Long-term health-related quality of life in persons diagnosed with an insulinoma in Finland 1980-2010.

OBJECTIVE: Insulinomas are rare pancreatic neoplasms, which can usually be cured by surgery. As the diagnostic delay is often long and the prolonged hyperinsulinemia may have long-term effects on health and the quality of life, we studied the long-term health-related quality of life (HRQoL) in insulinoma patients. DESIGN, PATIENTS AND MEASUREMENTS: The HRQoL of adults diagnosed with an insulinoma in Finland in 1980-2010 was studied with the 15D instrument, and the results were compared to those of an age- and gender-matched sample of the general population. The minimum clinically important difference in the total 15D score has been defined as ±0.015. The clinical characteristics, details of insulinoma diagnosis and treatment, and the current health status of the subjects were examined to specify the possible determinants of long-term HRQoL. RESULTS: Thirty-eight insulinoma patients participated in the HRQoL survey (response rate 75%). All had undergone surgery with a curative aim, a median of 13 (min 7, max 34) years before the survey. The insulinoma patients had a clinically importantly and statistically significantly better mean 15D score compared with the controls (0.930 ± 0.072 vs 0.903 ± 0.039, P = .046) and were significantly better off regarding mobility, usual activities and eating. Among the insulinoma patients, younger age at the time of survey, higher level of education and smaller number of chronic diseases were associated with better overall HRQoL. CONCLUSIONS: In the long term, the overall HRQoL of insulinoma patients is slightly better than that of the general population.

Effector T Cell Resistance to Suppression and STAT3 Signaling during the Development of Human Type 1 Diabetes.

Dysregulation of regulatory T cell (Treg)-mediated suppression and, in particular, resistance of CD4+ effector T cells (Teffs) to suppression have been implicated in the pathogenesis of human type 1 diabetes (T1D). However, the mechanistic basis behind this resistance and the time frame during which it develops in relation to the onset of clinical T1D remain unclear. In this study, we analyzed the capacity of peripheral blood Teffs isolated both from patients with T1D and from prediabetic at-risk subjects positive for multiple diabetes-associated autoantibodies (AAb+) to be suppressed by Tregs. Because STAT3 activation through IL-6 has previously been implicated in mediating Teff resistance, we also investigated the surface expression of IL-6R as well as IL-6- and TCR-mediated phosphorylation of STAT3 in T cells from our study subjects. Teff resistance to suppression was observed both in patients with newly diagnosed and long-standing T1D but not in AAb+ subjects and was shown to be STAT3 dependent. No alterations in IL-6R expression or IL-6-mediated STAT3 activation were observed in T cells from patients with T1D or AAb+ subjects. However, faster STAT3 activation after TCR stimulation without concomitant increase in IL-6 expression was observed in T cells from patients with T1D. These experiments suggest that Teff resistance in T1D patients is STAT3 dependent but not directly linked with the capacity of Teffs to produce or respond to IL-6. In conclusion, Teff resistance to Treg-mediated suppression is likely a feature of disease progression in human T1D and can potentially be targeted by immune therapies that block STAT3 activation.

Working people with type 1 diabetes in the Finnish population.

BACKGROUND: The incidence of type 1 diabetes is increasing worldwide. Since so little is known about work life of individuals with type 1 diabetes, we examined incidence and prevalence trends of type 1 diabetes among working-aged Finns. We also investigated the employment rate and how workers with type 1 diabetes perceive their health and work ability, and their intended retirement age. METHODS: We analyzed changes in the incidence, prevalence, and employment rate using nationwide multi-register-based FinDM data, and estimated a Self-Rated Health, Work Ability Score, and inquired about retirement intentions of 767 working individuals with type 1 diabetes in a cross-sectional survey. All estimates were compared to the corresponding data of the Finnish general population. RESULTS: The average annual age-standardized incidence rate of type 1 diabetes among men aged 18-39 was 29 per 100,000/year; the incidence rate has increased by 33% from 1992 to 2007. Among women, the incidence remained at 16 per 100,000/year. Among working-aged (18-64) people, the age-standardized prevalence of type 1 diabetes increased by 39% among women and 33% among men. Two out of every three working aged individuals with type 1 diabetes were in the labor force; this is about 10% lower than in the Finnish population. The average age-standardized employment rate among those individuals with type 1 diabetes belonging to the labor force was 82%, compared to 84% in the general population. Working individuals with type 1 diabetes rated their health and work ability as being slightly lower than the general working population, but nonetheless, there were no significant differences in retirement intentions. CONCLUSIONS: Between 1992 and 2007, the number of working-aged people and workers with type 1 diabetes increased by 35%. Most workers with type 1 diabetes manage as well at work as the general population. Special attention should be paid to workers with type 1 diabetes when they are diagnosed and/or report moderate or poor work ability.

[Treatment of primary hypothyroidism in adult patients]. / Aikuisen primaarisen hypotyreoosin hoito.

The diagnosis of hypothyroidism is based on the findings of an increased serum TSH (above the reference range) and decreased serum free T4 (below the reference range) concentration. Treatment of subclinical hypothyroidism is indicated if serum THS is above 10 mU/l. For less severe forms of subclinical hypothyroidism, the treatment should be individually tailored. The treatment of choice is synthetic human levothyroxine. The goals for treatment are amelioration of symptoms and normalization of TSH and free T4 concentrations.

A population-based study on the prevalence of NASH using scores validated against liver histology.

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. Diagnosis of NASH requires a liver biopsy. We estimated the prevalence of NASH non-invasively in a population-based study using scores validated against liver histology. METHODS: Clinical characteristics, PNPLA3 genotype at rs738409, and serum cytokeratin 18 fragments were measured in 296 consecutive bariatric surgery patients who underwent a liver biopsy to discover and validate a NASH score ('NASH score'). We also defined the cut-off for NASH for a previously validated NAFLD liver fat score to diagnose NASH in the same cohort ('NASH liver fat score'). Both scores were validated in an Italian cohort comprising of 380, mainly non-bariatric surgery patients, who had undergone a liver biopsy for NASH. The cut-offs were utilized in the Finnish population-based D2D-study involving 2849 subjects (age 45-74 years) to estimate the population prevalence of NASH. RESULTS: The final 'NASH Score' model included PNPLA3 genotype, AST and fasting insulin. It predicted NASH with an AUROC 0.774 (0.709, 0.839) in Finns and 0.759 (0.711, 0.807) in Italians (NS). The AUROCs for 'NASH liver fat score' were 0.734 (0.664, 0.805) and 0.737 (0.687, 0.787), respectively. Using 'NASH liver fat score' and 'NASH Score', the prevalences of NASH in the D2D study were 4.2% (95% CI: 3.4, 5.0) and 6.0% (5.0, 6.9%). Sensitivity analysis was performed by taking into account stochastic false-positivity and false-negativity rates in a Bayesian model. This analysis yielded population prevalences of NASH of 3.1% (95% stimulation limits 0.2-6.8%) using 'NASH liver fat score' and 3.6% (0.2-7.7%) using 'NASH Score'. CONCLUSIONS: The population prevalence of NASH in 45-74 year old Finnish subjects is ∼ 5%.

Perceived sufficiency of physical activity levels among adults at high risk of type 2 diabetes: the FIN-D2D study.

BACKGROUND: Any increase from a low level of physical activity reduces the risk of type 2 diabetes. However, lack of awareness of one's physical activity level insufficiency may act as an obstacle to increased physical activity. PURPOSE: This study assessed the determinants of perceived physical activity levels (PALs) among adults at high risk of diabetes and the associations with self-reported physical activity. METHODS: In total, 10,149 adults participated in the FIN-D2D lifestyle intervention at baseline. Opportunistic screening was used in identifying high-risk individuals. Physical activity and perceived PAL sufficiency were assessed and compared. Key risk factors for diabetes and psychosocial and demographic characteristics were analyzed as determinants using logistic regression. RESULTS: PAL sufficiency was rated realistically by 73 % of men and 75 % of women. Perception of sufficient PAL was more likely among individuals with a smaller waist circumference, a higher level of perceived fitness, and no exercise intention. In men, a higher age, and in women, a lower education, and a lower occupational status, also increased the likelihood of perceiving PAL as sufficient. Out of all the participants, 65 % of men and 66 % of women were inactive. Among the inactive participants, 20 (men) and 16 % (women) overestimated their PAL sufficiency. In both genders, such overestimation was predicted by dyslipidemia, a lower waist circumference, a higher level of perceived fitness, and no exercise intention; also (among men) by a higher age and a family history of diabetes, and (among women) by a lower occupational status, and a lower BMI. CONCLUSIONS: In diabetes prevention, it is important to recognize the groups that perceive their PAL as sufficient since they may not see increased PAL as a tool for decreasing their risk of diabetes.

Perceived need to increase physical activity levels among adults at high risk of type 2 diabetes: a cross-sectional analysis within a community-based diabetes prevention project FIN-D2D.

BACKGROUND: Increased physical activity is a cornerstone of type 2 diabetes prevention. The perception of a need to change is considered essential in behaviour change processes. However, the existing literature on individuals' perceived need to change health behaviour is limited. In order to improve understanding of diabetes prevention through increased physical activity levels (PAL), we assessed factors associated with perceiving a need to increase PAL among adults at high risk of diabetes. METHODS: Opportunistic screening was used within a primary-care based lifestyle intervention covering 10 149 men and women at high risk of type 2 diabetes. Data were obtained at baseline visits. The explored determinants were demographic, anthropometric/clinical, behavioural and psychosocial characteristics, along with four categories of PAL awareness. Logistic regression was used in the analysis. RESULTS: 74% of men (n = 2 577) and 76% of women (n = 4 551) perceived a need to increase their PAL. The participants most likely to perceive this need were inactive, had a larger waist circumference, rated their PAL as insufficient, and were at the contemplation stage of change. Smoking, elevated blood pressure, dyslipidaemia, and a family history of diabetes were not associated with this perception. The likelihood was also greater among women with less perceived fitness and less education. Demographic factors other than education did not determine participants' perceived need to increase PAL. PAL overestimators were less likely to perceive the need to increase their PAL than realistic inactive participants. CONCLUSIONS: Subjective rather than objective health factors appear to determine the perception of a need to increase PAL among adults at high risk of diabetes. Client perceptions need to be evaluated in health counselling in order to facilitate a change in PAL. Practical descriptions of the associations between metabolic risk factors, PAL, and diabetes are needed in order to make the risk factors concrete for at-risk individuals.

Coronary artery disease-related genetic variant on chromosome 10q11 is associated with carotid intima-media thickness and atherosclerosis.

OBJECTIVE: To investigate whether chromosome 10q11.21 influences common carotid intima-media thickness (IMT) and atherosclerosis and whether it is associated with stromal cell-derived factor-1α (SDF-1α) plasma levels. METHODS AND RESULTS: Variation on chromosome 10q11.21 has been consistently associated with coronary artery disease. The genetic variant lies upstream of the gene encoding SDF-1α. We genotyped 3 population cohorts (Bruneck [age range, 45 to 94 years; 50.0% men; n=738], Health2000 [age range, 46 to 76 years; 55.4% men; n=1237], and essential hypertension in families collected in the region of Oxford [HTO] [age range, 19 to 88 years; 47.9% men; n=770]) for single-nucleotide polymorphism rs501120 at the 10q11.21 locus and conducted a meta-analysis in these cohorts to ascertain a relationship between the polymorphism and carotid IMT. The analysis showed that individuals with the T/T genotype had a significantly higher carotid IMT than individuals with the C/T or C/C genotype (pooled weighted mean difference, 23 µm [95% CI, 9 to 37 µm], P=0.0014 under a fixed-effects model; and 23 µm [95% CI, 6 to 41 µm], P=0.009 under a random-effects model). In the Bruneck cohort, in which data for carotid atherosclerosis and plasma SDF-1α levels were available, we observed an association of the T/T genotype with a higher burden of atherosclerosis and increased susceptibility to the development of atherosclerosis during a 5-year follow-up (multivariable odds ratio, 1.73 [95% CI, 1.18 to 2.52]; P=0.005 for the recessive model) and an association between the T/T genotype and lower SDF-1α levels (2.62 ng/mL for T/T versus 2.74 ng/mL for C/C or C/T; P=0.023). CONCLUSIONS: The coronary heart disease-related variant at the 10q11.21 locus is associated with carotid IMT and atherosclerosis.

Associations of cardiovascular risk factors, carotid intima-media thickness and manifest atherosclerotic vascular disease with carpal tunnel syndrome.

BACKGROUND: The role of atherosclerosis in carpal tunnel syndrome (CTS) has not previously been addressed in population studies. The aim of this study was to investigate the associations of cardiovascular risk factors, carotid artery intima-media thickness (IMT), and clinical atherosclerotic diseases with CTS. METHODS: In this cross sectional study, the target population consisted of subjects aged 30 or over who had participated in the national Finnish Health Survey in 2000-2001. Of the 7977 eligible subjects, 6254 (78.4%) were included in our study. Carotid IMT was measured in a sub-sample of subjects aged 45 to 74 (N=1353). RESULTS: Obesity (adjusted odds ratio (OR) 2.4, 95% confidence interval (CI) 1.1-5.4), high LDL cholesterol (OR 3.8, 95% CI 1.6-9.1 for >190 vs. <129 mg/dL), high triglycerides (OR 2.7, 95% CI 1.2-6.1 for >200 vs. <150 mg/dL), hypertension (OR 3.4, 95% CI 1.6-7.4) and cardiac arrhythmia (OR 10.2, 95% CI 2.7-38.4) were associated with CTS in subjects aged 30-44. In the age group of 60 years or over, coronary artery disease (OR 1.9, 95% CI 1.1-3.5), valvular heart disease (OR 2.3, 95% CI 1.0-5.0) and carotid IMT (1.4, 95% CI 0.9-2.1 for each 0.23 mm increase) were associated with CTS. Carotid IMT was associated with CTS only in subjects with hypertension or clinical atherosclerotic vascular disease, or in those who were exposed to physical workload factors. CONCLUSIONS: Our findings suggest an association between CTS and cardiovascular risk factors in young people, and carotid IMT and clinical atherosclerotic vascular disease in older people. CTS may either be a manifestation of atherosclerosis, or both conditions may share similar risk factors.

Long-term outcomes of lifestyle intervention to prevent type 2 diabetes in people at high risk in primary health care.

AIMS: The Finnish National Diabetes Prevention Program (FIN-D2D) was the first large-scale diabetes prevention program in a primary health care setting in the world. The risk reduction of type 2 diabetes was 69% after one-year intervention in high-risk individuals who were able to lose 5% of their weight. We investigated long-term effects of one-year weight change on the incidence of type 2 diabetes, cardiovascular events, and all-cause mortality. METHODS: A total of 10,149 high-risk individuals for type 2 diabetes were identified in primary health care centers and they were offered lifestyle intervention to prevent diabetes. Of these individuals who participated in the baseline screening, 8353 had an oral glucose tolerance test (OGTT). Complete follow-up data during one-year intervention were available for 2730 individuals and those were included in the follow-up analysis. The long-term outcome events were collected from national health registers after the median follow-up of 7.4 years. RESULTS: Among individuals who lost weight 2.5-4.9% and 5% or more during the first year, the hazard ratio for the incidence of drug-treated diabetes was 0.63 (95% CI 0.49-0.81, p = 0.0001), and 0.71 (95% CI 0.56-0.90, p = 0.004), respectively, compared with those with stable weight. There were no significant differences in cardiovascular events or all-cause mortality among study participants according to one-year weight changes. CONCLUSIONS: High-risk individuals for type 2 diabetes who achieved a moderate weight loss by one-year lifestyle counseling in primary health care had a long-term reduction in the incidence of drug-treated type 2 diabetes. The observed moderate weight loss was not associated with a reduction in cardiovascular events.

Long-term morbidity and mortality in patients diagnosed with an insulinoma.

OBJECTIVE: Insulinomas are rare functional pancreatic neuroendocrine tumours. As previous data on the long-term prognosis of insulinoma patients are scarce, we studied the morbidity and mortality in the Finnish insulinoma cohort. DESIGN: Retrospective cohort study. METHODS: Incidence of endocrine, cardiovascular, gastrointestinal and psychiatric disorders, and cancers was compared in all the patients diagnosed with an insulinoma in Finland during 1980-2010 (n = 79, including two patients with multiple endocrine neoplasia type 1 syndrome), vs 316 matched controls, using the Mantel-Haenszel method. Overall survival was analysed with Kaplan-Meier and Cox regression analyses. RESULTS: The median length of follow-up was 10.7 years for the patients and 12.2 years for the controls. The long-term incidence of atrial fibrillation (rate ratio (RR): 2.07 (95% CI: 1.02-4.22)), intestinal obstruction (18.65 (2.09-166.86)), and possibly breast (4.46 (1.29-15.39) and kidney cancers (RR not applicable) was increased among insulinoma patients vs controls, P < 0.05 for all comparisons. Endocrine disorders and pancreatic diseases were more frequent in the patients during the first year after insulinoma diagnosis, but not later on. The survival of patients with a non-metastatic insulinoma (n = 70) was similar to that of controls, but for patients with distant metastases (n = 9), the survival was significantly impaired (median 3.4 years). CONCLUSIONS: The long-term prognosis of patients with a non-metastatic insulinoma is similar to the general population, except for an increased incidence of atrial fibrillation, intestinal obstruction, and possibly breast and kidney cancers. These results need to be confirmed in future studies. Metastatic insulinomas entail a markedly decreased survival.

Characteristics and outcomes of the Finnish ectopic ACTH syndrome cohort.

PURPOSE: Ectopic ACTH syndrome (EAS) is rare. We established a national cohort to increase awareness and address unmet needs. METHODS: The Finnish national EAS cohort includes 60 patients diagnosed in 1997-2016. We assessed clinical features, diagnostic work-ups, treatments, incidence, and outcomes of subgroups occult tumor (OT), well-differentiated neuroendocrine tumor G1/G2 (NETG1/G2) and NET G3/neuroendocrine carcinoma (NETG3/NEC). RESULTS: The distribution of OT, NETG1/G2, and NETG3/NEC was 10 (17%), 20 (33%), and 30 (50%), respectively; and median follow-up 22 months (0-249). Annual incidence (0.20-0.93 per million inhabitants) and tumor subgroups (OT vs. NEC) varied across the country. The longest diagnostic delay from EAS onset to radiological tumor identification was 48 months. In NET/NEC, 6/50 (12%) were diagnosed 1-24 years before EAS onset. Osteoporotic fractures (32%) and severe infections (55%) were common. The CRH stimulation test accurately diagnosed EAS in 25/31 (81%). Metyrapone (≤6 g daily, prescribed in 88%) was well tolerated. In NETG1/G2, 13/20 (65%) underwent curative resection of the primary tumor; four experienced recurrence within 2-12 years. In OT, 70% underwent bilateral adrenalectomy. Five-year overall survival in OT, NETG1/G2, and NETG3/NEC was 90%, 55%, and 0%, respectively (P < 0.001). Morning cortisol, hypokalemia, infections, metastatic disease, and acute onset were negative, whereas resection of the primary tumor and bilateral adrenalectomy were positive predictors of survival. CONCLUSIONS: NET/NEC may precede EAS onset by several years. In NETG1/G2, recurrences may occur > 10 years after successful primary surgery. Tumor subgroup (OT, NETG1/G2, NEC) was an independent predictor of survival.

Coronary artery disease-associated locus on chromosome 9p21 and early markers of atherosclerosis.

BACKGROUND: Genome-wide association studies have recently identified a locus on chromosome 9p21 that influences risk of coronary artery disease (CAD). The effect of the locus on early markers of atherosclerosis is unknown. We examined its association with carotid intima-media thickness (CIMT) and brachial flow-mediated dilatation (FMD). METHODS AND RESULTS: We genotyped 2277 individuals, age 24 to 39 years, from the Cardiovascular Risk in Young Finns Study with CIMT and FMD measurements and 1295 individuals, age 46 to 76 years, from the Health 2000 Survey with CIMT for rs1333049, the chromosome 9p21 variant showing the strongest association with CAD. Both mean and maximum CIMT were significantly higher (P<0.001) in the older subjects of the Health 2000 Survey compared with the Young Finns Study. However, there was no association of the rs1333049 genotype with either mean or maximum CIMT at either age (P=0.959 and 0.977 for the 2 phenotypes in the Young Finns Study and P=0.714 and 0.725 in the Health 2000 Survey). Similarly, there was no association of the locus with variation in FMD in the Young Finns cohort (P=0.521). CONCLUSIONS: The chromosome 9p21 locus does not influence CAD risk through a mechanism that also affects CIMT or induces early changes in FMD.

Food neophobia associates with poorer dietary quality, metabolic risk factors, and increased disease outcome risk in population-based cohorts in a metabolomics study.

BACKGROUND: Food neophobia is considered a behavioral trait closely linked to adverse eating patterns and reduced dietary quality, which have been associated with increased risk of obesity and noncommunicable diseases. OBJECTIVES: In a cross-sectional and prospective study, we examined how food neophobia is associated with dietary quality, health-related biomarkers, and disease outcome incidence in Finnish and Estonian adult populations. METHODS: The study was conducted based on subsamples of the Finnish DIetary, Lifestyle, and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) cohort (n = 2982; age range: 25-74 y) and the Estonian Biobank cohort (n = 1109; age range: 18-83 y). The level of food neophobia was assessed using the Food Neophobia Scale, dietary quality was evaluated using the Baltic Sea Diet Score (BSDS), and biomarker profiles were determined using an NMR metabolomics platform. Disease outcome information was gathered from national health registries. Follow-up data on the NMR-based metabolomic profiles and disease outcomes were available in both populations. RESULTS: Food neophobia associated significantly (adjusted P < 0.05) with health-related biomarkers [e.g., ω-3 (n-3) fatty acids, citrate, α1-acid glycoprotein, HDL, and MUFA] in the Finnish DILGOM cohort. The significant negative association between the severity of food neophobia and ω-3 fatty acids was replicated in all cross-sectional analyses in the Finnish DILGOM and Estonian Biobank cohorts. Furthermore, food neophobia was associated with reduced dietary quality (BSDS: ß: -0.03 ± 0.006; P = 8.04 × 10-5), increased fasting serum insulin (ß: 0.004 ± 0.0013; P = 5.83 × 10-3), and increased risk of type 2 diabetes during the ∼8-y follow-up (HR: 1.018 ± 0.007; P = 0.01) in the DILGOM cohort. CONCLUSIONS: In the Finnish and Estonian adult populations, food neophobia was associated with adverse alteration of health-related biomarkers and risk factors that have been associated with an increased risk of noncommunicable diseases. We also found that food neophobia associations with ω-3 fatty acids and associated metabolites are mediated through dietary quality independent of body weight.

The metabolic syndrome predicts incident stroke: a 14-year follow-up study in elderly people in Finland.

BACKGROUND AND PURPOSE: Limited information is available on the role of the metabolic syndrome (MetS) to predict stroke. We investigated the relationship of the MetS and its single components, defined by 6 different criteria, with stroke in a prospective population-based study. METHODS: The MetS was defined according to the World Health Organization, the European Group for the Study of Insulin Resistance, the National Cholesterol Education Program (NCEP), the American College of Endocrinology, the International Diabetes Federation, and the American Heart Association (updated NCEP) criteria. We investigated the relationship of the MetS with stroke using Cox regression analyses in 991 Finnish subjects without diabetes, aged 65 to 74 years at baseline, and followed-up for 14 years. RESULTS: The MetS defined by the World Health Organization, European Group for the Study of Insulin Resistance, NCEP, International Diabetes Federation, and updated NCEP criteria was significantly associated with incident stroke (fatal and nonfatal) when adjusted for confounding variables (HR, 1.52 to 1.72). After exclusion of subjects with myocardial infarction, these 5 definitions still predicted stroke (HR, 1.49 to 1.80). Of the single components of the MetS, the following predicted stroke in multivariable models when subjects with myocardial infarction were excluded: impaired glucose tolerance (2-hour glucose in an oral glucose tolerance test, 7.8 to 11.0 mmol/L) by the World Health Organization and American College of Endocrinology criteria (HR, 1.66); insulin resistance (HR, 1.60) by the European Group for the Study of Insulin Resistance criteria; and central obesity (HR, 1.52) by the NCEP criteria. CONCLUSIONS: The MetS defined by the 6 criteria except for the American College of Endocrinology definition predicts stroke in elderly subjects. However, impaired glucose tolerance alone is as strong a predictor of stroke as is the MetS defined by the World Health Organization, NCEP and updated NCEP criteria.

Concealment of type 1 diabetes at work in Finland: a mixed-method study.

OBJECTIVES: To explore the possible reasons for concealing type 1 diabetes (T1D) at work. METHODS: The main set of data came from a cross-sectional survey (response rate 49.3%), the participants of which were 688 wage earners with T1D. Concealment of T1D was measured by asking respondents have they ever during their working career hidden their diabetes from their (A) colleagues and (B) line manager. Furthermore, semistructured interviews (n=20) were conducted to obtain deeper understanding. Questionnaire data were analysed using logistic regression analyses and qualitative interviews with inductive thematic analysis. RESULTS: About 30% of wage earners with T1D had concealed their condition during their working career from their colleagues and almost 20% from their line manager. Individuals aged 18-44 years age were more likely to conceal their T1D from their colleagues than older workers during their working career. Not disclosing T1D to the extended family (OR 5.24 (95% CI 2.06 to 13.35)), feeling an outsider at work (OR 2.47 (95% CI 1.58 to 3.84)), being embarrassed by receiving special attention at work (OR 1.99 (95% CI 1.33 to 2.96)) and neglecting treatment at work (OR 1.59 (95% CI 1.01 to 2.48)) were all associated with concealment of T1D from colleagues. The youngest age group of 18-24 years were more likely to conceal their T1D from their line managers than the older age groups during their working career. Not disclosing T1D to the extended family (OR 4.41 (95% CI 1.72 to 11.32)), feeling like an outsider at work (OR 2.51 (1.52 to 4.14)) and being embarrassed by receiving special attention at work (OR 1.81 (95% CI 1.13 to 2.91)) were associated with concealment of T1D from line managers. From the interviews, five main themes related to concealment emerged, expressing fears related to the consequences of telling: (1) being perceived as weak, (2) job discrimination, (3) unwanted attention, (4) being seen as a person who uses their T1D for seeking advantages and (5) losing privacy. CONCLUSIONS: A considerable proportion of wage earners with T1D are concealing their diagnosis often because of feelings associated with stigma. Both overemphasis and underestimation of T1D at work by the colleagues or line manager may lead to concealing T1D and may thus be harmful to self-management of T1D. The obstacles in disclosing T1D might be diminished by giving adequate information at the workplace about the condition and its significance.

The effect of age and gender on the genetic regulation of serum 25-hydroxyvitamin D - the FIN-D2D population-based study.

In addition to sunlight and dietary sources, several genes in the metabolic pathway of vitamin D affect serum 25-hydroxyvitamin D (25OHD) concentration. It is not known whether this genetic regulation is influenced by host characteristics. We investigated the effect of age and gender on the genetic regulation of serum 25OHD concentration. In total, 2868 Finnish men and women aged 45-74 years participated in FIN-D2D population-based health survey in 2007. Of the 2822 participants that had serum 25OHD concentration available, 2757 were successfully genotyped. Age and gender-dependent association of SNPs with serum 25OHD concentration was studied in 10 SNPs with previously found association with vitamin D metabolites. Associations of 3 SNPs with serum 25OHD concentration were dependent on age with greater effects on younger (≤60 y) than older (>60 y) adults (rs10783219 in VDR, rs12512631 in GC and rs3794060 in NADSYN1/DHCR7; pinteraction = 0.03, 0.02 and 0.01, respectively). The results suggested a novel association between serum 25OHD concentration and rs8082391 in STAT5B gene in men but not in women (pinteraction = 0.01). After multiple testing correction with false discovery rate method, two age-dependent interactions (rs3794060 in NADSYN1/DHCR7 gene and rs12512631 in GC gene) remained statistically significant. This is the first study to suggest that genetic regulation of serum 25OHD concentration is age-dependent. Our results also indicated a novel association between serum 25OHD concentration and SNP in STAT5B gene in men. The results need to be confirmed in future studies preferably in a larger sample.

Characteristics and Outcomes of 79 Patients with an Insulinoma: A Nationwide Retrospective Study in Finland.

OBJECTIVE: Insulinomas are rare pancreatic tumours. Population-based data on their incidence, clinical picture, diagnosis, and treatment are almost nonexistent. The aim of this study was to clarify these aspects in a nationwide cohort of insulinoma patients diagnosed during three decades. DESIGN AND METHODS: Retrospective analysis on all adult patients diagnosed with insulinoma in Finland during 1980-2010. RESULTS: Seventy-nine patients were diagnosed with insulinoma over the research period. The median follow-up from diagnosis to last control visit was one (min 0, max 31) year. The incidence increased from 0.5/million/year in the 1980s to 0.9/million/year in the 2000s (p = 0.002). The median diagnostic delay was 13 months and did not change over the study period. The mean age at diagnosis was 52 (SD 16) years. The overall imaging sensitivity improved from 39% in the 1980s to 98% in the 2000s (p < 0.001). Seventy-one (90%) of the patients underwent surgery with a curative aim, two (3%) had palliative surgery, and 6 (8%) were inoperable. There were no significant differences in the types of surgical procedures between the 1980s, 1990s, and 2000s; tumour enucleations comprised 43% of the operations, distal pancreatic resections 45%, and pancreaticoduodenectomies 12%, over the whole study period. Of the patients who underwent surgery with a curative aim, 89% had a full recovery. Postoperative complications occurred in half of the patients, but postoperative mortality was rare. CONCLUSIONS: The incidence of insulinomas has increased during the past three decades. Despite the improved diagnostic options, diagnostic delay has remained unchanged. To shorten the delay, clinicians should be informed and alert to consider the possibility of hypoglycemia and insulinoma, when symptomatic attacks are investigated in different sectors of the healthcare system. Developing the surgical treatment is another major target, in order to lower the overall complication rate, without compromising the high cure rate of insulinomas.

Home-measured blood pressure is more strongly associated with atherosclerosis than clinic blood pressure: the Finn-HOME Study.

BACKGROUND: The aim of this study was to assess whether carotid intima-media thickness (IMT) is more strongly associated with home-measured blood pressure (BP) than clinic BP. Other risk factors associated with carotid atherosclerosis were also investigated. METHODS: We studied a representative unselected sample of the Finnish adult population (758 subjects aged 45-74 years). Subjects included in the study underwent a clinical interview, carotid ultrasonography, and measurement of clinic BP (mean of two measurements using a mercury sphygmomanometer) and home BP (mean of 14 duplicate measurements during 1 week using a validated, automatic device). Fasting blood samples for serum lipids and glucose were drawn. RESULTS: The Pearson correlation coefficients for carotid IMT and home/clinic BP differed significantly in favour of home measurement for systolic BP (0.34 versus 0.25, P < 0.001), diastolic BP (0.20 versus 0.07, P < 0.001) and pulse pressure (0.37 versus 0.27, P < 0.001). In a linear regression model (R = 0.32, P < 0.001), age (P < 0.001), home systolic BP (P = 0.002), serum triglycerides (P = 0.006), male sex (P = 0.009), smoking (P = 0.017), diabetes (P = 0.035), and low-density lipoprotein cholesterol (P = 0.041) were independently associated with increased IMT. The association between home BP and carotid IMT did not increase with the number of home measurements. CONCLUSION: BP is one of the most important factors in the pathogenesis of atherosclerosis. Home-measured BP is more strongly associated with carotid atherosclerosis than clinic BP, even for a low number of measurements. These data support the application of home BP measurement in clinical practice.

The association between carotid intima-media thickness and sciatica.

OBJECTIVE: Both clinical and epidemiologic studies have shown an association between atherosclerotic changes in the aorta or lumbar arteries and lumbar disc degeneration. However, the association between atherosclerosis and sciatica remains unknown. The aim of this study was to investigate the association between carotid intima-media thickness and sciatica. METHODS: The target population consisted of people aged 45 to 74 years, who had participated in a Finnish nationwide population study during the period 2000 to 2001 and lived within 200 km of the 6 study clinics. Of the 1867 eligible subjects, 1386 (74%) were included in the study. We used high-resolution B-mode ultrasound imaging to measure intima-media thickness, and local or radiating low back pain was determined by a standard interview and clinical signs of sciatica through a physician's clinical examination. RESULTS: Carotid intima-media thickness was associated with continuous radiating low back pain and with a positive unilateral clinical sign of sciatica among men only. After adjustment for potential confounders, each standard deviation (0.23 mm) increment in carotid intima-media thickness showed an odds ratio of 1.6 (95% confidence interval 1.1-2.3) for continuous radiating low back pain and 1.7 (95% confidence interval 1.3-2.1) for a positive unilateral clinical sign of sciatica. Carotid intima-media thickness was not associated with local low back pain. CONCLUSION: Sciatica may be a manifestation of atherosclerosis, or both conditions may share common risk factors.