Increase in adiposity from childhood to adulthood predicts a metabolically obese phenotype in normal-weight adults.

Normal weight is associated with a favorable cardiometabolic risk profile and low risk of type 2 diabetes and cardiovascular disease. However, some normal-weight individuals-the "metabolically obese normal weight" (MONW)-show a cardiometabolic risk profile similar to the obese. Previous studies have shown that older age, central body fat distribution, and unfavorable lifestyle increase the risk of MONW. However, the role of early-life factors in MONW remains unknown. We examined the associations of early-life factors with adult MONW in 1178 individuals from the Cardiovascular Risk in Young Finns study who were followed up from childhood to adulthood. The strongest early predictor for adult MONW was an increase in BMI from childhood to adulthood (p = 3.1 × 10-11); each 1 SD increase in BMI z-score from childhood to adulthood led to a 2.56-fold increase in the risk of adult MONW (CI 95% = 1.94-3.38). Other significant predictors of adult MONW were male sex (OR = 2.38, 95% = 1.63-3.47, p = 7.0 × 10-6), higher childhood LDL cholesterol (OR = 1.41 per 1 SD increase in LDL cholesterol, CI 95% = 1.14-1.73, p = 0.001), and lower HDL cholesterol (OR = 1.51 per 1 SD decrease in HDL cholesterol, CI 95% = 1.23-1.85, p = 5.4 × 10-5). Our results suggest that an increase in adiposity from childhood to adulthood is detrimental to cardiometabolic health, even among individuals remaining normal weight.

Longitudinal physical activity trajectories from childhood to adulthood and their determinants: The Young Finns Study.

Determining lifelong physical activity (PA) trajectories and their determinants is essential to promote a physically active lifestyle throughout the life-course. We aimed to identify PA trajectories from childhood to midlife and their determinants in a longitudinal population-based cohort. This study is a part of the Cardiovascular Risk in Young Finns Study. From 1980, a population-based cohort (N = 3596; 1764 boys/1832 girls, age 3-18 years) has been followed up for 31 years. PA indices were formed based on self-reported data (between age 9-49 years) on frequency, duration, and intensity of leisure (during childhood) or high-intensity (at later age) PA and on sports club participation/competitions. PA trajectories were analyzed using group-based trajectory modeling. Childhood (age 12 years), young adulthood (age 24 years), and early midlife (age 37 years) determinants were analyzed. Five PA trajectories were identified: persistently active (6.6%), decreasingly active (13.9%), increasingly active (13.5%), persistently low active (51.4%, reference group), persistently inactive (14.6%). In childhood, rural residential area (OR 0.45, 95% CI 0.21-0.96) and high academic performance (OR 2.18; 95% CI 1.58-3.00) associated with persistently active group. In early midlife, smoking (OR 1.66; 95% CI 1.07-2.58) associated with persistently inactive group, regular alcohol drinking (OR 2.91; 95% CI 1.12-7.55) with persistently active group and having children (OR 2.07; 95% CI 1.27-3.38) with decreasingly active group. High adulthood education associated with both decreasingly (OR 1.87; 95% CI 1.05-3.35) and increasingly (OR 2.09; 95% CI 1.19-3.68) active groups. We identified five PA trajectories from childhood into midlife. Most prominent determinants were academic achievement, education, having children and health habits (i.e. smoking/alcohol use).

Longitudinal investigation of adenovirus 36 seropositivity and human obesity: the Cardiovascular Risk in Young Finns Study.

BACKGROUND/OBJECTIVES: Adenovirus-36 (Adv-36) infection is associated with exaggerated adipogenesis in cell culture and the development of obesity in animal models and humans, but a causal relationship remains unproven. Our objective was to determine whether serological evidence of Adv-36 infection in childhood and/or adulthood is associated with adult obesity. SUBJECTS/METHODS: Paired plasma concentrations of Adv-36 antibodies were measured by a novel enzyme-linked immunosorbent assay in a subgroup (n=449) of the Cardiovascular Risk in Young Finns Study in childhood (mean age 11.9 years) and adulthood (mean age 41.3 years). The study group included (1) individuals who had maintained normal-weight status (2) those who became obese adults from a normal-weight status in childhood and (3) those that were overweight/obese as a child and obese as an adult. RESULTS: Mean (s.d.) time between baseline and follow-up was 29.4 (3.2) years (range 21-31 years). A total of 24.4% of individuals who were normal weight throughout life were seropositive for Adv-36 during child and/or adulthood as compared with 32.3% of those who became obese adults (P=0.11). Those who became obese in adulthood were more likely to be Adv-36 seropositive as adults compared with those who maintained normal weight (21.3% vs. 11.6%, P=0.02). This difference was mediated by a decline in Adv-36 seropositivity between child and adulthood in those maintaining normal weight. No differences were observed in body mass index across the life course, nor in waist circumference in adult life, between those who were Adv-36 seronegative or seropositive at any age. CONCLUSIONS: Individuals who gained weight across the life course were more likely to be Adv-36 seropositive in adult life than those who did not gain weight. However, analysis of change in weight status in relation to Adv-36 positivity did not support a causal role for Adv-36 in the development of obesity.

Depressive symptoms are associated with lower bone mineral density in young adults with high job strain. The Cardiovascular Risk in Young Finns Study.

BACKGROUND: Job strain has been associated with depressive symptoms, and depression has been associated with low bone mineral density (BMD). PURPOSE: The associations between BMD and job strain have not been studied. We examined the relations between BMD, job strain, and depressive symptoms in a population-based group of young adults in Finland. METHOD: Ultrasonic measurement of BMD at the calcaneus was performed on 777 participants (men 45 %, aged 30-45) drawn from the Cardiovascular Risk in Young Finns Study. Job strain was assessed by self-administered questionnaires by the combination of job demands and job control. Depressive symptoms were assessed with a modified Beck Depression Inventory. The effects of job strain on BMD were studied with multivariable analyses with age, sex, BMI, vitamin D, and calcium intake, physical activity, cigarette smoking, alcohol use, and depressive symptoms as covariates. RESULTS: Depressive symptoms were independently associated with lower BMD T score in participants with high job strain (ß = -0.241, p = 0.02), but depressive symptoms were not significantly associated with BMD in the low (ß = -0.160, p = 0.26) and intermediate (ß = -0.042, p = 0.66) job strain categories. CONCLUSION: The results suggest that job strain modifies the association between depressive symptoms and BMD. Depressed individuals with high work-related stress might be in increased risk of lower bone mineral density.

Linkage of familial combined hyperlipidaemia to chromosome 1q21-q23.

More than half of the patients with angiographically confirmed premature coronary heart disease (CHD) have a familial lipoprotein disorder. Familial combined hyperlipidaemia (FCHL) represents the most common genetic dyslipidemia with a prevalence of 1.0-2.0%. FCHL is estimated to cause 10-20% of premature CHD and is characterized by elevated levels of cholesterol, triglycerides, or both. Attempts to characterize genes predisposing to FCHL have been hampered by its equivocal phenotype definition, unknown mode of inheritance and genetic heterogeneity. In order to minimize genetic heterogeneity, we chose 31 extended FCHL families from the isolated Finnish population that fulfilled strictly defined criteria for the phenotype status. We performed linkage analyses with markers from ten chromosomal regions that contain lipid-metabolism candidate genes. One marker, D1S104, adjacent to the apolipoprotein A-II (APOA2) gene on chromosome 1, revealed a lod score of Z = 3.50 assuming a dominant mode of inheritance. Multipoint analysis combining information from D1S104 and the neighbouring marker D1S1677 resulted in a lod score of 5.93. Physical positioning of known genes in the area (APOA2 and three selectin genes) outside the linked region suggests a novel locus for FCHL on 1q21-q23. A second paper in this issue (Castellani et al.) reports the identification of a mouse combined hyperlipidaemia locus in the syntenic region of the mouse genome, thus further implicating a gene in this region in the aetiology of FCHL.

Selenium status and blood lipids: the cardiovascular risk in Young Finns study.

BACKGROUND: Concern has been recently raised about possible adverse cardio-metabolic effects of high selenium status, such as increased risks of diabetes and hyperlipidaemia. However, most of the evidence comes from selenium-replete populations such as that of the United States. OBJECTIVES: To examine cross-sectional and longitudinal associations of serum selenium with cardiovascular risk factors in Finland where selenium levels were amongst the lowest in the world until the early 1980s before the implementation of a nationwide selenium fertilization programme. METHODS: Serum selenium was measured in 1235 young Finns aged 3-18 years at baseline in 1980 (prefertilization) and in a subgroup (N = 262) at the 6-year follow-up (1986, postfertilization). During the 27-year follow-up, serum lipids, blood pressure, body mass index and smoking were assessed five times (1980, 1983, 1986, 2001 and 2007). RESULTS: Mean (±SD) serum selenium concentrations were 74.3 ± 14.0 ng mL(-1) in 1980 and 106.6 ± 12.5 ng mL(-1) in 1986 (average increase 32.3 ng mL(-1); 95% CI: 30.3 to 34.3, P < 0.0001). In univariate and multivariable cross-sectional models in 1980 and 1986, increased serum selenium levels were consistently associated with increased total, HDL and Low-density lipoprotein (LDL) cholesterol. However, the average longitudinal changes in lipids were -0.20 mmol L(-1) (95% CI: -0.30 to -0.10, P < 0.0001) for total cholesterol, 0.06 mmol L(-1) (95% CI: 0.03 to 0.10, P < 0.0001) for HDL cholesterol, and -0.23 mmol L(-1) (95% CI: -0.31 to -0.14, P < 0.0001) for LDL cholesterol. Selenium measured in 1986 was not associated with lipids assessed in 2001 and 2007. CONCLUSIONS: Cross-sectional findings from the Young Finns study corroborate positive associations of selenium status with serum lipids. However, longitudinal evidence does not support the causality of this link.

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.

A prospective cohort study of deficient maternal nurturing attitudes predicting adulthood work stress independent of adulthood hostility and depressive symptoms.

Stressful childhood environments arising from deficient nurturing attitudes are hypothesized to contribute to later stress vulnerability. We examined whether deficient nurturing attitudes predict adulthood work stress. Participants were 443 women and 380 men from the prospective Cardiovascular Risk in Young Finns Study. Work stress was assessed as job strain and effort-reward imbalance in 2001 when the participants were from 24 to 39 years old. Deficient maternal nurturance (intolerance and low emotional warmth) was assessed based on mothers' reports when the participants were at the age of 3-18 years and again at the age of 6-21 years. Linear regressions showed that deficient emotional warmth in childhood predicted lower adulthood job control and higher job strain. These associations were not explained by age, gender, socioeconomic circumstances, maternal mental problems or participant hostility, and depressive symptoms. Deficient nurturing attitudes in childhood might affect sensitivity to work stress and selection into stressful work conditions in adulthood. More attention should be paid to pre-employment factors in work stress research.

The benefits of sustained leisure-time physical activity on job strain.

BACKGROUND: The long-term effects of leisure-time physical activity (LTPA) on job strain have not been assessed in a large prospective population-based cohort study. AIMS: To examine the relationship between the LTPA and the prevalence of job strain. METHODS: The participants were 861 full-time employees (406 men and 455 women), aged 24-39 years in 2001, from the ongoing Cardiovascular Risk in Young Finns Study. LTPA was assessed using a self-report questionnaire in 1992 and in 2001. The participants were grouped into four categories according to tertiles of LTPA index at two time points: persistently active, increasingly active, decreasingly active and persistently inactive. Job strain was measured in 2001 by indicators of job demands and job control. RESULTS: Baseline LTPA was inversely associated with job strain (P < 0.001) and job demands (P < 0.05) and directly associated with job control (P < 0.05) in both sexes in a model adjusted for the change in 9-year LTPA, age, educational level, occupational status and smoking. Compared with persistently active participants, persistently inactive participants had a 4.0-fold higher job strain after adjustment for the confounders. Similarly, persistently inactive participants had a 2.7-fold higher job demands and a 1.8-fold lower job control. Decreasing physical activity was independently associated with high job strain (P < 0.01) and with low job control (P < 0.01). CONCLUSIONS: Participation in regular LTPA during leisure may help young adults to cope with job strain. A long-term benefit of LTPA may play a role in the development of mental well-being.

Sustained participation in youth sport decreases metabolic syndrome in adulthood.

OBJECTIVE: to explore the effect of organized youth sport on metabolic syndrome (MetS) in adulthood. DESIGN: Longitudinal study data from the cardiovascular risk in young Finns study. SUBJECTS: A total of 1493 males (n=704) and females (n=789) aged 3, 6, 9, 12, 15 and 18 years were randomly selected from five university towns and their rural surroundings in 1980. They were followed up for 21 years. In 2001 they were 24, 27, 30, 33, 36 and 39 years old. MEASUREMENTS: Youth sports participation data (participation in sport-club training and competitions) were assessed in 1980 and 1983 using a self-report questionnaire completed in connection with a medical examination. Participants were divided into athletes and non-athletes at each measurement point, and then classified into four groups: Persistent athlete, Starter, Leaver and Non-athlete. A mean score of youth sport was assessed by calculating the average of four consecutive measurements (1980-1989). MetS risk in 2001 was defined as a categorical variable based on the guidelines of the European Group for the Study of Insulin Resistance (EGIR) and as a continuous MetS-score variable by summing the z-scores of individual metabolic variables. RESULTS: In males and females, intense participation in youth sports over 3 years was inversely and significantly associated with clustered MetS score and prevalence of MetS defined by EGIR in adulthood (P<0.05). The association remained significant after adjustment for age, baseline clustered MetS score, smoking and total caloric intake and after additional adjustments for adult leisure-time physical activity. Starters during 3 years were less likely to have MetS than non-athletes. Leavers were at a higher risk for MetS than persistent athletes. These associations were attenuated in males by adjustment for all potential confounders. Similar associations were found using EGIR MetS as an outcome. CONCLUSIONS: Sustained participation in organized sport lasting at least 3 years in youth is associated with reduced risk for developing MetS in adulthood.

Genetics of C-reactive protein and complement factor H have an epistatic effect on carotid artery compliance: the Cardiovascular Risk in Young Finns Study.

Atherosclerosis is characterized by a prominent inflammatory component and C-reactive protein (CRP) has been implicated to modulate the complement activity in atherosclerotic arteries via complement factor H (CFH) binding. In this study, we examined whether the gene-gene interactions between CRP haplotypes and CFH Tyr402His functional polymorphism exerted an effect on early atherosclerosis. Single nucleotide polymorphisms (SNPs) in CFH (Tyr402His) and CRP (-717A>G, -286C >T>A, +1059G>C, +1444C>T and +1846G>A) were genotyped in the participants of the Cardiovascular Risk in Young Finns Study (n=1698, aged 24-39 years). The CRP SNPs were further constructed into haplotypes and their interactive effects with the CFH Tyr402His polymorphism on the early atherogenic vascular changes [i.e. carotid artery compliance (CAC) and intima-media thickness (IMT)] were examined. After risk factor adjustment, a significant gene-gene interaction (P=0.007) on CAC was observed between CRP haplotype ATGTG and CFH Tyr402His polymorphism in males. Furthermore, logistic regression analysis verified the risk-modifying interactive effect on CAC between these loci (OR 3.70, 95% CI 1.37-10.02, P=0.010). No effects on CAC were observed in females and no effects on IMT were detected in either sex. We conclude that the combined presence of CRP haplotype ATGTG and CFH 402His allele may be disadvantageous to carotid artery elasticity in males.

CRP and FCGR2A genes have an epistatic effect on carotid artery intima-media thickness: the Cardiovascular Risk in Young Finns Study.

The role of the inflammatory mediator C-reactive protein (CRP) in atherosclerosis is recognized although its specific functions are not entirely clear. CRP binds to the Fcgamma receptor2A (FcgammaR2A) and its polymorphism, FCGR2A (Arg131His), strongly influences the binding. We wanted to evaluate the CRP-mediated proatherogenic process on early atherosclerosis and investigated whether CRP and FCGR2A show an interactive effect on carotid intima-media thickness (IMT). Polymorphisms of FCGR2A (Arg131His) and CRP (-717A > G, -286C > T > A, +1059G > C, +1444C > T and +1846G > A) were genotyped and their effects on IMT were analyzed in 2260 young adults participating in the Cardiovascular Risk in Young Finns Study. CRP haplotypes were constructed based on the CRP polymorphisms. The FCGR2A(Arg131His) polymorphism did not have an independent effect on IMT but a significant gene-gene interaction, epistasis, between FCGR2A and CRP genetics on IMT was found. The epistatic effect was seen in men at haplotype and genotypic level; both CRP haplotype GCGCG (-717, -286, +1059, +1444 and +1846) and CRP-717A > G polymorphism interacted with FCGR2A(Arg131His) on IMT. After adjustment with classical risk factors the P-values for interaction were P = 0.013 and P = 0.010, respectively. No associations were observed in women. In conclusion, this study showed that the effect of CRP genetics on early atherosclerotic changes is modulated by the FCGR2A genetics.

Twenty-four-month alpha-galactosidase A replacement therapy in Fabry disease has only minimal effects on symptoms and cardiovascular parameters.

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of alpha-galactosidase A enzyme activity. Decreased enzyme activity leads to accumulation of glycosphingolipids in different tissues including endothelial cells and smooth-muscle cells and cardiomyocytes, and cardiovascular complications are common in the disease. Since 2001, specific enzyme replacement therapy (ERT) with alpha-galactosidase A has been available. It has been reported to improve clinical symptoms and quality of life. However, limited and controversial data on its efficacy to cardiac involvement have been published. Nine patients (5 male) with Fabry disease were included in an open-label prospective follow-up study of 24-month ERT. Comprehensive cardiovascular evaluation was performed by MRI, stress echocardiography and quality of life assessment. Plasma globotriaosylceramide decreased from 6.2 to 1.4 microg/ml during ERT (p<0.05). The only other measured parameters that changed significantly were resting heart rate that decreased from 79 to 67 bpm (p<0.01) and end-systolic volume that decreased by 12.4 ml (p<0.05). The other parameters consisting of quality of life, self-estimated cardiovascular condition, diastolic function, exercise capacity, ECG parameters, ejection fraction and ventricular mass did not change. ERT has only minimal effect on symptoms and cardiovascular morphology and function in Fabry disease. Therefore, effective conventional medical therapy is still of major importance in Fabry disease. Larger ERT studies are warranted, especially in women, to solve current open questions, such as the age at which ERT should be started, optimal dosage and intervals between infusions. Furthermore, longer follow-up studies are needed to assess the effects of ERT on prognosis.

Is the association between job strain and carotid intima-media thickness attributable to pre-employment environmental and dispositional factors? The Cardiovascular Risk in Young Finns Study.

OBJECTIVES: Most previous studies of job strain and cardiovascular risk have been limited to adult data. It remains unclear whether this association might be explained by factors already present before entering the labour market. This study examined whether pre-employment family factors and participants' own dispositional factors contribute to the relationship between job strain and carotid intima-media thickness (CIMT) among male employees. METHODS: The sample consisted of 494 men from the Cardiovascular Risk in Young Finns Study. Parental socioeconomic position and parental life dissatisfaction were assessed at 9-21 years of age and components of type A behaviour (Hunter-Wolf) were assessed at 12-24 years of age before the participants had entered the labour market. Job strain, education and CIMT were assessed at 27-39 years of age when all participants were employed. RESULTS: There was an association between higher job strain and increased CIMT in adulthood (mean 0.59 mm; 95% CI 0.42 to 0.76) which was only slightly affected on adjustment for parental socioeconomic position and parental life dissatisfaction as well as participants' education. However, the job strain/CIMT relationship attenuated by 17% to non-significant after taking into account the effect of the participants' type A behaviour components. CONCLUSIONS: In this contemporary cohort of men, lack of leadership (a type A behaviour component) contributed to the association between job strain and CIMT 15 years later, whereas pre-employment family factors had only a modest effect on this association.

Coronary flow reserve is reduced in young men with IDDM.

Disturbances of coronary circulation have been reported in diabetic patients with microvascular complications but without obstructive coronary atherosclerosis. The aim of the present study was to investigate coronary flow reserve in young adult patients with IDDM but without microalbuminuria and diabetic autonomic neuropathy. Coronary flow reserve was determined in 12 nonsmoking male patients with IDDM (age 30.0 +/- 6.6 years) and 12 healthy matched volunteers. Groups were similar with respect to blood pressure and serum lipid concentrations, and no subject had a positive family history of coronary heart disease. The patients with IDDM had normal exercise echocardiography and autonomic nervous function tests. Five patients had minimal background retinopathy, and none had microalbuminuria. Positron emission tomography and [15O]H2O were used to measure myocardial blood flow at rest and after dipyridamole administration. The studies were performed during euglycemic hyperinsulinemia (serum insulin approximately 70 mU/l). The baseline myocardial blood flow was similar in patients with IDDM and in control subjects (0.84 +/- 0.18 vs. 0.88 +/- 0.25 ml x g(-1) x min(-1), NS). The myocardial blood flow during hyperemia was 29% lower in patients with IDDM (3.17 +/- 1.57) compared with the control subjects (4.45 +/- 1.37 ml x g(-1) x min(-1), P < 0.05). Consequently, coronary flow reserve (the ratio of flow during hyperemia and at rest) was lower in diabetic patients than in control subjects (3.76 +/- 1.69 vs. 5.31 +/- 1.86, P < 0.05) and the total coronary resistance during hyperemia was higher in diabetic patients (53.7 +/- 31.5) compared with the control subjects (31.4 +/- 11.6 mmHg x min x g x ml(-1), P < 0.05). The coronary flow reserve was similar in diabetic patients with and without mild background retinopathy. No association was found between the coronary flow reserve and serum lipid or HbA1c values in either group. Coronary flow reserve is impaired in young adult males with IDDM and no or minimal microvascular complications and without any evidence of coronary heart disease. This abnormality cannot be explained by standard coronary heart disease risk factors. The results imply early impairment of coronary vascular reactivity in IDDM patients, which may represent an early precursor of future coronary heart disease or may contribute to the pathogenesis of diabetic cardiomyopathy.

In vivo low density lipoprotein oxidation relates to coronary reactivity in young men.

OBJECTIVES: This study was undertaken to examine the relation of in vivo low density lipoprotein (LDL) oxidation and other lipid risk factors to coronary reactivity in normal subjects. BACKGROUND: Experimental studies have shown that oxidized LDL (ox-LDL) particles are injurious to the vascular wall by impairing its normal vasodilator function. METHODS: We used noninvasive positron emission tomographic (PET) imaging with intravenous dipyridamole to measure coronary flow reserve, a marker of coronary endothelial and smooth muscle function, in 30 healthy men (mean [+/-SD] age 34.4 +/- 3.2 years). As a marker of in vivo LDL oxidation, the autoantibody titer against ox-LDL was measured by the enzyme-linked immunosorbent assay method. RESULTS: Plasma levels of autoantibody titer against ox-LDL were inversely associated with coronary flow reserve (r = -0.42, p = 0.023). High LDL cholesterol levels (above median > 3.0 mmol/liter) were associated with a low coronary flow reserve only in subjects expressing simultaneously high levels of ox-LDL titer (above median). Subjects with simultaneously high levels of LDL cholesterol and ox-LDL titer had lower coronary flow reserve values than subjects in other groups (3.89 vs. > 5.0 in other groups, p = 0.066). CONCLUSIONS: These data provide evidence for the role of ox-LDL in affecting the coronary reactivity in vivo and support the concept that oxidative modification of LDL particles provides a mechanism by which high LDL concentrations exhibit injurious effects on the coronary vascular bed.

Correlation of serum lipids with diabetes control in sulfonylurea-treated diabetic patients.

The relationships between fasting blood glucose, glycosylated hemoglobin A1, and several lipid parameters were studied in 67 non-insulin-dependent diabetic patients (19 men, 48 women) being treated with tolbutamide, chlorpropamide, or glibenclamide. All patients were over 60 yr of age with a mean age of 76.4 +/- 6.7 yr (+/- SD). There were positive associations between fasting blood glucose and serum cholesterol, LDL cholesterol, and serum triglycerides. A strong association between total cholesterol and triglycerides was also evident. Diabetes control and HDL cholesterol did not correlate with each other. A weak inverse correlation existed between fasting blood glucose and the HDL cholesterol/total cholesterol ratio. HDL cholesterol concentrations were low in the diet- and drug-treated diabetic patients. No deleterious sulfonylurea effects on cholesterol, LDL cholesterol, and triglyceride concentrations or HDL cholesterol/total cholesterol ratio were noted.

Glucagon-stimulated and postprandial plasma C-peptide values as measures of insulin secretory capacity.

Basal, postprandial (2 h after breakfast), and glucagon-stimulated plasma C-peptide concentrations were determined in a group of 36 adult diabetic patients. Basal and postprandial C-peptide values were measured on consecutive days to estimate the degree of variation of C-peptide secretion. In a subgroup of 15 diabetic patients treated chronically with diet and oral hypoglycemic agents (sulfonylureas or a combination of sulfonylureas and metformin), we studied whether administration of sulfonylureas immediately before breakfast had any effect on postprandial C-peptide values. Absolute differences between two consecutive fasting C-peptide concentrations in insulin-requiring patients were less than 0.1 nM in all but 1 patient, in whom the difference was 0.18 nM. In subjects treated with oral hypoglycemic agents the median difference was 0.12 nM (range 0-0.38 nM). Absolute differences between two consecutive postprandial C-peptide concentrations were all less than 0.1 nM in insulin-requiring patients. No significant difference was found between postprandial C-peptide concentrations with or without preceding administration of oral hypoglycemic agents (medians 1.35 and 1.30 nM, respectively). Glucagon-stimulated C-peptide concentrations were somewhat higher than the postprandial values. However, equal discrimination between insulin-requiring and non-insulin-requiring diabetic patients was found by measuring postprandial or glucagon-stimulated C-peptide concentrations.

Microalbuminuria. Invalidity of simple concentration-based screening tests for early nephropathy due to urinary volumes of diabetic patients.

OBJECTIVE: To evaluate the possibility of replacing quantitative albumin excretion rate (AER) measurements with rapid screening tests for microalbuminuria. RESEARCH DESIGN AND METHODS: Dipstick-negative specimens from 363 consecutive insulin-dependent diabetes mellitus (IDDM) and 46 non-insulin-dependent diabetes mellitus (NIDDM) patients from primary-care and hospital clinics (11% inpatients) within the district of Turku University Hospital were studied. Albumin concentrations and 12-h nightly excretion rates (N-AER) were measured by nephelometry (sensitivity 2 mg/L). RESULTS: An increased N-AER (greater than 15 micrograms/min) was seen in 99 IDDM (27%) and 15 NIDDM (33%) patients. The median urinary volume was 900 ml/12 h, with a maximum of 3000 ml. At the level of 20 mg albumin/L, the sensitivity to detect elevated N-AER was 70% among IDDM patients and 60% among NIDDM patients. At a lower albumin concentration of 10 mg/L, the sensitivities were increased to 91 and 87% in IDDM and NIDDM patients, respectively, but the specificities were reduced to 77 and 71%, respectively. CONCLUSIONS: To evaluate incipient nephropathy, we recommend quantitative measurements of N-AER from timed urine collections only. Dipstick tests are either insensitive or nonspecific.

Relations of life-style with lipids, blood pressure and insulin in adolescents and young adults. The Cardiovascular Risk in Young Finns Study.

The associations of life-style variables, namely type of dietary fat, alcohol use, smoking, obesity, physical activity and oral contraceptive use with serum lipids, insulin and blood pressure were studied in 1398 adolescents and young adults aged 15-24 years. Smokers were more often physically inactive and regular users of alcohol compared to non-smokers. In females, smoking and alcohol use were more prevalent among oral contraceptive users. Independent effects of life-style variables on lipids, blood pressure and insulin were assessed with multiple linear regression models. In both sexes, body mass index was positively related to low density lipoprotein cholesterol (LDL-C), triglycerides (TG), systolic (SBP) and diastolic (DBP) blood pressure and insulin, and negatively with high density lipoprotein cholesterol (HDL-C). Leisure time physical activity was associated with lower levels of insulin among males. Smoking was related with 0.07 mmol/l lower HDL-C levels and about 0.09 mmol/l higher TG levels in males. In both sexes, smoking was related with lower levels of SBP. In males, alcohol use was associated with 0.05 mmol/l higher level of HDL-C (P = 0.06). In females, alcohol use was associated with lower levels of LDL-C and TG. Oral contraceptive use was associated with approximately 0.15 mmol/l higher levels of TG and about 4.0 mmHg higher SBP. Preferring butter over margarine as dietary fat was associated with 0.26 and 0.19 mmol/l higher levels of LDL-C in males and females, respectively. Accumulation of adverse life-habits contributed to the clustering of an atherogenic lipid profile and high blood pressure. In males, those with 4 selected life-habits present, namely obesity, smoking, inactivity and the use of butter, had 5.5 times greater risk (95% confidence interval 1.4-20.7) of belonging to the group with high LDL-C, low HDL-C and high DBP compared to those with zero or one life-habits present. These data demonstrate that life-habits show clustering in adolescents and young adults. Individuals with many adverse life-style risk factors present are at increased risk of having an atherogenic lipid and blood pressure profile.