Seroprevalence of Sindbis virus and associated risk factors in northern Sweden.

Mosquito-borne Sindbis virus (SINV) cause disease characterized by rash, fever and arthritis which often leads to long-lasting arthralgia. To determine the seroprevalence of SINV and associated risk factors in northern Sweden, a randomly selected population aged between 25 and 74 years were invited to join the MONICA study. Serum from 1611 samples were analysed for specific IgG antibodies. Overall, 2·9% had IgG against SINV. More men (3·7%) than women (2·0%) were SINV seropositive (P = 0·047) and it was more common in subjects with a lower educational level (P = 0·013) and living in small, rural communities (P < 0·001). Seropositivity was associated with higher waist circumference (P = 0·1), elevated diastolic blood pressure (P = 0·037), and history of a previous stroke (P = 0·011). In a multiple logistic regression analysis, adjusting for known risk factors for stroke, seropositivity for SINV was an independent predictor of having had a stroke (odds ratio 4·3, 95% confidence interval 1·4-13·0, P = 0·011).

A rightward shift of the distribution of fasting and post-load glucose in northern Sweden between 1990 and 2009 and its predictors. Data from the Northern Sweden MONICA study.

AIMS: Most Swedish studies show stable diabetes prevalence despite increasing obesity, but glucose levels may shift upwards below the diagnostic threshold for diabetes. Our aim was to explore trends in glucose distribution in northern Sweden; whether these trends were uniformly distributed throughout the spectrum of glucose concentrations; and to relate trends to traditional risk factors and the obesity-related adipokine leptin. METHODS: The project consisted of four cross-sectional surveys between 1990 and 2009, with 7069 participants aged 25-64 years. The overall participation rate was 74.4%. Trend analyses of glucose concentrations along the entire distribution and linear regression in relation to survey years and risk markers were used. RESULTS: Fasting and post-load glucose increased in women (both P < 0.001) and post-load glucose in men (P = 0.004). The increase was seen in most deciles of glucose concentrations. The prevalence of impaired glucose tolerance doubled in women to 14.5% and tripled in men to 10.1% (both P = 0.004). The prevalence of impaired fasting glucose rose in women from 4.5 to 7.7% (P < 0.001). The prevalence of diabetes was unchanged-6.4% in 2009. In men, leptin, together with traditional risk factors, explained 7.8 and 10.8% of the variance in fasting (P = 0.008) and post-load (P < 0.001) glucose, respectively. CONCLUSIONS: Increasing fasting and post-load glucose concentrations were seen in most deciles of the glucose distribution, indicating a shift in the entire population. Leptin was significantly associated with fasting and post-load glucose in men.

Low-carbohydrate, high-protein score and mortality in a northern Swedish population-based cohort.

BACKGROUND/OBJECTIVE: Long-term effects of carbohydrate-restricted diets are unclear. We examined a low-carbohydrate, high-protein (LCHP) score in relation to mortality. SUBJECTS/METHODS: This is a population-based cohort study on adults in the northern Swedish county of Västerbotten. In 37,639 men (1460 deaths) and 39,680 women (923 deaths) from the population-based Västerbotten Intervention Program, deciles of energy-adjusted carbohydrate (descending) and protein (ascending) intake were added to create an LCHP score (2-20 points). Sex-specific hazard ratios (HR) were calculated by Cox regression. RESULTS: Median intakes of carbohydrates, protein and fat in subjects with LCHP scores 2-20 ranged from 61.0% to 38.6%, 11.3% to 19.2% and 26.6% to 41.5% of total energy intake, respectively. High LCHP score (14-20 points) did not predict all-cause mortality compared with low LCHP score (2-8 points), after accounting for saturated fat intake and established risk factors (men: HR for high vs low 1.03 (95% confidence interval (CI) 0.88-1.20), P for continuous = 0.721; women: HR for high vs low 1.10 (95% CI 0.91-1.32), P for continuous = 0.229). For cancer and cardiovascular disease, no clear associations were found. Carbohydrate intake was inversely associated with all-cause mortality, though only statistically significant in women (multivariate HR per decile increase 0.95 (95% CI 0.91-0.99), P = 0.010). CONCLUSION: Our results do not support a clear, general association between LCHP score and mortality. Studies encompassing a wider range of macronutrient consumption may be necessary to detect such an association.

Patients with diabetes are not more likely to have atypical symptoms when seeking care of a first myocardial infarction. An analysis of 4028 patients in the Northern Sweden MONICA Study.

AIM: To describe symptoms of a first myocardial infarction in men and women with and without diabetes. METHODS: We conducted a population-based study of 4028 people aged 25-74 years, with first myocardial infarction registered in the Northern Sweden Multinational MONItoring of trends and determinants in CArdiovascular disease (MONICA) myocardial infarction registry between 2000 and 2006. Symptoms were classified as typical or atypical according to the World Health Organization MONICA manual. RESULTS: Among patients with diabetes, 90.1% reported typical symptoms of myocardial infarction; the corresponding proportion among patients without diabetes was 91.5%. In the diabetes group, 88.8% of women and 90.8% of men had typical symptoms of myocardial infarction. No differences were found in symptoms of myocardial infarction between women with and without diabetes or between men with and without diabetes. Atypical symptoms were more prevalent in the older age groups (> 65 years) than in the younger age groups (< 65 years). The increases were approximately equal among men and women, with and without diabetes. Diabetes was not an independent predictor for having atypical symptoms of myocardial infarction. CONCLUSIONS: Typical symptoms of myocardial infarction were equally prevalent in patients with and without diabetes and there were no sex differences in symptoms among persons with diabetes. Diabetes was not a predictor of atypical symptoms.

The disparity between long-term survival in patients with and without diabetes following a first myocardial infarction did not change between 1989 and 2006: an analysis of 6,776 patients in the Northern Sweden MONICA Study.

AIMS/HYPOTHESIS: Long-term survival after myocardial infarction (MI) has improved in the population, but data on diabetic patients is lacking. We analysed survival for up to 18 years after a first MI in patients with or without diabetes. METHODS: The Northern Sweden MONICA Myocardial Infarction Registry was linked to the Cause-of-Death Registry for a total of 6,776 patients, 25-64 years of age, with a first MI during 1989-2006. Prehospital deaths were included. Follow-up ended on 30 August 2008. RESULTS: Sixteen per cent had diabetes. Median follow-up time was 6.8 years, and the study included 50,667 patient-years. One third of the non-diabetic patients died vs half of the diabetic patients. Median survival for non-diabetic men was 227 months and for diabetic men 123 months. Corresponding figures for the non-diabetic and diabetic women were 222 and 81 months respectively. Men with diabetes had an age-adjusted HR for all-cause mortality of 1.56 (95% CI 1.39, 1.79) vs men without diabetes. Mortality risk was higher among diabetic women, HR 1.97 (1.62, 2.39) (diabetes × sex interaction, p = 0.03). Survival increased for three consecutive cohorts and was higher in non-diabetic patients for all durations of follow-up and in all three cohorts. The interaction of diabetes x cohort was not significant over time (p = 0.5) and HRs did not differ either. CONCLUSIONS/INTERPRETATION: Long-term survival after a first MI is markedly lower in diabetic patients, especially among women, over an 18-year observation time. Although survival has improved in diabetic patients, the effect of diabetes upon mortality has not diminished.

The Evaluation of Screening and Early Detection Strategies for Type 2 Diabetes and Impaired Glucose Tolerance (DETECT-2) update of the Finnish diabetes risk score for prediction of incident type 2 diabetes.

AIMS/HYPOTHESIS: The Finnish diabetes risk questionnaire is a widely used, simple tool for identification of those at risk for drug-treated type 2 diabetes. We updated the risk questionnaire by using clinically diagnosed and screen-detected type 2 diabetes instead of drug-treated diabetes as an endpoint and by considering additional predictors. METHODS: Data from 18,301 participants in studies of the Evaluation of Screening and Early Detection Strategies for Type 2 Diabetes and Impaired Glucose Tolerance (DETECT-2) project with baseline and follow-up information on oral glucose tolerance status were included. Incidence of type 2 diabetes within 5 years was used as the outcome variable. Improvement in discrimination and classification of the logistic regression model was assessed by the area under the receiver-operating characteristic (ROC) curve and by the net reclassification improvement. Internal validation was by bootstrapping techniques. RESULTS: Of the 18,301 participants, 844 developed type 2 diabetes in a period of 5 years (4.6%). The Finnish risk score had an area under the ROC curve of 0.742 (95% CI 0.726-0.758). Re-estimation of the regression coefficients improved the area under the ROC curve to 0.766 (95% CI 0.750-0.783). Additional items such as male sex, smoking and family history of diabetes (parent, sibling or both) improved the area under the ROC curve and net reclassification. Bootstrapping showed good internal validity. CONCLUSIONS/INTERPRETATION: The predictive value of the original Finnish risk questionnaire could be improved by adding information on sex, smoking and family history of diabetes. The DETECT-2 update of the Finnish diabetes risk questionnaire is an adequate and robust predictor for future screen-detected and clinically diagnosed type 2 diabetes in Europid populations.

Large improvements in major cardiovascular risk factors in the population of northern Sweden: the MONICA study 1986-2009.

OBJECTIVES: the incidence of cardiovascular disease has declined rapidly in Sweden since the 1980s. We explored changes in major cardiovascular risk factors in northern Sweden between 1986 and 2009. DESIGN: since 1986, six population surveys have been carried out in northern Sweden using procedures of the World Health Organization MONICA project. The population age range was 25-64 years in 1986 and 1990, and 25-74 years from 1994. Trends were analysed using generalized linear models. RESULTS: a total of 10586 subjects were included in the surveys. Blood pressure decreased by 4.9/3.9 mmHg in women and 1.8/1.5 mmHg in men aged 25-64 years between 1986 and 2009. In men and women aged 65-74 years, the decrease was 12.6/6.1 mmHg between 1994 and 2009. From 1994, the use of blood pressure-lowering drugs increased, particularly among the older subgroup. The prevalence of smoking halved between 1986 and 2009; 11% of women and 9% of men were smokers in 2009. Cholesterol levels decreased by 0.9 mmol L(-1) in the younger age group (25-64 years), and the use of lipid-lowering agents increased from 1994. Among subjects aged 25-64 years, one in five was obese in 2009, which was twice as many as in 1986, and body mass index (BMI) increased by 1.5 kg m(-2) , corresponding to an increase in weight of 4 kg. There was no further increase in BMI from 2004. The prevalence of diabetes did not change between 1986 and 2009. The proportion that received a university education increased markedly in all age groups, especially in women, during the study period. CONCLUSIONS: significant improvements were observed in major cardiovascular risk factors in northern Sweden between 1986 and 2009.

Abdominal and gynoid adipose distribution and incident myocardial infarction in women and men.

OBJECTIVE: The relationships between objectively measured abdominal and gynoid adipose mass with the prospective risk of myocardial infarction (MI) has been scarcely investigated. We aimed to investigate the associations between fat distribution and the risk of MI. SUBJECTS: Total and regional fat mass was measured using dual-energy X-ray absorptiometry (DEXA) in 2336 women and 922 men, of whom 104 subsequently experienced an MI during a mean follow-up time of 7.8 years. RESULTS: In women, the strongest independent predictor of MI was the ratio of abdominal to gynoid adipose mass (hazard ratio (HR)=2.44, 95% confidence interval (CI) 1.79-3.32 per s.d. increase in adipose mass), after adjustment for age and smoking. This ratio also showed a strong association with hypertension, impaired glucose tolerance and hypertriglyceridemia (P<0.01 for all). In contrast, the ratio of gynoid to total adipose mass was associated with a reduced risk of MI (HR= 0.57, 95% CI 0.43-0.77), and reduced risk of hypertension, impaired glucose tolerance and hypertriglyceridemia (P<0.001 for all). In men, gynoid fat mass was associated with a decreased risk of MI (HR=0.69, 95% CI 0.48-0.98), and abdominal fat mass was associated with hypertriglyceridemia (P for trend 0.02). CONCLUSION: In summary, fat distribution was a strong predictor of the risk of MI in women, but not in men. These different results may be explained by the associations found between fat distribution and hypertension, impaired glucose tolerance and hypertriglyceridemia.

Consumption of filtered and boiled coffee and the risk of first acute myocardial infarction; a nested case/referent study.

BACKGROUND AND AIM: In northern Sweden, consumption of both filtered and boiled coffee is common. Boiled coffee, especially popular in rural areas, is known to raise blood lipids, a risk factor for acute myocardial infarction (MI). To our knowledge, only one epidemiological study, a case-control study from Sweden, has investigated boiled coffee in MI, noting an increased risk at high consumption levels in men, and no association in women. The aim of the present nested case-referent study was to relate consumption of filtered and boiled coffee to the risk of first MI. METHODS AND RESULTS: The study subjects were 375 cases (303 men, 72 women) and 1293 matched referents from the population-based Northern Sweden Health and Disease Study. Coffee consumption was assessed by food frequency questionnaire. Risk estimates were calculated by conditional logistic regression. A statistically significant positive association was found between consumption of filtered coffee and MI risk in men [odds ratio for consumption > or = 4 times/day versus < or = 1 time/day 1.73 (95% CI 1.05-2.84)]. In women, a similar association was observed, but for boiled coffee [odds ratio 2.51 (95% CI 1.08-5.86)]. After adjustment for current smoking, postsecondary education, hypertension, and sedentary lifestyle, the results for women were no longer statistically significant. CONCLUSION: Consumption of filtered coffee was positively associated with the risk of a first MI in men. A similar tendency was observed for boiled coffee in women, but the result was not statistically significant in multivariate analysis. Further investigation in a larger study is warranted.

Plasma folate and total homocysteine levels are associated with the risk of myocardial infarction, independently of each other and of renal function.

OBJECTIVES: To investigate the relationship between plasma folate, vitamin B12 and total homocysteine concentrations, dietary intake of folate and vitamins B12, B6 and B2, and the risk of first acute myocardial infarction (MI). DESIGN: Nested case-referent study with up to 13 years of follow-up. SETTING: The population-based Northern Sweden Health and Disease Study, with 73 879 participants at the time of case ascertainment. SUBJECTS: A total of 571 MI cases (406 men) and 1569 matched referents. Of the cases, 530 had plasma samples available, and 247 had dietary B-vitamin intake data. RESULTS: Plasma concentrations of folate were inversely associated, and total homocysteine positively associated, with the risk of MI, independently of each other and of a number of established and novel cardiovascular risk factors, including renal function [multivariate odds ratio for highest vs. lowest quintile of folate 0.52 (95% CI 0.31-0.84), P for trend = 0.036, and homocysteine 1.92 (95% CI 1.20-3.09), P for trend = 0.006]. For plasma vitamin B12 concentrations, and vitamin B12, B6 and B2 intake, no clear risk relationship was apparent. Though not statistically significant, the results for folate intake were consistent with those for plasma concentrations. CONCLUSIONS: In this large prospective study of a population without mandatory folic acid fortification, both folate and homocysteine were strongly associated with the risk of myocardial infarction, independently of each other and of renal function. Although randomized trials of folic acid supplementation are needed to determine causality, our findings highlight the potential importance of folate, or sources of folate, in incident cardiovascular disease.

Blood lipid levels in relation to glucose status in European men and women without a prior history of diabetes: the DECODE Study.

OBJECTIVE: Dyslipidaemia is present not only in diabetic but also in prediabetic subjects. The purpose of this study is to investigate the relationship between lipid and glucose levels in a large European population without a prior history of diabetes. RESEARCH DESIGN AND METHODS: Data from the population-based studies of 8960 men and 10,516 women aged 35-74 years representing 15 cohorts in 8 European countries were jointly analyzed. Multivariate adjusted linear regression analyses with standardized coefficients (beta) were performed to estimate the relationship between lipid and plasma glucose. RESULTS: In subjects without a prior history of diabetes, positive relationships were shown between fasting plasma glucose (FPG) and total cholesterol (TC) (beta=0.06 and 0.03, respectively for men and women, p<0.01), triglycerides (TG) (beta=0.14 and 0.12, p<0.001), non-high-density lipoprotein cholesterol (non-HDL-C) (beta=0.06 and 0.03, p<0.01) and TC to HDL ratio (beta=0.06 and 0.05, p<0.001) but a negative trend between FPG and HDL-C (beta=-0.02, p>0.05 in men and beta=-0.03, p<0.05 in women). The relationship between lipid and 2-h plasma glucose (2hPG) followed a similar pattern as that for FPG, except that TC was not increased and HDL-C was reduced in both sexes in subjects with impaired glucose tolerance (IGT). CONCLUSIONS: For cardiovascular prevention, the different lipid patterns between impaired fasting glucose (IFG) and IGT may deserve further attention to evaluate the combined risks of dyslipidaemia and elevated glucose levels below the diagnostic threshold of diabetes.

Increased abdominal obesity, adverse psychosocial factors and shorter telomere length in subjects reporting early ageing; the MONICA Northern Sweden Study.

BACKGROUND: The rate of biological ageing is individual and represents the steady decrease in physiological and mental functions. Adverse social factors have been shown to influence this process. Self-perceived early ageing (SEA) might be a useful indicator of early biological ageing and increased mortality risk. The aim of this population-based study was to identify markers of SEA, including telomere length. METHODS: We studied 1502 subjects (744 men, 758 women) from Northern Sweden. These subjects underwent a physical examination, blood sampling (including telomere length) and completed a self-administered questionnaire about their subjective age, social situation, lifestyle, and self-rated health (SRH). Age- and SRH-adjusted statistical analyses were made comparing SEA subjects with same-sex controls. RESULTS: In all, 7.9% of men and 12.1% of women reported SEA. These subjects had significantly (p<0.0001) wider waist circumference and higher body mass index than controls. SEA men showed higher fasting glucose and SEA women showed higher total cholesterol levels than controls (p=0.020 and p=0.015, respectively). In addition, SEA women more often reported infrequent physical exercise (p=0.006), mental problems (p=0.064) and worse SRH (p=0.001) than controls. In a random sub-sample, telomere length was significantly shorter in SEA subjects (n=139) than controls (n=301; p=0.02), but not after full adjustment for BMI. CONCLUSIONS: Self-perceived early ageing is not uncommon and is associated with abdominal obesity, poor self-rated health, lower education, and shorter telomere length. This could link adverse social factors with features of the metabolic syndrome as well as with early biological ageing, of importance for targeting preventive programmes.

The risk of myocardial infarction and sudden cardiac death amongst snuff users with or without a previous history of smoking.

OBJECTIVES: To investigate the risk of a first myocardial infarction (MI) and sudden cardiac death (SCD) amongst male snuff users. DESIGN: We used a prospective incident case-referent study design nested in the population-based Västerbotten Intervention Program and the Northern Sweden MONICA study. SUBJECTS: Tobacco habits and cardiovascular risk factors were assessed at baseline screening and compared in 525 male MI cases (including 93 SCD cases) and 1798 matched referents. RESULTS: Myocardial infarction occurred on average 4 years and 2 months after the baseline screening. No increased risk for MI was found amongst snuff users without a previous history of smoking compared with nontobacco users after adjustments for body mass index, leisure time physical activity, educational level and cholesterol level (OR 0.82; 95% CI, 0.46-1.43). For snuff users with a previous history of smoking, the adjusted OR was 1.25 (95% CI, 0.80-1.96). Significantly increased risk for MI was found in current smokers with or without current snuff use. For SCD cases with survival time<24 h, the adjusted OR for snuff users without previous history of smoking was 1.18 (95% CI, 0.38-3.70) and for cases with survival time<1 h the OR was 0.38 (95% CI, 0.08-1.89). CONCLUSIONS: We found no increased risk for MI amongst snuff users without a previous history of smoking. Amongst snuff users with a previous history of smoking, the tendency towards an increased risk for MI may reflect the residual risk from former smoking. This study does not support the hypothesis that the risk for SCD is increased amongst snuff users.

Time trends in population cholesterol levels 1986-2004: influence of lipid-lowering drugs, obesity, smoking and educational level. The northern Sweden MONICA study.

OBJECTIVES: To explore time trends in population total cholesterol. DESIGN AND SETTING: Five population-based cross-sectional surveys, 1986-2004 in the northern Sweden MONICA study included 8827 men and women. RESULTS: Age-adjusted cholesterol level declined in men, 25-64 years old, from 6.38 to 5.78 mmol L(-1) and in women from 6.32 to 5.51 mmol L(-1). Between 1994 and 2004, subjects 65-74 years old were included, and their levels also decreased, in men from 6.35 to 5.76 mmol L(-1) and in women from 7.11 to 6.24 mmol L(-1). The decrease was continuous over surveys and age groups, except in young and middle-aged men where no further decline was found after 1999. Cohorts born 1920-1939 showed decreased cholesterol over the period, whilst no change was noted for those born thereafter. In 2004, one-fourth of men and one-third of women 25-74 years achieved levels below 5.0 mmol L(-1). Subjects with low educational level, body mass index > or =25 or smokers all had higher cholesterol levels which persisted during the 18-year period. In 2004, the 9% who used lipid-lowering drugs are estimated to contribute, at most, to 0.13 mmol L(-1) lower cholesterol in the population. CONCLUSION: Large decreases in cholesterol levels occurred in the 18-year period. Less smoking may contribute to, and increasing obesity attenuate, this trend whilst lipid-lowering drugs have had little effect until recently. Socio-economic inequalities persist.

Favourable trends in the incidence and outcome of myocardial infarction in nondiabetic, but not in diabetic, subjects: findings from the MONICA myocardial infarction registry in northern Sweden in 1989-2000.

BACKGROUND: The aim of this study was to compare time trends in incidence, case fatality and mortality due to myocardial infarction (MI) in patients with or without diabetes. METHODS: This study was based on the Northern Sweden MONICA Project MI registry with a target population of about 200,000 inhabitants in the age group 35--64 years in the two northernmost counties of Sweden. During 1989--2000, 6254 patients who had had an MI according to MONICA criteria were included in this study: 4569 patients had a first MI and 1685 had a recurrent MI. Sixteen per cent of the men and 20% of the women had had diabetes mellitus diagnosed prior the MI. RESULTS: Over the 12-year period, there was a declining trend in incidence and case fatality in first MI. Also, the event rates (first ever and recurrent MI) declined in men without diabetes. In women without diabetes favourable time trends were seen in first ever MI, recurrent MI and in case fatality. There were no favourable time trends for any of these outcomes in patients with diabetes. CONCLUSION: In nondiabetic subjects below the age of 65, the incidence of, and case-fatality in, MI declined. This led to a decreased mortality over the 12-year period. These favourable trends over time were not observed in diabetic subjects.

Low level of tissue plasminogen activator activity in non-diabetic patients with a first myocardial infarction.

OBJECTIVE: To explore the role of tissue plasminogen activator (tPA) activity and plasminogen activator inhibitor type 1 (PAI-1) in survivors of a first myocardial infarction (MI). Insulin and proinsulin were analysed as potential risk factors. DESIGN: Case-control study in northern Sweden. SUBJECTS: A total of 115 patients under 65 years of age with a first MI were enrolled and recalled for further examination 3 months later. Twenty-seven patients were excluded, 17 with known diabetes and 10 who did not come to the follow-up, giving a final number of 88 patients, 73 men and 15 women. Patients were age- and sex-matched with control subjects drawn from the local cohort in the MONICA population survey 1994. MAIN OUTCOME MEASURES: We compared MI patients and controls using univariate and multiple regression analyses including odds ratios (OR). RESULTS: PAI-1 activity, fibrinogen, postload insulin and -proinsulin were significantly higher and tPA activity significantly lower in MI patients in the univariate analysis. In a multiple regression analysis, including also age, sex and cardiovascular risk factors, these parameters were divided in quartiles. The lowest quartile of tPA activity was significantly associated with MI (OR = 19.1; CI 3.0-123) together with the highest quartiles of fibrinogen (OR = 25; CI 5.2-120) but other variables were not. CONCLUSION: Low tPA activity, i.e. low fibrinolytic activity, characterized nondiabetic subjects after a first MI which is not explained by concomitant disturbances in metabolic and anthropometric variables.

Physicians' perceptions of possibilities and obstacles prior to implementing a computerised drug prescribing support system.

Seeks to identify physicians' perceptions of possibilities and obstacles prior to implementing a computerised drug prescribing support system. Details a descriptive, qualitative study, with semi-structured individual interviews of 21 physicians in the Accident and Emergency Department of South Stockholm General Hospital. Identifies four descriptive categories for possibilities and obstacles. Concludes that gaining access to patient drug history enables physicians to carry out work in a professional way--a need the computerised prescription support system was not developed for and thus cannot fulfil. Alerts and producer-independent drug information are valuable in reducing workload. However, technical prerequisites form the base for a successful implementation. Time must be given to adapt to new ways of working.

Influence of smoking and snus on the prevalence and incidence of type 2 diabetes amongst men: the northern Sweden MONICA study.

OBJECTIVE: To explore the effect of smoking and smokeless tobacco, 'snus', on the risk of type 2 diabetes. DESIGN: Population-based cross-sectional and prospective follow-up study in northern Sweden. SUBJECTS: A total of 3384 men, aged 25-74 years, who participated in the MONICA study in 1986, 1990, 1994 or 1999, 1170 of whom had an oral glucose tolerance test. In 1999, 1757 men from previous cohorts returned for re-examination. Main outcome measures. We compared the prevalence of type 2 diabetes or pathological glucose tolerance (PGT) amongst tobacco users to that of nonusers at entry into the study and at follow-up, using odds ratios. RESULTS: Compared with never users, the age-adjusted risk of prevalent clinically diagnosed diabetes for ever smokers was 1.88 (CI 1.17-3.0) and for smokers 1.74 (0.94-3.2). Corresponding odds ratios for snus users were 1.34 (0.65-2.7) and 1.18 (0.48-2.9). We found no increased risk of prevalent PGT in snus users or smokers. Former smokers and snus users had an insignificantly increased risk for PGT. Compared with nonusers, the age-adjusted risk of developing clinically diagnosed diabetes during follow-up was 4.63 (1.37-16) in consistent exclusive smokers, 3.20 (1.16-8.8) in ex-smokers and no cases in consistent snus users. The risk of PGT during follow-up was not increased in consistent tobacco users but evident, although not statistically significant, in those who quit snus during the follow-up period, 1.85 (0.60-5.7). Adjustment for physical activity and alcohol consumption did not change the major findings. CONCLUSIONS: The risk of diabetes for snus users was not significantly increased. Smoking was associated with prevalent and incident cases of diabetes. Ex-tobacco users tended towards more PGT.

Species, strain and developmental variations in hippocampal neuronal and endothelial nitric oxide synthase clarify discrepancies in nitric oxide-dependent synaptic plasticity.

Nitric oxide (NO) has been implicated in long-term potentiation (LTP) in pyramidal neurons in cellular area 1 (CA1) of the hippocampus. However, considerable confusion exists about the exact role of NO, and the contribution of the endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) isoforms of NO synthase to NO-dependent LTP (NO-LTP), with results often varying, depending on the organism and experimental paradigm used. Using immunohistochemistry and in situ hybridization, we contrast NO synthase expression and activity in rat, mouse, and human hippocampus. nNOS is prominently expressed in all CA1 pyramidal cells of C57B6 mice and humans, while in rats and SV129 mice, its levels are much lower and restricted to the caudal hippocampus. By contrast, eNOS is restricted to endothelial cells. We observe N-methyl-D-aspartate-dependent citrulline production in pyramidal cells of mouse hippocampus, which is absent in nNOS(Delta/Delta) animals. Finally, we observe robust nNOS expression in human CA1 pyramidal cells.The considerable axial, developmental, strain and species-dependent variations in nNOS expression in CA1 pyramidal neurons can explain much of the variation observed in reports of NO-dependent LTP. Moreover, our data suggest that NO produced by eNOS in endothelial cells may play a paracrine role in modulating LTP.