Evaluation of serum zonulin for use as an early predictor for gestational diabetes.

Diet has an important role in regulating intestinal permeability and subsequently the risk for metabolic disorders. In this observational study, we examined whether serum intestinal permeability marker zonulin, could be used as a predictor for gestational diabetes mellitus (GDM). Serum zonulin concentration was measured in early pregnancy in overweight or obese pregnant women (n=88) at risk for developing GDM. Serum zonulin was associated with higher odds of GDM (adjusted OR for 1 ng ml-1 increase in zonulin: 1.08, 95% CI: 1.02-1.15; P=0.009), diagnosed by a 2-h 75-g oral glucose tolerance test at late pregnancy. The optimal cutoff value was 43.3 ng ml-1, with sensitivity of 88% (95% CI: 71-100%) and specificity of 47% (95% CI: 33-58%). The area under the ROC-curve was 0.67 (95% CI: 0.54-0.81). Our results show an association between increased early-pregnancy serum zonulin concentration and GDM, suggesting zonulin as a possible predictor for GDM.

Metformin vs. insulin in gestational diabetes. A randomized study characterizing metformin patients needing additional insulin.

AIMS: We compared metformin with insulin as treatment of gestational diabetes mellitus (GDM). Furthermore, we aimed to characterize metformin-treated patients needing additional insulin to achieve prespecified glucose targets. METHODS: We conducted a single centre randomized controlled study with non-inferiority design comparing metformin and insulin in the treatment of 217 GDM patients having birth weight as primary outcome variable. RESULTS: There were no significant differences in mean birth weight expressed in grams [+15 (90% confidence interval (CI): -121 to 89)] or SD units [+0.04 (90% CI: -0.27 to 0.18)] between the metformin and insulin groups. There were no significant differences in neonatal or maternal data between the groups. Only 23 (20.9%) of the 110 patients in the metformin group needed additional insulin. Compared with the patients on metformin only, those needing additional insulin were older (p = 0.04), their oral glucose tolerance test had been performed earlier and diabetes therapy started earlier in gestation (p = 0.01 and p = 0.004, respectively). The risk for additional insulin was 4.6-fold in women with baseline serum fructosamine concentration above median compared with those below median. CONCLUSIONS: Metformin is an effective alternative to insulin in the treatment of GDM patients. Serum fructosamine may help in predicting the adequacy of metformin treatment alone.

Proteinuria modifies the effect of systolic blood pressure on total and cardiovascular disease mortality in patients with type 2 diabetes.

OBJECTIVES: Hypertension and proteinuria are major risk factors for cardiovascular disease (CVD) mortality in patients with type 2 diabetes. Blood pressure (BP) targets have been progressively lowered in these patients to prevent or delay the progression of nephropathy. However, no long-term population-based studies have been reported on the interaction between BP and proteinuria with respect to total and CVD mortality in patients with type 2 diabetes. DESIGN: We prospectively followed 881 middle-aged type 2 diabetic patients, free of CVD events at baseline, for up to 18 years. Participants were categorized into four groups according to baseline systolic BP (<130, 130-139, 140-159 and ≥160 mmHg) and further stratified by proteinuria (≤150 or >150 mg L(-1)). Cox proportional hazards model was used to estimate the joint association between systolic BP and proteinuria and the risk of mortality. RESULTS: During follow-up, 607 patients died including 395 because of CVD. After adjustment for confounding factors, total and CVD mortality were significantly higher in patients with proteinuria and systolic BP <130 mmHg compared with those with systolic BP between 130 and 160 mmHg. The prognosis was similar in patients with systolic BP <130 mmHg or ≥160 mmHg. Among patients without proteinuria, systolic BP <130 mmHg was associated with a nonsignificant reduction in mortality. CONCLUSIONS: Type 2 diabetic patients with proteinuria and with systolic BP <130 mmHg may have an increased risk of CVD mortality. The presence of proteinuria should be taken into account when defining the target systolic BP level for the prevention of fatal CVD events in patients with type 2 diabetes.

Proteinuria modifies the effects of physical activity on total and cardiovascular disease mortality rates in patients with type 2 diabetes.

AIMS/HYPOTHESIS: Physical activity reduces cardiovascular disease (CVD) and total mortality rates in patients with type 2 diabetes. However, it is not known whether or not the effects of physical activity on mortality rates depend on the presence of proteinuria in type 2 diabetic patients. METHODS: We prospectively followed up 577 patients with type 2 diabetes who were aged 45 to 64 years and were free of CVD at baseline. Participants were stratified according to the presence of proteinuria (300 mg/l) and the degree of physical activity (0-4 metabolic equivalent tasks [MET] or >4 MET). The Cox proportional hazards model was used to estimate the association of physical activity and proteinuria with risk of mortality. RESULTS: During the 18-year follow-up, 356 patients died, of whom 217 died from CVD. Physically more active patients had significantly reduced total, CVD and CHD mortality rates if they did not have proteinuria. In contrast, physically active proteinuric patients had significantly increased total and CVD mortality rates (HR 1.83, 95% CI 1.00-3.36, p=0.049) in univariate analyses, with HR 2.43 (95% CI 1.09-5.40, p=0.030) in multivariate analyses. CONCLUSIONS/INTERPRETATION: Physical activity reduces total and CVD mortality rates in type 2 diabetic patients without proteinuria. However, in proteinuric patients, no protective effect was observed. Larger studies are needed to confirm the latter finding and to define which exercise intensity leads to possible harmful effects.

Follow-ups of the Cardiovascular Risk in Young Finns Study in 2001 and 2007: levels and 6-year changes in risk factors.

OBJECTIVES: To examine cardiovascular risk factor levels in 2007 and their 6-year changes between 2001 and 2007 using the data collected in the follow-ups of the Cardiovascular Risk in Young Finns Study. DESIGN: Population-based follow-up study. SUBJECTS: A total of 2204 healthy Finnish adults aged 30-45 years (1210 women; 994 men). MAIN OUTCOME MEASURES: Levels in 2007 and changes between 2001 and 2007 of lipids, insulin, glucose, blood pressure, smoking, body mass index, alcohol consumption, waist and hip circumferences. RESULTS: The mean serum total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglyceride concentrations in 30- to 45-year-old adults were 5.05, 3.09, 1.34 and 1.40 mmol L(-1), respectively. Significant changes (P < 0.05) between 2001 and 2007 in 30- to 39-year-old subjects included a decrease in total cholesterol (-6.6% in men, -5.8% in women), LDL-cholesterol (-10.2% and -11.6%) and an increase in diastolic blood pressure (3.5% and 3.9%). Waist circumference (1.8% and 5.5%) and systolic blood pressure increased in 36-39 year olds (2.3% and 2.3%). HDL-cholesterol increased in 30- to 33-year-old women (5.8%) Glucose levels increased in 30- to 39-year-old women (3.7%) and 36- to 39-year-old men (3.6%). Smoking prevalence decreased in 36- to 39-year-old men from 29.8% to 22.2%. CONCLUSIONS: The 6-year changes in total cholesterol, LDL-cholesterol and HDL-cholesterol in young Finns were favourable between 2001 and 2007. However, waist circumference, glucose and blood pressure levels increased. Therefore, continuous efforts are still needed in fighting against cardiovascular risk factors.

Dietary and lifestyle counselling reduces the clustering of overweight-related cardiometabolic risk factors in adolescents.

AIM: The aim of this study was to evaluate the impact of individualised dietary and lifestyle counselling, primarily aimed to decrease serum low-density lipoprotein cholesterol, on the clustering of overweight-related cardiometabolic risk factors in children. DESIGN AND PARTICIPANTS: The 7-month-old study children were randomized either to counselling (n = 540) or control group (n = 522). MAIN OUTCOME MEASURES: The 5- to 15-year-old participants who fulfilled the international criteria were classified as overweight. Being in the highest [lowest for high-density lipoprotein (HDL) cholesterol] age- and gender-specific quintile of body mass index (BMI), blood pressure, serum triglycerides, HDL cholesterol or glucose was considered a risk factor. A cluster was defined as having high BMI and > or = 2 other risk factors. RESULTS: The counselling did not reduce the prevalence of overweight in 5- to 15-year-old participants. From age 7 onwards, the proportion of children with > or = 2 risk factors was lower in the intervention than in the control group (p = 0.005). At the age of 15 years, 13.0% of girls and 10.8% of boys in the intervention group and 17.5% of girls and 18.8% of boys in the control group had the risk factor cluster (p = 0.046 for main effect of the study group). Having even one risk factor at the age of 5 years predicted the clustering of risk factors at the age of 15 years (OR: 3.8, p < 0.001). CONCLUSION: Repeated, individualized dietary and lifestyle counselling may reduce the clustering of overweight-related cardiometabolic risk factors in adolescents even though the counselling is not intense enough to prevent overweight.

Metabolic syndrome and short-term heart rate variability in young adults. The cardiovascular risk in young Finns study.

AIMS: Heart rate variability (HRV) can be used to estimate autonomic nervous control of the cardiovascular system. In middle-aged subjects, the metabolic syndrome (MetS) is associated with lower HRV. We hypothesized that alterations in autonomic balance are already present in young adults with the MetS, and analysed the association of short-term HRV with the MetS (using the National Cholesterol Education Program definition), in 1889 subjects aged 24-39 years. METHODS: Short-term (3 min) HRV analysis included high-frequency (HF), low-frequency (LF) and total (TP) spectral components of HRV and LF/HF ratio. RESULTS: The presence of the MetS was associated with lower HF, LF and TP in men and women, and with higher LF/HF ratio in women. In men, waist circumference was the strongest individual MetS component that associated with HRV. After adjustments for age and heart rate, MetS was associated with lower HF and higher LF/HF ratio in women, but only with a lower TP in men (all P < 0.05). CONCLUSIONS: MetS is associated with lower HRV in young adults. The individual components of MetS are differentially associated with HRV in men and in women. Our results are consistent with lower vagal activity and a possible increase in sympathetic predominance in women with the MetS. This sex difference in vagal activity and sympathovagal balance may partly explain the greater increase in cardiovascular risk associated with MetS in women than in men.

Migration at early age from a high to a lower coronary heart disease risk country lowers the risk of subclinical atherosclerosis in middle-aged men.

BACKGROUND: Study of migrants offers a natural model to assess environmental risk of coronary heart disease (CHD) in countries differing in CHD occurrence. In Sweden, CHD risk has been markedly lower than in Finland from where a large migration occurred in the 1970s. OBJECTIVES: To study the structural and functional markers of subclinical atherosclerosis in twin pairs discordant for migration with the main focus on age at migration, length of residence and integration into Swedish society after migration from a high to a lower CHD risk country. METHODS: Carotid intima-media thickness (IMT) and brachial artery endothelial function (EF) were assessed with high-resolution ultrasound and a set of cardiovascular, socio-economic and psychosocial risk factors were estimated in 76 middle-aged male twin pairs discordant for migration from Finland to Sweden. RESULTS: Men who had migrated in adolescence had lower IMT values compared with their co-twins living in Finland (0.665 +/- 0.114 vs. 0.802 +/- 0.167 mm, P = 0.009). Also men who integrated well to Swedish society had lower (0.720 +/- 0.154 vs. 0.799 +/- 0.207 mm, P = 0.013) IMT values than their twin brothers living in Finland. Associations between IMT and migration age and between IMT and integration remained significant in multivariate analyses of several CHD risk factors. The intrapair difference in IMT was significantly associated with immigration age and integration (ANOVA, P = 0.0082), the difference being greatest among pairs where the brother living in Sweden had migrated at early age and integrated well to Swedish society. EF was better in men who had migrated to Sweden before the age of 21 years, but not later, compared with their co-twins in Finland (6.4 +/- 4.6% vs. 3.8 +/- 3.6%, P = 0.025). CONCLUSIONS: Migration at an early age and good integration are beneficial to vascular health associated with moving from a high to a lower CHD risk country, suggesting that an environment-sensitive period influences atherogenesis before adulthood.

Expression of common familial dyslipidemias in early childhood.

Early identification of common familial dyslipidemias may prevent premature atherosclerotic disease. This study estimated the diagnostic values of few early childhood repeatedly deviant lipid samples by the knowledge of the parent's dyslipidemia. The first 7 years of age data of 353 children with their parents were evaluated from atherosclerosis risk-factor intervention study controls. Parents' low high-density-lipoprotein-cholesterol concentration (hypo-HDL-C), and high total cholesterol concentration-HDL-C (hyper-non-HDL-C) were defined. True hypo-HDL-C and hyper-non-HDL-C children were defined when their respective individual longitudinal means were beyond the appropriate lipid quintiles. Sensitivities, specificities, positive and negative predictive values of the early lipid samples were estimated with individual standard deviation models and bootstrap confidence. Hypo-HDL-C children proportions were 15.3% of all, and 20.9% of the children from the hypo-HDL-C parents (p=0.26). Hyper-non-HDL-C children were 16.7% of all and 31.8% of the children from the hyper-non-HDL-C parents (p=0.008). One early non-HDL-C sample in the highest quintile predicted 56% of the hyper-non-HDL-C children from healthy parents, but 83% of the hyper-non-HDL-C children from the hyper-non-HDL-C parents. Mean of three samples improved the latter prediction to 91%. This showed that if hypercholesterolemic parent's child expressed repeatedly hyper-non-HDL-C, it predicts true dyslipidemia of the child.

Migration and differences in dietary habits-a cross sectional study of Finnish twins in Sweden.

OBJECTIVE: To compare dietary habits between Finnish twin migrants to Sweden and their co-twins always living in Finland, and to analyse how migration influenced food consumption patterns in the migrants. SUBJECTS/METHODS: Same-sexed twin pairs born in Finland below 75 years of age, with at least one twin migrating to Sweden (n=1083 pairs). Dietary habits were assessed by a food frequency questionnaire included in a comprehensive mailed questionnaire (response rate 71%). For 76 male twin pairs, information was also collected by a dietary history interview inquiring the habitual diet during the previous year. RESULTS: Migrant twins in Sweden had a lower intake of typical Finnish foods like dark bread and berries, and an increased consumption of fresh fruit compared with co-twins living in Finland. The migrants consumed less potatoes and more rice and pasta. Sweet pastries were consumed less often by the migrants and they also tended to more often cut out visible fat of meat and on the other hand add salt to dishes. Among men the migrants had a lower alcohol intake than their co-twins living in Finland. CONCLUSIONS: Migration from Finland to Sweden is associated with differences in the food pattern that reflect population differences in eating habits between the two countries. The differences include a reduced consumption of typical Finnish foods like dark bread and berries and are of bidirectional nature from the point of view of cardiovascular health.

Associations of methylenetetrahydrofolate reductase C677T polymorphism with markers of subclinical atherosclerosis: the Cardiovascular Risk in Young Finns Study.

OBJECTIVE: To study whether the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism or serum homocysteine concentration is associated with carotid artery intima media thickness (IMT), carotid artery compliance (CAC) or brachial artery flow mediated dilatation (FMD) in a healthy Finnish adult population. METHODS: Cross-sectional data obtained in 2001 for the Cardiovascular Risk in Young Finns Study were used. Carotid artery IMT, CAC and brachial FMD were measured by ultrasound and serum homocysteine concentrations using a commercial immunoassay kit. We studied 1,440 subjects (aged 24-39 years). Genotyping was performed using the 5' nuclease TaqMan assay. RESULTS: Homocysteine values differed between genotypes in women and men (ANOVA, p<0.001 for both sex groups): the genotype raised values in the order of CC, CT, TT. There was a significant difference in CAC values between the MTHFR genotypes in men (ANOVA, p = 0.008), and the CC genotype had the lowest values. In multivariate linear regression analysis adjusted for other major coronary risk factors (e.g. age, smoking, body mass index, systolic blood pressure, C-reactive protein), the association remained significant (R (2) = 25.8 %, beta = 0.091; p = 0.02). Homocysteine level was directly associated with CAC in the whole population (R (2) = 18.0 %, beta = 0.012; p = 0.014) and in women (R (2) = 9.3%, beta = 0.02; p = 0.013), but not in men (R (2) = 15.2 %, beta = 0.004; p = 0.444). We found no association between homocysteine level or the MTHFR polymorphism and carotid IMT or brachial artery FMD. CONCLUSIONS: The findings suggest that the MTHFR polymorphism does not influence IMT or FMD, but that the T allele may have an effect on CAC in men.

Increased serum levels of advanced glycation endproducts predict total, cardiovascular and coronary mortality in women with type 2 diabetes: a population-based 18 year follow-up study.

AIMS/HYPOTHESIS: AGEs, modification products formed by glycation or glycoxidation of proteins and lipids, have been linked to premature atherosclerosis in patients with diabetes. We investigated whether increased serum levels of AGEs predict total, cardiovascular (CVD) or CHD mortality in a population-based study. SUBJECTS AND METHODS: Serum levels of AGEs were determined by immunoassay in a random sample of 874 Finnish diabetic study participants (488 men, 386 women), aged 45-64 years. These participants were followed for 18 years for total, CVD and CHD mortality. RESULTS: Multivariate Cox regression models revealed that serum levels of AGEs were significantly associated with total (p = 0.002) and CVD mortality (p = 0.021) in women, but not in men. Serum levels of AGEs in the highest sex-specific quartile predicted all-cause (hazards ratio [HR] 1.51; 95% confidence intervals [CI], 1.14-1.99; p = 0.004), CVD (HR 1.56; 95% CI 1.12-2.19; p = 0.009), and CHD (HR 1.68; 95% CI 1.11-2.52; p = 0.013) mortality in women, even after adjustment for confounding factors, including high-sensitivity C-reactive protein. CONCLUSIONS/INTERPRETATION: Increased serum levels of AGEs predict total and CVD mortality in women with type 2 diabetes.

The prevalence of the metabolic syndrome in young adults. The Cardiovascular Risk in Young Finns Study.

OBJECTIVES: The prevalence of the metabolic syndrome is increasing worldwide. We studied its prevalence in Finnish young adults. Three definitions were applied: National Cholesterol Education Program (NCEP), European Group for the Study of Insulin Resistance (EGIR) and International Diabetes Federation (IDF) criteria. We also investigated the secular trend in the metabolic syndrome amongst 24-year-old adults from 1986 to 2001. DESIGN: Population-based follow-up study. SUBJECTS: 2182 healthy young adults (1007 men; 1175 women) aged 24-39 years. MAIN OUTCOME MEASURES: Metabolic syndrome and its components. RESULTS: The prevalence of the metabolic syndrome was 13.0% with NCEP criteria, 9.8% with EGIR criteria and 14.3% with IDF criteria. With NCEP and IDF criteria, the prevalence increased with age in both sexes, but more dramatically in men. There was over sixfold increase in the metabolic syndrome from 4.0% to 25.2% (P < 0.0001) in men between ages 24 and 39 years using the IDF criteria. Increases in obesity and serum triglycerides accounted much for the increase in the prevalence by age. The significant secular trend was seen between years 1986 and 2001 in 24-year-old subjects. The prevalence of the metabolic syndrome increased significantly from 1.0% to 7.5% (P < 0.0001) in 15 years. CONCLUSIONS: There is a substantial increase in the prevalence of the metabolic syndrome in healthy young adults between ages 24 and 39 driven mostly by the increase in obesity. The prevalence of the metabolic syndrome is higher amongst Finnish young adult men compared with women. The secular trend between 1986 and 2001 suggest a dramatic increase in the prevalence of the metabolic syndrome in 24-year-old young adults. Condensed abstract The prevalence of the metabolic syndrome may be increasing in young people. We studied the prevalence of the metabolic syndrome in 2182 young Finnish adults aged 24-39 years using NCEP, EGIR and IDF criteria. The prevalence of the metabolic syndrome was higher amongst Finnish men than women and increased dramatically with age. There was also a dramatic increase in the prevalence of the metabolic syndrome in 24-year-old adults between 1986 and 2001.

Development of overweight in an atherosclerosis prevention trial starting in early childhood. The STRIP study.

CONTEXT: Recent data indicate a marked increase in the prevalence of obesity among school-aged children. Thus, efficacious programmes that prevent overweight development in children are urgently needed. OBJECTIVE: To evaluate the impact of repeatedly given, individualised dietary and lifestyle counselling on the prevalence of overweight during the first 10 years of life. DESIGN AND PARTICIPANTS: This study was a part of the Special Turku Coronary Risk Factor Intervention Project for Children (STRIP), which is a prospective, randomised trial aimed at reducing the exposure of the intervention children to the known risk factors of atherosclerosis. At the child's age of 7 months, 1062 children were assigned to an intervention group (n=540) or to a control group (n=522). The intervention children received individualised counselling focused on healthy diet and physical activity biannually. Height and weight of the children were measured at least once a year. MAIN OUTCOME MEASURE: Prevalence of overweight and obesity among the intervention and control children by sex and age. Children were classified as overweight or obese if their weight for height was >20% or > or =40% above the mean weight for height of healthy Finnish children, respectively. RESULTS: After the age of 2 years, there were continuously fewer overweight girls in the intervention group than in the control group. At the age of 10 years, 10.2% of the intervention girls and 18.8% of the control girls were overweight (P=0.0439), whereas 11.6% of the intervention boys and 12.1% of the control boys were overweight (P approximately 1.00). Only three children in the intervention group were obese at some age point, whereas 14 control children were classified as obese at some age point. CONCLUSION: Individualised dietary and lifestyle counselling given twice a year since infancy decreases prevalence of overweight in school-aged girls even without any primary energy restrictions.

Proteinuria and metabolic syndrome as predictors of cardiovascular death in non-diabetic and type 2 diabetic men and women.

AIMS/HYPOTHESIS: Proteinuria predicts cardiovascular disease (CVD), but it is unclear whether this is explained by the association of the metabolic syndrome with proteinuria. Therefore, we investigated proteinuria and the metabolic syndrome as independent predictors of CVD death in men and women. METHODS: The cohort comprised 574 non-diabetic men, 707 non-diabetic women, 371 diabetic men and 349 diabetic women, all free of CVD at baseline. Modified World Health Organization criteria were used to define the metabolic syndrome, and a urinary protein concentration of >or=0.1 g/l (or >or=0.2 g/l) to define proteinuria. The endpoint was CVD mortality during the 18-year follow-up. RESULTS: Among non-diabetic men, CVD mortality per 1,000 person-years was as follows: no metabolic syndrome, no urinary protein group: 5.3; no metabolic syndrome, positive for urinary protein: 8.9; positive for metabolic syndrome, no urinary protein: 13.3; and positive for metabolic syndrome and urinary protein: 14.9. For non-diabetic women the corresponding values were: 0.9, 2.3, 4.9 and 7.9, respectively. Among diabetic men, CVD mortality per 1,000 person-years was 15.2, 32.5, 23.6 and 42.0 for the respective groups. Among diabetic women it was 25.3, 38.0, 26.3 and 40.3 (urinary protein in all cases defined as >or=0.1 g/l). In multivariate Cox models including both urinary protein and metabolic syndrome, the hazard ratios (HRs, 95% CI) of proteinuria for CVD mortality were 1.5 (0.9-2.4) in non-diabetic men, 1.8 (0.8-4.2) in non-diabetic women, 1.6 (1.0-2.6) in diabetic men and 1.6 (1.1-2.3) in diabetic women. Urinary protein as a continuous variable was associated with CVD mortality in all groups. The corresponding HRs for metabolic syndrome were: 1.6 (0.9-2.7), 4.0 (1.7-9.7), 1.5 (1.1-2.0) and 1.1 (0.8-1.5). CONCLUSIONS/INTERPRETATION: Proteinuria predicted CVD mortality independently of the presence of metabolic syndrome in non-diabetic and diabetic subjects. Metabolic syndrome predicted CVD mortality in non-diabetic women and in diabetic men, independently of the presence of proteinuria.

Longitudinal trends in consumption of vegetables and fruit in Finnish children in an atherosclerosis prevention study (STRIP).

OBJECTIVE: To assess prospectively the consumption of fruit and vegetables and its' correlation to the parental consumption in boys and girls taking part in an atherosclerosis prevention study (Special Turku Coronary Risk Factor Intervention Project for Children (STRIP) study). HYPOTHESIS: Nutrition counselling focused on cardiovascular health effects vegetable and fruit consumption. DESIGN: A prospective, randomised, clinical trial. SUBJECTS: Children were recruited to the STRIP study between 1989 and 1992. At the age of 7 months, children were randomised to the intervention (n = 540) or the control group (n = 522) and were followed up until the age of 11 years. INTERVENTION: Families in the intervention group have, since randomisation, received biannual individualised dietary counselling aimed at reduction of cardiovascular risk factors, especially saturated fat intake. Food records were used to assess fruit and vegetable consumption of children and parents. RESULTS: The percentage of total energy intake provided by fruit and vegetables decreased when the children grew older (P for age <0.001). The 1- to 10-year-old intervention boys consumed more vegetables (mean difference 3.18 g/day; CI 1.48-4.86; P < 0.001) and fruit (mean difference 10.1 g/day; CI 5.28-14.94; P < 0.001) than did the control. Mother's consumption correlated with the consumption of their daughters and sons, whereas father's consumption correlated only with the consumption of their sons. CONCLUSIONS: Finnish children taking part in the atherosclerosis prevention study had a remarkably low fruit and vegetable consumption, which furthermore decreased with age. The children's consumption correlated with the parental consumption, except between boys and mothers. A slight intervention effect was present only among boys.

Improved fibrinolysis by an intensive lifestyle intervention in subjects with impaired glucose tolerance. The Finnish Diabetes Prevention Study.

AIMS/HYPOTHESIS: The aim of this study was to investigate the effects of lifestyle intervention on the levels of plasminogen activator inhibitor (PAI-1) and fibrinogen in subjects participating in the Finnish Diabetes Prevention Study (DPS). METHODS: In five DPS centres, 321 subjects with impaired glucose tolerance (intervention group, n=163; control group, n=158) had their PAI-1 and fibrinogen levels measured at baseline and at the 1-year follow-up. Additional 3-year follow-up assessments were carried out in a sample of 97 subjects in one of the DPS centres (Turku). The intervention programme included an intensive lifestyle intervention aiming at weight reduction, healthy diet and increased physical activity. RESULTS: During the first intervention year, PAI-1 decreased by 31% in the intervention group but showed no change in the control group (p<0.0001). In the Turku subgroup, the decrease in PAI-1 persisted throughout the 3-year follow-up. Changes in PAI-1 were associated with the number of lifestyle changes made during the first year (p=0.008). Weight reduction was the most important factor explaining the decrease in PAI-1. Changes in fibrinogen levels did not differ between the groups. CONCLUSIONS/INTERPRETATION: In addition to the previously reported reduction in the risk of type 2 diabetes in DPS participants with impaired glucose tolerance, the intensive dietary and exercise intervention had beneficial long-term effects on fibrinolysis as indicated by the reduced levels of PAI-1. These results suggest that elevated PAI-1 levels in obese subjects with impaired glucose tolerance are mostly reversible by lifestyle changes, especially those geared to weight reduction.

Lifetime glycaemic exposure predicts reduced coronary vasoreactivity in Type 1 diabetic subjects.

AIMS: Subjects with Type 1 diabetes have impaired coronary vasoreactivity but the independent role of glycaemic control on myocardial perfusion is less clear. We examined the effect of lifetime glycaemic exposure on coronary vasoreactivity in 43 otherwise healthy Type 1 diabetic subjects. METHODS: Myocardial blood flow was calculated basally and during pharmacologically induced hyperaemia in the fasting state and during euglycaemic hyperinsulinaemic clamp (at an insulin infusion rate of 1 mU/kg per min for 60 min) using positron emission tomography and (15)O-water. Glycaemic exposure was estimated as glycosylated haemoglobin A(1c) (HbA(1c)) months. RESULTS: Hyperaemic myocardial blood flow was inversely associated with log HbA(1c) months in the fasting state (r = -0.72, P < 0.01) and during clamp (r = -0.35, P < 0.05). These correlations remained significant after adjustment for lipid values, blood pressures, sex, smoking, body mass index (BMI) and age (r = -0.70, P < 0.05 and r = -0.35, P < 0.05, respectively). No significant correlation was detected between hyperaemic flow and HbA(1c) or plasma glucose values measured immediately preceding the PET study. CONCLUSIONS: The present study demonstrates that the lifetime glycaemic exposure appears to be a better predictor of reduced coronary vasoreactivity than recent glycaemic control in Type 1 diabetic subjects. Reduced coronary vasoreactivity in diabetic subjects with poor glycaemic control and/or long duration of diabetes may represent an early precursor of coronary artery disease.

Enhancement of insulin-stimulated myocardial glucose uptake in patients with Type 2 diabetes treated with rosiglitazone.

AIMS: Peroxisome proliferator-activated receptor gamma (PPARgamma) activators have recently been identified as regulators of cellular proliferation, inflammatory responses and lipid and glucose metabolism. These agents prevent coronary arteriosclerosis and improve left ventricular remodelling and function in heart failure after myocardial infarction. Improvement in myocardial metabolic state may be one of the mechanisms behind these findings. The aim of this study was to investigate the effects of rosiglitazone on myocardial glucose uptake in patients with Type 2 diabetes. Placebo and metformin were used as control treatments. METHODS: Forty-four patients were randomized to treatment with rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.) or placebo in a 26-week double-blinded trial. Myocardial glucose uptake was measured using [(18)F]-2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and positron emission tomography (PET) during euglycaemic hyperinsulinaemia before and after the treatment. RESULTS: Rosiglitazone increased insulin-stimulated myocardial glucose uptake by 38% (from 38.7 +/- 3.4 to 53.3 +/- 3.6 micromol 100 g(-1) min(-1), P = 0.004) and whole body glucose uptake by 36% (P = 0.01), while metformin treatment had no significant effect on myocardial (40.5 +/- 3.5 vs. 36.6 +/- 5.2, NS) or whole body glucose uptake. Myocardial work as determined by the rate-pressure-product was similar between the groups. Neither treatment had any significant effect on fasting serum free fatty acids (FFA) but the FFA levels during hyperinsulinaemia were more suppressed in the rosiglitazone group (-47%, P = 0.02). Myocardial glucose uptake correlated inversely to FFA concentrations both before (r =-0.54, P = 0.002) and after (r = -0.43, P = 0.01) the treatment period in the pooled data. Furthermore, the increase in myocardial glucose uptake correlated inversely with interleukin-6 (IL-6) concentrations (r = -0.58, P = 0.03). CONCLUSIONS: In addition to the improvement in whole body insulin sensitivity, rosiglitazone treatment enhances insulin stimulated myocardial glucose uptake in patients with Type 2 diabetes, most probably due to its suppression of the serum FFAs.

High-sensitivity C-reactive protein and impaired coronary vasoreactivity in young men with uncomplicated type 1 diabetes.

AIMS/HYPOTHESIS: Elevated high-sensitivity C-reactive protein (hsCRP) concentrations indicate increased risk of future coronary events. The association between hsCRP and coronary vasoreactivity has not yet been examined in type 1 diabetic subjects. METHODS: We studied 18 young men who were non-smokers and who had uncomplicated type 1 diabetes. The diabetic subjects were divided into two groups, according to their median hsCRP concentration, as follows: (i) subjects with slightly elevated hsCRP (median 0.76 mg/l, range 0.47-4.73 mg/l, n=8); and (ii) subjects with low hsCRP (median 0.32 mg/l, range 0.11-0.35 mg/l, n=10). In addition we investigated 22 non-diabetic age-matched subjects (hsCRP: median 0.42 mg/l, range 0.11-1.31 mg/l). Resting myocardial blood flow and hyperaemic adenosine-stimulated flow during euglycaemic-hyperinsulinaemic clamp were determined using positron emission tomography and oxygen-(15)-labelled water. RESULTS: Diabetic subjects with slightly elevated hsCRP had significantly higher hsCRP concentrations than non-diabetic subjects (p=0.008). Resting myocardial blood flow was similar (NS) in diabetic subjects with slightly elevated hsCRP (0.79+/-0.19 ml.g(-1).min(-1)) or low hsCRP (0.81+/-0.15 ml.g(-1).min(-1)) and non-diabetic subjects (0.80+/-0.19 ml.g(-1).min(-1)). Adenosine infusion induced a significant increase in blood flow in all study subjects (p<0.001) but was blunted in diabetic subjects with slightly elevated hsCRP (3.42+/-0.61 ml.g(-1).min(-1)) when compared with diabetic subjects with low hsCRP (5.08+/-1.65 ml.g(-1).min(-1), p=0.02) or non-diabetic subjects (4.51+/-1.36 ml.g(-1).min(-1), p=0.04). Adenosine-stimulated flow was inversely correlated with hsCRP concentrations in all diabetic subjects (r=-0.70, p=0.001). CONCLUSIONS/INTERPRETATION: In young subjects with uncomplicated type 1 diabetes, even slightly elevated hsCRP concentrations are associated with reduced coronary vasoreactivity.