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  • Siljander, Heli (Helsingin yliopisto, 2010)
    Background and aims. Type 1 diabetes (T1D), an autoimmune disease in which the insulin producing beta cells are gradually destroyed, is preceded by a prodromal phase characterized by appearance of diabetes-associated autoantibodies in circulation. Both the timing of the appearance of autoantibodies and their quality have been used in the prediction of T1D among first-degree relatives of diabetic patients (FDRs). So far, no general strategies for identifying individuals at increased disease risk in the general population have been established, although the majority of new cases originate in this population. The current work aimed at assessing the predictive role of diabetes-associated immunologic and metabolic risk factors in the general population, and comparing these factors with data obtained from studies on FDRs. Subjects and methods. Study subjects in the current work were subcohorts of participants of the Childhood Diabetes in Finland Study (DiMe; n=755), the Cardiovascular Risk in Young Finns Study (LASERI; n=3475), and the Finnish Type 1 Diabetes Prediction and Prevention Study (DIPP) Study subjects (n=7410). These children were observed for signs of beta-cell autoimmunity and progression to T1D, and the results obtained were compared between the FDRs and the general population cohorts. --- Results and conclusions. By combining HLA and autoantibody screening, T1D risks similar to those reported for autoantibody-positive FDRs are observed in the pediatric general population. Progression rate to T1D is high in genetically susceptible children with persistent multipositivity. Measurement of IAA affinity failed in stratifying the risk assessment in young IAA-positive children with HLA-conferred disease susceptibility, among whom affinity of IAA did not increase during the prediabetic period. Young age at seroconversion, increased weight-for-height, decreased early insulin response, and increased IAA and IA-2A levels predict T1D in young children with genetic disease susceptibility and signs of advanced beta-cell autoimmunity. Since the incidence of T1D continues to increase, efforts aimed at preventing T1D are important, and reliable disease prediction is needed both for intervention trials and for effective and safe preventive therapies in the future. Our observations confirmed that combined HLA-based screening and regular autoantibody measurements reveal similar disease risks in pediatric general population as those seen in prediabetic FDRs, and that risk assessment can be stratified further by studying glucose metabolism of prediabetic subjects. As these screening efforts are feasible in practice, the knowledge now obtained can be exploited while designing intervention trials aimed at secondary prevention of T1D.
  • Molander, Pauliina (Helsingin yliopisto, 2014)
    In the era of TNFα-blocking therapy, MH and even DR have been suggested as new therapeutic targets in both CD and UC. Recent studies have indicated that DR may be achieved in roughly half of IBD patients on TNFα-blocking maintenance therapy, resulting in more favorable treatment outcomes. However, considering the potential side-effects and economic issues associated with long-term immunosuppressive therapy with TNFα-blocking agents, the possibility of discontinuing therapy should be evaluated at least once after achieving DR. At present, no widely accepted recommendations for discontinuing TNFα-blocking therapy are available. Based on the results of our study, only for about half of patients in DR were candidates for discontinuation of TNF-blocking medication for various reasons. Nevertheless, up to 67% of IBD patients in DR at the time of cessation of TNFα-blocking therapy remained in clinical remission during the 12-month follow-up, and moreover, the majority of these patients also remained in endoscopic remission. Therefore, withdrawal of therapy could be considered in IBD patients in DR even after one-year treatment. Reassuringly, in case of a relapse, the response to restart of TNFα-blocking therapy seems to be effective and well-tolerated. To evaluate treatment response and possible relapse during maintenance therapy or after discontinuation of TNFα-blocking therapy, FC seems to be a reliable surrogate marker to replace endoscopic assessment. A normal FC after induction with TNFα-blocking agents predicts sustained remission in the majority of patients with active luminal disease receiving scheduled treatment. However, an objective cut-off value for treatment response and relapse risk is to some extent still undefined. To predict IBD relapse and identify patients requiring a close follow-up in clinical practice, FC seems to be a useful surrogate marker, as it increases and remains elevated as early as 6 months before symptomatic relapse. FC measurements should therefore be included in monitoring IBD patient s treatment response in everyday clinical practice.
  • Geneid, Ahmed (Helsingin yliopisto, 2013)
    Over the last decades, school teachers and singers have been more or less the focus of voice research, due to their specific occupational needs. Now, other population groups as well start to draw attention. These new groups include workers exposed to organic dusts in various workplaces with possible laryngeal reactions. The second group includes children operated on for subglottic stenosis with possible effects on voice and related quality of life. The third are nursery teachers insufficiently studied through field research for possible voice problems. This thesis aims to shed light on these newly emerging vulnerable groups in terms of assessing their voices through questionnaires, perceptual and acoustic voice assessment, and videolaryngoscopic examination. The thesis includes four studies. Nine subjects with suspected occupational rhinitis or asthma participated in Studies I and II. They had single blinded exposures to organic dust and placebo substances. Subjective and perceptual voice assessment was done in addition to acoustic analysis of 180 samples using glottal inverse filtering. In Study III, children s voices were perceptually assessed as well as their health- and voice-related quality of life. In Study IV, 119 female kindergarten teachers responded to a questionnaire on voice habits, voice symptoms, and impact of various working conditions on voice. In addition, videolaryngoscopy examinations took place in these teachers workplaces. Studies I and II showed that some self-assessed voice and throat symptoms changed significantly after organic dust exposure, although perceptual assessment failed to record these changes. However, inverse filtering analysis revealed changes that represent the ones reported by the subjects. In Study III, voice-related quality of life and perceptual assessment of the study group showed lower scores than the controls . Study IV showed that 71.5% of the teachers examined reported frequent strain on the voice. Organic findings were observed in 10.9% of the subjects and did not correlate with subjective voice symptoms. The thesis added new information on these high-risk groups, identifying an occupational voice-disorder risk group related to laryngeal reactions rather than voice abuse. It also added information on the long-term effects of surgery for subglottic stenosis in early infancy. Nevertheless, field videolaryngoscopy was quite accurate in determining the percentage of organic findings among nursery teachers.
  • Saarinen, Ilona (Helsingfors universitet, 2012)
    The aim of this retrospective case-control study was to investigate association between post-term pregnancy and ABO blood groups and Rhesus factor. The original data was derived from the Helsinki University Central Hospital over a 4-year period (n=58,036 deliveries). The data on ABO blood groups and Rhesus factors were collected from Weblab-database and combined with the original data. There were 378 cases (post-term) and 8,626 controls (gestational age 37+0 – 41+6) after data linkage. Statistical comparisons were performed using Chi-Square and Mann-Whitney U-tests. The association between blood groups and the length of the pregnancy was analyzed by binary unconditional logistic regression. The AB blood group, and especially AB+ blood group, was associated with 1.5- and 1.6-fold higher risk of post term pregnancy, respectively. The Rhesus factor was not associated with higher or lower risk. Thus, gravidas without anti-A, anti-B and anti-D antibodies seem to have the highest risk for postterm pregnancy.
  • Karhula, Kati (Helsingin yliopisto, 2015)
    Health care personnel often have irregular working hours and stressful work characteristics, which may challenge employees possibilities to sleep and recover sufficiently. The aim of this study was to examine the association of stressful work characteristics, measured as job strain, with sleep and psychophysiological recovery in shift working health care professionals. As part of the Finnish Public Sector Study, 95 participants were recruited from hospital wards that belonged to the top (high job strain, HJS, n=42) or bottom quartiles on job strain (low job strain, LJS, n=53) as determined by the average job strain score among the employees of the ward. These participants experienced job strain at least as high (HJS group) or as low (LJS group) as the average on their ward. Measurements included a Trier Social Stress Test (TSST), and 3-week field measures of sleep-wake rhythm with sleep diary and actigraphy. The 3-week rosters included three pre-selected, circadian rhythm and recovery controlled measurement days, one morning shift, one night shift and a day off, and the following measurements: ratings of sleepiness (Karolinska Sleepiness Scale), Psychomotor Vigilance Test (PVT), 24h heart rate variability (HRV) measurements and saliva samples of stress biomarkers (cortisol and alpha-amylase). The rosters of the HJS group included more single days off and quick returns than the rosters of the LJS group. Severe sleepiness (KSS score of ≥7) was more common in the HJS group in quick returns. The HJS group reported poorer recovery from all work shifts and after morning shifts than the LJS group. High job strain was not associated with extended working hours. The HJS group had more difficulties in initiating sleep after evening shifts, more often reduced sleep efficiency before morning shifts, and took fewer and shorter naps before the first night shift than the LJS group. Additionally, the HJS group had more often lapses in the PVT during night shifts. Insufficient sleep (31%) and sleep complaints (often 68%) were common in shift workers regardless of the job strain group. The TSST resulted in, on average, a 2.27-fold increase in cortisol concentration in the HJS group and a 1.48-fold increase in the LJS group (non-significant group difference). The HJS group also had higher salivary alpha-amylase levels 30 minutes after awakening in the morning shift. Apart from that, the salivary cortisol and alpha-amylase levels, profiles and total secretion showed no statistically significant stress group differences. Heart rate and HRV, before and during sleep, were similar in both job strain groups. Shift work contributed to impaired sleep in both the high and low job strain groups, although the sleep impairments were more pronounced in the HJS group. Associations between job strain and psychophysiological stress-related reactions and recovery were modest. Intervention studies are needed to determine whether increasing recovery time by reducing the number of quick returns and single days off would also reduce job strain and improve sleep quality among shift workers. Emphasising the importance of sufficient sleep might promote shift workers´ recovery and well-being.
  • Lawson, Tom (2000)
    Body weight is closely related to several known cardiovascular risk factors and may also have an independent effect on the risk of coronary heart disease (CHD). The cardiovascular risk factor levels of the Finnish population have been assessed in Finland since 1972, though in the beginning the surveys were done to evaluate the North Karelia Project, which was a community-based preventive program and a National cardiovascular risk factors monitoring system was developed to assess the effectiveness of the national strategy. The purpose of this report was to examine cross-sectional data to assess the independent contribution of Body mass index (BMI) and Waist-hip-ratio (WHR) to the risk of Cardiovascular disease (CVD) and to find out the importance of WHR for the incidence of chronic diseases in 4110 Finnish men and 4084 Finnish women between the ages 25-74 years old who were participants in the 1997 examinations of FINMONICA-Project and were not treated for with cardiovascular medication. BMI was used as a measure of obesity and WHR as fat distribution measurements and both were adjusted for age, on cholesterols, and blood pressures in separate models for men and women in the data. Obesity were estimated from body weight, height and the body fat from skinfold-thickness measurements. The analysis is confined to the relationships between the risk factors and this risk factors was divided into two groups, the first consisting of the operational measures of cholesterols level and blood pressures respectively High density lipoprotein cholesterol (HDL), Non high density lipoprotein cholesterol (NHDL), Ratio of HDL and NHDL (HNR), Systollinen blood pressure (SYS1) and Diastollinen blood pressure (DIAS1), while the second consist of obesity (BMI) and body fat (WHR). The analysis was done to study the interaction effect of obesity and body fat on cholesterols level and blood pressures. BMI and WHR interaction effect was only significant in NHDL (P > 0.0071) and almost significant in HNR (P > 0.0789) in men and no significant interaction in women. This gender difference could easily have been overlooked if gender had been included in the analyses of variance as an explanatory factor.
  • Komulainen, Kaisla (Helsingin yliopisto, 2015)
    Adolescent delinquency is a prevalent concern, which carries with psychological and societal costs. Deviant peer affiliation and criminogenic attitudes, as well as personality traits are known to be associated with delinquency, but their interlinked effects are less studied. The present study examines the role of personality in a deviant socialization context. Specifically, I examine whether peer deviance and criminogenic attitudes (1) mediate and/or (2) moderate the associations of the Five-Factor Model personality traits with delinquency. The data included respondents (n=4855) to the cross-sectional Finnish Self-Report Delinquency Study 2012, aged 14-17 years. Delinquency was assessed on the basis of 17 different deviant behaviors; the reported frequencies of engaging in each of them were scaled using a graded response model. Peer deviance and criminogenic attitudes were assessed via respondents’ selfreports; two distinct attitudinal indicators (deviant and neutralizing attitudes) were included. Personality was assessed with a 15-item BFI-S questionnaire. A structural equation model was conducted to examine the mediation pathways. The moderation effects were examined with linear regression analysis. Delinquency was associated with higher extraversion, lower agreeableness, lower conscientiousness, and lower neuroticism. Peer deviance and criminogenic attitudes partially mediated the associations of extraversion, agreeableness, and conscientiousness with delinquency. The association between neuroticism and delinquency was fully mediated via criminogenic attitudes. Peer deviance strengthened the associations of low neuroticism, low agreeableness, and low conscientiousness with delinquency. Deviant and neutralizing attitudes strengthened the associations of high extraversion and low agreeableness with delinquent conduct. The findings suggest that personality may provide novel insights into the etiology of delinquency in a context of deviant socialization. Implications of the personality-based approach and directions for further research are discussed.
  • Laaksonen , Matti (Helsingin yliopisto, 2010)
    The Enamel matrix derivative Emdogain® (EMD) is a commercially available tissue extract preparation of porcine enamel origin. Studies have shown EMD to be clinically useful in promoting periodontal regeneration. EMD has been widely used in periodontal therapy for over ten years, but the mechanism of its action and the exact composition are not completely clear. EMD is predominantly amelogenin (>90%). However, unlike amelogenin, EMD has a number of growth factor-like effects and it has been shown to enhance the proliferation, migration and other cellular functions of periodontal ligament fibroblasts and osteoblasts. In contrast, the effects of EMD on epithelial cell lines and in particular on oral malignant cells have not been adequately studied. In addition, EMD has effects on the production of cytokines by several oral cell lines and the product is in constant interaction with different oral enzymes. Regardless of the various unknown properties of EMD, it is said to be clinically safe in regenerative procedures, also in medically compromised patients. The aim of the study was to examine whether gingival crevicular fluid (GCF), which contains several different proteolysis enzymes, could degrade EMD and alter its biological functions. In addition, the objective was to study the effects of EMD on carcinogenesis-related factors, in particular MMPs, using in vitro and in vivo models. This study also aimed to contribute to the understanding of the composition of EMD. GCF was capable of degrading EMD, depending on the periodontal status, with markedly more degradation in all states of periodontal disease compared to healthy controls. EMD was observed to stimulate the migration of periodontal ligament fibroblasts (PLF), whereas EMD together with GCF could not stimulate this proliferation. In addition, recombinant amelogenin, the main component of EMD, decreased the migration of PLFs. A comparison of changes induced by EMD and TGF-β1 in the gene profiles of carcinoma cells showed TGF-β1 to regulate a greater number of genes than EMD. However, both of the study reagents enhanced the expression of MMP-10 and MMP-9. Furthermore, EMD was found to induce several factors closely related to carcinogenesis on gene, protein, cell and in vivo levels. EMD enhanced the production of MMP-2, MMP-9 and MMP-10 proteins by cultured carcinoma cells. In addition, EMD stimulated the migration and in vitro wound closure of carcinoma cells. EMD was also capable of promoting metastasis formation in mice. In conclusion, the diseased GCF, containing various proteases, causes degradation of EMD and decreased proliferation of PLFs. Thus, this in vitro study suggests that the regenerative effect of EMD may decrease due to proteases present in periodontal tissues during the inflammation and healing of the tissues in vivo. Furthermore, EMD was observed to enhance several carcinoma-related factors and in particular the production of MMPs by benign and malignant cell lines. These findings suggest that the clinical safety of EMD with regard to dysplastic mucosal lesions should be further investigated.
  • Lallukka, Tea (Helsingin yliopisto, 2008)
    Adverse health behaviors as well as obesity are key risk factors for chronic diseases. Working conditions also contribute to health outcomes. It is possible that the effects of psychosocially strenuous working conditions and other work-related factors on health are, to some extent, explained by adverse behaviors. Previous studies about the associations between several working conditions and behavioral outcomes are, however, inconclusive. Moreover, the results are derived mostly from male populations, one national setting only, and with limited information about working conditions and behavioral risk factors. Thus, with an interest in employee health, this study was set to focus on behavioral risk factors among middle-aged employees. More specifically, the main aim was to shed light on the associations of various working conditions with health behaviors, weight gain, obesity, and symptoms of angina pectoris. In addition to national focus, international comparisons were included to test the associations across countries thereby aiming to produce a more comprehensive picture. Furthermore, a special emphasis was on gaining new evidence in these areas among women. The data derived from the Helsinki Health Study, and from collaborative partners at the Whitehall II Study, University College London, UK, and the Toyama University, Japan. In Helsinki, the postal questionnaires were mailed in 2000-2002 to employees of the City of Helsinki, aged 40 60 years (n=8960). The questionnaire data covered e.g., socio-economic indicators and working conditions such as Karasek s job demands and job control, work fatigue, working overtime, work-home interface, and social support. The outcome measures consisted of smoking, drinking, physical activity, food habits, weight gain, obesity, and symptoms of angina pectoris. The international cohorts included comparable data. Logistic regression analysis was used. The models were adjusted for potential confounders such as age, education, occupational class, and marital status subject to specific aims. The results showed that working conditions were mostly unassociated with health behaviors, albeit some associations were found. Low job strain was associated with healthy food habits and non-smoking among women in Helsinki. Work fatigue, in turn, was related to drinking among men and physical inactivity among women. Work fatigue and working overtime were associated with weight gain in Helsinki among both women and men. Finally, work fatigue, low job control, working overtime, and physically strenuous work were associated with symptoms of angina pectoris among women in Helsinki. Cross-country comparisons confirmed mostly non-existent associations. High job strain was associated with physical inactivity and smoking, and passive work with physical inactivity and less drinking. Working overtime, in turn, related to non-smoking and obesity. All these associations were, however, inconsistent between cohorts and genders. In conclusion, the associations of the studied working conditions with the behavioral risk factors lacked general patters, and were, overall, weak considering the prevalence of psychosocially strenuous work and overtime hours. Thus, based on this study, the health effects of working conditions are likely to be mediated by adverse behaviors only to a minor extent. The associations of work fatigue and working overtime with weight gain and symptoms of angina pectoris are, however, of potential importance to the subsequent health and work ability of employees.
  • Martikainen, Silja (Helsingin yliopisto, 2010)
    This thesis examines the associations between personality traits and sleep quantity and quality in young adults. Additionally the possible effects of birth status on these associations are examined. The data used in this thesis is part of a birth cohort study (Helsinki Study of Very Low Birth Weight Adults). The personality traits are based on the five-factor model of personality. The sleep quantity and quality are based on actigraphy assessments. Four hypothesis were made about the personality and sleep associations: (1) neuroticism is related to a lesser quality of sleep, (2) there will be more significant associations between personality traits and sleep quality than between personality traits and sleep quantity, (3) the Very Low Birth Weight (VLBW) as well as, (4) the Small for Gestational Age (SGA) status will affect the associations. Linear regressions were used to study the associations between personality traits and sleep quality and quantity. Whenever an association was significant, it was tested whether this association was moderated first, by the VLBW and second, by the SGA status of the participant. The results were mostly in line with previous research especially demonstrating the negative association between neuroticism and the quality of sleep and suggesting that vulnerability to stress decreases sleep quality. Also it was found that agreeableness and conscientiousness were associated with better sleep quality and extraversion was associated with lower sleep quantity. In addition SGA status moderated the personality and sleep associations. It is proposed that there are two factors behind the interaction. First, prenatally developing mechanisms have an effect on the development of sleep as well as personality. Second, differences in the postnatal environment, for instance the parenting practices, can account for this finding. Future research could focus especially on what kind of prenatal disturbances SGA infants have in the development of mechanisms related to sleep and personality. Also focusing on the differences in parental interaction might shed more light on the results.
  • Laaksonen, Marika (Helsingin yliopisto, 2008)
    Heredity explains a major part of the variation in calcium homeostasis and bone strength, and the susceptibility to osteoporosis is polygenetically regulated. Bone phenotype results from the interplay between lifestyle and genes, and several nutritional factors modulate bone health throughout life. Thus, nutrigenetics examining the genetic variation in nutrient intake and homeostatic control is an important research area in the etiology of osteoporosis. Despite continuing progress in the search for candidate genes for osteoporosis, the results thus far have been inconclusive. The main objective of this thesis was to investigate the associations of lactase, vitamin D receptor (VDR), calcium sensing receptor (CaSR) and parathyroid hormone (PTH) gene polymorphisms and lifestyle factors and their interactions with bone health in Finns at varying stages of the skeletal life span. Markers of calcium homeostasis and bone remodelling were measured from blood and urine samples. Bone strength was measured at peripheral and central bone sites. Lifestyle factors were assessed with questionnaires and interviews. Genetic lactase non-persistence (the C/C-13910 genotype) was associated with lower consumption of milk from childhood, predisposing females in particular to inadequate calcium intake. Consumption of low-lactose milk and milk products was shown to decrease the risk for inadequate calcium intake. In young adulthood, bone loss was more common in males than in females. Males with the lactase C/C-13910 genotype may be more susceptible to bone loss than males with the other lactase genotypes, although calcium intake predicts changes in bone mass more than the lactase genotype. The BsmI and FokI polymorphisms of the VDR gene were associated with bone mass in growing adolescents, but the associations weakened with age. In young adults, the A986S polymorphism of the calcium sensing receptor gene was associated with serum ionized calcium concentrations, and the BstBI polymorphism of the parathyroid gene was related to bone strength. The FokI polymorphism and sodium intake showed an interaction effect on urinary calcium excretion. A novel gene-gene interaction between the VDR FokI and PTH BstBI gene polymorphisms was found in the regulation of PTH secretion and urinary calcium excretion. Further research should be carried out with more number of Finns at varying stages of the skeletal life span and more detailed measurements of bone strength. Research should concern mechanisms by which genetic variants affect calcium homeostasis and bone strength, and the role of diet-gene and gene-gene interactions in the pathogenesis of osteoporosis.
  • Luotola, Kari (Helsingin yliopisto, 2011)
    The upstream proinflammatory interleukin-1 (IL-1) cytokines, together with a naturally occurring IL-1 receptor antagonist (IL-1Ra), play a significant role in several diseases and physiologic conditions. The IL-1 proteins affect glucose homeostasis at multiple levels contributing to vascular injuries and metabolic dysregulations that precede diabetes. An association between IL-1 gene variations and IL-1Ra levels has been suggested, and genetic studies have reported associations with metabolic dysregulation and altered inflammatory responses. The principal aims of this study were to: 1) examine the associations of IL-1 gene variation and IL-1Ra expression in the development and persistence of thyroid antibodies in subacute thyroiditis; 2) investigate the associations of common variants in the IL-1 gene family with plasma glucose and insulin concentrations, glucose homeostasis measures and prevalent diabetes in a representative population sample; 3) investigate genetic and non-genetic determinants of IL-1Ra phenotypes in a cross-sectional setting in three independent study populations; 4) investigate in a prospective setting (a) whether variants of the IL-1 gene family are predictors for clinically incident diabetes in two population-based observational cohort studies; and (b) whether the IL-1Ra levels predict the progression of metabolic syndrome to overt diabetes during the median follow-up of 10.8 and 7.1 years. Results from on patients with subacte thyroiditis showed that the systemic IL-1Ra levels are elevated during a specific proinflammatory response and they correlated with C-reactive protein (CRP) levels. Genetic variation in the IL-1 family seemed to have an association with the appearance of thyroid peroxidase antibodies and persisting local autoimmune responses during the follow-up. Analysis of patients suffering from diabetes and metabolic traits suggested that genetic IL-1 variation and IL-1Ra play a role in glucose homeostasis and in the development of type 2 diabetes. The coding IL-1 beta SNP rs1143634 was associated with traits related to insulin resistance in cross-sectional analyses. Two haplotype variants of the IL-1 beta gene were associated with prevalent diabetes or incident diabetes in a prospective setting and both of these haplotypes were tagged by rs1143634. Three variants of the IL-1Ra gene and one of the IL-1 beta gene were consistently identified as significant, independent determinants of the IL-1Ra phenotype in two or three populations. The proportion of the phenotypic variation explained by the genetic factors was modest however, while obesity and other metabolic traits explained a larger part. Body mass index was the strongest predictor of systemic IL-1Ra concentration overall. Furthermore, the age-adjusted IL-1Ra concentrations were elevated in individuals with metabolic syndrome or diabetes when compared to those free of metabolic dysregulation. In prospective analyses the systemic IL-1Ra levels were found as independent predictors for the development of diabetes in people with metabolic syndrome even after adjustment for multiple other factors, including plasma glucose and CRP levels. The predictive power of IL-1Ra was better than that of CRP. The prospective results also provided some evidence for a role of common IL-1 alpha promoter SNP rs1800587 in the development of type 2 diabetes among men and suggested that the role may be gender specific. Likewise, common variations in the IL-1 beta coding region may have a gender specific association with diabetes development. Further research on the potential benefits of IL-1Ra measurements in identifying individuals at high risk for diabetes, who then could be targeted for specific treatment interventions, is warranted. It has been reported in the recent literature that IL-1Ra secreted from adipose tissue has beneficial effects on glucose homeostasis. Furthermore, treatment with recombinant human IL-1Ra has been shown to have a substantial therapeutic potential. The genetic results from the prospective analyses performed in this study remain inconclusive, but together with the cross-sectional analyses they suggest gender-specific effects of the IL-1 variants on the risk of diabetes. Larger studies with more extensive genotyping and resequencing may help to pinpoint the exact variants responsible and to further elucidate the biological mechanisms for the observed associations. This would improve our understanding of the pathways linking inflammation and obesity with glucose and insulin metabolism.