Prognostic significance of prolonged PR interval in the general population.

AIMS: Prolonged PR interval, or first degree AV block, has been traditionally regarded as a benign electrocardiographic finding in healthy individuals, until recent studies have suggested that it may be associated with increased mortality and morbidity. The aim of this study was to further elucidate clinical and prognostic importance of prolonged PR interval in a large middle-aged population with a long follow-up. METHODS AND RESULTS: We evaluated 12-lead electrocardiograms of 10 785 individuals aged 30-59 years (mean age 44 years, 52% males) recorded between 1966 and 1972, and followed the subjects for 30 ± 11 years. Prolonged PR interval was defined as PR >200 ms, with further analysis performed using PR ≥220 ms. Main endpoints were all-cause mortality, cardiovascular mortality, and sudden cardiac death, and other endpoints included hospitalizations due to cardiovascular causes. During the baseline examination, prolonged PR interval >200 ms was present in 2.1% of the subjects, but PR interval normalized to ≤200 ms in 30% of these individuals during the follow-up. No increase in mortality or in hospitalizations due to coronary artery disease, heart failure, atrial fibrillation, or stroke was associated with prolonged PR interval (P = non-significant for all endpoints). These results were not changed after multivariate adjustment or in several subanalyses. CONCLUSION: In the middle-aged general population, prolonged PR interval normalizes in a substantial proportion of subjects during the time course, and it is not associated with an increased risk of all-cause or cardiovascular mortality.

Prevalence and prognostic significance of T-wave inversions in right precordial leads of a 12-lead electrocardiogram in the middle-aged subjects.

BACKGROUND: T-wave inversion in right precordial leads V(1) to V(3) is a relatively common finding in a 12-lead ECG of children and adolescents and is infrequently found also in healthy adults. However, this ECG pattern can also be the first presentation of arrhythmogenic right ventricular cardiomyopathy. The prevalence and prognostic significance of T-wave inversions in the middle-aged general population are not well known. METHODS AND RESULTS: We evaluated 12-lead ECGs of 10 899 Finnish middle-aged subjects (52% men, mean age 44 ± 8.5 years) recorded between 1966 and 1972 for the presence of inverted T waves and followed the subjects for 30 ± 11 years. Primary end points were all-cause mortality, cardiac mortality, and arrhythmic death. T-wave inversions in right precordial leads V(1) to V(3) were present in 54 (0.5%) of the subjects. In addition, 76 (0.7%) of the subjects had inverted T waves present only in leads other than V(1) to V(3). Right precordial T-wave inversions did not predict increased mortality (not significant for all end points). However, inverted T waves in leads other than V(1) to V(3) were associated with an increased risk of cardiac and arrhythmic death (P<0.001 for both). CONCLUSIONS: T-wave inversions in right precordial leads are relatively rare in the general population, and are not associated with adverse outcome. Increased mortality risk associated with inverted T waves in other leads may reflect the presence of an underlying structural heart disease.

Dietary intervention in infancy and later signs of beta-cell autoimmunity.

BACKGROUND: Early exposure to complex dietary proteins may increase the risk of beta-cell autoimmunity and type 1 diabetes in children with genetic susceptibility. We tested the hypothesis that supplementing breast milk with highly hydrolyzed milk formula would decrease the cumulative incidence of diabetes-associated autoantibodies in such children. METHODS: In this double-blind, randomized trial, we assigned 230 infants with HLA-conferred susceptibility to type 1 diabetes and at least one family member with type 1 diabetes to receive either a casein hydrolysate formula or a conventional, cow's-milk-based formula (control) whenever breast milk was not available during the first 6 to 8 months of life. Autoantibodies to insulin, glutamic acid decarboxylase (GAD), the insulinoma-associated 2 molecule (IA-2), and zinc transporter 8 were analyzed with the use of radiobinding assays, and islet-cell antibodies were analyzed with the use of immunofluorescence, during a median observation period of 10 years (mean, 7.5). The children were monitored for incident type 1 diabetes until they were 10 years of age. RESULTS: The unadjusted hazard ratio for positivity for one or more autoantibodies in the casein hydrolysate group, as compared with the control group, was 0.54 (95% confidence interval [CI], 0.29 to 0.95), and the hazard ratio adjusted for an observed difference in the duration of exposure to the study formula was 0.51 (95% CI, 0.28 to 0.91). The unadjusted hazard ratio for positivity for two or more autoantibodies was 0.52 (95% CI, 0.21 to 1.17), and the adjusted hazard ratio was 0.47 (95% CI, 0.19 to 1.07). The rate of reported adverse events was similar in the two groups. CONCLUSIONS: Dietary intervention during infancy appears to have a long-lasting effect on markers of beta-cell autoimmunity--markers that may reflect an autoimmune process leading to type 1 diabetes. (ClinicalTrials.gov number, NCT00570102.).

Early repolarization: electrocardiographic phenotypes associated with favorable long-term outcome.

BACKGROUND: Early repolarization (ER) in inferior/lateral leads of standard ECGs increases the risk of arrhythmic death. We tested the hypothesis that variations in the ST-segment characteristics after the ER waveforms may have prognostic importance. METHODS AND RESULTS: ST segments after ER were classified as horizontal/descending or rapidly ascending/upsloping on the basis of observations from 2 independent samples of young healthy athletes from Finland (n=62) and the United States (n=503), where ascending type was the dominant and common form of ER. Early repolarization was present in 27/62 (44%) of the Finnish athletes and 151/503 (30%) of the US athletes, and all but 1 of the Finnish (96%) and 91/107 (85%) of US athletes had an ascending/upsloping ST variant after ER. Subsequently, ECGs from a general population of 10 864 middle-aged subjects were analyzed to assess the prognostic modulation of ER-associated risk by ST-segment variations. Subjects with ER ≥0.1 mV and horizontal/descending ST variant (n=412) had an increased hazard ratio of arrhythmic death (relative risk 1.43; 95% confidence interval 1.05 to 1.94). When modeled for higher amplitude ER (>0.2 mV) in inferior leads and horizontal/descending ST-segment variant, the hazard ratio of arrhythmic death increased to 3.14 (95% confidence interval 1.56 to 6.30). However, in subjects with ascending ST variant, the relative risk for arrhythmic death was not increased (0.89; 95% confidence interval 0.52 to 1.55). CONCLUSIONS: ST-segment morphology variants associated with ER separates subjects with and without an increased risk of arrhythmic death in middle-aged subjects. Rapidly ascending ST segments after the J-point, the dominant ST pattern in healthy athletes, seems to be a benign variant of ER.

Long-term outcome associated with early repolarization on electrocardiography.

BACKGROUND: Early repolarization, which is characterized by an elevation of the QRS-ST junction (J point) in leads other than V(1) through V(3) on 12-lead electrocardiography, has been associated with vulnerability to ventricular fibrillation, but little is known about the prognostic significance of this pattern in the general population. METHODS: We assessed the prevalence and prognostic significance of early repolarization on 12-lead electrocardiography in a community-based general population of 10,864 middle-aged subjects (mean [+/-SD] age, 44+/-8 years). The primary end point was death from cardiac causes, and secondary end points were death from any cause and death from arrhythmia during a mean follow-up of 30+/-11 years. Early repolarization was stratified according to the degree of J-point elevation (> or = 0.1 mV or > 0.2 mV) in either inferior or lateral leads. RESULTS: The early-repolarization pattern of 0.1 mV or more was present in 630 subjects (5.8%): 384 (3.5%) in inferior leads and 262 (2.4%) in lateral leads, with elevations in both leads in 16 subjects (0.1%). J-point elevation of at least 0.1 mV in inferior leads was associated with an increased risk of death from cardiac causes (adjusted relative risk, 1.28; 95% confidence interval [CI], 1.04 to 1.59; P=0.03); 36 subjects (0.3%) with J-point elevation of more than 0.2 mV in inferior leads had a markedly elevated risk of death from cardiac causes (adjusted relative risk, 2.98; 95% CI, 1.85 to 4.92; P<0.001) and from arrhythmia (adjusted relative risk, 2.92; 95% CI, 1.45 to 5.89; P=0.01). Other electrocardiographic risk markers, such as a prolonged QT interval corrected for heart rate (P=0.03) and left ventricular hypertrophy (P=0.004), were weaker predictors of the primary end point. CONCLUSIONS: An early-repolarization pattern in the inferior leads of a standard electrocardiogram is associated with an increased risk of death from cardiac causes in middle-aged subjects.

Polychlorinated biphenyls in prospectively collected serum and Parkinson's disease risk.

Evidence suggests possible Parkinson's disease (PD)-relevant neural effects of exposure to polychlorinated biphenyls. Limited epidemiological evidence suggests that polychlorinated biphenyl exposure may increase PD risk, but no studies have involved biomarkers of polychlorinated biphenyl exposure before PD onset. We examined the prospective association between serum polychlorinated biphenyls and PD. We conducted a nested case-control study within the Finnish Mobile Clinic Health Examination Survey with serum samples collected during 1968-1972 and analyzed in 2005-2007 for polychlorinated biphenyls. Incident PD cases were identified through the Social Insurance Institution's registry and were confirmed by medical record review (n = 101). Controls (n = 349) were matched on age, sex, municipality, and vital status. We used logistic regression to estimate adjusted odds ratios. There was no evidence of increasing risk of PD with increasing polychlorinated biphenyl exposure in adjusted analyses. Instead, there was a trend toward lower odds of PD with increasing serum polychlorinated biphenyl concentrations, which was most pronounced for the sum of all measured polychlorinated biphenyl congeners and the sum of dioxin-like congeners. Compared with that of those in the lowest quintile, the odds ratio of PD among those in the highest quintile of total polychlorinated biphenyls was 0.29 (95% confidence interval, 0.12-0.70; P trend = .02) and for dioxin-like congeners was 0.34 (95% confidence interval, 0.13-0.90; P trend = .05). These results do not support an increased risk of PD from polychlorinated biphenyl exposure and instead suggest a possible protective effect of polychlorinated biphenyl exposure.

QRS-T angle as a predictor of sudden cardiac death in a middle-aged general population.

AIMS: Spatial QRS-T angle measured from a 12-lead electrocardiogram (ECG) has been shown to predict cardiac mortality. However, there is a paucity of studies on the prognostic significance of frontal QRS-T angle, which is more readily available from the standard 12-lead ECG. The purpose of the present study was to investigate the importance of wide frontal QRS-T angle, QRS-axis, and T-wave axis as cardiac risk predictors in general population. METHODS AND RESULTS: We evaluated the 12-lead ECGs of 10 957 Finnish middle-aged subjects from the general population recorded between 1966 and 1972, and followed them for 30 ± 11 years. QRS-T angle 0 to 90°, QRS-axis -30 to 90°, and T-wave axis 0 to 90° were considered normal. The primary endpoint was death from arrhythmia, and the secondary endpoints were all-cause mortality and non-arrhythmic cardiac mortality. QRS-T angle ≥ 100° was present in 2.0% of the subjects, and it was associated with an increased risk of sudden arrhythmic death [relative risk (RR) 2.26; 95% confidence interval (CI) 1.59-3.21; P< 0.001) and all-cause mortality (RR 1.57; CI 1.34-1.84; P< 0.001), but not with non-arrhythmic cardiac mortality (RR 1.34; CI 0.93-1.92; P= 0.13). The prognostic significance of wide QRS-T angle was mainly due to abnormal T-wave axis, which predicted death from arrhythmia (RR 2.13; CI 1.63-2.79; P< 0.001), all-cause mortality (RR 1.39; 1.24-1.55; P< 0.001), and non-arrhythmic cardiac death (RR 1.87; CI 1.50-2.34; P< 0.001). CONCLUSION: Frontal QRS-T angle ≥ 100° increases the risk of arrhythmic death, this being mainly the result of an altered T-wave axis.

Breastfeeding patterns of mothers with type 1 diabetes: results from an infant feeding trial.

BACKGROUND: Both the initiation and maintenance of breastfeeding have been reported to be negatively affected by maternal type 1 diabetes (T1D). The aim of this study was to prospectively examine the breastfeeding patterns among mothers with and without T1D participating in a large international randomized infant feeding trial (TRIGR). METHODS: Families with a member affected by T1D and with a newborn infant were invited into the study. Those who had HLA-conferred genetic susceptibility for T1D tested at birth with gestation > 35 weeks and were healthy were eligible to continue in the trial. Among the 2160 participating children, 1096 were born to women with T1D and 1064 to unaffected women. Information on infant feeding was acquired from the family by frequent prospective dietary interviews. RESULTS: Most (>90%) of the infants of mothers with and without T1D were initially breastfed. Breastfeeding rates declined more steeply among mothers with than without T1D being 50 and 72% at 6 months, respectively. Mothers with T1D were younger, less educated and delivered earlier and more often by caesarean section than other mothers (p < 0.01). After adjusting for all these factors associated with the termination of breastfeeding, there was no difference in the duration of breastfeeding among mothers with and without T1D. CONCLUSIONS: Maternal diabetes status per se was not associated with shorter breastfeeding. The lower duration of breastfeeding in mothers with T1D is largely explained by their more frequent caesarean sections, earlier delivery and lower age and education.

Positive change in the utilization of antihypertensive and lipid-lowering drugs among adult CHD patients in Finland: results from a large national database between 2000 and 2006.

AIM: To assess the changes in the utilization of antihypertensive, and lipid-lowering drugs among all adult Finnish coronary heart disease (CHD) patients between 2000 and 2006, and to evaluate the treatment and control of hypertension and dyslipidemia in a population-based sample of CHD patients. METHODS: From the databases of the Social Insurance Institution of Finland, 192,440 CHD patients aged 30 years or more in 2000 and 206,394 in 2006, respectively, were identified. Changes in the utilization of antihypertensive and lipid-lowering drugs were determined. In addition, from the Health 2000 Survey representing the whole Finnish population aged 30 years or more, 527 CHD patients were identified, to assess their characteristics and control of hypertension and dyslipidemia. RESULTS: Between the fall of 2000 and spring of 2001, 75% of the CHD patients were classified as hypertensives and 85% of these used antihypertensive medication. From 2000 to 2006, the utilization of lipid-lowering, and antihypertensive drugs increased from 33 to 52% and from 74 to 78%, respectively. Moreover, combination antihypertensive medication increased from 37 to 48%. Amidst the patients using antihypertensive drugs, the use of renin-angiotensin system blockers increased from 27 to 46% because of more than a three-fold increase in the use of angiotensin receptor blockers. CONCLUSION: Utilization of antihypertensive agents (especially angiotensin receptor blockers) and lipid-lowering drugs has increased remarkably by the end of 2006. However, the treatments are still far from optimal.

The relative importance of modifiable potential risk factors of type 2 diabetes: a meta-analysis of two cohorts.

Lifestyle factors predict type 2 diabetes occurrence, but their effect in high- and low-risk populations is poorly known. This study determines the prediction of low-risk lifestyle on type 2 diabetes in those with and without metabolic syndrome in a pooled sample of two representative Finnish cohorts, collected in 1978-1980 and 2000-2001. Altogether 8,627 individuals, aged 40-79 years, and free of diabetes and cardiovascular disease at baseline were included in this study. A low-risk lifestyle was defined based on body mass index, exercise, alcohol consumption, smoking, and serum vitamin D concentration. The metabolic syndrome was defined according to the International Diabetes Federation including obesity, blood pressure, serum HDL cholesterol, serum triglycerides, and fasting glucose. During a 10-year follow-up, altogether 226 type 2 diabetes cases occurred. Overweight was the strongest predictor of type 2 diabetes (population attributable fraction (PAF) = 77%, 95% confidence interval (CI): 53, 88%). Together with lack of exercise, unsatisfactory alcohol consumption, smoking, and low vitamin D concentration it explained 82% of the cases. Altogether 62% (CI: 47, 73%) of the cases were attributable to the metabolic syndrome and 92% (CI: 67, 98%) to the most unfavourable combination of its components. The metabolic syndrome did not modify the prediction of lifestyle factors but persons with normal blood pressure benefited more from positive changes in exercise, alcohol consumption, and smoking than those with elevated blood pressure (P for interaction = 0.01). In conclusion, modification of lifestyle factors apparently reduces type 2 diabetes risk, especially in persons with normal blood pressure.

Coronary heart disease and cardiac conduction abnormalities in persons with psychotic disorders in a general population.

We investigated the prevalence of coronary heart disease (CHD) and myocardial infarction (MI) in persons with DSM-IV psychotic disorders. We also examined cardiac conduction abnormalities, and the role of antipsychotic medication in them. The study was based on a nationally representative survey of 8028 persons aged 30 years or over from Finland. Diagnoses of CHD and MI were based on electrocardiographic findings, health examination, and register information. QTc was calculated using the Bazett formula, and Minnesota classification was used for conduction abnormalities. We found that large Q-waves suggesting past MI were significantly more frequent in persons with schizophrenia, while the prevalence of CHD in persons with psychotic disorders did not differ significantly from the remaining study sample. Prevalence of prolonged QTc interval was significantly increased in persons with schizophrenia and in users of typical antipsychotics. However, low-potency antipsychotic use but not diagnosis of schizophrenia remained an independent predictor of prolonged QTc interval in a logistic regression. Low-potency antipsychotic use was associated with ventricular conduction defects, and high-potency antipsychotic use with premature beats. Symptoms and signs of CHD should be actively monitored patients with schizophrenia, and the electrocardiogram should be monitored for all types of changes in persons receiving antipsychotic medication.

Increasing resources effected equity in access to revascularizations for patients with diabetes.

OBJECTIVES: To examine differences in access to coronary revascularization among a cohort of coronary patients with and without diabetes in 1995-2002 in Finland and to examine how rapidly increasing resources effected socioeconomic equity in access to these operations. DESIGN: An individual level nationwide register-based study of newly diagnosed CHD (coronary heart disease) patients (aged 40-79) in Finland. Rates for revascularizations were calculated per 1 000 person years. Socioeconomic differences were examined using Cox regression. RESULTS: Revascularization rates increased from 354 to 443 per 1 000 person years among men with CHD and from 301 to 366 among patients with diabetes. Among women with CHD the numbers were 224 and 249 and among patients with diabetes 208 and 325. Comparing trends for first revascularization between patient groups with and without diabetes differences increased somewhat among men. Among women, revascularization rates increased more among diabetic patients. Lower revascularization rates among lower socioeconomic groups were found throughout the study period in both patient groups. CONCLUSIONS: Simultaneously with large increase in cardiac operation rates, revascularization observed more common among women with diabetes compared to those without. However socioeconomic inequity in access to revascularizations among both genders remained even after increase in resources.

Socioeconomic differences in mortality among diabetic people in Finland.

AIMS: A clear socioeconomic gradient in mortality emerged among diabetic people in Finland from the early 1980s to the early 1990s. The present study examines whether this development continued between 1991 and 2003. METHODS: People with diabetes aged 30-79 in 1991-2002 were identified in the national registers, and followed up for mortality until 31 December 2003. The data comprised 1,407,025 person years and 59,917 deaths. RESULTS: From 1991-1994 to 1995-1999, the all-cause mortality among diabetic people decreased 20% for men and 26% for women among non-manual workers compared with 14% and 19% respectively among manual workers. The socioeconomic differences increased particularly in mortality from coronary heart disease and causes related to smoking and excessive alcohol use. From 1995-1999 to 2000-2003 the socioeconomic mortality disparity remained stable except for emerging socioeconomic differences in neoplasm deaths among women. Persons with type 1 diabetes showed much larger socioeconomic differences in deaths from alcohol related diseases (RR: men 1.97, women 2.13) compared to persons with type 2 diabetes (RR: men 1.20, women 1.05). CONCLUSIONS: During the 1990s disparities in mortality between socioeconomic groups among diabetic people increased due to a more favourable trend among non-manual workers compared to manual workers in deaths from coronary heart disease and causes of death related to smoking and excessive alcohol use. From the late 1990s to 2000-2003, inequality in mortality remained stable except for emerging socioeconomic differences in neoplasm deaths among women.

Changing patterns of secondary preventive medication among newly diagnosed coronary heart disease patients with diabetes in Finland: a register-based study.

AIMS: Information on medicine use among coronary heart disease (CHD) patients with diabetes in unselected patient populations is scarce. This study examines the use of medication to prevent new cardiac events among newly diagnosed CHD patients with diabetes comparing them to patients without diabetes and examines socioeconomic differences in medicine use in these patient groups. METHODS: Data on CHD patients (43,501 men and 31,125 women) with or without diabetes were individually linked from nationwide registers (covering both patients treated in ambulatory and in hospital inpatient care). Age-standardised rates for medication use were calculated and differences between patient groups examined using Poisson regression. RESULTS: beta-blocker use was high in all patient groups in 1997-2002, angiotensin-converting enzyme (ACE) inhibitor and angiotensin II antagonist use increased and remained higher among patients with diabetes. More than half of men and women with diabetes used ACE inhibitors and one out of five used angiotensin II antagonists in 2002. Lipid-lowering medication use increased, especially among women. In 1997-98 it was lower in lower socioeconomic groups; among men with diabetes the use remained lower than among others. CONCLUSIONS: beta-blocker use was constant and ACE inhibitor and angiotensin II antagonist use increased. Lipid-lowering medication use increased considerably after a health insurance reform in 2000, in which elevated reimbursement of drug costs (75%) was extended to include all CHD patients with hyperlipidaemia.Socioeconomic differences in medication use disappeared after the reform. However, lipid-lowering medication use remained at a lower level among men with diabetes, suggesting that their treatment did not follow guidelines.

Vitamin D status and the risk of cardiovascular disease death.

Accumulating evidence suggests that inadequate vitamin D levels may predispose people to chronic diseases. The authors aimed to investigate whether serum 25-hydroxyvitamin D (25(OH)D) level predicts mortality from cardiovascular disease (CVD). The study was based on the Mini-Finland Health Survey and included 6,219 men and women aged > or =30 years who were free from CVD at baseline (1978-1980). During follow-up through 2006, 640 coronary disease deaths and 293 cerebrovascular disease deaths were identified. Levels of 25(OH)D were determined from serum collected at baseline. Cox's proportional hazards model was used to assess the association between 25(OH)D and risk of CVD death. After adjustment for potential confounders, the hazard ratio for total CVD death was 0.76 (95% confidence interval (95% CI): 0.60, 0.95) for the highest quintile of 25(OH)D level versus the lowest. The association was evident for cerebrovascular death (hazard ratio = 0.48, 95% CI: 0.31, 0.75) but not coronary death (hazard ratio = 0.91, 95% CI: 0.70, 1.18). A low vitamin D level may be associated with higher risk of a fatal CVD event, particularly cerebrovascular death. These findings need to be replicated in other populations. To demonstrate a causal link between vitamin D and CVD, randomized controlled trials are required.

Depression and C-reactive protein: population-based Health 2000 Study.

OBJECTIVE: To test whether depression is independently associated with elevated levels of C-reactive protein (CRP) in a large nationwide population-based sample. METHODS: Depression and CRP were assessed in 6005 Finns aged >30 years, as part of the ongoing population-based Health 2000 Study. Depression was determined by responses to the Beck's Depression Inventory (BDI-21) and by Composite International Diagnostic Interview (CIDI). RESULTS: Higher scores on BDI-21 were related to higher CRP levels (beta = 0.12, p < .001) in men and (beta = 0.08, p < .001) in women. In men, but not in women, this relationship persisted after adjustment for a number of other known risk factors. In men, the more recent dysthymic disorder or at least moderate depressive episode defined using CIDI was related to elevated CRP levels (beta = 0.06, p = .006). CONCLUSIONS: Depressive symptoms may be partly responsible for inflammatory processes, and inflammatory processes may induce depressive symptoms in men.

Fish consumption and the incidence of cerebrovascular disease.

Studies of the beneficial role of fish consumption in the prevention of CVD are not consistent in their findings, particularly those studies that focus on the risk of stroke. The aim of the present study is to investigate the relationship between the consumption of different types of fish and the subsequent incidence of cerebrovascular disease (CVA). We prospectively evaluated the association between consumption of different types of fish and CVA in 3958 men and women aged 40-79 years who were free of heart disease and had participated in a health examination survey from 1967 to 1972. A total of 659 incident cases of CVA occurred during a follow-up until the end of 1994. A dietary history interview method provided data on habitual consumption of fish and other foods over the preceding year at baseline. Total fish intake did not predict CVA, but consumption of salted fish suggested an increased risk of intracerebral haemorrhage. The relative risk of intracerebral haemorrhage between the highest tertile of salted fish consumption and non-consumers was 1.98 (95 % CI 1.02, 3.84; P for trend = 0.06) after adjustment for age, sex, energy intake, smoking, BMI, physical activity, geographic area, occupation, diabetes, use of post-menopausal hormones, serum cholesterol, hypertension, and consumptions of butter, vegetables, fruits and berries. The relationship between fish consumption and stroke risk is not straightforward. How the fish is prepared for consumption may play an important role, affecting the association.

NPAS2 and PER2 are linked to risk factors of the metabolic syndrome.

BACKGROUND: Mammalian circadian clocks control multiple physiological events. The principal circadian clock generates seasonal variations in behavior as well. Seasonality elevates the risk for metabolic syndrome, and evidence suggests that disruption of the clockwork can lead to alterations in metabolism. Our aim was to analyze whether circadian clock polymorphisms contribute to seasonal variations in behavior and to the metabolic syndrome. METHODS: We genotyped 39 single-nucleotide polymorphisms (SNP) from 19 genes which were either canonical circadian clock genes or genes related to the circadian clockwork from 517 individuals drawn from a nationwide population-based sample. Associations between these SNPs and seasonality, metabolic syndrome and its risk factors were analyzed using regression analysis. The p-values were corrected for multiple testing. RESULTS: Our findings link circadian gene variants to the risk factors of the metabolic syndrome, since Npas2 was associated with hypertension (P-value corrected for multiple testing = 0.0024) and Per2 was associated with high fasting blood glucose (P-value corrected for multiple testing = 0.049). CONCLUSION: Our findings support the view that relevant relationships between circadian clocks and the metabolic syndrome in humans exist.

Serum vitamin D and subsequent occurrence of type 2 diabetes.

BACKGROUND: Low vitamin D status has been suggested as a risk factor for type 2 diabetes. Although the epidemiologic evidence is scarce, 2 recent studies have suggested an association. The present study investigated the relation of serum vitamin D with type 2 diabetes incidence using pooled data from these 2 cohorts. METHODS: Two nested case-control studies, collected by the Finnish Mobile Clinic in 1973-1980, were pooled for analysis. The study populations consisted of men and women aged 40-74 years and free of diabetes at baseline. During a follow-up period of 22 years, 412 incident type 2 diabetes cases occurred, and 986 controls were selected by individual matching. Serum vitamin D (serum 25(OH)D) was determined from frozen samples, stored at baseline. Pooled estimates of the relationship between serum vitamin D concentration and type 2 diabetes incidence were calculated. RESULTS: Men had higher serum vitamin D concentrations than women and showed a reduced risk of type 2 diabetes in their highest vitamin D quartile. The relative odds between the highest and lowest quartiles was 0.28 (95% confidence interval = 0.10-0.81) in men and 1.14 (0.60-2.17) in women after adjustment for smoking, body mass index, physical activity, and education. CONCLUSIONS: The results support the hypothesis that high vitamin D status provides protection against type 2 diabetes. Residual confounding may contribute to this association.

Incidence of schizophrenia in a nationwide cohort of patients with type 1 diabetes mellitus.

CONTEXT: Patients with schizophrenia have an increased risk of type 2 diabetes mellitus. However, very few studies have dealt with the association of type 1 diabetes and schizophrenia. Preliminary evidence points to a possible inverse association. OBJECTIVE: To investigate the incidence of schizophrenia in a nationwide cohort of patients with type 1 diabetes born in 1950 through 1959 in Finland. DESIGN: A cohort study of individuals born in 1950 through 1959 with a follow-up of 1969 through 1991. SETTING: Finland. PATIENTS: All individuals born in 1950 through 1959 with type 1 diabetes were identified through nationwide registers. The incidence of schizophrenia until 1992 among the total 1950-1959 cohort and in individuals with type 1 diabetes was calculated using information from 3 health care registers. MAIN OUTCOME MEASURE: Incidence of schizophrenia. RESULTS: The incidence of schizophrenia was 0.21 per 10 000 person-years in the group with type 1 diabetes and 0.56 per 10 000 person-years in the group without type 1 diabetes (P < .001). CONCLUSION: The incidence of schizophrenia is decreased in patients with type 1 diabetes.