Metformin versus insulin therapy for gestational diabetes: Effects on offspring anthropometrics and metabolism at the age of 9 years: A follow-up study of two open-label, randomized controlled trials.

AIMS: To compare anthropometrics, and lipid and glucose metabolism in the 9-year-old offspring of mothers treated with metformin or insulin for gestational diabetes mellitus (GDM). MATERIALS AND METHODS: This was a Finnish two-centre, 9-year follow-up study of two open-label, randomized controlled trials comparing the effects observed in the offspring of mothers who received metformin and insulin treatment for GDM. Measurements included anthropometrics, blood pressure, lipoproteins, and oral glucose tolerance tests. This study was registered with ClinicalTrials.gov, number NCT02417090. RESULTS: At the age of 9 years 172 children (55% of the original study cohort, 82 from the metformin and 90 from the insulin group) participated in the study. No differences were found between the 9-year-old offspring groups in anthropometric variables, including body mass index and waist-to-height ratio. The offspring in the metformin group had higher high-density lipoprotein (HDL) cholesterol concentrations (1.72 vs. 1.54 mmol/L; P = 0.039) but lower low-density lipoprotein cholesterol (2.39 vs. 2.58 mmol/L; P = 0.046) and apolipoprotein B concentrations (0.63 vs. 0.67 g/L; P = 0.043) than the offspring in the insulin group. The difference in HDL cholesterol concentration was found to be significant only in boys (P = 0.003). The 2-hour glucose value in the oral glucose tolerance test was 0.6-mmol/L lower in boys from the metformin group than in those from the insulin group (P = 0.015). CONCLUSIONS: Metformin treatment for GDM is associated with similar offspring growth and glucose metabolism but a more favourable lipid profile at the age of 9 years as compared to insulin treatment.

Comparison of glucose metabolism and anthropometry in women with previous gestational diabetes treated with metformin vs. insulin: 9-year follow-up of two randomized trials.

INTRODUCTION: The main aim was to study whether the long-term incidences of type 2 diabetes, pre-diabetes and metabolic syndrome differed between women who were treated with metformin or insulin for gestational diabetes. MATERIAL AND METHODS: This 9-year follow-up study of two open-label randomized trials compares metformin and insulin treatments of gestational diabetes. In all, 165 women, 88 previously treated with insulin and 77 treated with metformin in the index pregnancy, were included in the analyses. An oral glucose tolerance test was performed, and measures of anthropometry, glucose metabolism, serum lipids and inflammatory markers were compared between the treatment groups. Disorders of glucose metabolism (pre-diabetes and type 2 diabetes) at the 9-year follow-up was the primary outcome of this study. This study was registered at ClinicalTrials.gov: NCT02417090. RESULTS: The incidences of pre-diabetes and type 2 diabetes (40.3% vs. 46.6%, odds ratio [OR] 0.77, 95% CI 0.40-1.50, p = 0.51), type 2 diabetes (14.3% vs. 15.9%, OR 0.88, 95% CI 0.34-2.26, p = 0.94), pre-diabetes (26.0% vs. 30.7%, OR 0.79, 95% CI 0.38-1.65, p = 0.62), and metabolic syndrome (45.9% vs. 55.2%, OR 0.69, 95% CI 0.35-1.35, p = 0.31) were comparable between the metformin and insulin groups. Moreover, there were no evident differences in the individual measures of anthropometry, glucose metabolism including HOMA-insulin resistance, serum lipids or inflammatory markers between the two treatment groups. CONCLUSIONS: Treatment of gestational diabetes with metformin vs. insulin during pregnancy is unlikely to have diverging long-term effects on maternal anthropometry, glucose metabolism or serum lipids. From this perspective, both treatments may be considered in gestational diabetes.

Physical inactivity from youth to adulthood and adult cardiometabolic risk profile.

Adults with a low physical activity (PA) level are at increased risk for cardiometabolic diseases, but little is known on the association between physical inactivity since youth and cardiometabolic health in adulthood. We investigated the association of persistent physical inactivity from youth to adulthood with adult cardiometabolic risk factors. Data were drawn from the ongoing Cardiovascular Risk in Young Finns Study with seven follow-ups between 1980 and 2011 (baseline age 3-18 years, n = 1961). Physical activity data from a standardized questionnaire was expressed as a PA-index. Using the PA-index, four groups were formed: 1)persistently physically inactive (n = 246), 2)decreasingly active (n = 305), 3)increasingly active (n = 328), and 4)persistently active individuals (n = 1082). Adulthood cardiometabolic risk indicators included waist circumference, body mass index (BMI), blood pressure, and fasting lipids, insulin, and glucose. Clustered cardiometabolic risk was defined using established criteria for metabolic syndrome. Persistently physically inactive group was used as a reference. Compared to the persistently physically inactive group, those who were persistently active had lower risk for adult clustered cardiometabolic risk (RR = 0.67;CI95% = 0.53-0.84; Harmonized criteria), obesity (BMI > 30 kg/m2, RR = 0.76;CI95% = 0.59-0.98), high waist circumference (RR = 0.82;CI95% = 0.69-0.98), and high triglyceride (RR = 0.60;CI95% = 0.47-0.75), insulin (RR = 0.58;CI95% = 0.46-0.74) and glucose (RR = 0.77;CI95% = 0.62-0.96) concentrations as well as low high-density lipoprotein cholesterol (HDLC) concentration (RR = 0.78;CI95% = 0.66-0.93). Comparable results were found when persistently physically inactive individuals were compared with those who increased PA. The results remained essentially similar after adjustment for education, diet, smoking, and BMI. Persistently physically inactive lifestyle since youth is associated with an unfavorable cardiometabolic risk profile in adulthood. Importantly, even minor increase in PA lowers the cardiometabolic risk.

Childhood predictors of adult fatty liver. The Cardiovascular Risk in Young Finns Study.

BACKGROUND & AIMS: Fatty liver is a potentially preventable cause of serious liver diseases. This longitudinal study aimed to identify childhood risk factors of fatty liver in adulthood in a population-based group of Finnish adults. METHODS: Study cohort included 2,042 individuals from the Cardiovascular Risk in Young Finns Study aged 3-18years at baseline in 1980. During the latest follow-up in 2011, the liver was scanned by ultrasound. In addition to physical and environmental factors related to fatty liver, we examined whether the genetic risk posed by a single nucleotide polymorphism in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) (rs738409) strengthens prediction of adult fatty liver. RESULTS: Independent childhood predictors of adult fatty liver were small for gestational age, (odds ratio=1.71, 95% confidence interval=1.07-2.72), variant in PNPLA3 (1.63, 1.29-2.07 per one risk allele), variant in the transmembrane 6 superfamily 2 gene (TM6SF2) (1.57, 1.08-2.30), BMI (1.30, 1.07-1.59 per standard deviation) and insulin (1.25, 1.05-1.49 per standard deviation). Childhood blood pressure, physical activity, C-reactive protein, smoking, serum lipid levels or parental lifestyle factors did not predict fatty liver. Risk assessment based on childhood age, sex, BMI, insulin levels, birth weight, TM6SF2 and PNPLA3 was superior in predicting fatty liver compared with the approach using only age, sex, BMI and insulin levels (C statistics, 0.725 vs. 0.749; p=0.002). CONCLUSIONS: Childhood risk factors on the development of fatty liver were small for gestational age, high insulin and high BMI. Prediction of adult fatty liver was enhanced by taking into account genetic variants in PNPLA3 and TM6SF2 genes. LAY SUMMARY: The increase in pediatric obesity emphasizes the importance of identification of children and adolescents at high risk of fatty liver in adulthood. We used data from the longitudinal Cardiovascular Risk in Young Finns Study to examine the associations of childhood (3-18years) risk variables with fatty liver assessed in adulthood at the age of 34-49years. The findings suggest that a multifactorial approach with both lifestyle and genetic factors included would improve early identification of children with a high risk of adult fatty liver.

Cardiovascular risk factors in 2011 and secular trends since 2007: the Cardiovascular Risk in Young Finns Study.

AIMS: Cardiovascular risk factor levels in 2011 and 4-year changes between 2007 and 2011 were examined using data collected in follow-ups of the Cardiovascular Risk in Young Finns Study. METHODS: The study population comprised 2063 Finnish adults aged 34-49 years (45% male). Lipid and blood pressure levels, glucose and anthropometry were measured and life style risk factors examined with questionnaires. RESULTS: Mean total cholesterol level in 2011 was 5.19 mmol/l, low density lipoprotein (LDL)-cholesterol 3.27 mmol/l, high density lipoprotein (HDL)-cholesterol 1.33 mmol/l, and triglycerides 1.34 mmol/l. Using American Diabetes Association criteria, Type 2 diabetes (T2D) was observed in 4.1% and prediabetes (fasting glucose 5.6-6.9 mmol/l or glycated hemoglobin 5.7-6.4%) diagnosed for 33.8% of the participants. Significant changes (P < 0.05) between 2007 and 2011 included an increase in waist circumference (3.3%) in women. In both sexes, systolic (-3.0% in women, -4.0% in men) and diastolic (-3.0% in women, -3.3% in men) blood pressure and triglycerides (-3.4% in women, -6.5% in men) decreased during follow-up. CONCLUSIONS: Previously observed favorable trends in ldl-cholesterol levels have leveled off among a sample of young and middle-aged adults in finland triglyceride and blood pressure levels have decreased over one-third of the study population had prediabetes and may be at increased risk for T2D:

Socioeconomic status, cardiovascular risk factors, and subclinical atherosclerosis in young adults: the cardiovascular risk in Young Finns Study.

OBJECTIVE: The goal of this study was to investigate the extent to which socioeconomic status (SES) in young adults is associated with cardiovascular risk factor levels and carotid intima-media thickness (IMT) and their changes over a 6-year follow-up period. METHODS AND RESULTS: The study population included 1813 subjects participating in the 21- and 27-year follow-ups of the Cardiovascular Risk in Young Finns Study (baseline age 24-39 years in 2001). At baseline, SES (indexed with education) was inversely associated with body mass index (P=0.0002), waist circumference (P<0.0001), glucose (P=0.01), and insulin (P=0.0009) concentrations; inversely associated with alcohol consumption (P=0.02) and cigarette smoking (P<0.0001); and directly associated with high-density lipoprotein cholesterol levels (P=0.05) and physical activity (P=0.006). Higher SES was associated with a smaller 6-year increase in body mass index (P=0.001). Education level and IMT were not associated (P=0.58) at baseline, but an inverse association was observed at follow-up among men (P=0.004). This became nonsignificant after adjustment with conventional risk factors (P=0.11). In all subjects, higher education was associated with a smaller increase in IMT during the follow-up (P=0.002), and this association remained after adjustments for conventional risk factors (P=0.04). CONCLUSION: This study shows that high education in young adults is associated with favorable cardiovascular risk factor profile and 6-year change of risk factors. Most importantly, the progression of carotid atherosclerosis was slower among individuals with higher educational level.

Metformin versus insulin for gestational diabetes: Adiposity variables and adipocytokines in offspring at age of 9 years.

AIMS: To compare body composition, visceral adiposity, adipocytokines, and low-grade inflammation markers in prepubertal offspring of mothers who were treated with metformin or insulin for gestational diabetes mellitus (GDM). METHODS: 172 offspring of 311 mothers randomized to receive metformin (n = 82) or insulin (n = 90) for GDMwere studied at 9 years of age (follow-up rate 55%). Measurements included anthropometrics, adipocytokines, markers of the low-grade inflammation, abdominal magnetic resonance imaging (MRI), magnetic liver spectrometry (MRS), and whole body dual-energy X-ray absorptiometry (DXA). RESULTS: Serum markers of low-grade inflammation, visceral adipose tissue volume, total fat percentage, and liver fat percentage were similar between the study groups. Serum adiponectin concentration was higher in children in the metformin group compared to insulin group (median 10.37 vs 9.50 µg/ml, p = 0.016). This difference between groups was observed in boys only (median 12.13 vs 7.50 µg/ml, p < 0.001). Leptin/adiponectin-ratio was lower in boys in the metformin group than in the insulin group (median 0.30 vs 0.75; p = 0.016). CONCLUSIONS: Maternal metformin treatment for GDM had no effects on adiposity, body composition, liver fat, or inflammation markers in prepubertal offspring compared to maternal insulin treatment but was associated with higher adiponectin concentration and lower leptin/adiponectin-ratio in boys.

Nonalcoholic Fatty Liver Disease Incidence and Remission and Their Predictors During 7 Years of Follow-up Among Finns.

CONTEXT: The incidence and remission of nonalcoholic fatty liver disease (NAFLD) are sparsely studied outside Asia. OBJECTIVE: This prospective study aimed to investigate NAFLD incidence and remission, and their predictors among a general Finnish population. METHODS: The applied cohort included 1260 repeatedly studied middle-aged participants with data on liver ultrasound and no excessive alcohol intake. Hepatic steatosis was assessed by liver ultrasound with a 7.2-year study interval. Comprehensive data on health parameters and lifestyle factors were available. RESULTS: At baseline, 1079 participants did not have NAFLD, and during the study period 198 of them developed NAFLD. Of the 181 participants with NAFLD at baseline, 40 achieved NAFLD remission. Taking multicollinearity into account, key predictors for incident NAFLD were baseline age (odds ratio 1.07; 95% CI, 1.02-1.13; P = .009), waist circumference (WC) (2.77, 1.91-4.01 per 1 SD; P < .001), and triglycerides (2.31, 1.53-3.51 per 1 SD; P < .001) and alanine aminotransferase (ALAT) (1.90, 1.20-3.00 per 1 SD; P = .006) concentrations as well as body mass index (BMI) change (4.12, 3.02-5.63 per 1 SD; P < .001). Predictors of NAFLD remission were baseline aspartate aminotransferase (ASAT) concentration (0.23, 0.08-0.67 per 1 SD; P = .007) and WC change (0.38, 0.25-0.59 per 1 SD; P < .001). CONCLUSION: During follow-up, NAFLD developed for every fifth participant without NAFLD at baseline, and one-fifth of those with NAFLD at baseline had achieved NAFLD remission. NAFLD became more prevalent during the follow-up period. From a clinical perspective, key factors predicting NAFLD incidence and remission were BMI and WC change independent of their baseline level.

Long-term tracking and population characteristics of lipoprotein (a) in the Cardiovascular Risk in Young Finns Study.

BACKGROUND AND AIMS: Lipoprotein (a) (Lp(a)) is a causal risk factor for cardiovascular diseases and its levels are under strict genetic control. Therefore, it is hypothesized that the concentration of Lp(a) remains stable throughout life. Finns have lower Lp(a) levels than central Europeans, but it is unknown whether there are differences within Finland, especially between the eastern and western parts of the country with known genetic duality and persistent differences in cardiovascular disease rates. We have examined the long-term stability of Lp(a) levels over 25 years in the Cardiovascular Risk in Young Finns Study (YFS), and the characteristics of individuals with different Lp(a) levels, including their geographical origin within Finland. METHODS: In YFS, the first large baseline examination was conducted in 1980 (baseline age, 3-18 years). Several follow-ups during the past 40 years have been conducted to investigate the determinants of cardiometabolic health. Lp(a) levels have been measured in study years 1986 (N = 2464, ages 9-24 years), 2001 (N = 2281, ages 24-39 years), 2007 (N = 2204, ages 35-45 years) and 2011 (N = 2044, ages 39-49 years). Tracking of Lp(a) was estimated by calculating Spearman's rank order correlations between the study years, and by cross-tabulating how many individuals diagnosed with either elevated or non-elevated Lp(a) levels in 1986, 2001 and 2007 remained in the same category in the latest follow-up in 2011. RESULTS: Spearman's correlation coefficients varied between r = 0.84-0.96. Most individuals (87-94%) who had a high Lp(a) level (>30 mg/dl) in any of the previous study years had a high level also in 2011. On average, the median Lp(a) levels were consistently ∼20% higher in the individuals originating from eastern Finland compared to those from western Finland, but there were no differences in the distribution of known genetic determinants between eastern and western Finns that would have explained the observed difference. CONCLUSIONS: These data confirm that Lp(a) levels remain very stable over the life-course. In line with the genetic duality between eastern and western parts of Finland, we observed about 20% higher Lp(a) levels in individuals originating from eastern Finland compared to those originating from western Finland.

Congenital Hypothyroidism and Hyperthyroidism Alters Adrenal Gene Expression, Development, and Function.

Background: The human adrenal cortex undergoes several rapid remodeling steps during its lifetime. In rodents, similar remodeling occurs postnatally in the "X-zone" layer through unknown mechanisms. Furthermore, little is known regarding the impact of thyroid hormone (TH) on adrenal glands in humans. Methods: To investigate the impact of TH on adrenal pathophysiology, we created two genetic murine models mimicking human nonautoimmune hypothyroidism and hyperthyroidism. Moreover, we analyzed serum thyrotropin (TSH) and steroid hormone concentrations in patients diagnosed with congenital hypothyroidism and premature adrenarche (PA). Results: We found that TH receptor beta-mediated hypertrophy of the X-zone significantly elevated the adrenal weights of hyperthyroid women. In the hypothyroid model, the X-zone was poorly developed in both sexes. Moreover, large reciprocal changes in the expression levels of genes that regulate adrenal cortical function were observed with both models. Unexpectedly, up- and downregulation of several genes involved in catecholamine synthesis were detected in the adrenal glands of the hypothyroid and hyperthyroid models, respectively. Furthermore, TSH and adrenal steroid concentrations correlated positively in pediatric patients with congenital hypothyroidism and PA. Conclusions: Our results revealed that congenital hypothyroidism and hyperthyroidism functionally affect adrenal gland development and related steroidogenic activity, as well as the adrenal medulla.

Inflammation in psychotic disorders: a population-based study.

We investigated inflammatory markers in psychotic disorders and their association with metabolic comorbidity, antipsychotic medication, smoking, alcohol use, physical condition, and mood. From the population-based Finnish Health 2000 study, we identified all persons with schizophrenia (n=45), other nonaffective psychosis (ONAP) (n=57), affective psychosis (n=37) and chose controls matched by age, sex, and region of residence. We found that persons with schizophrenia had significantly higher sIL-2Rα, IL-1RA and C-reactive protein (CRP), persons with ONAP significantly higher IL-1RA and CRP and persons with affective psychosis almost significantly higher TNF-α compared to their matched controls. Current antipsychotic use was associated with elevated IL-1RA and CRP. After taking metabolic and lifestyle-related variables that associated with inflammatory markers into account, only antipsychotic medication remained associated with elevated IL-1RA and TNF-α which are markers related to the activation of innate immune system. CRP was influenced by both antipsychotic medication and nonaffective psychosis. sIL-2Rα, a marker of T-cell activation, was associated with depressive symptoms, schizophrenia, and affective psychosis. We conclude that in persons with psychotic disorders, activation of mononuclear phagocyte system was mostly related to metabolic comorbidity and antipsychotic medication use, whereas T-cell activation had a more direct relationship with both psychotic disorders and depressive symptoms.

Evaluation of multiplex immunoassays, used for determination of adiponectin, resistin, leptin, and ghrelin from human blood samples, in comparison to ELISA assays.

BACKGROUND: Many different multiplex biomarker immunoassays based on Luminex®-technology have been developed during recent years. We have evaluated the performance of two multiplex immunoassays for determination of adiponectin, resistin, ghrelin and leptin in comparison to corresponding, conventional ELISA assays. METHODS: Human serum or plasma samples were analysed by commercially available multiplex and ELISA immunoassays manufactured by Millipore Corp. RESULTS: The correlation between tested multiplex and ELISA immunoassays was good, r > 0.9 for all analytes. The agreement between the methods was acceptable but there were differences in analytical levels. Intra- and inter-assay variation was comparable between both assays. The coefficient of variation for all analytes, independent of method, was ≤15% and for most of them <10%. CONCLUSION: The performance of the tested multiplex assays was reasonable and they can be considered as valid options to the conventional ELISA assays. However, results obtained with the two different techniques are not necessarily interchangeable due to differences in the concentration levels.

Plasma osteopontin is not associated with vascular markers of subclinical atherosclerosis in a population of young adults without symptoms of cardiovascular disease. The Cardiovascular Risk in Young Finns Study.

OBJECTIVE: Osteopontin is used as a biomarker for measuring the severity of atherosclerosis, but the role of osteopontin in the pathogenesis of atherosclerosis is not clear. METHODS: The distribution and determinants of osteopontin were studied in a randomized cohort of 1,817 young adults (aged 30­45 years) without clinical symptoms of atherosclerosis. RESULTS: The mean ± SD osteopontin concentration was 60.7 ± 15.6 µg/mL in men and 51.7 ± 16.0 µg/mL in women. In multivariable models the correlates of osteopontin explained 6.9% (Model R² of the total variation in osteopontin in men, including CRP (ß = 3.02, p < 0.0001), SHBG (ß = 0.21, p < 0.0001), total cholesterol (ß = − 1.78, p = 0.002), age (ß = − 0.26, p = 0.02) and alcohol use (ß = 0.57, p = 0.04) and of these CRP had the greatest influence (Partial R² = 2.1%). In women, multivariable correlates of osteopontin included CRP (ß = 2.90, p < 0.0001), total cholesterol (ß = − 1.99, p = 0.002), insulin (ß = − 1.76, p = 0.001), physical activity (ß = 0.66, p = 0.03), adiponectin (ß = 0.25, p = 0.008) and diastolic blood pressure (ß = 0.14, p = 0.003). These five variables explained 6.7% (Model R²) of the total variation in osteopontin, with CRP (Partial R² = 2.7%) having the greatest influence. Osteopontin was not associated with carotid intima-media thickness, carotid elasticity, brachial endothelial function or the presence of a carotid plaque in either sex. CONCLUSION: We found no evidence of association between osteopontin levels and early vascular markers of atherosclerosis in asymptomatic young adults, suggesting that osteopontin is not implicated in the preclinical atherosclerotic changes in vascular structure and function.

Cardiovascular risk scores in the prediction of subclinical atherosclerosis in young adults: evidence from the cardiovascular risk in a young Finns study.

AIM: To study the utility of risk scores in the prediction of subclinical atherosclerosis in young adults. METHODS AND RESULTS: Participants were 2204 healthy Finnish adults aged 24-39 years in 2001 from a population-based follow-up study Cardiovascular Risk in Young Finns. We examined the performance of the Framingham, Reynolds, Systematic Coronary Risk Evaluation (SCORE), PROCAM, and Finrisk cardiovascular risk scores to predict subclinical atherosclerosis, that is carotid artery intima-media thickness (IMT) and plaque, carotid artery distensibility (CDist), and brachial artery flow-mediated dilatation (FMD) 6 years later. In a 6-year prediction of high IMT (highest decile or plaque), areas under the receiver operating characteristic curves (AUC) for baseline Finrisk (0.733), SCORE (0.726), PROCAM (0.712), and Reynolds (0.729) risk scores were similar as for Framingham risk score (0.728, P always ≥0.15). All risk scores had a similar discrimination in predicting low CDist (lowest decile) (0.652, 0.642, 0.639, 0.658, 0.652 respectively, P always ≥0.41). In the prediction of low FMD (lowest decile), Finrisk, PROCAM, Reynolds, and Framingham scores had similar AUCs (0.578, 0.594, 0.582, 0.568, P always ≥0.08) and SCORE discriminated slightly better (AUC=0.596, P<0.05). The prediction of subclinical outcomes was consistent when estimated from other statistical measures of discrimination, reclassification, and calibration. CONCLUSION: Cardiovascular disease risk scores had equal value in predicting subclinical atherosclerosis measured by IMT and CDist in young adults. SCORE was more accurate in predicting low FMD than Framingham risk score.

Effects of 20-year infancy-onset dietary counselling on cardiometabolic risk factors in the Special Turku Coronary Risk Factor Intervention Project (STRIP): 6-year post-intervention follow-up.

BACKGROUND: Primordial and primary prevention is the cornerstone for cardiometabolic health. In the randomised, controlled Special Turku Coronary Risk Factor Intervention Project (STRIP; n=1116), a 20-year dietary counselling intervention was given to children biannually from infancy, and cardiometabolic health benefits had been observed among the participants in the intervention group. Here, we report on the key results of the first follow-up done 6 years after the end of the intervention, at age 26 years. METHODS: The randomised controlled STRIP study recruited children at age 5 months from well-baby clinics in Turku, Finland, and randomly assigned them to either an intervention or control group; group allocation was unmasked. The intervention introduced participants to a heart-healthy diet, characterised by low proportional intake of saturated fat and cholesterol, by dietary counselling and nutrition education sessions to parents and children from the age of 7 months to 20 years. Children in the control group received only the basic health education given at Finnish well-baby clinics and school health care. We assessed diet, lifestyle, and cardiometabolic risk factor data, including blood pressure, anthropometry, serum biochemistry (lipids, apolipoproteins, glucose, and insulin), and homoeostatic model assessment of insulin resistance (HOMA-IR) in the participants at age 26 years. FINDINGS: 1116 children were included in the original STRIP study, of whom 551 provided data at the age 26 years follow-up, and data for 507 participants were analysed (243 in the intervention group and 264 in the control group). At follow-up, those who had been in the intervention group had slightly lower mean intake of saturated fat as a proportion of total energy intake than the control group (13·0% [SD 3·3] vs 13·7% [3·6], p=0·049). A higher proportion of participants in the intervention group achieved the targeted monounsaturated and polyunsaturated fat to saturated fat ratio of more than 2:1 than the control group (78 [39%] of 200 vs 70 [30%] of 235; risk ratio [RR] 1·16 [95% CI 1·01-1·33]; p=0·035). A higher proportion of intervention group participants met the ideal total cholesterol concentration of less than 5·17 mmol/L (194 [81%] of 240 vs 187 [72%] of 261; RR 1·45 [1·05-2·01], p=0·024) and optimal LDL cholesterol concentration of less than 3·0 mmol/L (166 [69%] of 240 vs 158 [61%] of 251; RR 1·30 [1·03-1·66], p=0·031). Those who received the intervention had lower glucose (5·00 mmol/L [SD 0·43] vs 5·07 mmol/L [0·46], p=0·040) and HOMA-IR (median 1·44 [IQR 1·09-1·91] vs 1·62 [1·22-2·09], p=0·037) than the participants in the control group. INTERPRETATION: Previously observed intervention effects during the 20-year counselling were largely maintained into adulthood 6 years after the withdrawal of the intervention. Dietary counselling introduced in infancy thus provided a sustained benefit to diet quality and cardiometabolic risk factor levels. FUNDING: Academy of Finland, Juho Vainio Foundation, Finnish Foundation for Cardiovascular Research, Finnish Ministry of Education and Culture, Finnish Cultural Foundation, Sigrid Jusélius Foundation, Special Governmental grants for Health Sciences Research (Turku University Hospital), Yrjö Jahnsson Foundation, Finnish Medical Foundation, and Turku University Foundation.

Associations of dyslipidemias from childhood to adulthood with carotid intima-media thickness, elasticity, and brachial flow-mediated dilatation in adulthood: the Cardiovascular Risk in Young Finns Study.

BACKGROUND: Dyslipidemias are the major cause for atherosclerosis. They may act synergistically with nonlipid risk factors to increase atherogenesis. In the present study, we examined the effects of dyslipidemias from childhood to adulthood and their interaction with nonlipid risk factors on markers of subclinical atherosclerosis. METHODS AND RESULTS: Study subjects were participants of the longitudinal Cardiovascular Risk in Young Finns Study started in 1980 (n=2265, age 3 to 18 years). To phenotype type IIa, IIb, and IV dyslipidemias and hypoHDL-cholesterolemia, we calculated age and sex-specific z scores for lipid values for each subject in 1980, 1983, 1986, and 2001. Subjects with mean z score over 90th percentile for LDL-cholesterol or triglycerides were considered having type IIa or IV dyslipidemia. Subjects with mean z score over 90th percentile for LDL-cholesterol and triglycerides had type IIb dyslipidemia, and those with mean z score below 10th percentile for HDL-cholesterol had hypoHDL-cholesterolemia. Compared to controls, subjects with type IIb dyslipidemia had increased carotid IMT (P<0.01). This difference remained significant when adjusted with other risk factors (P<0.05). Carotid IMT also increased significantly more with increasing number of nonlipid risk factors (P<0.001) or presence of the metabolic syndrome (P<0.05) in subjects with type IIb than in controls. Subjects with type IIb or type IV dyslipidemia had decreased carotid elasticity (P<0.05), but these differences became nonsignificant (P>0.3) when adjusted with blood pressure. CONCLUSIONS: Our findings suggest that type IIb dyslipidemia has deleterious effects on vasculature already since childhood. Subjects with type IIb dyslipidemia are more vulnerable to the effects of cardiovascular risk factors and metabolic syndrome.

Whole blood microRNA levels associate with glycemic status and correlate with target mRNAs in pathways important to type 2 diabetes.

We analyzed the associations between whole blood microRNA profiles and the indices of glucose metabolism and impaired fasting glucose and examined whether the discovered microRNAs correlate with the expression of their mRNA targets. MicroRNA and gene expression profiling were performed for the Young Finns Study participants (n = 871). Glucose, insulin, and glycated hemoglobin (HbA1c) levels were measured, the insulin resistance index (HOMA2-IR) was calculated, and the glycemic status (normoglycemic [n = 534]/impaired fasting glucose [IFG] [n = 252]/type 2 diabetes [T2D] [n = 24]) determined. Levels of hsa-miR-144-5p, -122-5p, -148a-3p, -589-5p, and hsa-let-7a-5p associated with glycemic status. hsa-miR-144-5p and -148a-3p associated with glucose levels, while hsa-miR-144-5p, -122-5p, -184, and -339-3p associated with insulin levels and HOMA2-IR, and hsa-miR-148a-3p, -15b-3p, -93-3p, -146b-5p, -221-3p, -18a-3p, -642a-5p, and -181-2-3p associated with HbA1c levels. The targets of hsa-miR-146b-5p that correlated with its levels were enriched in inflammatory pathways, and the targets of hsa-miR-221-3p were enriched in insulin signaling and T2D pathways. These pathways showed indications of co-regulation by HbA1c-associated miRNAs. There were significant differences in the microRNA profiles associated with glucose, insulin, or HOMA-IR compared to those associated with HbA1c. The HbA1c-associated miRNAs also correlated with the expression of target mRNAs in pathways important to the development of T2D.

Childhood Exposure to Passive Smoking and Bone Health in Adulthood: The Cardiovascular Risk in Young Finns Study.

CONTEXT: Passive smoke exposure has been linked to the risk of osteoporosis in adults. OBJECTIVE: We examined the independent effects of childhood passive smoke exposure on adult bone health. DESIGN/SETTING: Longitudinal, the Cardiovascular Risk in Young Finns Study. PARTICIPANTS: The study cohort included 1422 individuals followed for 28 years since baseline in 1980 (age 3 to 18 years). Exposure to passive smoking was determined in childhood. In adulthood, peripheral bone traits were assessed with peripheral quantitative CT (pQCT) at the tibia and radius, and calcaneal mineral density was estimated with quantitative ultrasound. Fracture data were gathered by questionnaires. RESULTS: Parental smoking in childhood was associated with lower pQCT-derived bone sum index in adulthood (ß± SE, -0.064 ± 0.023 per smoking parent; P = 0.004) in multivariate models adjusted for age, sex, active smoking, body mass index, serum 25-OH vitamin D concentration, physical activity, and parental socioeconomic position. Similarly, parental smoking was associated with lower heel ultrasound estimated bone mineral density in adulthood (ß± SE, -0.097 ± 0.041 per smoking parent; P = 0.02). Parental smoking was also associated with the incidence of low-energy fractures (OR, 1.28; 95% CI, 1.01 to 1.62). Individuals with elevated cotinine levels (3 to 20 ng/mL) in childhood had lower bone sum index with pQCT (ß± SE, -0.206 ± 0.057; P = 0.0003). Children whose parents smoked and had high cotinine levels (3 to 20 ng/mL) had significantly lower pQCT-derived bone sum index compared with those with smoking parents but had low cotinine levels (<3 ng/mL) (ß± SE, -0.192 ± 0.072; P = 0.008). CONCLUSIONS AND RELEVANCE: Children of parents who smoke have evidence of impaired bone health in adulthood.

Comparison of three commercial tests for buprenorphine screening in urine.

BACKGROUND: Rapid and sensitive tests for detecting buprenorphine and its metabolites for drug-screening situations have been long awaited. From the tests available, we have evaluated two on-site drugs-of-abuse testing devices using competitive binding immunoassays and one homogeneous enzyme immunoassay measured on an automated analyser. METHODS: A total of 49 urine specimens were tested using three different kits. Two were point-of-care devices, a cassette test, QuikPac II OneStep Buprenorphine Test, and a strip test, QuikStrip OneStep Buprenorphine Test. The other was the CEDIA Buprenorphine Assay performed on a Roche Modular P analyser. The confirmation analyses were performed using liquid chromatography-mass spectrometry. RESULTS: The sensitivities of the three methods ranged from 88% to 100% and specificities from 91% to 100%. All three kits, especially the cassette and strip devices differed markedly from each other with respect to interpretation of the test result and to clarity of the test performance. Increasing the read time of the QuikStrip device from 5 to 30 min resulted in an increase in false-negative test results. CONCLUSIONS: Our results indicate that special care should be taken when selecting immunology-based point-of-care methods for measurement of buprenorphine.

Consumption of chokeberry (Aronia mitschurinii) products modestly lowered blood pressure and reduced low-grade inflammation in patients with mildly elevated blood pressure.

Previous studies suggest that consumption of chokeberries may improve cardiovascular disease risk factor profiles. We hypothesized that chokeberries (Aronia mitschurinii) have beneficial effects on blood pressure, low-grade inflammation, serum lipids, serum glucose, and platelet aggregation in patients with untreated mild hypertension. A total of 38 participants were enrolled into a 16-week single blinded crossover trial. The participants were randomized to use cold-pressed 100% chokeberry juice (300 mL/d) and oven-dried chokeberry powder (3 g/d), or matched placebo products in random order for 8 weeks each with no washout period. The daily portion of chokeberry products was prepared from approximately 336 g of fresh chokeberries. Urinary excretion of various polyphenols and their metabolites increased during the chokeberry period, indicating good compliance. Chokeberries decreased daytime blood pressure and low-grade inflammation. The daytime ambulatory diastolic blood pressure decreased (-1.64 mm Hg, P = .02), and the true awake ambulatory systolic (-2.71 mm Hg, P = .077) and diastolic (-1.62 mm Hg, P = .057) blood pressure tended to decrease. The concentrations of interleukin (IL) 10 and tumor necrosis factor α decreased (-1.9 pg/mL [P = .008] and -0.67 pg/mL [P = .007], respectively) and tended to decrease for IL-4 and IL-5 (-4.5 pg/mL [P = .084] and -0.06 pg/mL [P = .059], respectively). No changes in serum lipids, lipoproteins, glucose, and in vitro platelet aggregation were noted with the chokeberry intervention. These findings suggest that inclusion of chokeberry products in the diet of participants with mildly elevated blood pressure has minor beneficial effects on cardiovascular health.