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Objectives:The life-course development of body mass index (BMI) may be driven by interactions between genes and obesity-inducing social environments. We examined whether lower parental or own education accentuates the genetic risk for higher BMI over the life course, and whether diet and physical activity account for the educational differences in genetic associations with BMI.Subjects/Methods:The study comprised 2441 participants (1319 women, 3–18 years at baseline) from the prospective, population-based Cardiovascular Risk in Young Finns Study. BMI (kg/m2) trajectories were calculated from 18 to 49 years, using data from six time points spanning 31 years. A polygenic risk score for BMI was calculated as a weighted sum of risk alleles in 97 single-nucleotide polymorphisms. Education was assessed via self-reports, measured prospectively from participants in adulthood and from parents when participants were children. Diet and physical activity were self-reported in adulthood.Results:Mean BMI increased from 22.6 to 26.6 kg/m2during the follow-up. In growth curve analyses, the genetic risk score was associated with faster BMI increase over time (b=0.02, (95% CI, 0.01–0.02, P<0.001)). The association between the genetic risk score and BMI was more pronounced among those with lower educational level in adulthood (b=−0.12 (95% CI, −0.23–0.01); P=0.036)). No interaction effect was observed between the genetic risk score and parental education (b=0.05 (95% CI, −0.09–0.18; P=0.51)). Diet and physical activity explained little of the interaction effect between the genetic risk score and adulthood education.Conclusions:In this prospective study, the association of a risk score of 97 genetic variants with BMI was stronger among those with low compared with high education. This suggests lower education in adulthood accentuates the risk of higher BMI in people at genetic risk.

ObjectiveTo examine whether heavy physical workload in young adulthood increases the risk of local and radiating low back pain (LBP) in midlife.MethodsLongitudinal nationally representative Young Finns Study data among women (n=414) and men (n=324), aged 18–24 years in 1986 (baseline), were used. Physical heaviness of work was reported at baseline and follow-up (2007), and local and radiating LBP at follow-up. Covariates were age, smoking and body mass index. Logistic regression was used to examine the associations between physical heaviness of work and LBP. Additionally, the mediating effect of back pain at baseline was examined (the Sobel test).ResultsAfter adjustment for the covariates, and as compared with sedentary/light physical workload, heavy physical workload was associated with radiating LBP among women (OR 4.09, 95% CI 1.62 to 10.31) and men (OR 2.01, 95% CI 1.06 to 3.82). Among men, early back pain mediated the association (p value from the Sobel test=0.006). Among women, early exposure to physically heavy work showed the most consistent associations, while early and late exposures were associated with radiating and local LBP among men. Persistently heavy physical work was associated with radiating LBP among women and men.ConclusionsPhysically heavy work at a young age can have a long-lasting effect on the risk of LBP, radiating LBP in particular. These results highlight the need to consider early and persistent exposures to prevent the adverse consequences of physical workload for the low back.

.Purpose:
To compare the effectiveness of intravenous (i.v.) methylprednisolone pulse therapy and oral prednisone when used as the initial treatment of patients with mild or moderate thyroid-associated ophthalmopathy.
Methods:
Thirty-three consecutive patients with thyroid-associated ophthalmopathy in Helsinki and Turku University Hospitals were randomly assigned either i.v. methylprednisolone pulse therapy (group A, n = 18) or oral prednisone (group B, n = 15). Treatment outcomes were measured by subjective changes in the grade of diplopia and quantitatively in several ophthalmic variables at 3 and 12 months. Any decision to proceed with additional treatment at 3 months was made on clinical grounds. The study was open in respect of both the initial treatment and the need for additional therapy.
Results:
No significant differences in the grade of diplopia, proptosis or soft tissue activity scores were noted between groups A and B from 0 to 3 months. However, group A required additional forms of therapy at 3 months less frequently than did group B (p = 0.038).
Conclusions:
Our data suggest that i.v. methylprednisolone pulse therapy and oral prednisone are equally effective as initial treatments for thyroid-associated ophthalmopathy where diplopia, proptosis and signs of soft tissue inflammation are concerned. When additional treatment is required, i.v. methylprednisolone pulse therapy may be more effective than oral prednisone. However, the study's limitations meant that any decision to give additional treatment after the initial therapy was made on clinical grounds.

Abstract: Objective: To study the effect of antihypertensive medications on autonomic nervous system in patients with hypertension and sleep apnea syndrome using frequency domain measures of heart rate and blood pressure variabilities. Methods: The β-receptor blocking agent atenolol (50 mg), the calcium antagonist isradipine SRO (2.5 mg), the diuretic hydrochlorothiazide (25 mg) and the ACE inhibitor spirapril (6 mg) once daily were given in a double-blind crossover schedule for 8 weeks. Cardiovascular autonomic control was assessed using frequency domain measures of heart rate variability during the spontaneous and controlled breathing tests. During orthostatic maneuver and cold pressor test the blood pressure variability analysis also was performed. Results: In general, the responses of heart rate and blood pressure variabilities were abnormal in the patients with arterial hypertension and sleep apnea syndrome compared to reference data. Of the four drugs, only atenolol effected heart rate and blood pressure variabilities as it shifted the autonomic regulation to the vagal direction. Other antihypertensive drugs did not change any parameter of heart rate or blood pressure variabilities. Conclusion: The short-term treatment with atenolol in patients with arterial hypertension and sleep apnea syndrome is associated with normalization of autonomic nervous control judged by heart rate and blood pressure variability. Thus, β-receptor blockade may have adjunctive beneficial effects beyond blood pressure reduction in these patients. However, the long-term effects of blood pressure reduction on autonomic nervous control remain to be studied.

OBJECTIVE: To study the effects of GH treatment for up to 42 months on bone mineral density (BMD) and bone turnover. DESIGN AND METHODS: BMD with dual energy X-ray absorptiometry, serum type I procollagen carboxy-terminal propeptide (PICP), serum type I collagen carboxy-terminal telopeptide (ICTP) and serum IGF-I were assessed in 71 adults with GH deficiency. There were 44 men and 27 women, aged 20 to 59 (median 43) years. Thirty-two patients completed 36 months and 20 patients 42 months of treatment. RESULTS: The BMD increased for up to 30-36 months and plateaued thereafter. In the whole study group, the maximum increase of BMD was 5.0% in the lumbar spine (P<0. 001), 5.9% (P<0.01) in the femoral neck, 4.9% (NS, P>0.05) in the Ward's triangle and 8.2% (P<0.001) in the trochanter area. The serum concentrations of PICP (202.6+/-11.5 vs 116.3+/-5.4 microg/l; mean+/-s.e.m.) and ICTP (10.5+/-0.6 vs 4.4+/-0.3 microg/l) doubled (P<0.001) during the first 6 months of GH treatment but returned to baseline by the end of the study (130.0+/-10.4 and 5.6+/-0.7 microg/l respectively), despite constantly elevated serum IGF-I levels (39. 6+/-4.1 nmol/l at 42 months vs 11.9+/-0.9 nmol/l at baseline; P<0.001). The responses to GH treatment of serum IGF-I, PICP, ICTP (P<0.001 for all; ANOVA) and of the BMD in the lumbar spine (P<0.05), in the femoral neck and the trochanter (P<0.001 for both) were more marked in men than in women. At the end of the study the BMD had increased at the four measurement sites by 5.7-10.6% (P<0.01-0.001) in patients with at least osteopenia at baseline and by 0.1-5.3% (NS P<0.05) in those with normal bone status (P<0.001 for differences between groups; ANOVA). Among patients who completed 36-42 months of treatment, the number of those with at least osteopenia was reduced to more than a half. The response of BMD to GH treatment was more marked in young than in old patients at three measurement sites (P<0. 05-<0.001; ANOVA). In the multiple regression analysis the gender and the pretreatment bone mass appeared to be independent predictors of three measurement sites, whereas the age independently determined only the vertebral BMD. CONCLUSIONS: GH treatment in GH-deficient adults increased BMD for up to 30-36 months, with a plateau thereafter. Concurrently with the plateau in BMD the bone turnover rate normalized. From the skeletal point of view GH-deficient patients exhibiting osteopenia or osteoporosis should be considered as candidates for GH supplementation of at least 3-4 years.

Low educational level is associated with an increased risk of coronary heart disease. The aim of the present study was to examine the relationships between education and common cardiovascular risk factors in young adults.

Eight hundred seventy-six men and women with diastolic blood pressure (DBP) of 95–115 mm Hg during a 4-week placebo period were included in a multicenter trial; 479 patients had previously been treated for hypertension. The patients were randomized to receive isradipine or metoprolol; both groups were comparable for age, weight, height, smoking habits, and duration of hypertension. By the end of the placebo period, 79 patients did not fulfill the final entry criteria and were withdrawn. The isradipine group consisted of 398 patients (164 women and 234 men), and the metoprolol group consisted of 399 patients (173 women and 226 men). The initial dose of isradipine was 1.25 mg twice daily (b.i.d.), and the initial dose of metoprolol was 50 mg b.i.d.; the doses were doubled after 4 weeks if DBP had not decreased to ≤90 mm Hg. After 8 weeks, the isradipine group began combination therapy with metoprolol 50 mg b.i.d. and the metoprolol group began combination therapy with isradipine 1.25 mg b.i.d. if DBP was not ≤90 mm Hg. After 8 weeks monotherapy, mean BP (MBP) was reduced by 13/11 mm Hg (161/104 to 148/93) in the isradipine group and by 15/12 mm Hg (160/103 to 145/91) in the metoprolol group. Monotherapy with isradipine normalized DBP to ≤90 mm Hg in 52 with a mean dose of 4.26 mg daily, and monotherapy with metoprolol normalized DBP in 58 with a mean dose of 155 mg daily. After combination therapy, BP was 144/89 mm Hg in the isradipine group and 144/90 mm Hg in the metoprolol group; BP was normalized in 68 in the isradipine group and 66 in the metoprolol group. Thirty-eight percent of patients in the isradipine group and 33 in the metoprolol group had transient side effects. The discontinuation-dropout rate in this 24-week study was 21 (83 patients) in the isradipine group and 18 (73 patients) in the metoprolol group. Quality of life analysis showed that muscular weakness, sweating, and exertional dyspnea occurred significantly more frequently in patients receiving metoprolol monotherapy than in patients receiving isradipine monotherapy. Serum lipids were measured at weeks 0 and 24. No changes were observed during isradipine monotherapy, whereas metoprolol monotherapy induced a significant increase from 1.75 to 2.06 mMin mean triglyceride level and a significant decrease from 1.32 to 1.24 mMin mean high-density lipoprotein (HDL) cholesterol level. Isradipine was a well-tolerated and efficacious antihypertensive drug with no untoward effects on serum lipids, whereas equally well-tolerated and efficacious metoprolol induced untoward lipid changes during a 24-week treatment period.

The relation between the loss of height and bone mineral density (BMD) at the lumbar spine and proximal femur was determined in 61 women aged 56–70 years suffering from rheumatoid arthritis. Statistically highly significant negative correlations were found between the loss of height and the spinal and femoral BMD. A loss of 4 cm or more in height over 10 years seems to be associated with a significant decrease of BMD, and it can be recommended as a clinical marker of osteoporosis.

Objective: To evaluate the contribution of the type of milk on serum cholesterol ester fatty acids in infants receiving mixed feeding, we analyzed 3-day dietary records and serum cholesterol ester fatty acid composition of 397 seven-month-old infants. Study design: The infants received, in addition to solid food, only one type of milk: human milk (n = 218), a ready-to-use liquid formula (n = 139), a powdered formula (n = 33), or soy formula (n = 7). Results: Mean fat intakes were low and varied from 28% to 31% of energy; the milks provided 43% to 64% of the fat. The mean polyunsaturated/saturated fat ratios of solid foods were from 0.52 to 0.63 and of milks from 0.20 to 0.45. Breast-fed infants' relative serum linoleic acid (18:2n-6) concentration was low (51.2%), whereas infants fed liquid formula had low serum oleic acid (18:1n-9) in accordance with low oleic acid content in that formula. The breast-fed infants had markedly higher serum concentrations of arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) than the infants fed any of the formulas. Conclusion: The typical fatty acid patterns of breast- or formula-fed infants were still evident in 7-month-old infants who already received 60% to 70% of their energy from solid food. Marked differences were seen also in the relative concentrations of docosahexaenoic acid and arachidonic acid despite their small contribution in cholesterol esters. (J Pediatr 1997;130:110-6)

Apolipoprotein E (apoE) polymorphism is a genetic determinant of plasma lipid levels and of coronary heart disease (CHD) risk. We determined the apoE phenotypes and plasma lipid levels in 1577 youths aged 3 to 18 years in 1980. The subjects were randomly selected from five areas of Finland. ApoE phenotyping was performed directly from plasma by isoelectric focusing and immunoblotting. The apoE allele frequencies in the population sample were epsilon 2 = 0.039, epsilon 3 = 0.767, and epsilon 4 = 0.194. There were no differences in the apoE phenotype distribution between East and West Finland or between sexes. The concentrations of serum total cholesterol, low density lipoprotein cholesterol, and apolipoprotein B increased with apoE phenotype in the order of E2/2, E3/2, E4/2, E3/3, E4/3, and E4/4. This increase was already seen in 3-year-old children; it was observed in both sexes, but was clearer in males than in females. The mean levels of high density lipoprotein (HDL) cholesterol, apolipoprotein A-I, triglyceride, Lp[a] lipoprotein, and the activity of lecithin:cholesterol acyltransferase did not differ between the apoE phenotypes. The observed differences in serum cholesterol remained fairly stable during the 6-year follow-up from 1980 to 1986, while the mean serum cholesterol concentration in the whole study population decreased by 6.3%. This study confirms the reported higher frequency of the epsilon 4 allele in Finns as compared to most other populations; this may contribute to the high rates of CHD in Finland as compared to most other populations. The results do not, however, explain the higher rate of CHD in East Finland in comparison to the western part of the country.

We studied a xanthomatous Achilles tendon and a normal Achilles tendon with the proton magnetic resonance imaging (MRI) and spectroscopy (MRS) at 1.5 T in a standard head coil. TheT2 maps and the localized proton spectra of the Achilles tendon were reconstructed. The normal tendon revealed no MR signal, whereas the xanthomatous tendon image consisted of variable signal intensities, for which the value ofT2 was significantly shorter (p=0.0002) than that of adipose tissue. The proton spectrum of this tendon xanthoma showed an increased water peak and unsaturated olefinic group intensity compared with the spectrum of the normal Achilles tendon area. The complex cholesterol molecule itself cannot be proven directly in a xanthomatous tendon, but its presence can be revealed with the help of the increased methyl and methylene groups of the fatty acids of the cholesteryl esters. This and other typical features describedin vitro for atheromatous tissue can be detectedin vivo in xanthomas.

We evaluated a new, third generation assay for serum thyrotropin (TSH) based on time-resolved fluorescence (AutoDelfia ®®hTSH Ultra) for the 1235 AutoDelfia automatic immunoassay system. The functional sensitivity of the TSH assay was 0.007 mIU 1−−1(between-assay CV, 20%). The between-assay imprecision was CV 4.1––7.7%, between TSH concentrations of 0.026 and 23.8 mIU 1−−1. The within-assay imprecision was CV 1.2––1.5% between TSH concentrations of 0.5 and 12 mIU 1−−1. The degree of agreement between the AutoDelfia hTSH Ultra assay and a second generation TSH-IRMA was studied. The mean difference was - 0.04 (SD 0.28) mIU 1−−1at concentrations between 0.22 and 52 mIU 1−−1. Serum TSH concentrations of euthyroid subjects, hypothyroid and hyperthyroid patients as well as those of patients with non-thyroidal illness, and thyroid carcinoma patients with TSH suppressive thyroxine treatment were analysed. The AutoDelfia automatic immunoassay system offers many benefits in sensitivity, precision, speed, output rate, time and convenience. Overnight runs are possible, and the system is easy to operate.

Lapinleimu H, Viikari J, Jokinen E, Routi T, Salo P, Hollo O, Niinikoski H, Rönnemaa T, Leino A, Välimäki I, Simell O. Cholesterol measurement by reflotron dry chemistry in infants, children and adults. Scand J Clin Lab Invest 1994; 54: 61-65.Cholesterol values measured with the Reflotron® dry chemistry (Boehringer Mannheim, Mannheim, Germany) and enzymatic (CHOD-PAP) routine method in 4150 venous blood samples from 580 infants aged 7 months, 1778 children aged 13 months to 19 years, and 1792 adults aged 18-63 years showed good correlation between the two assay systems (r > 0.92). However, the mean cholesterol concentrations were 4.5%, 3.7% and 2.3% lower in infants, children and adults, respectively, if measured with the Reflotron analyser as compared with values obtained with the CHOD-PAP method. These differences in the values were greater when cholesterol values were low (significance for the slope of regression line, p < 0.001). Values were below the detection limit of the Reflotron assay (2.59 mmoll-1) in 104 (4.4%) and 4 (0.2%) of all paediatric and adult samples, respectively. When measured with the CHOD-PAP method, 75 (72%) and 3 (75%) of these same samples showed values which exceeded the 2.59mmoir' detection limit. We conclude that Reflotron dry chemistry analyser is precise in fast measurement of serum cholesterol both in all paediatric subjects and adults. A particular problem in paediatric age groups is that about 4% of children have values below the detection limit of the Reflotron analyser.

A fast and cheap precipitation method for the separation of HDL subclasses has been evaluated. It starts with precipitation of apo-B containing lipoproteins with PEG-6000 after which HDL2 is precipitated with dextran sulphate-Mg2+. A concentration of 0.72 g/l dextran sulphate was found to be suitable for the separation of HDL subclasses. HDL subclasses obtained by precipitation gave proper density profiles at density gradient centrifugations. The correlations between results obtained by this method and by sequential and density gradient centrifugation are good, r = 0.99 and 0.72, respectively.

Objective: To determine the influence of gender, apolipoprotein E phenotypes, and diet on the interindividual variances in serum lipid and lipoprotein concentrations in children at 7 and 13 months of age. Study design: Prospective randomized intervention trial. Half of 1062 families with 7-month-old infants received dietary and lifestyle counseling aimed at partially replacing saturated fat with mono- and polyunsaturated fat and reducing exposure to other known atherosclerosis risk factors. This study comprises all trial children who at 8 months of age received, in addition to solid food, only breast milk or only formula (N = 553). Forward stepwise multiple regression analysis was used in the evaluation of the contributions of gender, apolipoprotein E phenotype, and diet. Results: Apolipoprotein E phenotypes, gender, and milk type provided independent information concerning serum lipid values at 7 and 13 months of age (three-way ANOVA, p < 0.01). At 7 months, milk type was the most significant predictor of total, non-high-density lipoprotein and high-density lipoprotein cholesterol and apolipoprotein B and A1 concentrations. At 13 months when the effects of gender (5%) and apolipoprotein E type (5%) were excluded, diet predicted only 2% of the variance in serum cholesterol concentration. The apolipoprotein E type predicted 8% of the variance in non-high-density lipoprotein cholesterol concentration and 7% of the variance in apolipoprotein B concentration (p < 0.001), together explaining only 3% of the variance in serum high-density lipoprotein cholesterol and apolipoprotein A1 concentrations. Conclusions: At 7 months of age diet is an important predictor of serum lipid and lipoprotein concentrations. At the age of 13 months the apolipoprotein E phenotype significantly predicts the concentrations of serum non-high-density lipoprotein cholesterol and apolipoprotein B. However, at both ages apolipoprotein E phenotype, gender, and diet together explain only from 1.4% to 15.5% of the variance in serum lipids and apolipoproteins, suggesting that other, presumably genetic, factors are major determinants. (J Pediatr 1997;131:825-32)

The authors studied the occurrence of common lifestyle risk factors, namely, nonprudent diet, smoking, physical inactivity, and frequent inebriation by alcohol in a cohort of young adults aged 18, 21, and 24 years (n = 484) as part of the Cardiovascular Risk in Young Finns Study in 1986. Risk habits showed significant clustering; the number of subjects was greater than expected in groups with zero and three of four risk habits and less than expected in the group with only one or two risk habits. Stepwise logistic regression analysis was used to find independent determinants for this clustering from a set of socioeconomic, demographic, and behavioral (type A components) determinants. The logistic model suggested several independent risk factors for risk habit clustering. These included male sex, aggressiveness, and past unemployment. Paying a lot of attention to health habits, higher education (being a student), good self-perceived health, and a high sense of responsibility seemed to be protective factors against risk habit clustering. The accumulation of risk habits was also associated with an atherogenic lipid and blood pressure profile (clustering of high density lipoprotein cholesterol/total cholesterol ratio, triglycerides, and diastolic blood pressure in their extreme tertiles). These findings show that common risk habits cluster among young adults. Knowledge about the determinants of this clustering will aid in the planning of future preventive strategies against cardiovascular diseases in young people.

The tracking of physical activity and its influence on selected coronary heart disease risk factors were studied in a 6-year (original survey in 1980, with follow-ups in 1983 and 1986) study of Finnish adolescents and young adults as part of the Cardiovascular Risk in Young Finns Study. The subjects in this analysis were aged 12, 15, and 18 years at baseline. Physical activity was assessed with a standardized questionnaire, and a sum index was derived from the product of intensity, frequency, and duration of leisure time physical activity. Complete data on physical activity index from each study year were available on 961 participants. Significant tracking of physical activity was observed with 3-year correlations of the index ranging from 0.35 to 0.54 in boys and from 0.33 to 0.39 in girls. Tracking was better in older age groups. Two groups of adolescents (active and sedentary groups) were formed at baseline according to high and low values of the index, respectively. Approximately 57% of those classified as inactive remained inactive after a 6-year follow-up. The corresponding value for active subjects was 44% (p < 0.01, active vs. inactive). The long-term effects of physically active and sedentary life-styles were studied by comparing groups of young adults who had remained active or inactive in every three examinations. Serum insulin and serum triglyceride concentrations were significantly lower in active young men. They had a more beneficial high density lipoprotein to total cholesterol ratio and thinner subscapular skinfolds. Among young women, significant differences were seen in adiposity (subscapular skinfold) and in serum triglyceride concentration. Physical activity was also related to less smoking in both sexes and, among young men, to lower consumption of saturated fatty acids and to higher polyunsaturated to saturated fatty acids ratio of the diet. In regression analyses adjusted for the 6-year change in obesity, smoking status, and diet, the change in physical activity was inversely associated with changes in serum insulin and triglycerides in boys. Independent association with triglycerides disappeared when insulin change was added to the model, suggesting that the effect may partly be mediated through insulin metabolism. The authors conclude that the level of physical activity tracks significantly from adolescence to young adulthood. Physical inactivity shows better tracking than does physical activity, and subjects who are constantly inactive express a less beneficial coronary risk profile compared with those who are constantly active.(ABSTRACT TRUNCATED AT 400 WORDS)

The authors analyzed tracking and predictiveness of serum lipid and lipoprotein measurements in Finnish children and young adults over a 12-year follow-up period. A representative sample of 3,596 healthy subjects aged 3-18 years was examined in 1980. The follow-up studies were done in 1983, 1986, 1989, and 1992. Data were available on serum lipids and lipoproteins, anthropometric measurements, dietary and smoking habits, and use of oral contraceptives. Complete data on serum lipids in 1980 and 1992 were available for 883 subjects (47% males), and they comprised the study cohort for this analysis. Significant tracking was found in each of the serum lipid variables studied. The range of 12-year correlations was 0.48-0.58, 0.53-0.58, 0.53-0.58, 0.57-0.59, and 0.33-0.37 for serum total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, the LDL:HDL cholesterol ratio, and triglycerides, respectively. Males showed more tracking than females; there was no clear age trend. Tracking of HDL2 cholesterol was better than that of HDL3 cholesterol (0.64 vs. 0.43, respectively; 3-year tracking). Apolipoproteins A-I and B showed similar amounts of tracking compared with HDL and LDL cholesterol, respectively. Approximately 50% of subjects who initially fell into the extreme quintiles of total cholesterol, LDL cholesterol, and HDL cholesterol were in the same quintiles after 12 years. In multiple regression analyses, childhood obesity, exercise, diet, and smoking habits did not markedly aid the prediction of adult serum lipid values. However, the use of two childhood measurements increased the amount of adult serum lipid variability explained. Although universal screening cannot be endorsed, these findings emphasize the importance of serum lipid measurements in the early detection of familial lipoprotein disorders and in the initial evaluation of coronary heart disease risk in childhood.

The lack of significant improvement in HbA1cduring insulin lispro treatment in previous studies may have been due to inadequate dietary adjustments. We tested whether reduction of snacks and a compensatory increase in main meals results in improved metabolic control when switching to lispro treatment. One hundred and forty‐one Type 1 diabetic patients, mean ± SD age 36 ± 9 years, diabetes duration 14 ± 10 years, had two daily NPH injections throughout the study. After a baseline visit, the patients used conventional soluble insulin preprandially thrice daily for 12 weeks. Thereafter they were switched to lispro insulin and advised to transfer ≥50 % of their snack carbohydrates to preceding main meals. Mean HbA1cat baseline was 8.05 %. After the conventional period and the 12‐week lispro period, HbA1cwas 7.81 and 7.70 % (p= 0.088), respectively. In those patients who diminished their snacks as advised (n= 67), HbA1cdecreased from 7.91 to 7.66 % (p= 0.014) during lispro, whereas no change was observed in patients not compliant with the dietary change. The number of hypoglycaemic episodes was lower during lispro period (blood glucose <2.5 mmol l−1: 1.43 vs 2.19 episodes, p= 0.004; symptomatic nocturnal hypoglycaemia 1.16 vs 1.67 episodes, p<0.001). When switching from conventional soluble to lispro insulin, reduction of snack carbohydrates is safe and results in slightly improved HbA1cin patients who are fully compliant with the dietary change. © 1998 John Wiley & Sons, Ltd.

Abstract.: Previous studies suggested a relation between polymorphism of the vitamin D receptor (VDR) gene and bone mineral density (BMD) at perimenopausal age. To enlighten the possible association of the VDR gene polymorphism and BMD, we studied young (20–29 years) adults whose BMD provides a measure of their maximal bone mass. After sequencing the DNA regions flanking the polymorphic BsmI site, we set up a specific solid-phase minisequencing technique to assay this allelic variation. BMD values were adjusted for age, sex, weight, physical activity, smoking, and calcium intake. Young subjects homozygous for the b allele (BsmI site present) had a significantly higher BMD in lumbar spine and femoral neck than those homozygous for the B allele (BsmI site absent). This data shows that the BsmI polymorphism of the VDR gene is associated with peak bone mass. The implication of this result regarding the prevention of osteoporosis deserves further attention.

Thyroid stimulating hormone (S-TSH) and thyroxine (S-T4) were measured in sera from 80 patients with breast cancer using radioimmunoassay. The patients had been irradiated after mastectomy 7.2±1.0 years earlier with 45 Gy in 3 to 4 weeks to parasternal, ipsilateral supraclavicular and axillary areas. Five patients (6%) had hypothyroidism with low S-T4 and elevated S-TSH levels. In addition, 12 patients (15%) had elevated (>5 mU/1) S-TSH levels and normal S-T4 values. Shielding of the thyroid during irradiation and long-term follow-up of thyroid function with repeated hormone assays are recommended.

A number of restriction fragment length polymorphisms (RFLPs) of the apolipoprotein B (apoB) and apolipoprotein A-I/C-III(apoA-I/C-III) genes have been found to be associated with serum lipoprotein levels in many adult populations. In order to examine whether these genetic polymorphisms influence serum lipoprotein levels in childhood and adolescence, we determined the apoB XbaI and apoA-I/C-III SstI genotypes and serum lipoprotein concentrations in 307 healthy Finns aged 9 to 21 years. In the age groups of 9, 12, and 15 years, subjects homozygous for the X2 allele (the XbaI site present) of the apoB gene had mean serum low-density lipoprotein (LDL) cholesterol levels (3.69, 3.43, and 3.15 mmol/l, respectively) that were 12-20% higher than those in subjects homozygous for the absence of this allele (3.08, 3.02, and 2.80 mmol/l, respectively). This association was more significant in males than in females. At the age of 9 to 18 years, subjects carrying the S2 allele (SstI site present) of the apoA-I/C-III gene complex had an approximately 6-15% higher mean serum LDL-cholesterol level than those homozygous for its absence. The combined genotype X2+S2+ (the simultaneous presence of the X2 allele and the S2 allele) was associated with an even more marked elevation of serum LDL-cholesterol level than either allele alone. As an example, the serum LDL cholesterol concentration was 20% higher in 9-year-old subjects with at least one X2 and one S2 allele than in those without either allele (3.55 vs. 2.97 mmol/l, P less than 0.005). The S2 allele was found to be significantly more frequent in eastern than in western Finland, whereas no significant areal differences were seen in the occurrence of the X2 allele. In conclusion, genetic variations of the apoB and apoA-I/C-III gene loci influence serum lipoprotein concentrations already in childhood.

Background: The purpose was to examine the epidemiology of Helicobacter pylori infection in Finnish children and adolescents.Methods: Blood samples taken from healthy subjects (n = 461) 3-18 years old were studied cross-sectionally for the presence of H. pylori antibodies. Additionally, blood samples drawn in 1980, 1983, 1986, and 1989 from 74 children born in 1977 were tested. Serum IgG-class antibodies to H. pylori were determined by an enzyme immunoassay.Results: In the cross-sectional series the mean antibody levels and the percentage of seropositive children increased with age. The overall seroprevalence was 10.2%. During the follow-up period from 3 to 12 years of age the seropositivity increased from 4.6% to 5.7%. On the basis of the seroconversions between 3 and 12 years of age the annual incidence of H. pylori infection was calculated to be only 0.3%.Conclusions: In children seropositivity for H. pylori of the IgG class is often a sign of an infection acquired in early childhood. It seems likely that the age-dependent increase in the seropositivity reflects cumulation of a chronic infertion.

Serum fructosamine determination was evaluated in the assessment of glycaemic control in diabetes mellitus. Intra- and inter-assay variation of the method was 0.5–0.8 and 1.5–2.9, respectively. The fructosamine concentration in serum was found to be stable for at least 10 days independent of prevailing serum glucose concentration is stored at 4 °C or colder. Stability of serum fructosamine with respect to rapid fluctuations of blood glucose was of the same order as that of HbA1c. The reference interval (mean±2 SD) for 92 non-diabetic individuals was 1.9–2.7 mmoll. Good correlation was found between HbA1c and serum fructosamine (r0.79)l Serum fructosamine and HbA1c correlated well with the mean blood glucose values of the preceding week (r0.88 and 0.75, respectively, p<0.001). Significant correlations of fructosamine and HbA1c with fasting blood glucose were also found (r0.53 and 0.55, respectively, p<0.001). Fructosamine determined simultaneously with fasting blood glucose in 65 oral glucose tolerance tests (OGTT) did not separate normal subjects from those with impaired glucose tolerance. Two of the three subjects with diabetic response in the OGTT had, however, elevated fructosamine concentrations. Determination of serum fructosamine is a technically simple, reproducible and moderately inexpensive method for the assessment of glycaemic control in diabetes mellitus. Standardization of the method is, however, not without problems. Uniformity of the calibration and assay protocol is essential for reliable interlaboratory comparison of results. Physiological states altering the rate of synthesis or elimination of serum proteins should be considered in the interpretation of fructosamine levels. Serum fructosamine determination has been used for a relatively short period as compared with the glycohaemoglobin assays. Further experience is necessary to evaluate the definitive value of the assay.

The composition of fatty acids in serum cholesteryl esters was analyzed with gas chromatography in 759 Finnish boys and girls aged 3-18 years in 1980 and again in the same subjects in 1983 and in 1986. The mean percentage of linoleate (18:2 n-6) increased from 50.85% in 1980 to 52.60% in 1986, while there was a decrease in myristate (14:0), palmitate (16:0), and eicosapentaenoate (20:5 n-3). The percentage of oleate (18:1) did not change. The stability (tracking) of cholesteryl ester fatty acid composition was examined by calculating linear correlation coefficients among the percentages of each fatty acid at the three study points. For linoleate, 3- and 6-year tracking correlations were 0.59-0.61 and 0.50, respectively; they were of about the same magnitude for arachidonate (20:4 n-6) and lower for the other fatty acids. Results indicate that the serum cholesteryl ester fatty acid composition has somewhat lower tracking than the total cholesterol concentration. The changes in the mean fatty acid composition of the study population obviously reflect a shift from saturated to unsaturated dietary fats.

In adults hyperinsulinaemia is associated with an atherogenic risk profile including obesity, low levels of HDL-cholesterol, high levels of triglycerides and elevated blood pressure. To examine these associations in the young we studied the cross-sectional relationships of insulin with obesity indices (body mass index, subscapular skinfold thickness), serum lipids and blood pressure in 1,865 children, adolescents and young adults aged 6–24 years. We also used longitudinal data to study the value of a single insulin measurement to predict high risk factor levels and clustering of multiple risk factors after a 6-year follow-up. In cross-sectional analyses the levels of triglycerides, HDL-cholesterol, systolic blood pressure and obesity indices were usually significantly different across the quartiles of fasting insulin in both sexes among children, adolescents and young adults. In general, no associations were seen with total cholesterol or LDL-cholesterol. In prospective analysis elevated baseline insulin was related to the incidence of hypertriglyceridaemia (≥95th percentile) at the follow-up. This relationship persisted even after adjustments for baseline obesity or 6-year change in obesity status. Moreover, baseline insulin concentration was higher in subjects who subsequently showed clustering of high triglycerides, low HDL-cholesterol and high systolic blood pressure levels at the follow-up. We conclude that high fasting insulin levels measured in children and adolescents predict the development of hypertriglyceridaemia years later. In addition, high insulin levels seem to precede the development of a potentially atherogenic risk factor profile including low HDL-cholesterol, high triglycerides and high systolic blood pressure.

A lateral tail vein of the rat is used as the route for continuous infusion. The animal is kept under neuroleptic tranquilisation during the infusion.

Blood glycated haemoglobin (HbAlc), serum fructosamine (FA), serum glycated albumin (GA), and serum glycated total protein (GTP) were determined in 61 subjects (19 pregnant women with gestational diabetes, 24 pregnant women with insulin-dependent diabetes mellitus [IDDM] and 18 non-pregnant subjects with IDDM). FA, GA, and GTP correlated with HbAlc similarly (r=0.791, 0.816, and 0.794, respectively, p < 0.001). In a subgroup of 22 subjects data on blood glucose home monitoring was recorded and used for calculating mean blood glucose as an index of average glycaemia preceding sampling of the glycation products. Mean blood glucose levels preceding sampling of HbAlc by 2 months and FA, GA, or GTP by three weeks correlated significantly with HbAlc (r=0.668, p < 0.001) and GA (r=0.441, p < 0.05) whereas no significant correlation was found between mean blood glucose and FA (r=0.003) or GTP (r=0.252). In conclusion, such methods which measure specifically the non-enzymatic glycation of a single species of protein (i.e. FPLC for HbAlc and affinity chromatography for GA) are to be preferred for assessing glycaemia.

This study was undertaken to compare results of modern serum thyroid hormone assays with cardiac systolic time intervals (STI) during thyroxine treatment in hypothyroid patients. The patients were assessed clinically (Billewicz index) and the STI and serum thyrotropin (TSH), total and free thyroxine (T4) and total and free triiodothyronine (T3) were determined in 16 hypothyroid women (Group I) treated with 50 μg increments of thyroxine, and in 13 women who had a history of thyroid carcinoma and high-dose thyroxine replacement therapy and had elevated thyroid hormone concentrations (Group II). The STI of 24 matched healthy female controls were used for reference of STI.The pre-ejection period (PEP) index and the PEP/LVET ratio (left ventricular ejection period) were greater in untreated overtly and mildly hypothyroid patients (p < 0.05) than in the controls. During stable thyroxine therapy [mean daily dosage for Group I 137.5 (7.3) μg and for Group II 220 (61) μg] the PEP correlated with serum free T4 (FT4), as measured by a two-step method (SpectriaR) (r = -0.55, p < 0.01, n = 29) and total T4 (r = -0.51, p < 0.05, n = 29), but not with TSH, T3, FT3 or FT4 measured by an analogue method Amerlex-MR. The TRH test was not valuable in follow-up because of the strong correlation between basal TSH and stimulated TSH values (r = 0.95).In conclusion, STI are useful for assessment of the thyroid state in untreated hypothyroid patients. Serum TSH becomes normal in the same time as STI and is the best for follow-up. If serum TSH is low and the patient is on stable thyroxine therapy, we recommend serum FT4 for monitoring thyroxine replacement. Two-step FT4 assays had the best correlation with STI, which has significance in patients with non-thyroidal illness.

A neutral polymer precipitation procedure for fractionation of human plasma lipoproteins is described. The method was also tested preliminarily for fractionation of rat plasma lipoproteins. Polyethylene glycol-6000 (PEG-6000) at a concentration of about 12% and at pH 7.9 precipitated human plasma very low density (VLDL) and low-density (LDL) lipoproteins completely. Precipitation was independent of time and temperature. VLDL and LDL could not be precipitated separately. Polyethylene glycol-6000 precipitation can be used for rapid determination of high-density (HDL) lipids and of the ratio of HDL to LDL lipids.

1. A density gradient flotation procedure for fractionation of plasma lipoproteins is described. The present method was tested for fractionation of plasma lipoproteins of man, rat, dog, rabbit, mouse, and guinea-pig. 2. After adjustment of the density of plasma samples to 1.250 they were overlayered with a stepwise NaCl-KBr-gradient (density 1.210-1.006) in a preparative centrifuge tube. 3. After 5-h centrifugation (66,000-94,000 × g) in a swing-out rotor, the very low density (VLDL) and low density (LDL) lipoproteins were well resolved from each other in samples of all species studied, whereas the high density lipoproteins (HDL) remained at the bottom of the tube together with the other plasma proteins. After 24-h centrifugation, the HDL fractions of rat, mouse, and dog had started to separate from the bulk of other proteins. During the 24-h centrifugation, however, the VLDL and LDL fractions had floated to the top of the tube and separation of the two was not possible in samples of any species. 4. When the lipoproteins were prc-purified by flotation at a density of 1.230, distinct fractions representing VLDL, LDL, and HDL, respectively, were obtained during subsequent 5-h density gradient centrifugations under the above conditions.

An improved technique has been developed for the separation and isolation of plasma lipoproteins with zonal Ultracentrifugation. The lipoproteins of 25 ml plasma were fractionated by flotation in a MSE type B-XV titanium rotor at 120,000 X g for 18 hours using a NaCl-KBr density gradient from d = 1.005 to d = 1.23. Very low density, low density and high density lipoproteins were separated from each other and from the other plasma proteins, and the high density lipoproteins were divided into two subfractions.

1. We studied the effect on plasma lipids of sotalol given orally over a 12 month period to patients with essential hypertension. 2. Plasma free fatty acid concentration was lower than initially at 1, 3, 6 and 12 months. The difference was significant (P < 0·01) at 1 and 3 months. 3. Plasma cholesterol (VLDL + LDL-cholesterol) increased during treatment. Plasma total cholesterol increased from 5·49 ± sd 0·94 mmol/l at the beginning to 6·37 ± 1·10 mmol/l at 12 months (P < 0·01). 4. HDL-cholesterol concentration and the ratio of HDL-cholesterol to total cholesterol decreased significantly. The ratios were 0·28 and 0·18 at the beginning and at 12 months respectively (P < 0·001). 5. Plasma triglycerides increased simultaneously from 1·14 ± 0·31 to 1·89 ± 0·99 mmol/l (P < 0·01).

Synovial fluid from the inflamed knee joints of 30 patients with rheumatoid arthritis (RA) contained 2.75 ±0.81 mmol/1 cholesterol (51% of the corresponding mean serum level) and 0.32 ±0.13 mmol/1 triglycerides (35% of the corresponding mean serum level). The ratio of synovial fluid triglycerides to cholesterol indicates that in RA the concentration of very low density lipoproteins (VLDL) is lower in synovial fluid than in serum. In a few patients, however, the "relative triglyceride concentration" in synovial fluid (i.e. synovial fluid tg/chol: serum tg/chol) was greater than 1. This concentration did not correlate, moreover, with the clinical activity of the disease.