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Biomedical subjects

T Rönnemaa

Publications and source records attributed to T Rönnemaa.

At least 37 records · Page 2Linked to original sources

Decreased large artery distensibility in borderline hypertension is related to increased in vivo low-density lipoprotein oxidation.

The present study tested the hypothesis that reduced arterial elasticity seen in hypertension is related to increased oxidation of LDL. Fifteen men with borderline hypertension (BHT), with blood pressure values classified as high normal (systolic blood pressure 130-140 mmHg or diastolic blood pressure 85-89 mmHg) were included. The control group comprised 22 men with normal blood pressure values (<135/80 mmHg) matched for age, body size and LDL-cholesterol level. Distensibility of aorta was measured using magnetic resonance imaging, and distensibility of the common carotid artery using ultrasound. Baseline LDL diene conjugation was used as a marker for ox-LDL. Aortic and carotid distensibilities were lower in the BHT men than in controls (1.4 +/- 0.6 vs. 1.9 +/- 0.6%/10 mmHg, p<0.05 for aortic distensibility; 2.9 +/- 0.9 vs. 3.6 +/- 0.6%/10 mmHg, p<0.05 for carotid distensibility). Ox-LDL was significantly higher in the BHT men than in controls (44 +/-15 vs. 28 +/- 8 micromol/L, p<0.01). In univariate analysis, ox-LDL associated with aortic distensibility (r=-0.43, p<0.05). In multivariate analysis, the differences in distensibilities between the groups disappeared when the values were adjusted for ox-LDL. These data show decreased arterial elasticity and increased LDL oxidation in young men with borderline hypertension, and suggest that oxidative modification of LDL particles may play a pathophysiological role in the development of reduced arterial distensibility in hypertension.

Adult↗

Effects of gender, apolipoprotein E phenotype and cholesterol-lowering by plant stanol esters in children: the STRIP study. Special Turku Coronary Risk Factor Intervention Project.

AIM: To evaluate the effects of gender, apolipoprotein E phenotype and cholesterol absorption and synthesis (estimated as serum plant sterol and cholesterol precursor sterol concentrations) on the cholesterol-lowering effect of plant stanol esters in children. METHODS: Eighty-one healthy, normocholesterolaemic 6-y-old children (45 boys) were recruited from the Special Turku Coronary Risk Factor Intervention Project (STRIP), a randomized prospective trial aiming at atherosclerosis prevention in childhood. This placebo-controlled, double-blind, cross-over study comprised two 3-mo study periods and a 6-wk wash-out period. During the study periods, 20 g of the children's daily dietary fat intake was replaced with plant stanol ester margarine or control margarine. RESULTS: In boys, plant stanol esters reduced serum total and low-density lipoprotein cholesterol concentrations by 6% (0.09 to 0.42 mmol/L) and 9% (0.09 to 0.36 mmol/L), respectively (p < 0.01 for both). In girls, the decreases in concentrations were 4% (0.03 to 0.38 mmol/L) and 6% (0.02 to 0.32 mmol/l) (p < 0.05 for both). The response rate did not differ between the genders. Serum total and low-density lipoprotein cholesterol concentrations decreased by 6% and 8% (p < 0.01 for both), respectively, in both children with the apolipoprotein E 3/4 or 4/4 (apoE4+) phenotype and the apolipoprotein E 2/3 or 3/3 (apoE4-) phenotype. Cholesterol absorption decreased both in the apoE4+ children and in the apoE4- children, but cholesterol synthesis consistently increased in the apoE4+ children only. CONCLUSION: Plant stanol esters reduce serum cholesterol concentration in healthy children irrespective of their gender or apoE4 phenotype.

Apolipoproteins E↗

Increased aortic intima-media thickness: a marker of preclinical atherosclerosis in high-risk children.

BACKGROUND: Autopsy studies in children have shown that atherosclerotic lesions begin to develop first in the intima of the aorta. Recent developments in ultrasound techniques have made it possible to visualize the intima-medial thickness of the abdominal aorta directly (aIMT). Therefore, we examined the feasibility of measuring aIMT in children and studied its value in distinguishing high-risk children from healthy controls compared with a more established marker of subclinical atherosclerosis, the common carotid artery intima-medial thickness (cIMT). METHODS AND RESULTS: IMTs were measured using high-resolution (13 MHz) ultrasound in 88 children (aged 11+/-2 years); 16 had hypercholesterolemia (LDL cholesterol, 5.1+/-1.2 mmol/L), 44 had type 1 diabetes (mean duration, 4.4+/-3.1 years; LDL cholesterol, 2.3+/-0.7 mmol/L), and 28 were healthy (controls; LDL cholesterol, 2.5+/-0.8 mmol/L). High-risk children had significantly increased aIMTs and cIMTs (both P<0.001) compared with controls. In controls, aIMT was similar to cIMT (P=NS), but aIMT was higher than cIMT in the children with hypercholesterolemia and diabetes (both P<0.01). Both markers showed excellent and approximately equal between-observer (<4%) and between-subject variation (<5%). CONCLUSIONS: Children with hypercholesterolemia and diabetes show increased IMTs compared with healthy controls, with a relatively greater increase in the aIMT than in the cIMT. Because atherosclerosis begins first in the intima of the aorta, these data suggest that the aIMT might provide the best currently available noninvasive marker of preclinical atherosclerosis in children.

Adolescent↗

Diabetic complications are associated with liver enzyme activities in people with type 1 diabetes.

This study was performed to clarify if diabetic complications are associated with liver enzyme activities in type 1 diabetic outpatients. Elevated activities of serum aminotransferases are a common sign of liver disease and are observed more frequently among people with diabetes than in the general population. Many studies have shown an association between specific diabetic complications and disturbances in various tissues, such as diabetic nephropathy and cardiovascular diseases, but only limited data are available on the possible association between diabetic complications and liver function. We studied 28 patients with type 1 diabetes. Mean age was 43.4+/-9.5 (S.D.), and duration of diabetes 25.2+/-9.7. Limited joint mobility (LJM) was assessed by the Rosenbloom's method. Background and proliferative retinopathy, and peripheral symmetrical polyneuropathy were also assessed. Activities of alanine amino transferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) in serum were determined. The metabolic control of the diabetes was evaluated by the glycosylated haemoglobin A(1c) (HbA(1c)) level and lipid values were also measured. ALT activity was associated with LJM (P<0.01) and with neuropathy (P<0.01). Association between GGT activity and LJM (P<0.01) and neuropathy (P<0.01) were also found. GGT activity was also associated with the severity of retinopathy (P<0.01). None of these associations was explained by confounding effects of diabetes duration, age, body mass index (BMI), HbA(1c) or alcohol consumption. In conclusion, diabetic complications such as LJM, retinopathy and neuropathy are associated with liver enzyme activities independent of alcohol consumption, BMI and metabolic control of diabetes.

Adult↗

Nutrition knowledge and food intake of seven-year-old children in an atherosclerosis prevention project with onset in infancy: the impact of child-targeted nutrition counselling given to the parents.

OBJECTIVE: To compare nutrition knowledge and food intake in 7-y-old intervention and control children in an atherosclerosis risk factor intervention trial after 6.5 y of nutrition counselling given to the parents. DESIGN, SUBJECTS AND METHODS: Intervention families in the Special Turku Coronary Risk Factor Intervention Project received child-oriented nutritional counselling one to three times a year since child's age of 7 months, aimed at reduced saturated fat and cholesterol intake. Children's nutrition knowledge was analysed in a time-restricted cohort of 70 seven-y-old (34 boys) intervention children and 70 control children (40 boys) with a picture identification test. For comparison, children's food intake was evaluated using scores developed for the project that reflected quality and quantity of fat and quantity of salt in children's two or three 4-day food diaries recorded between 5.5 and 7 y of age. RESULTS: Child-targeted nutrition counselling of the intervention families only slightly increased intervention children's knowledge of heart-healthy foods (42.6% vs 34.9% correct answers by the intervention and control children, P = 0.057). Only < or = 20% of the children were able to adequately justify their answers in the test. The food diaries of the intervention children comprised more foods low in saturated fat and high in unsaturated fat than those of the control children (57.1% vs 41.7% of the maximum score for low fat foods, P = 0.0001; 48.9% vs 37.7% for high unsaturated fat foods, P = 0.0009, respectively), but the intervention and control children consumed similar amounts of low-salt foods (P = 0.23). Nutrition knowledge and food use scores correlated poorly (r = -0.20-0.35). CONCLUSIONS: Child-targeted nutrition counselling repeatedly given to the parents during and after child's infancy strongly influenced food choice scores of the 5.5-7-y-old children but failed to influence children's salt intake or scores in a nutrition knowledge picture test.

Arteriosclerosis↗

Biochemical markers of type III and I collagen: association with retinopathy and neuropathy in type 1 diabetic subjects.

AIMS: Connective tissue alterations may contribute to the development of diabetic long-term complications in eyes, kidneys and peripheral nerves. Collagen deposition may be increased in micro- and macrovascular disease in diabetic subjects. We tested whether biochemical markers of type III and I collagen metabolism are associated with retinopathy and neuropathy in Type 1 diabetes. METHODS: A total of 28 patients, mean age 43.4 +/- 9.5 (sd) and duration of diabetes 25.2 +/- 9.7 years, were studied. Stereoscopic colour fundus photographs were taken for assessment of retinopathy which was classified as no, background or proliferative. Concentrations of aminoterminal propeptide of type III procollagen (PIIINP), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal cross-linked telopeptide of type I collagen (ICTP) in serum and urinary excretion of cross-linked N-telopeptides of type I collagen (NTX) and deoxypyridinoline crosslinks (DPyr) into urine were measured. RESULTS: Average serum PIIINP was higher in subjects with proliferative (3.2 +/- 1.1 microg/l) than without proliferative retinopathy (2.5 +/- 0.6 microg/l) (P = 0.03). Average serum PICP was higher in subjects without retinopathy (181.7 +/- 19.5 microg/l) than in subjects with background retinopathy (132.1 +/- 42.7 microg/l) (P = 0.02). Concentrations of other collagen markers were not different in subjects with or without retinopathy. No association between collagen markers and neuropathy was found. CONCLUSIONS: The increased synthesis of type III collagen, reflecting deposition of matrix and basement membrane connective tissue, may be involved in the pathogenesis of proliferative retinopathy in Type 1 diabetic subjects. On the other hand, we observed decreased synthesis of Type I collagen, which can result in weakened vascular integrity in subjects with retinopathy.

Adult↗

Dietary plant sterols alter the serum plant sterol concentration but not the cholesterol precursor sterol concentrations in young children (the STRIP Study). Special Turku Coronary Risk Factor Intervention Project.

Plant sterol supplementation reduces serum cholesterol concentration but may increase serum plant sterol concentrations, especially in children. We determined whether natural dietary plant sterols derived mainly from vegetable oil or margarine in early childhood affect serum concentrations of plant sterols (campesterol and sitosterol) and cholesterol precursor sterols (Delta-8 cholestenol, desmosterol, and lathosterol), reflecting endogenous cholesterol synthesis. We measured the serum sterol concentrations using gas liquid chromatography in 20 healthy 13-mo-old intervention children in a randomized, prospective study designed to decrease exposure of the children to known environmental atherosclerosis risk factors and in 20 control children. The diet of the intervention children was rich in plant sterols due to replacement of milk fat with vegetable fat, whereas the diet of the control children contained only small amounts of plant sterols. The intervention children consumed twice as much plant sterols as the control children (P < 0.001). Their serum concentrations of campesterol and sitosterol were 75% and 44% higher, respectively, than those in the control children (P < 0.001 for both), but serum cholesterol precursor sterol concentrations did not differ between the two groups. We conclude that doubling dietary plant sterol intake almost doubles serum plant sterol concentrations in 13-mo-old children, but has no effect on endogenous cholesterol synthesis. Relative intestinal absorption of natural plant sterols from the diet in early childhood is similar to that in adults.

Arteriosclerosis↗

Apolipoprotein E phenotype regulates cholesterol absorption in healthy 13-month-old children--The STRIP Study.

High serum cholesterol concentration is one of the key risk factors in development of atherosclerosis, which may begin early in life and later progress to symptomatic coronary heart disease. In adults, apoE polymorphism strongly influences cholesterol metabolism, as subjects with apoE 3/4 or 4/4 (collectively called apoE4) phenotype absorb cholesterol effectively and thus also have higher cholesterol absorption-reflecting plant sterol concentrations in serum than subjects with other apoE phenotypes. Because of the inverse correlation of absorption and synthesis of cholesterol, concentrations of cholesterol synthesis-reflecting serum cholesterol precursor sterols are lower in subjects with apoE4 than in subjects with other phenotypes. To analyze whether apoE phenotype affects cholesterol absorption and synthesis in early childhood, we measured serum plant sterol (campesterol and sitosterol) and cholesterol precursor sterol (desmosterol and lathosterol) concentrations in healthy 13-month old children using gas-liquid chromatography. The 36 study children were participants in a randomized prospective trial (the Special Turku Coronary Risk Factor Intervention Project) aimed at decreasing exposure of the children to environmental atherosclerosis risk factors. The 16 apoE4 children had 30% to 50% higher cholesterol-adjusted campesterol and sitosterol concentrations in serum than the 20 apoE 3/3 children (p = 0.002 and p = 0.02, respectively). The concentrations of cholesterol precursor sterols in serum did not differ between the two groups of children. We conclude that the young apoE4 children may absorb cholesterol and plant sterols more effectively than the children with apoE 3/3 phenotype without compensatory reduction in endogenous synthesis of cholesterol.

Apolipoproteins E↗

Evidence for spatial heterogeneity in insulin- and exercise-induced increases in glucose uptake: studies in normal subjects and patients with type 1 diabetes.

It is unknown whether resistance to insulin- or exercise-stimulated glucose uptake reflects a spatially uniform or nonuniform decrease in glucose uptake within skeletal muscle. We compared the distributions of muscle glucose uptake and blood flow in eight patients with type 1 diabetes (age 24 +/- 1 yr, body mass index 22.0 +/- 0.8 kg/m2) and seven age- and weight-matched normal subjects using positron emission tomography, [18F]-fluoro-deoxy-glucose, and [15O]-water. Both groups were studied during euglycemic hyperinsulinemia and one-legged exercise. Heterogeneity was evaluated by calculating relative dispersion (SD divided by mean * 100%) of glucose uptake (RD(g)) and flow (RD(f)) in all pixels within a region of interest in femoral muscle. At rest insulin-stimulated glucose uptake was significantly lower in the type 1 diabetic patients (42 +/- 7 micromol/kg per min) than in the normal subjects (78 +/- 9 micromol/kg per min, P < 0.001), while muscle blood flows were similar (26 +/- 1 vs. 31 +/- 3 ml/kg muscle per min, respectively). The exercise-induced increment in glucose uptake but not in blood flow was also significantly lower in the type 1 diabetic patients than in the normal subjects. Heterogeneity of glucose uptake but not of blood flow was greater in the insulin-resistant type 1 diabetic patients both at rest (RD(g) 31 +/- 1 vs. 25 +/- 2%, patients with type 1 diabetes vs. normal subjects, P < 0.05) and during exercise, compared with normal subjects (27 +/- 1 vs. 21 +/- 2%, respectively, P < 0.05). Exercise increased both glucose uptake and blood flow several-fold and significantly decreased both RD(g) and RD(f). Heterogeneity of RD(g), was inversely associated with total glucose uptake (r = -0.54, P < 0.001, pooled data) and was highest in the most insulin-resistant patients. We concluded that both glucose uptake and blood flow are characterized by heterogeneity in human skeletal muscle, whose magnitude is inversely proportional to respective mean values. This implies that an increase in glucose uptake in human skeletal muscle is not a phenomenon, by which each unit increases its glucose uptake by a fixed amount but rather a spatially heterogeneous process.

Adult↗

Resistance to exercise-induced increase in glucose uptake during hyperinsulinemia in insulin-resistant skeletal muscle of patients with type 1 diabetes.

Insulin and exercise have been shown to activate glucose transport at least in part via different signaling pathways. However, it is unknown whether insulin resistance is associated with a defect in the ability of an acute bout of exercise to enhance muscle glucose uptake in vivo. We compared the abilities of insulin and isometric exercise to stimulate muscle blood flow and glucose uptake in 12 men with type 1 diabetes (age 24 +/- 1 years, BMI 23.0 +/- 0.4 kg/m(2)) and in 11 age- and weight-matched nondiabetic men (age 25 +/- 1 years, BMI 22.3 +/- 0.6 kg/m(2)) during euglycemic hyperinsulinemia (1 mU. kg(-1). min(-1) insulin infusion for 150 min). One-legged exercise was performed at an intensity of 10% of maximal isometric force for 105 min (range 45-150). Rates of muscle blood flow, oxygen consumption, and glucose uptake were quantitated simultaneously in both legs using [(15)O]water, [(15)O]oxygen, [(18)F]-2-fluoro-2-deoxy-D-glucose, and positron emission tomography. Resting rates of oxygen consumption were similar during hyperinsulinemia between the groups (2.4 +/- 0.3 vs. 2.0 +/- 0.5 ml. kg(-1) muscle. min(-1); normal subjects versus patients with type 1 diabetes, NS), and exercise increased oxygen consumption similarly in both groups (25.3 +/- 4.3 vs. 20.1 +/- 3.0 ml. kg(-1) muscle. min(-1), respectively, NS). Rates of insulin-stimulated muscle blood flow and the increments in muscle blood flow induced by exercise were also similar in normal subjects (129 +/- 14 ml. kg(-1). min(-1)) and in patients with type 1 diabetes (115 +/- 12 ml. kg(-1). min(-1)). The patients with type 1 diabetes exhibited resistance to both insulin stimulation of glucose uptake (34 +/- 6 vs. 76 +/- 9 micromol. kg(-1) muscle. min(-1), P < 0.001) and also to the exercise-induced increment in glucose uptake (82 +/- 15 vs. 162 +/- 29 micromol. kg(-1) muscle. min(-1), P < 0.05). We conclude that the ability of exercise to increase insulin-stimulated glucose uptake in vivo is blunted in patients with insulin-resistant type 1 diabetes compared with normal subjects. This could be caused by either separate or common defects in exercise- and insulin-stimulated pathways.

Adult↗

Two loci on chromosomes 2 and X for premature coronary heart disease identified in early- and late-settlement populations of Finland.

Coronary heart disease (CHD) is a complex disorder constituting a major health problem in Western societies. To assess the genetic background of CHD, we performed a genomewide linkage scan in two study samples from the genetically isolated population of Finland. An initial study sample consisted of family material from the northeastern part of Finland, settled by a small number of founders approximately 300 years ago. A second study sample originated from the southwestern region of Finland, settled approximately 2,000 years ago. Families were ascertained through probands exhibiting premature CHD, defined as >50% stenosis of at least two coronary arteries at a young age, as verified by coronary angiography. Both study samples and the pooled data set provided evidence for linkage in two chromosomal regions. A region on chromosome 2q21.1-22 yielded two-point LOD scores of 3.2, 1.9, and 3.7, in the affected sib-pair (ASP) analyses of the northeastern, southwestern, and pooled study samples. The corresponding multipoint maximum-likelihood scores (MLSs) for these three study samples were 2.4, 1.3, and 3.0. In addition, a region on chromosome Xq23-26 resulted in two-point LOD scores of 1.9, 3.5, and 2.9 and in multipoint MLSs of 3.4, 3.1, and 2.5, respectively. In conclusion, this study identifies two loci likely to contribute to premature CHD: one on chromosome 2q21.1-22 and another on chromosome Xq23-26.

Age of Onset↗

Prospective, randomized, infancy-onset trial of the effects of a low-saturated-fat, low-cholesterol diet on serum lipids and lipoproteins before school age: The Special Turku Coronary Risk Factor Intervention Project (STRIP).

BACKGROUND: We showed previously that repeated dietary counseling during the first 3 years of life reduces the concentration of serum nonfasting cholesterol. We have now extended the study to children 5 years of age and analyzed fasting blood samples, enabling LDL cholesterol calculations for the first time. METHODS AND RESULTS: Families of 7-month-old infants (n=1062) were randomized to a control group (n=522) or an intervention group (n=540) that received individualized dietary counseling with the aims of a fat intake of 30% to 35% of daily energy, a saturated/monounsaturated/polyunsaturated fatty acid ratio of 1:1:1, and a cholesterol intake of <200 mg/d. Nutrient intakes were studied biannually, nonfasting serum lipid values were studied annually, and fasting values were studied at 5 years of age. The intervention children always had lower intakes of saturated fat and cholesterol than the control children. The intervention boys had 0.39 mmol/L (P:<0.0001) lower mean serum cholesterol values than the control boys between 13 and 60 months of age, but among girls, the difference was of marginal significance (0.15 mmol/L, P:=0.052). Five-year-old intervention boys had 9% lower mean serum LDL cholesterol concentrations than the control boys (P:=0.0002; 95% CI, -0.39 to -0.12 mmol/L), whereas no difference was observed in girls. In both sexes, serum triglyceride concentrations were similar in the 2 groups. CONCLUSIONS: The restriction of saturated fat and cholesterol intake by repeated, individualized dietary counseling since infancy resulted in lower serum total and LDL cholesterol concentrations at 5 years of age. However, the effect was significant only in boys.

Age of Onset↗

Cardiovascular risk factors clustering with endogenous hyperinsulinaemia predict death from coronary heart disease in patients with Type II diabetes.

AIMS/HYPOTHESIS: Information on the association of hyperinsulinaemia with coronary heart disease (CHD) in patients with Type II (non-insulin-dependent) diabetes is limited and controversial. Therefore, we carried out a prospective study to examine the predictive value of fasting plasma insulin and "hyperinsulinaemia cluster" with regard to the risk of CHD mortality. METHODS: At baseline risk factors for CHD were determined in 902 patients aged 45 to 64 years with Type II diabetes not treated by insulin (499 men and 403 women). These patients were followed up to 7 years for CHD mortality. RESULTS: Coronary heart disease mortality (16.2% in men, 9.2% in women) increased significantly in men with increasing plasma insulin tertiles (p = 0.006) and in both sexes combined (p = 0.010) but not in women (p = 0.090). The predictive value of hyperinsulinaemia with regard to death from CHD was independent of conventional cardiovascular risk factors but not of risk factors clustering with hyperinsulinaemia. By applying factor analysis and principal component analysis we showed that "hyperinsulinaemia cluster" (a factor having high positive loadings for body mass index, triglycerides and insulin; and a high negative loading for high-density lipoprotein cholesterol) was predictive of death from CHD in patients with Type II diabetes (hazard ratio with 95% confidence intervals 1.43 (1.18, 1.73), p < 0.001). CONCLUSION/INTERPRETATION: Our results support the notion that cardiovascular risk factors clustering with endogenous hyperinsulinaemia increase the risk of death from CHD in patients with Type II diabetes not treated with insulin.

Age Factors↗

Apolipoprotein E4 phenotype increases non-fasting serum triglyceride concentration in infants - the STRIP study.

As genetically determined apolipoprotein E (apo E) phenotypes influence serum cholesterol concentration, we analysed whether serum triglyceride values are also affected by the apo E phenotypes in infants. Non-fasting serum triglyceride values were measured in 7- and 13-month-old participants in the STRIP project, a randomised, prospective trial aimed at reducing children's exposure to known atherosclerosis risk factors (n=1062). The mean+/-S.D. non-fasting serum triglyceride concentrations in 7-month-old infants with apo E4/4 (n=36), E3/4 (n=209), E3/3 (n=412), and E2/3 (n=66) were 2. 05+/-1.24, 1.81+/-0.90, 1.63+/-0.90, and 1.71+/-0.83 mmol/l, respectively. Triglyceride concentrations were higher in infants with apo E4/4 or 3/4 than in those with apo E3/3 (P-value for difference 0.01 and 0.009, respectively). The apo E phenotype similarly influenced non-fasting serum triglyceride concentrations at the age of 13 months. The differences in serum triglyceride values in apo E4(+) infants (apo E3/4 and 4/4 infants combined) and apo E4(-) infants (apo E2/3 and 3/3 infants combined) occurred independently of the relative weight of the infant, milk type used at 7 months of age (breast milk or formula), and time elapsed from the previous meal. To conclude, apo E phenotypes regulate non-fasting serum triglyceride values in healthy infants. Apo E3/4 and apo E4/4 predispose infants to higher values than apo E3/3 phenotype, suggesting that the varepsilon4 allele may increase atherosclerosis risk also via it's effect on postprandial triglyceride metabolism.

Apolipoprotein E4↗