Long-term morbidity and mortality in patients diagnosed with an insulinoma.

OBJECTIVE: Insulinomas are rare functional pancreatic neuroendocrine tumours. As previous data on the long-term prognosis of insulinoma patients are scarce, we studied the morbidity and mortality in the Finnish insulinoma cohort. DESIGN: Retrospective cohort study. METHODS: Incidence of endocrine, cardiovascular, gastrointestinal and psychiatric disorders, and cancers was compared in all the patients diagnosed with an insulinoma in Finland during 1980-2010 (n = 79, including two patients with multiple endocrine neoplasia type 1 syndrome), vs 316 matched controls, using the Mantel-Haenszel method. Overall survival was analysed with Kaplan-Meier and Cox regression analyses. RESULTS: The median length of follow-up was 10.7 years for the patients and 12.2 years for the controls. The long-term incidence of atrial fibrillation (rate ratio (RR): 2.07 (95% CI: 1.02-4.22)), intestinal obstruction (18.65 (2.09-166.86)), and possibly breast (4.46 (1.29-15.39) and kidney cancers (RR not applicable) was increased among insulinoma patients vs controls, P < 0.05 for all comparisons. Endocrine disorders and pancreatic diseases were more frequent in the patients during the first year after insulinoma diagnosis, but not later on. The survival of patients with a non-metastatic insulinoma (n = 70) was similar to that of controls, but for patients with distant metastases (n = 9), the survival was significantly impaired (median 3.4 years). CONCLUSIONS: The long-term prognosis of patients with a non-metastatic insulinoma is similar to the general population, except for an increased incidence of atrial fibrillation, intestinal obstruction, and possibly breast and kidney cancers. These results need to be confirmed in future studies. Metastatic insulinomas entail a markedly decreased survival.

The effects of a 2-year physical activity and dietary intervention on plasma lipid concentrations in children: the PANIC Study.

PURPOSE: We studied the effects of a physical activity and dietary intervention on plasma lipids in a general population of children. We also investigated how lifestyle changes contributed to the intervention effects. METHODS: We carried out a 2-year controlled, non-randomized lifestyle intervention study among 504 mainly prepubertal children aged 6-9 years at baseline. We assigned 306 children to the intervention group and 198 children to the control group. We assessed plasma concentrations of total, LDL, HDL, and VLDL cholesterol, triglycerides, HDL triglycerides, and VLDL triglycerides. We evaluated the consumption of foods using 4-day food records and physical activity using a movement and heart rate sensor. We analyzed data using linear mixed-effect models adjusted for age at baseline, sex, and pubertal stage at both time points. Furthermore, specific lifestyle variables were entered in these models. RESULTS: Plasma LDL cholesterol decreased in the intervention group but did not change in the control group ( - 0.05 vs. 0.00 mmol/L, regression coefficient (ß) = - 0.0385, p = 0.040 for group*time interaction). This effect was mainly explained by the changes in the consumption of high-fat vegetable oil-based spreads (ß = - 0.0203, + 47% change in ß) and butter-based spreads (ß = - 0.0294, + 30% change in ß), moderate-to-vigorous physical activity (ß = - 0.0268, + 30% change in ß), light physical activity (ß = - 0.0274, + 29% change in ß) and sedentary time (ß = - 0.0270, + 30% change in ß). The intervention had no effect on other plasma lipids. CONCLUSION: Lifestyle intervention resulted a small decrease in plasma LDL cholesterol concentration in children. The effect was explained by changes in quality and quantity of dietary fat and physical activity. CLINICAL TRIAL REGISTRY NUMBER: NCT01803776, ClinicalTrials.gov.

Post-weight loss changes in fasting appetite- and energy balance-related hormone concentrations and the effect of the macronutrient content of a weight maintenance diet: a randomised controlled trial.

PURPOSE: We investigated the effects of the macronutrient composition of diets with differing satiety values on fasting appetite-related hormone concentrations after weight loss and examined whether the hormone secretion adapted to changes in body fat mass (FM) and fat-free mass (FFM) during the weight maintenance period (WM). METHODS: Eighty-two men and women with obesity underwent a 7-week very-low-energy diet (VLED) and were then randomised to a higher-satiety food (HSF) group or a lower-satiety food (LSF) group during 24-weeks of the WM. The groups consumed isoenergetic foods with different satiety ratings and macronutrient compositions. RESULTS: During the WM, the HSF group consumed more protein and dietary fibre and less fat than the LSF group, but the groups showed similar changes in body weight and fasting appetite-related hormones. In the whole study sample, VLED induced 12 kg (p < 0.001) weight loss. At the end of the WM, weight regain was 1.3 kg (p = 0.004), ghrelin concentration increased, whereas leptin, insulin, and glucose concentrations decreased compared to pre-VLED levels (p < 0.001 for all). Peptide YY did not differ from pre-VLED levels. Changes in ghrelin levels were inversely associated with changes in FFM during weeks 0-12 of the WM (p = 0.002), while changes in leptin and insulin levels were positively associated with changes in FM during weeks 0-12 (p = 0.015 and p = 0.038, respectively) and weeks 12-24 (p < 0.001 and p = 0.022) of the WM. CONCLUSIONS: The macronutrient composition of an isoenergetic WM diet did not affect fasting appetite-related hormone concentrations. Leptin and insulin adjusted to the reduced FM, whereas ghrelin reflected FFM during the first months of the WM. TRIAL REGISTRATION: isrctn.com, ID 67529475.

A 2 year physical activity and dietary intervention attenuates the increase in insulin resistance in a general population of children: the PANIC study.

AIMS/HYPOTHESIS: We studied for the first time the long-term effects of a combined physical activity and dietary intervention on insulin resistance and fasting plasma glucose in a general population of predominantly normal-weight children. METHODS: We carried out a 2 year non-randomised controlled trial in a population sample of 504 children aged 6-9 years at baseline. The children were allocated to a combined physical activity and dietary intervention group (306 children at baseline, 261 children at 2-year follow-up) or a control group (198 children, 177 children) without blinding. We measured fasting insulin and fasting glucose, calculated HOMA-IR, assessed physical activity and sedentary time by combined heart rate and body movement monitoring, assessed dietary factors by a 4 day food record, used the Finnish Children Healthy Eating Index (FCHEI) as a measure of overall diet quality, and measured body fat percentage (BF%) and lean body mass by dual-energy x-ray absorptiometry. The intervention effects on insulin, glucose and HOMA-IR were analysed using the intention-to-treat principle and linear mixed-effects models after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The measures of physical activity, sedentary time, diet and body composition at baseline and 2 year follow-up were entered one-by-one as covariates into the models to study whether changes in these variables might partly explain the observed intervention effects. RESULTS: Compared with the control group, fasting insulin increased 4.65 pmol/l less (absolute change +8.96 vs +13.61 pmol/l) and HOMA-IR increased 0.18 units less (+0.31 vs +0.49 units) over 2 years in the combined physical activity and dietary intervention group. The intervention effects on fasting insulin (regression coefficient ß for intervention effect -0.33 [95% CI -0.62, -0.04], p = 0.026) and HOMA-IR (ß for intervention effect -0.084 [95% CI -0.156, -0.012], p = 0.023) were statistically significant after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The intervention had no effect on fasting glucose, BF% or lean body mass. Changes in total physical activity energy expenditure, light physical activity, moderate-to-vigorous physical activity, total sedentary time, the reported consumption of high-fat (≥60%) vegetable oil-based spreads, and FCHEI, but not a change in BF% or lean body mass, partly explained the intervention effects on fasting insulin and HOMA-IR. CONCLUSIONS/INTERPRETATION: The combined physical activity and dietary intervention attenuated the increase in insulin resistance over 2 years in a general population of predominantly normal-weight children. This beneficial effect was partly mediated by changes in physical activity, sedentary time and diet but not changes in body composition. TRIAL REGISTRATION: ClinicalTrials.gov NCT01803776 Graphical abstract.

Intake of Camelina Sativa Oil and Fatty Fish Alter the Plasma Lipid Mediator Profile in Subjects with Impaired Glucose Metabolism - A Randomized Controlled Trial.

n-3 and n-6 polyunsaturated fatty acids (PUFAs) and their lipid mediator metabolites are associated with inflammation. We investigated the effect of dietary intake of plant- and animal-derived n-3 PUFAs and fish protein on the circulatory concentrations of lipid mediators. Seventy-nine subjects with impaired fasting glucose who completed the controlled dietary intervention after randomization to the fatty fish (FF, n=20), lean fish (LF, n=21), Camelina sativa oil (CSO, n=18) or control group (n=20) for 12 weeks were studied. Lipid mediator profiling from fasting plasma samples before and after the intervention was performed by liquid chromatography-mass spectrometry (LC-MS/MS). The FF diet increased concentrations of 18-hydroxyeicosapentaenoic acid (18-HEPE) and 4- and 17-hydroxydocosahexaenoic acid (4-, 17-HDoHE) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. Concentrations of lipid mediators derived from α-linolenic acid (ALA) increased and arachidonic acid (AA) derived 5-iso prostaglandin F2α-VI decreased in the CSO group. There were no significant changes in lipid mediators in the LF group. The dietary intake of both plant and animal-based n-3 PUFAs increased circulatory concentrations of lipid mediators with potential anti-inflammatory properties.

The effect of different sources of fish and camelina sativa oil on immune cell and adipose tissue mRNA expression in subjects with abnormal fasting glucose metabolism: a randomized controlled trial.

BACKGROUND/OBJECTIVES: Molecular mechanisms linking fish and vegetable oil intakes to their healthy metabolic effects may involve attenuation of inflammation. Our primary aim was to examine in a randomized controlled setting whether diets enriched in fatty fish (FF), lean fish (LF) or ALA-rich camelina sativa oil (CSO) differ in their effects on the mRNA expression response of selected inflammation-related genes in peripheral blood mononuclear cells (PBMCs) and subcutaneous adipose tissue (SAT) in subjects with impaired fasting glucose. SUBJECTS/METHODS: Samples from 72 participants randomized to one of the following 12-week intervention groups, FF (n = 19), LF (n = 19), CSO (n = 17) or a control group (n = 17), were available for the PBMC study. For SAT, 39 samples (n = 8, n = 10, n = 9, n = 12, respectively) were available. The mRNA expression was measured at baseline and 12 weeks by TaqMan® Low Density Array. RESULTS: In PBMCs, LF decreased ICAM1 mRNA expression (P < 0.05), which was different (P = 0.06, Bonferroni correction) from the observed increase in the FF group (P < 0.05). Also, compared to the control group, LF decreased ICAM1 mRNA expression (P < 0.05). Moreover, the change in ICAM1 mRNA expression correlated positively with the intake of FF (P < 0.05) and negatively with the intake of LF (P < 0.05), independently of study group. A diet enriched in CSO, a rich source of alpha-linolenic acid (ALA), decreased PBMC IFNG mRNA expression (P < 0.01). The intake of CSO in the CSO group, but not the increase in plasma ALA proportions, correlated inversely with the IFNG mRNA expression in PBMCs (P = 0.08). In SAT, when compared with the control group, the effect of FF on decreasing IL1RN mRNA expression was significant (P < 0.03). CONCLUSION: We propose that CSO intake may partly exert its benefits through immuno-inflammatory molecular regulation in PBMCs, while modulation of ICAM1 expression, an endothelial/vascular-related gene, may be more dependent on the type of fish consumed.

Longitudinal associations of physical activity and sedentary time with cardiometabolic risk factors in children.

BACKGROUND: There are few prospective studies on the associations of changes in objectively measured vigorous physical activity (VPA∆ ), moderate-to-vigorous physical activity (MVPA∆ ), light physical activity (LPA∆ ), and sedentary time (ST∆ ) with changes in cardiometabolic risk factors (∆ ) in children. We therefore investigated these relationships among children. METHODS: The participants were a population sample of 258 children aged 6-8 years followed for 2 years. We assessed PA and ST by a combined heart rate and movement sensor; computed continuous age- and sex-adjusted z-scores for waist circumference, blood pressure, and fasting insulin, glucose, triglycerides, and high-density lipoprotein (HDL) cholesterol; and constructed a cardiometabolic risk score (CRS) of these risk factors. Data were analyzed using linear regression models adjusted for age, sex, the explanatory and outcome variables at baseline, and puberty. RESULTS: VPA∆ associated inversely with CRS∆ (ß = -0.209, P = 0.001), body fat percentage (BF%)∆ (ß = -0.244, P = 0.001), insulin∆ (ß = -0.220, P = 0.001), and triglycerides∆ (ß = -0.164, P = 0.012) and directly with HDL cholesterol∆ (ß = 0.159, P = 0.023). MVPA∆ associated inversely with CRS∆ (ß = -0.178, P = 0.012), BF%∆ (ß = -0.298, P = <0.001), and insulin∆ (ß = -0.213, P = 0.006) and directly with HDL cholesterol∆ (ß = 0.184, P = 0.022). LPA∆ only associated negatively with CRS∆ (ß = -0.163, P = 0.032). ST∆ associated directly with CRS∆ (ß = 0.218, P = 0.003), BF%∆ (ß = 0.212, P = 0.016), and insulin∆ (ß = 0.159, P = 0.049). CONCLUSIONS: Increased VPA and MVPA and decreased ST were associated with reduced overall cardiometabolic risk and major individual risk factors. Change in LPA had weaker associations with changes in these cardiometabolic risk factors. Our findings suggest that increasing at least moderate-intensity PA and decreasing ST decrease cardiometabolic risk in children.

Intake of Fatty Fish Alters the Size and the Concentration of Lipid Components of HDL Particles and Camelina Sativa Oil Decreases IDL Particle Concentration in Subjects with Impaired Glucose Metabolism.

SCOPE: Intake of long-chain n-3 PUFAs affects the lipoprotein subclass profile, whereas the effect of shorter chain n-3 PUFAs remains unclear. We investigated the effect of fish and camelina sativa oil (CSO) intakes on lipoprotein subclasses. METHODS AND RESULTS: Altogether, 79 volunteers with impaired glucose metabolism were randomly assigned to CSO, fatty fish (FF), lean fish (LF), or control group for 12 weeks. Nuclear magnetic resonance spectroscopy was used to determine lipoprotein subclasses and their lipid components. The average HDL particle size increased in the FF group (overall p = 0.032) as compared with the control group. Serum concentrations of cholesterol in HDL and HDL2 (overall p = 0.024 and p = 0.021, respectively) and total lipids and phospholipids in large HDL particles (overall p = 0.012 and p = 0.019, respectively) increased in the FF group, differing significantly from the LF group. The concentration of intermediate-density lipoprotein (IDL) particles decreased in the CSO group (overall p = 0.033) as compared with the LF group. CONCLUSION: Our study suggests that FF intake causes a shift toward larger HDL particles and increases the concentration of lipid components in HDL, which may be associated with the antiatherogenic properties of HDL. Furthermore, CSO intake decreases IDL particle concentration. These changes may favorably affect cardiovascular risk.

Body fat mass, lean body mass and associated biomarkers as determinants of bone mineral density in children 6-8years of age - The Physical Activity and Nutrition in Children (PANIC) study.

Lean body mass (LM) has been positively associated with bone mineral density (BMD) in children and adolescents, but the relationship between body fat mass (FM) and BMD remains controversial. Several biomarkers secreted by adipose tissue, skeletal muscle, or bone may affect bone metabolism and BMD. We investigated the associations of LM, FM, and such biomarkers with BMD in children. We studied a population sample of 472 prepubertal Finnish children (227 girls, 245 boys) aged 6-8years. We assessed BMD, LM, and FM using whole-body dual-energy x-ray absorptiometry and analysed several biomarkers from fasting blood samples. We studied the associations of LM, FM, and the biomarkers with BMD of the whole body excluding the head using linear regression analysis. LM (standardized regression coefficient ß=0.708, p<0.001), FM (ß=0.358, p<0.001), and irisin (ß=0.079, p=0.048) were positive correlates for BMD adjusted for age, sex, and height in all children. These associations remained statistically significant after further adjustment for LM or FM. The positive associations of dehydroepiandrosterone sulphate (DHEAS), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), leptin, free leptin index, and high-sensitivity C-reactive protein and the negative association of leptin receptor with BMD were explained by FM. The positive associations of DHEAS and HOMA-IR with BMD were also explained by LM. Serum 25-hydroxyvitamin D was a positive correlate for BMD adjusted for age, sex, and height and after further adjustment for FM but not for LM. LM and FM were positive correlates for BMD also in girls and boys separately. In girls, insulin, HOMA-IR, leptin, and free leptin index were positively and leptin receptor was negatively associated with BMD adjusted for age, height, and LM. After adjustment for age, height, and FM, none of the biomarkers was associated with BMD. In boys, leptin and free leptin index were positively and leptin receptor was negatively associated with BMD adjusted for age, height, and LM. After adjustment for age, height and FM, 25(OH)D was positively and IGF-1 and leptin were negatively associated with BMD. FM strongly modified the association between leptin and BMD. LM but also FM were strong, independent positive correlates for BMD in all children, girls, and boys. Irisin was positively and independently associated with BMD in all children. The associations of other biomarkers with BMD were explained by LM or FM.

Camelina Sativa Oil, but not Fatty Fish or Lean Fish, Improves Serum Lipid Profile in Subjects with Impaired Glucose Metabolism-A Randomized Controlled Trial.

SCOPE: The aim of the study is to examine whether lean fish (LF), fatty fish (FF), and camelina sativa oil (CSO), a plant-based source of alpha-linolenic acid (ALA), differ in their metabolic effects in subjects with impaired glucose metabolism. METHODS AND RESULTS: Altogether 79 volunteers with impaired fasting glucose, BMI 25-36 kg m-2 , age 43-72 years, participated in a 12-week randomized controlled trial with four parallel groups, that is, the FF (four fish meals/week), LF (four fish meals/week), CSO (10 g d-1 ALA), and control (limited intakes of fish and sources of ALA) groups. The proportions of eicosapentaenoic acid and DHA increase in plasma lipids in the FF group, and the proportion of ALA increase in the CSO group (p < 0.0001 for all). In the CSO group, total and LDL-cholesterol (C) concentrations decrease compared with the FF and LF groups; LDL-C/HDL-C and ApoB/ApoA-I ratios decrease compared with the LF group. There are no significant changes in glucose metabolism or markers of low-grade inflammation. CONCLUSIONS: A diet enriched in CSO improves serum lipid profile as compared with a diet enriched in FF or LF in subjects with impaired fasting glucose, with no differences in glucose metabolism or concentrations of inflammatory markers.

Fasting serum hippuric acid is elevated after bilberry (Vaccinium myrtillus) consumption and associates with improvement of fasting glucose levels and insulin secretion in persons at high risk of developing type 2 diabetes.

SCOPE: Urinary hippuric acid has been proposed as a biomarker for fruit, vegetable, and polyphenol consumption. We assessed how serum hippuric acid changes after a bilberry-enriched diet (BB; high anthocyanin intake) and another berry diet including strawberries, raspberries, and cloudberries (SRC; lower anthocyanin intake) and how these changes associate with insulin and glucose metabolism. METHODS AND RESULTS: Hippuric acid was measured with LC-QTOF-MS metabolite profiling analysis from fasting serum samples at baseline and after an 8-week intervention in 47 individuals with features of the metabolic syndrome who were randomized to either a BB diet (n = 15), an SRC diet (n = 20) or a control diet (n = 12). Fasting serum hippuric acid increased significantly (3.5-fold, p = 0.001) only in the BB group and correlated with changes in fasting plasma glucose concentration (r = -0.54, p < 0.05) and insulin secretion (r = 0.59, p < 0.05). These associations were confirmed in the Finnish Diabetes Prevention Study (n = 198). CONCLUSION: Fasting serum hippuric acid is increased after consumption of anthocyanin-rich bilberries, and may contribute to the beneficial effect of bilberry consumption through its associations with better glycemic control and ß-cell function.

Effect of a 2-y dietary and physical activity intervention on plasma fatty acid composition and estimated desaturase and elongase activities in children: the Physical Activity and Nutrition in Children Study.

BACKGROUND: Evidence on the effects of lifestyle interventions on plasma fatty acid composition in children is limited. OBJECTIVE: We investigated the effects of a dietary and physical activity intervention on plasma fatty acid composition of cholesteryl esters (CEs) and phospholipids and estimated desaturase and elongase activities in children. DESIGN: We conducted a 2-y controlled dietary and physical activity intervention based on Finnish nutrition and physical activity recommendations in a population sample of 506 children aged 6-8 y. We assessed plasma fatty acid composition by gas chromatography and estimated desaturase and elongase activities as the ratio of product fatty acids to precursor fatty acids. We analyzed data by using linear mixed models adjusted for age and sex. RESULTS: The proportion of total polyunsaturated fatty acids (PUFAs) in CEs tended to increase in the intervention group compared with the control group (P = 0.007 for group × time interaction). The proportion of total PUFAs in phospholipids (P = 0.019 for group × time interaction) and the proportion of linoleic acid in CEs (P = 0.038 for group × time interaction) decreased in the control group. The proportion of α-linolenic acid in CEs (P < 0.001 for group × time interaction) increased and in phospholipids (P = 0.015 for group × time interaction) tended to increase in the intervention group. The proportion of stearic acid in CEs decreased in the intervention group (P = 0.001 for group × time interaction). The proportion of oleic acid in CEs (P = 0.002 for group × time interaction) increased and in phospholipids (P = 0.023 for group × time interaction) tended to increase in the control group. Estimated elongase activity in CEs decreased in the control group (P = 0.050 for group × time interaction). Intervention had no effect on estimated desaturase activities. CONCLUSIONS: Dietary and physical activity intervention had a beneficial effect on plasma fatty acid composition in children by preventing the decrease in the proportion of total PUFAs and linoleic acid and by increasing the proportion of α-linolenic acid. This study was registered at clinicaltrials.gov as NCT01803776.

Cross-sectional associations of plasma fatty acid composition and estimated desaturase and elongase activities with cardiometabolic risk in Finnish children--The PANIC study.

BACKGROUND: Knowledge on the association of plasma fatty acid (FA) composition in triacylglycerol (TG) and phospholipid (PL) fractions with cardiometabolic risk in population-based samples of children is lacking. OBJECTIVE: We investigated the associations of proportions of FA in plasma TG and PL fractions as well as estimated desaturase and elongase activities with cardiometabolic risk in a population sample of 384 children aged 6-8 years. METHODS: Plasma FA composition was analyzed by gas chromatography. Desaturase and elongase activities were estimated as product-to-precursor FA ratios. Cardiometabolic risk was assessed using a continuous cardiometabolic risk score (CRS) variable. RESULTS: Higher proportions of myristic and palmitoleic acids in plasma TG and PL were associated with a higher CRS. A lower proportion of linoleic acid in plasma TG was related to a higher CRS. Estimated stearoyl-CoA-desaturase and Δ6-desaturase activities in plasma TG and PL were directly associated with CRS, whereas estimated elongase activity in plasma TG and PL was inversely related to CRS. CONCLUSIONS: Greater proportions of myristic and palmitoleic acids and a smaller proportion of linoleic acid in plasma, as well as higher estimated stearoyl-CoA-desaturase and Δ6-desaturase activities and a lower estimated elongase activity, are associated with cardiometabolic risk factors among children. These findings reinforce the evidence that FA metabolism is closely associated with cardiometabolic risk, starting already from childhood.

Metabolic syndrome and the risk of sudden cardiac death in middle-aged men.

BACKGROUND: Little is known about the relationship between metabolic syndrome and sudden cardiac death (SCD). We examined the association of metabolic syndrome, as defined by World Health Organization (WHO), International Diabetes Federation (IDF), National Cholesterol Education Program (NCEP) and American Heart Association (AHA)--IDF interim criteria, with incident SCD. We also assessed the association of a continuous metabolic risk score with SCD. METHODS: A total of 1466 middle-aged men participating in a prospective population-based cohort study from eastern Finland with no history of coronary heart disease or diabetes at baseline were included. RESULTS: During the average follow-up of 21 years 85 SCDs occurred. Men with the metabolic syndrome as defined by the WHO, NCEP, IDF and interim criteria had a 2.2-2.6 fold, increased risk for SCD, after adjusting for lifestyle and traditional cardiovascular risk factors not included in the metabolic syndrome definition (P<0.001-0.011). A one-standard deviation increase in the metabolic risk score (composed of the sum of Z-scores for waist circumference, insulin, glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, and blood pressure) was associated with a 1.68-fold higher (95% CI 1.33-2.11) risk of SCD. Even when adjusting further for systolic blood pressure, HDL cholesterol and body mass index, the association remained significant for the interim criteria and the metabolic risk score, but not for WHO, NCEP, or IDF definitions. CONCLUSIONS: Men with metabolic syndrome are at increased risk for SCD. Incident SCD associated with the IDF/AHA interim criteria and metabolic risk clustering estimated by a score is not explained by obesity or traditional cardiovascular risk factors. KEY MESSAGES: Men with metabolic syndrome are at increased risk for sudden cardiac death. Incident sudden cardiac death associated with metabolic risk clustering estimated by a score in not explained by obesity or traditional cardiovascular risk factors. Prevention of the metabolic syndrome may help reduce the health burden of SCD.

Cross-linking of sodium caseinate-structured emulsion with transglutaminase alters postprandial metabolic and appetite responses in healthy young individuals.

The physico-chemical and interfacial properties of fat emulsions influence lipid digestion and may affect postprandial responses. The aim of the present study was to determine the effects of the modification of the interfacial layer of a fat emulsion by cross-linking on postprandial metabolic and appetite responses. A total of fifteen healthy individuals (26.5 (sem 6.9) years and BMI 21.9 (sem 2.0) kg/m2) participated in a cross-over design experiment in which they consumed two isoenergetic (1924 kJ (460 kcal)) and isovolumic (250 g) emulsions stabilised with either sodium caseinate (Cas) or transglutaminase-cross-linked sodium caseinate (Cas-TG) in a randomised order. Blood samples were collected from the individuals at baseline and for 6 h postprandially for the determination of serum TAG and plasma NEFA, cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), glucose and insulin responses. Appetite was assessed using visual analogue scales. Postprandial TAG and NEFA responses and gastric emptying (GE) rates were comparable between the emulsions. CCK increased more after the ingestion of Cas-TG than after the ingestion of Cas (P< 0.05), while GLP-1 responses did not differ between the two test emulsions. Glucose and insulin profiles were lower after consuming Cas-TG than after consuming Cas (P< 0.05). The overall insulin, glucose and CCK responses, expressed as areas above/under the curve, did not differ significantly between the Cas and Cas-TG meal conditions. Satiety ratings were reduced and hunger, desire to eat and thirst ratings increased more after the ingestion of Cas-TG than after the ingestion of Cas (P< 0.05). The present results suggest that even a subtle structural modification of the interfacial layer of a fat emulsion can alter the early postprandial profiles of glucose, insulin, CCK, appetite and satiety through decreased protein digestion without affecting significantly on GE or overall lipid digestion.

Assessment of body composition by dual-energy X-ray absorptiometry, bioimpedance analysis and anthropometrics in children: the Physical Activity and Nutrition in Children study.

OBJECTIVE AND METHODS: We compared InBody720 segmental multifrequency bioimpedance analysis (SMF-BIA) with Lunar Prodigy Advance dual-energy X-ray absorptiometry (DXA) in assessment of body composition among 178 predominantly prepubertal children. Segmental agreement analysis of body compartments was carried out, and inter-relationships of anthropometric and other measures of body composition were defined. Moreover, the relations of different reference criteria for excess body fat were evaluated. RESULTS: The prevalence of excess body fat varies greatly according to the used criteria. Intraclass and Pearson's correlations between SMF-BIA and DXA were >0·92 in total body and >0·74 in regional measures. SMF-BIA underestimated percentage body fat (%BF) and fat mass (FM), and overestimated lean mass (LM) and percentage LM with significant offset trend bias. Higher adiposity increased offsets, and overall agreement was poorer in girls. On average, %BF offsets (girls/boys) and limits of agreement (LA) were 3·9/1·6% [(-)1·4-9·2%/(-)3·4-6·7%]. Interestingly percentage offsets of fat content (%BF: 18·9/10·1%, FM: 18·8/11·1%) showed no significant bias trends indicating that the corresponding absolute methodological offset depends on the amount of fat content. The smallest percentage offset was found with LM: 4·3/0·1%, referring offset (LA) of 0·88/0·03 kg (±2·05/±1·71 kg). Correspondingly, segmental LM had poorer agreement than total body LM. All anthropometrics except for the waist-to-hip ratio showed strong correlations (r = 0·76-0·95) with abdominal and total body fat. CONCLUSION: Segmental multifrequency bioimpedance analysis is precise enough for total-LM analysis and had also sufficient trueness for total body composition analysis to be used in epidemiological purposes. There is need to generate scientifically and clinically relevant criteria and reference values for excess body fat.

Associations of physical activity and sedentary behavior with academic skills--a follow-up study among primary school children.

BACKGROUND: There are no prospective studies that would have compared the relationships of different types of physical activity (PA) and sedentary behavior (SB) with academic skills among children. We therefore investigated the associations of different types of PA and SB with reading and arithmetic skills in a follow-up study among children. METHODS: The participants were 186 children (107 boys, 79 girls, 6-8 yr) who were followed-up in Grades 1-3. PA and SB were assessed using a questionnaire in Grade 1. Reading fluency, reading comprehension and arithmetic skills were assessed using standardized tests at the end of Grades 1-3. RESULTS: Among all children more recess PA and more time spent in SB related to academic skills were associated with a better reading fluency across Grades 1-3. In boys, higher levels of total PA, physically active school transportation and more time spent in SB related to academic skills were associated with a better reading fluency across the Grades 1-3. Among girls, higher levels of total PA were related to worse arithmetic skills across Grades 1-3. Moreover, total PA was directly associated with reading fluency and arithmetic skills in Grades 1-3 among girls whose parents had a university degree, whereas these relationships were inverse in girls of less educated parents. CONCLUSIONS: Total PA, physically active school transportation and SB related to academic skills may be beneficial for the development of reading skills in boys, whereas factors that are independent of PA or SB may be more important for academic skills in girls. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01803776.

Physical activity and sedentary behaviour in relation to cardiometabolic risk in children: cross-sectional findings from the Physical Activity and Nutrition in Children (PANIC) Study.

BACKGROUND: Lower levels of physical activity (PA) and sedentary behaviour (SB) have been associated with increased cardiometabolic risk among children. However, little is known about the independent and combined associations of PA and SB as well as different types of these behaviours with cardiometabolic risk in children. We therefore investigated these relationships among children. METHODS: The subjects were a population sample of 468 children 6-8 years of age. PA and SB were assessed by a questionnaire administered by parents and validated by a monitor combining heart rate and accelerometry measurements. We assessed body fat percentage, waist circumference, blood glucose, serum insulin, plasma lipids and lipoproteins and blood pressure and calculated a cardiometabolic risk score using population-specific Z-scores and a formula waist circumference + insulin + glucose + triglycerides - HDL cholesterol + mean of systolic and diastolic blood pressure. We analysed data using multivariate linear regression models. RESULTS: Total PA was inversely associated with the cardiometabolic risk score (ß = -0.135, p = 0.004), body fat percentage (ß = -0.155, p < 0.001), insulin (ß = -0.099, p = 0.034), triglycerides (ß = -0.166, p < 0.001), VLDL triglycerides (ß = -0.230, p < 0.001), VLDL cholesterol (ß = -0.168, p = 0.001), LDL cholesterol (ß = -0.094, p = 0.046) and HDL triglycerides (ß = -0.149, p = 0.004) and directly related to HDL cholesterol (ß = 0.144, p = 0.002) adjusted for age and gender. Unstructured PA was inversely associated with the cardiometabolic risk score (ß = -0.123, p = 0.010), body fat percentage (ß = -0.099, p = 0.027), insulin (ß = -0.108, p = 0.021), triglycerides (ß = -0.144, p = 0.002), VLDL triglycerides (ß = -0.233, p < 0.001) and VLDL cholesterol (ß = -0.199, p < 0.001) and directly related to HDL cholesterol (ß = 0.126, p = 0.008). Watching TV and videos was directly related to the cardiometabolic risk score (ß = 0.135, p = 0.003), body fat percentage (ß = 0.090, p = 0.039), waist circumference (ß = 0.097, p = 0.033) and systolic blood pressure (ß = 0.096, p = 0.039). Resting was directly associated with the cardiometabolic risk score (ß = 0.092, p = 0.049), triglycerides (ß = 0.131, p = 0.005), VLDL triglycerides (ß = 0.134, p = 0.009), VLDL cholesterol (ß = 0.147, p = 0.004) and LDL cholesterol (ß = 0.105, p = 0.023). Other types of PA and SB had less consistent associations with cardiometabolic risk factors. CONCLUSIONS: The results of our study emphasise increasing total and unstructured PA and decreasing watching TV and videos and other sedentary behaviours to reduce cardiometabolic risk among children. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01803776.

Validation of metabolic syndrome score by confirmatory factor analysis in children and adults and prediction of cardiometabolic outcomes in adults.

AIMS/HYPOTHESIS: We validated the metabolic syndrome (MetS) score by confirmatory factor analysis (CFA) in children, middle-aged men, and older women and men and by investigating the relationships of the MetS score to incident type 2 diabetes, myocardial infarction, and cardiovascular and overall death in middle-aged men. METHODS: We assessed the core features of MetS, calculated the MetS score using z scores for waist circumference, insulin, glucose, triacylglycerols, HDL-cholesterol and blood pressure, and carried out CFA to investigate whether MetS represents a single entity in population samples of 491 children, 1,900 middle-aged men, 614 older women and 555 older men from Finland. We also followed-up incident type 2 diabetes for 11 years and other outcomes for 17-18 years in middle-aged men. RESULTS: We carried out second-order CFAs in which the MetS was represented by a second-order latent variable underlying four latent variables characterised by abdominal obesity, insulin resistance, dyslipidaemia and raised blood pressure in different age groups. These second-order factors and factors derived from first-order CFA using previously proposed models were strongly associated with a composite MetS score in all age groups (r = 0.84-0.94) and similarly predicted type 2 diabetes, cardiovascular outcomes and mortality in middle-aged men. The risk of type 2 diabetes, myocardial infarction, cardiovascular death and overall death increased 3.67-, 1.38-, 1.56- and 1.44-fold, respectively, for a 1 SD increase in the MetS score. CONCLUSIONS: The MetS can be described as a single entity in all age groups. The MetS score is a valid tool for research evaluating cardiometabolic risk in different age groups. Further research is needed to define cut-off points for risk estimation in clinical practice.

Heart rate dynamics after combined strength and endurance training in middle-aged women: heterogeneity of responses.

The loss of complexity in physiological systems may be a dynamical biomarker of aging and disease. In this study the effects of combined strength and endurance training compared with those of endurance training or strength training alone on heart rate (HR) complexity and traditional HR variability indices were examined in middle-aged women. 90 previously untrained female volunteers between the age of 40 and 65 years completed a 21 week progressive training period of either strength training, endurance training or their combination, or served as controls. Continuous HR time series were obtained during supine rest and submaximal steady state exercise. The complexity of HR dynamics was assessed using multiscale entropy analysis. In addition, standard time and frequency domain measures were also computed. Endurance training led to increases in HR complexity and selected time and frequency domain measures of HR variability (P<0.01) when measured during exercise. Combined strength and endurance training or strength training alone did not produce significant changes in HR dynamics. Inter-subject heterogeneity of responses was particularly noticeable in the combined training group. At supine rest, no training-induced changes in HR parameters were observed in any of the groups. The present findings emphasize the potential utility of endurance training in increasing the complex variability of HR in middle-aged women. Further studies are needed to explore the combined endurance and strength training adaptations and possible gender and age related factors, as well as other mechanisms, that may mediate the effects of different training regimens on HR dynamics.