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.

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 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.

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.

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.

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.

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.

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.

Diabetes and impaired glucose metabolism is associated with more cold-related cardiorespiratory symptoms.

AIMS: Diabetes and impaired glucose metabolism cause metabolic, neural and circulatory disturbances that may predispose to adverse cooling and related symptoms during the cold season. This study assessed the prevalence of cold-related cardiorespiratory symptoms in the general population according to glycaemic status. METHODS: The study population consisted of 2436 men and 2708 women aged 45-74years who participated in the National FINRISK cold sub-studies in 2002 and 2007. A questionnaire assessed cold-related symptoms (respiratory, cardiac, peripheral circulation). Glycaemic status was determined based on fasting blood glucose, oral glucose tolerance tests or reported diagnosis of diabetes and categorized into normal glucose metabolism, impaired fasting blood glucose, impaired glucose tolerance, screening-detected type 2 diabetes and type 2 diabetes. RESULTS: Type 2 diabetes was associated with increased odds for cold-related dyspnoea [Adjusted OR 1.72 (95% CI, 1.28-2.30)], chest pain [2.10 (1.32-3.34)] and respiratory symptoms [1.85 (1.44-2.38)] compared with normal glucose metabolism. Screened type 2 diabetes showed increased OR for cold-related dyspnoea [1.36 (1.04-1.77)], cough [1.41 (1.06-1.87)] and cardiac symptoms [1.51 (1.04-2.20)]. Worsening of glycaemic status was associated with increased odds for cold-related dyspnoea (from 1.16 in impaired fasting glucose to 1.72 in type 2 diabetes, P=0.000), cough (1.02-1.27, P=0.032), chest pain (1.28-2.10, P=0.006), arrhythmias (0.87-1.74, P=0.020), cardiac (1.11-1.99, P=0.000), respiratory (1.14-1.84, P=0.000) and all symptoms (1.05-1.66, P=0.003). CONCLUSIONS: Subjects with diabetes and pre-diabetes experience more cold-related cardiorespiratory symptoms and need instructions for proper protection from cold weather to reduce adverse health effects.

Circulating CXCR5+PD-1+ICOS+ Follicular T Helper Cells Are Increased Close to the Diagnosis of Type 1 Diabetes in Children With Multiple Autoantibodies.

Although type 1 diabetes (T1D) is primarily perceived as a T cell-driven autoimmune disease, islet autoantibodies are the best currently available biomarker for autoimmunity and disease risk. These antibodies are produced by autoreactive B cells, the activation of which is largely dependent on the function of CD4+CXCR5+ follicular T helper cells (Tfh). In this study, we have comprehensively characterized the Tfh- as well as B-cell compartments in a large cohort of children with newly diagnosed T1D or at different stages of preclinical T1D. We demonstrate that the frequency of CXCR5+PD-1+ICOS+-activated circulating Tfh cells is increased both in children with newly diagnosed T1D and in autoantibody-positive at-risk children with impaired glucose tolerance. Interestingly, this increase was only evident in children positive for two or more biochemical autoantibodies. No alterations in the circulating B-cell compartment were observed in children with either prediabetes or diabetes. Our results demonstrate that Tfh activation is detectable in the peripheral blood close to the presentation of clinical T1D but only in a subgroup of children identifiable by positivity for multiple autoantibodies. These findings suggest a role for Tfh cells in the pathogenesis of human T1D and carry important implications for targeting Tfh cells and/or B cells therapeutically.

Mortality in acromegaly: a 20-year follow-up study.

OBJECTIVE: It is unclear whether mortality still is increased in acromegaly and whether there are gender-related differences. We dynamically assessed outcome during long-term follow-up in our nationwide cohort. PATIENTS AND METHODS: We studied standardized mortality ratios (SMRs) relative to the general population and causes of death in acromegaly (n=333) compared with age- and gender-matched controls (n=4995). RESULTS: During 20 (0-33) years follow-up, 113 (34%) patients (n=333, 52% women) and 1334 (27%) controls (n=4995) died (P=0.004). SMR (1.9, 95% CI: 1.53-2.34, P<0.001) and all-cause mortality (OR 1.6, 95% CI: 1.2-2.2, P<0.001) were increased in acromegaly. Overall distribution of causes of death (P<0.001) differed between patients and controls but not cardiovascular (34% vs 33%) or cancer deaths (27% vs 27%). In acromegaly, but not in controls, causes of deaths shifted from 44% cardiovascular and 28% cancer deaths during the first decade, to 23% cardiovascular and 35% cancer deaths during the next two decades. In acromegaly, cancer deaths were mostly attributed to pancreatic adenocarcinoma (n=5), breast (n=4), lung (n=3) and colon (n=3) carcinoma. In acromegaly, men were younger than women at diagnosis (median 44.5 vs 50 years, P<0.001) and death (67 vs 76 years, P=0.0015). Compared with controls, women (36% vs 25%, P<0.01), but not men (31% vs 28%, P=0.44), had increased mortality. CONCLUSIONS: In acromegaly, men are younger at diagnosis and death than women. Compared with controls, mortality is increased during 20 years of follow-up, especially in women. Causes of deaths shift from predominantly cardiovascular to cancer deaths.

[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.

Work-related diabetes distress among Finnish workers with type 1 diabetes: a national cross-sectional survey.

BACKGROUND: Diabetes distress is common among people with type 1 diabetes, but knowledge is scarce regarding the perceived burden of reconciling work with this disease. This cross-sectional study investigated work-related diabetes distress among Finnish workers with type 1 diabetes. METHODS: A questionnaire was mailed to 2500 randomly sampled 18- to 65-year-old Finns with type 1 diabetes; 49.3 % responded. Work-related diabetes distress was measured by combining worry and exhaustion in reconciling work with diabetes. Self-perceived work-related diabetes distress was evaluated in the context of physical and psychosocial work conditions, job demands, work ability, general stress, diabetes acceptance, glycosylated hemoglobin (HbA1c) level, high blood glucose maintenance at work, and depressive symptoms. The data were analyzed with the use of cross-tabulation, chi-square tests, ANOVA analysis, Spearman correlation coefficients, and structural equation modeling. RESULTS: Of the respondents, 70 % experienced work-related diabetes distress. Problems with physical work conditions (ß = 0.27), work ability (ß = -0.21), difficulty in accepting diabetes (ß = 0.18), and job demands (ß = 0.14) were found to be associated with work-related diabetes distress. This distress was strongly associated with the maintenance of a high blood glucose level at work (ß = 0.34). In turn, a high blood glucose level at work was associated with a high HbA1c level (ß = 0.29). Work-related diabetes distress and depressive symptoms had a bi-directional association (ß = 0.06 and ß = 0.14). Difficulty accepting diabetes had three-dimensional associations: work-related diabetes distress (ß = 0.18), depressive symptoms (ß = 0.13), and high HbA1c level (ß = 0.12). There was no notable association between work-related diabetes distress and general stress. CONCLUSIONS: Work-related diabetes distress is common among workers with type 1 diabetes, and it may influence metabolic control. This stress could be prevented by adapting physical work conditions. People with type 1 diabetes should also be encouraged to pursue their full educational potential, and psychological support should be provided for those with difficulty accepting their diabetes.

Changes in lifestyle modestly reduce the estimated cardiovascular disease risk in one-year follow-up of the Finnish diabetes prevention program (FIN-D2D).

AIMS: The purpose of this study was to assess whether changes in self-rated physical activity and diet during a type 2 diabetes (T2D) prevention program were associated with changes in estimated 10-year risk for cardiovascular disease (CVD) events and mortality in people at high risk for T2D. METHODS: Individuals were identified and offered lifestyle counseling as part of the Finnish diabetes prevention program. Ten-year risk for estimated CVD events and mortality were calculated with Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE) formula. FRS was available for 774 men and 1474 women and SCORE for 961 men and 1766 women. RESULTS: During the one-year follow-up, 9.6% of the men reported both an increase in physical activity and improved dietary pattern, 4.1% an increase in physical activity, 39.3% an increase in improved dietary pattern, while 47.0% reported no lifestyle changes. Corresponding numbers for women were 14.2%, 3.8%, 39.2% and 42.7%. Estimated 10-year risk for CVD events decreased 3.5% in men and 1.5% in women reporting an increase in physical activity and improvement in diet, compared to an increase of 0.15% in men (p<0.001, between groups) and decrease of 0.43% (p=0.027, between groups) in women with no lifestyle changes after adjustment for age and baseline FRS. Numbers needed to treat to prevent one CVD event by lifestyle changes were 25 for men and 59 for women. Lifestyle changes had no effect on estimated CVD mortality risk. CONCLUSIONS: Lifestyle counseling offered in primary health care for one year results in favorable changes in lifestyle, and lowered the estimated 10-year risk for CVD events.

Lifestyle intervention in prevention of type 2 diabetes in women with a history of gestational diabetes mellitus: one-year results of the FIN-D2D project.

BACKGROUND: Lifestyle interventions are effective in preventing type 2 diabetes (T2D). Women with history of gestational diabetes mellitus (GDM) may have barriers to lifestyle changes, and the previous results of lifestyle interventions are contradictory reporting either favorable outcomes or no significant beneficial effects. Our aim was to compare cardio-metabolic risk profile and responses to a 1-year lifestyle intervention program in women with and without history of GDM. METHODS: The Implementation Project of the Program for Prevention of Type 2 Diabetes (FIN-D2D) was conducted in Finland in five hospital districts. Altogether 1,661 women aged ≤45 years participated in the program. One-year follow-up was available for 393 women who did not have screen-detected T2D at baseline, and 265 of them had at least one intervention visit [115 (43.4%) women with history of GDM and 150 (56.6%) without history of GDM]. RESULTS: At baseline, women with GDM had similar baseline glucose tolerance but better anthropometric characteristics, blood pressure, and lipid profile than women without GDM after adjustment for age. Beneficial changes in cardiovascular risk profile existed among women with and without GDM during follow-up and the effect of lifestyle intervention was similar between the groups, except that low-density lipoprotein cholesterol improved only in women with GDM. Altogether, 4.0% of those with GDM and 5.0% of those without GDM developed T2D (p=0.959 adjustment for age). CONCLUSIONS: The effect of a 1-year lifestyle intervention in primary healthcare setting was similar regardless of history of GDM, both women with and without GDM benefitted from participation in the lifestyle intervention.

Combination of LC-MS/MS aldosterone and automated direct renin in screening for primary aldosteronism.

BACKGROUND: Aldosterone to renin ratio (ARR) is used in screening for primary aldosteronism (PA). However, there are only few studies on the influence of assay methods on ARR and its cut-off limits. METHODS: Plasma direct renin immunoreactivity by chemiluminescence immunoassay (DR) was compared to renin activity assay (PRA), and a specific liquid chromatography-mass spectrometric method (LC-MS/MS) to radioimmunoassay (RIA) for plasma aldosterone. There were 75 samples for renin assays, and 42 samples of 39 patients for both renin and aldosterone assays. PA screening was considered positive if ARR by the aldosterone RIA:PRA was ≥800pmol/L:µg/L/h or by LC-MS/MS:DR≥44pmol/L:ng/L. RESULTS: The correlation between the DR and PRA methods (n=75, r(2)=0.845) and between LC-MS/MS and RIA (n=42, r(2)=0.973) was high in general, but low between the renin methods (n=49, r(2)=0.435) at low PRA values. When ARR was used in screening for PA, there were three divergent cases (positive only by alternative methods), but when applied in combination with criteria for elevated aldosterone, the methods showed good agreement, resulting in eight positive and 31 negative screening results. CONCLUSIONS: The automated DR assay combined with LC-MS/MS method for aldosterone provides a rapid, reliable, and specific method for screening of PA.

Circulating cell-free DNA is associated with cardiometabolic risk factors: the Health 2000 Survey.

Cell-free circulating DNA (cf-DNA) has recently arisen as a promising biomarker in acute cardiovascular pathologies and as a mortality predictor in myocardial infarction. We wanted to investigate whether the baseline cf-DNA concentration could serve as an indicator of increased cardiovascular risk and early atherosclerosis. The study population consisted of 1337 participants (aged 46-77 years) in the Health 2000 Survey. cf-DNA was quantified directly in plasma using the fluorescence-based Quant-iT™ high-sensitivity DNA assay kit. Increased cf-DNA levels paralleled a cluster of cardiometabolic risk factors, such as high blood pressure, unfavorable lipid metabolism profile and systemic inflammation in both sexes. In addition, higher cf-DNA levels indicated decreased arterial elasticity and glucose intolerance in women not using hormonal replacement therapy (HRT). The cf-DNA level was also observed to be an independent determinant for Young's elastic modulus but not for carotid artery compliance or beta stiffness index in the women not using HRT. Hence, we conclude that cf-DNA could serve as an auxiliary biomarker in cardiometabolic risk assessment and as an indicator of arterial stiffness in women not using HRT.

Do depressive symptoms have an impact on the effectiveness of lifestyle counseling in prevention of type 2 diabetes? One-year follow-up of FIN-D2D.

AIM: To examine whether depressive symptoms are associated with the effectiveness of lifestyle counseling on cardio-metabolic risk profile and glucose homeostasis during one-year follow-up in individuals at high risk for type 2 diabetes (T2D). METHODS: A total of 10,149 individuals took part in the implementation project of the national diabetes prevention program (FIN-D2D) conducted in primary health care setting in Finland. At baseline, altogether 2798 non-diabetic individuals participated in the one-year follow-up, and 2275 of them had at least one group or individual counseling visit. RESULTS: 4.0% of the individuals (n=78) had depressive symptoms, while 96.0% (n=1889) were free of depressive symptoms at baseline. Individuals who had depressive symptoms had higher body mass index and waist circumference at baseline than individuals without depressive symptoms. In terms of changes in cardio-metabolic risk profile and glucose homeostasis the effectiveness of lifestyle counseling was parallel between individuals with and without depressive symptoms during the one-year follow-up. CONCLUSIONS: Effectiveness of lifestyle counseling did not differ between individuals with and without depressive symptoms. Individuals with depressive symptoms should not be excluded from lifestyle intervention programs.