)
  • Association between symptoms of neuropathy, nerve conduction and levels of heat shock protein 27 in type 2 diabetes
  • 2010
  • Konferensbidrag (refereegranskat)abstract
    • <p><strong>Background and aims:</strong> Increased levels of serum HSP27 (sHSP27) are associated with distal symmetric polyneuropathy (DSPN) in type 1 diabetic patients. However, the association between nerve function and sHSP27 has not been studied in subjects with type 2 diabetes (T2D) and impaired glucose tolerance (IGT). Thus, our objectives were to investigate the association between nerve conduction in the legs, symptoms of distal polyneuropathy and sHSP27 levels. <strong>Methods:</strong> Subjects were consecutively recruited from the population-based Västerbotten Intervention Program; controls (n=39, m/f=19/20, mean age=61± 0.6 years), IGT (n=29, m/f=15/14, mean age=61± 0.8 years), T2D (n=51, m/f=30/21, mean age=61± 1.3 years). Nerve conduction studies were performed. Z-scores for motor conduction velocity (CV) of the peroneal nerve, and the sensory CV and amplitude of the sural nerve were measured and compiled into a composite Z-score of the right leg (Z-score leg). Neurological Disability Score (NDS), including examination of sensory perception, reflexes and muscle strength, were used to evaluate symptoms of neuropathy in the leg. NDS and Z-score leg were categorized into tertiles, respectively. sHSP27 levels were measured and divided into low and high levels.<strong> Results:</strong> Subjects in the highest NDS tertile had lower sHSP27 levels (328 ± 287 pg/mL) compared to subjects in the lowest NDS tertile (558 ± 404 pg/mL, p=0.04). Subjects in the lowest tertile of Z-score leg were in the lowest sHSP27 group (63%) compared to the subjects in the highest group (38%, p=0.034). The highest tertile of Z-score leg was associated with high levels of sHSP27 (OR 3.8, 95% CI 1.2; 11.5, p=0.02); adjusted for age and sex. However, this association was attenuated when adjusted for T2D status (OR 3.1, 95% CI 0.9; 9.9, p=0.06).<strong> Conclusion:</strong> In summary, increased sHSP27 levels were associated with an increasing Z-score of the leg; thus, a better nerve conduction, and fewer symptoms using the whole study population. The attenuation of the association when including diabetic status indicates an altered HSP27 production in T2D patients compared to controls and subjects with IGT.</p>
  • Lodefalk, Maria, 1968-, et al. (författare)
  • Food habits, energy and nutrient intake in adolescents with Type 1 diabetes mellitus
  • 2006
  • Ingår i: Diabetic Medicine. - Oxon, United Kingdom : Wiley-Blackwell. - 0742-3071 .- 1464-5491. ; 23:11, s. 1225-1232
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>AIMS: The aims were to describe the food habits of adolescents with Type 1 diabetes (Type 1 DM) and to compare them with healthy control subjects; to describe the distribution of energy-providing nutrients in patients and compare it with current recommendations and previous reports; and finally, to investigate associations between dietary intake and glycaemic control. METHODS: One hundred and seventy-four adolescents with Type 1 DM and 160 age- and sex-matched healthy control subjects completed a validated food frequency questionnaire, and 38 randomly chosen patients completed a prospective 4-day food record. RESULTS: Patients ate more regularly, and more often ate fruit and fruit juice, potatoes and root vegetables, meat, fish, egg, offal and sugar-free sweets than control subjects. Control subjects more often ate ordinary sweets and snacks. Patients chose coarse rye bread and dairy products with less fat to a greater extent than control subjects. Patients were heavier than control subjects. The intake of saturated fat was higher in patients compared with recommendations and, for boys with diabetes, the intake of protein was higher than recommended. Patients with poorer glycaemic control ate vegetables, fruit and fish less often than patients with better control. CONCLUSIONS: The food habits of adolescents with Type 1 DM were healthier than those of control subjects. The intake of energy-providing nutrients was in line with current recommendations and showed improvements compared with previous reports, with the exception of fibre intake. The association between dietary intake and glycaemic control needs further investigation in prospective studies.</p>
  • Jansson, Stefan P.O., 1959-, et al. (författare)
  • Mortality trends in subjects with and without diabetes during 33 years of follow up
  • 2009
  • Ingår i: Diabetes Care. - Alexandria, USA : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 33:3, s. 551-556
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Objective:</strong> Mortality rates have declined substantially over the past decades in the general population, but the situation among diabetic subjects is less clear. The aim of this study was to analyze mortality trends in diabetic and nondiabetic subjects during 1972–2004.</p><p><strong>Research design and methods:</strong> Since 1972, all patients with diabetes are entered in a diabetes register at Laxå Primary Health Care Center; 776 incident cases were recorded up to 2001. The register has been supplemented with a nondiabetic population of 3,880 subjects and with data from the National Cause of Death Register during 1972 to 2004.</p><p><strong>Results:</strong> During the 33-year follow-up period, 233 (62.0%) diabetic women and 240 (60.0%) diabetic men and 995 (52.9%) nondiabetic women and 1,082 (54.1%) nondiabetic men died. The age-adjusted hazard ratio (HR) for all-cause mortality among diabetic and nondiabetic subjects was 1.17 (<em>P</em> &lt; 0.0021) for all, 1.22 (<em>P</em> &lt; 0.007) for women, and 1.13 (<em>P</em> = 0.095) for men. The corresponding cardiovascular disease (CVD) mortality HRs were 1.33 (<em>P</em> &lt; 0.0001), 1.41 (<em>P</em> &lt; 0.0003), and 1.27 (<em>P</em> &lt; 0.0093), respectively. The CVD mortality reduction across time was significant in nondiabetic subjects (<em>P</em> &lt; 0.0001) and in men with diabetes (<em>P</em> = 0.014) but not in diabetic women (<em>P</em> = 0.69). The results regarding coronary heart disease (CHD) were similar (<em>P</em> &lt; 0.0001, <em>P</em> &lt; 0.006, and <em>P</em> = 0.17, respectively). The CVD and CHD mortality rate change across time was fairly linear in all groups.</p><p><strong>Conclusions:</strong> Diabetic subjects had less mortality rate reduction during follow-up than nondiabetic subjects. However the excess mortality risk for diabetic subjects was smaller than that found in other studies.</p>
  • Elfström, Peter, 1974-, et al. (författare)
  • Risk of primary adrenal insufficiency in patients with celiac disease
  • 2007
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - Chevy Chase, Md. : Endocrine Society. - 0021-972X .- 1945-7197. ; 92:9, s. 3595-3598
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Objectives: Earlier research has suggested a positive association between Addison’s disease (AD) and celiac disease (CD).Wehave here investigated the risk of AD in individuals with CD from a general population cohort.Methods: Through the Swedish national registers we identified 14,366 individuals with a diagnosis of CD (1964–2003) and 70,095 reference individuals matched for age, sex, calendar year, and county of residence. We used Cox regression to estimate hazard ratios (HRs) for subsequent AD. Analyses were restricted to individuals with more than 1 yr of follow-up and without AD prior to study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for CD in individuals with prior AD.Results: There was a statistically significantly positive association between CD and subsequent AD [HR _ 11.4; 95% confidence interval (CI) _ 4.4 –29.6]. This risk increase was seen in both children and adults and did not change with adjustment for diabetes mellitus or socioeconomic status. When we restricted reference individuals to inpatients, the adjusted HR for AD was 4.6 (95% CI _ 1.9 –11.4). Individuals with prior AD were at increased risk of CD (odds ratio _ 8.6; 95% CI _ 3.4 –21.8).Conclusions: This study found a highly increased risk of AD in individuals with CD. This relationship was independent of temporal sequence. We therefore recommend that individuals with AD should be screened for CD. We also suggest an increased awareness of AD in individuals with CD.</p>
  • Paterson, R. W., et al. (författare)
  • A targeted proteomic multiplex CSF assay identifies increased malate dehydrogenase and other neurodegenerative biomarkers in individuals with Alzheimer's disease pathology.
  • 2016
  • Ingår i: Translational psychiatry. - 2158-3188. ; 6:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease (AD) is the most common cause of dementia. Biomarkers are required to identify individuals in the preclinical phase, explain phenotypic diversity, measure progression and estimate prognosis. The development of assays to validate candidate biomarkers is costly and time-consuming. Targeted proteomics is an attractive means of quantifying novel proteins in cerebrospinal and other fluids, and has potential to help overcome this bottleneck in biomarker development. We used a previously validated multiplexed 10-min, targeted proteomic assay to assess 54 candidate cerebrospinal fluid (CSF) biomarkers in two independent cohorts comprising individuals with neurodegenerative dementias and healthy controls. Individuals were classified as 'AD' or 'non-AD' on the basis of their CSF T-tau and amyloid Aβ1-42 profile measured using enzyme-linked immunosorbent assay; biomarkers of interest were compared using univariate and multivariate analyses. In all, 35/31 individuals in Cohort 1 and 46/36 in Cohort 2 fulfilled criteria for AD/non-AD profile CSF, respectively. After adjustment for multiple comparisons, five proteins were elevated significantly in AD CSF compared with non-AD CSF in both cohorts: malate dehydrogenase; total APOE; chitinase-3-like protein 1 (YKL-40); osteopontin and cystatin C. In an independent multivariate orthogonal projection to latent structures discriminant analysis (OPLS-DA), these proteins were also identified as major contributors to the separation between AD and non-AD in both cohorts. Independent of CSF Aβ1-42 and tau, a combination of these biomarkers differentiated AD and non-AD with an area under curve (AUC)=0.88. This targeted proteomic multiple reaction monitoring (MRM)-based assay can simultaneously and rapidly measure multiple candidate CSF biomarkers. Applying this technique to AD we demonstrate differences in proteins involved in glucose metabolism and neuroinflammation that collectively have potential clinical diagnostic utility.
  • Åkerman, Linda, 1983- (författare)
  • Aspects of the Pre-Diabetic Period in Type 1 Diabetes
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Type 1 diabetes (T1D) is an autoimmune disease characterized by insulin deficiency, due to immune-mediated destruction of beta cells. Current knowledge regarding the period preceding disease onset comes, to a large extent, from studying risk cohorts based on relatives of T1D-patients, as they have an increased disease risk. Among T1D patients in general, however, few have the disease in their immediate family. It is therefore important to study risk cohorts from the general population as well. An ongoing autoimmune reaction can often be seen in the blood long before disease onset, by detection of autoantibodies directed towards beta cell antigens. By autoantibody screening among participants in the ABIS (All Babies in the South-east of Sweden) cohort, we could identify a group of children from the general population with increased risk for T1D, positive for multiple autoantibodies. They were enrolled in a 2-year prospective follow-up aiming to characterize the prediabetic period and to identify factors indicative of progression/non-progression to T1D. We assessed glucose homeostasis and autoantibody titers over time, and searched for risk-biomarkers by analyzing the expression of immune-related genes (Th1-Th2-Th3) in peripheral blood mononuclear cells (PBMC) from these children, in comparison to healthy children and newly diagnosed T1D patients. In the same groups we also compared serum micro RNA (miRNA) profiles, knowing that miRNA molecules have desirable biomarker properties. We found that two specific autoantibodies, IA2A and ZnT8A, were detected at higher concentrations in risk-individuals who progressed to overt T1D during or after the follow-up period, compared to those who still have not. We also observed disturbed glucose homeostasis long before onset in the progressors, but it was seen among those who remain symptom free as well. Further, we found support for the possible role of insulin resistance as an accelerator of the disease process. For gene expression and serum miRNA, few differences were observed between risk-individuals and healthy children overall. However, for PBMC gene expression and serum miRNA both, there were associations to beta cell function and glucose homeostasis, and for miRNA also to islet autoantibodies. Although specific profiles for prediction of disease onset or identification of risk-individuals could not be found, these results are interesting and deserve to be evaluated further. As part of another sub-study within ABIS, the effects of physical activity on glucose homeostasis were assessed in healthy schoolchildren. The level of physical activity, measured by pedometers, was related to insulin resistance and beta cell-stress, and decreased physical activity was associated with increased insulin resistance and load on the insulin-producing beta cells, already at school-age.</p>
  • Hoey, Hilary, et al. (författare)
  • Parent and health professional perspectives in the management of adolescents with diabetes : development of assessment instruments for international studies
  • 2006
  • Ingår i: Quality of Life Research. - 0962-9343 .- 1573-2649. ; 15:6, s. 1033-1042
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>OBJECTIVE: Assessment of quality of life (QOL) in adolescents with diabetes requires patient, parent and health professional input. Psychometrically robust instruments to assess parent and professional perspectives are required. RESEARCH DESIGN AND METHODS: Questionnaires concerning adolescent QOL were developed for completion by parents and health professionals. In an international study assessing QOL in 2,101 adolescents with diabetes (median age 14 years, range 10-18; from 17 countries including Europe, Japan and North America), parents and health professionals completed their respective questionnaires between March and August 1998. RESULTS: Feasibility and acceptability of the new questionnaires were indicated by high questionnaire completion rates (adolescents 92%; parents 89%; health professionals 94%). Internal consistency was confirmed (Cronbach's alpha coefficients 0.80 parent; 0.86 health professional). Correlations of Diabetes Quality of Life Questionnaire for Youths (DQOLY) scores with parent and health professional global QOL ratings were generally low (r ranging from 0.12 to 0.36). Parent-rated burden decreased incrementally across adolescence, particularly for girls. Professional-rated burden followed a similar profile but only after age 15 years. Until then, burden was rated as uniformly high. Clinically relevant discrepancies in parent and professional burden scores were noted for one-parent families and families where adolescents had been referred for psychological help. In both cases, health professionals but not one-parent families perceived these as high burden situations. The clinical significance of this relates to the significantly poorer metabolic control recorded for adolescents in both situations. CONCLUSIONS: Parent and health professional questionnaires were found to have adequate internal consistency, and convergent and discriminant validity in relation to key clinical and QOL outcomes. The questionnaires are brief, easy to administer and score. They may also enable comparisons across countries and languages to facilitate development of international health outcome parameters. The inclusion of the parent and health professional perspectives completes a comprehensive assessment of adolescent QOL relevant to diabetes.</p>
  • Lindahl, Bernt, et al. (författare)
  • A randomized lifestyle intervention with 5-year follow-up in subjects with impaired glucose tolerance : pronounced short-term impact but long-term adherence problems
  • 2009
  • Ingår i: Scandinavian Journal of Public Health. - 1403-4948 .- 1651-1905. ; 37:4, s. 434-442
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>AIMS: To compare data on cardiovascular risk factor changes in lipids, insulin, proinsulin, fibrinolysis, leptin and C-reactive protein, and on diabetes incidence, in relation to changes in lifestyle. METHODS: The study was a randomized lifestyle intervention trial conducted in northern Sweden between 1995 and 2000, in 168 individuals with impaired glucose tolerance (IGT) and body mass index above 27 at start. The intensive intervention group (n = 83) was subjected to a 1-month residential lifestyle programme. The usual care group (n = 85) participated in a health examination ending with a single counselling session. Follow-up was conducted at 1, 3 and 5 years. RESULTS: At 1-year follow-up, an extensive cardio-metabolic risk factor reduction was demonstrated in the intensive intervention group, along with a 70% decrease of progress to type 2 diabetes. At 5-year follow-up, most of these beneficial effects had disappeared. Reported physical activity and fibre intake as well as high-density lipoprotein cholesterol were still increased, and fasting insulin and proinsulin were lower. CONCLUSIONS: The intervention affected several important cardio-metabolic risk variables beneficially, and reduced the risk for type 2 diabetes, but the effects persisted only as long as the new lifestyle was maintained. Increased physical activity seemed to be the behaviour that was most easy to preserve.</p>
  • Särnblad, Stefan, 1963-, et al. (författare)
  • Dietary fat intake predicts 1-year change in body fat in adolescent girls with type 1 diabetes
  • 2006
  • Ingår i: Diabetes Care. - 0149-5992 .- 1935-5548. ; 29:6, s. 1227-1230
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>OBJECTIVE</strong>: The purpose of this study was to determine whether objectively measured physical activity and dietary macronutrient intake differentially predict body fat in adolescent girls with type 1 diabetes and control girls.</p><p><strong>RESEARCH DESIGN AND METHODS</strong>: This study comprised 23 girls (12-19 years) with type 1 diabetes and 19 age-matched healthy control girls. At baseline, physical activity and energy intake were assessed for 7 consecutive days by accelerometry and a structured food diary, respectively. Body composition was measured by dual-energy X-ray absorptiometry at baseline and after 1 year.</p><p><strong>RESULTS</strong>: Fat intake was positively related to a 1-year change in percentage body fat (P = 0.006), after adjustment for total energy intake. No significant interaction was observed (case-control group x main exposure), indicating that the association between fat intake and gain in body fat was similar in both groups. Physical activity did not predict gain in body fat; however, total physical activity was positively associated with a gain in lean body mass (P &lt; 0.01). Girls treated with six daily dosages of insulin increased their percentage of body fat significantly more than those treated with four daily injections (P &lt; 0.05).</p><p><strong>CONCLUSIONS</strong>: In this prospective case-control study, we found that fat intake predicted gain in percentage of body fat in both adolescent girls with type 1 diabetes and healthy control girls. The number of daily insulin injections seems to influence the accumulation of body fat in girls with type 1 diabetes.</p>
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