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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 p = 0.004), ghrelin concentration increased, whereas leptin, insulin, and glucose concentrations decreased compared to pre-VLED levels (p 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 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.

Funder: Opetus- ja Kulttuuriministeriö; doi: http://dx.doi.org/10.13039/501100003126, Funder: Sosiaali- ja Terveysministeriö; doi: http://dx.doi.org/10.13039/501100008487, 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 (β) = − 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 (β = − 0.0203, + 47% change in β) and butter-based spreads (β = − 0.0294, + 30% change in β), moderate-to-vigorous physical activity (β = − 0.0268, + 30% change in β), light physical activity (β = − 0.0274, + 29% change in β) and sedentary time (β = − 0.0270, + 30% change in β). 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

Blood lipid fractions serve as objective biomarkers of dietary fat intake. It is unclear which fatty acid pool most accurately reflects the dietary intakes of different n-3 PUFAs. We aimed to investigate the effect of fish and camelina sativa oil (CSO) intakes on fatty acid composition of erythrocyte membranes (EM), plasma phospholipids (PL), cholesteryl esters (CE) and triglycerides (TG). We also aimed to identify the most appropriate blood lipid fraction for assessing n-3 PUFA intake.Altogether 79 volunteers with impaired glucose metabolism were randomly assigned either to CSO, fatty fish, lean fish or control groups for 12 weeks. Fatty acid compositions of lipid pools were measured by gas chromatography. The proportion of alpha-linolenic acid (ALA) increased in all lipid pools in the CSO group (false discovery rate (FDR) p 0.001 for all). Similarly, the proportions of EPA and DHA increased in all lipid fractions in the fatty fish group (FDR p 0.001 for EM, PL and CE; FDR p = 0.005 for TG; FDR p 0.001 for EM, PL, CE; FDR p 0.007 for TG, respectively). Changes in the dietary intakes of ALA, EPA and DHA correlated with the changes in their proportions in all lipid pools (r = 0.3-0.5, p 0.05).There is no difference in the ability of blood lipid fractions in reflecting the dietary intake of different n-3 PUFAs over a time period of 12 weeks in subjects with high baseline omega-3 index. This trial was registered in Clinicaltrials.gov (NCT01768429).

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.

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 β for intervention effect −0.33 [95% CI −0.62, −0.04], p = 0.026) and HOMA-IR (β 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

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 F

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∆ (β = -0.209, P = 0.001), body fat percentage (BF%)∆ (β = -0.244, P = 0.001), insulin∆ (β = -0.220, P = 0.001), and triglycerides∆ (β = -0.164, P = 0.012) and directly with HDL cholesterol∆ (β = 0.159, P = 0.023). MVPA∆ associated inversely with CRS∆ (β = -0.178, P = 0.012), BF%∆ (β = -0.298, P =

We studied differences in physical activity (PA), sedentary behaviour (SB), and the types of PA and SB between Finnish girls and boys and children from different socioeconomic backgrounds (SES). We assessed PA, SB, parental education, and household income using detailed questionnaires in a representative population sample of 486 children (238 girls, 248 boys) aged 6-8 years. Girls spent on average 1.7 h/day and boys 2.0 h/day in total PA (p = 0.002). Altogether 66% of girls and 54% of boys had less than 2 h of total PA per day (p = 0.012). Girls had lower levels of unsupervised PA (45 vs. 54 min/day, p = 0.001), supervised PA (1.5 vs. 1.9 h/week, p = 0.009), and PA during school recess (1.8 vs. 1.9 h/week, p = 0.032) than boys. Girls had higher levels of total SB (3.8 vs. 3.4 h/day, p = 0.015) but lower levels of screen-based SB (1.5 vs. 1.9 h/day, p 0.001) than boys. Lower parental education and household income were associated with lower levels of supervised PA in girls (p = 0.011 and p = 0.008, respectively) and in boys (p = 0.006 and p = 0.003, respectively). Lower parental education and household income were also related to higher levels of screen-based SB in boys (p = 0.005 and p 0.001, respectively) but not in girls. Girls have lower levels of total, unsupervised, and supervised PA, PA during recess, and screen-based SB but higher levels of total SB than boys. Lower parental education and household income are associated with lower levels of supervised PA in both genders and higher levels of screen-based SB in boys.

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.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.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 (P0.001-0.011). 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.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.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.

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 P = 0.06, Bonferroni correction) from the observed increase in the FF group (P ICAM1 mRNA expression (P ICAM1 mRNA expression correlated positively with the intake of FF (P P IFNG mRNA expression (P 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 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.

Impaired expression of heat shock proteins (HSPs) and increased oxidative stress may contribute to the pathophysiology of diabetes by disrupted tissue protection. Acute exercise induces oxidative stress, whereas exercise training up-regulates endogenous antioxidant defenses and HSP expression. Although diabetic nephropathy is a major contributor to diabetic morbidity, information regarding the effect of HSPs on kidney protection is limited. This study evaluated the effects of eight-week exercise training on kidney HSP expression and markers of oxidative stress at rest and after acute exercise in rats with or without streptozotocin-induced diabetes. Induction of diabetes increased DNA-binding activity of heat shock factor-1, but decreased the expression of HSP72, HSP60, and HSP90. The inflammatory markers IL-6 and TNF-alpha were increased in the kidney tissue of diabetic animals. Both exercise training and acute exercise increased HSP72 and HSP90 protein levels only in non-diabetic rats. On the other hand, exercise training appeared to reverse the diabetes-induced histological changes together with decreased expression of TGF-beta as a key inducer of glomerulosclerosis, and decreased levels of IL-6 and TNF-alpha. Notably, HSP72 and TGF-beta were negatively correlated. In conclusion, impaired HSP defense seems to contribute to kidney injury vulnerability in diabetes and exercise training does not up-regulate kidney HSP expression despite the improvements in histopathological and inflammatory markers.

Objective. Insulinomas are rare pancreatic tumours. Population-based data on their incidence, clinical picture, diagnosis, and treatment are almost nonexistent. The aim of this study was to clarify these aspects in a nationwide cohort of insulinoma patients diagnosed during three decades. Design and Methods. Retrospective analysis on all adult patients diagnosed with insulinoma in Finland during 1980–2010. Results. Seventy-nine patients were diagnosed with insulinoma over the research period. The median follow-up from diagnosis to last control visit was one (min 0, max 31) year. The incidence increased from 0.5/million/year in the 1980s to 0.9/million/year in the 2000s (p=0.002). The median diagnostic delay was 13 months and did not change over the study period. The mean age at diagnosis was 52 (SD 16) years. The overall imaging sensitivity improved from 39% in the 1980s to 98% in the 2000s (p<0.001). Seventy-one (90%) of the patients underwent surgery with a curative aim, two (3%) had palliative surgery, and 6 (8%) were inoperable. There were no significant differences in the types of surgical procedures between the 1980s, 1990s, and 2000s; tumour enucleations comprised 43% of the operations, distal pancreatic resections 45%, and pancreaticoduodenectomies 12%, over the whole study period. Of the patients who underwent surgery with a curative aim, 89% had a full recovery. Postoperative complications occurred in half of the patients, but postoperative mortality was rare. Conclusions. The incidence of insulinomas has increased during the past three decades. Despite the improved diagnostic options, diagnostic delay has remained unchanged. To shorten the delay, clinicians should be informed and alert to consider the possibility of hypoglycemia and insulinoma, when symptomatic attacks are investigated in different sectors of the healthcare system. Developing the surgical treatment is another major target, in order to lower the overall complication rate, without compromising the high cure rate of insulinomas.

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 (sem6·9) years and BMI 21·9 (sem2·0) 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 (PPP

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., final draft, peerReviewed

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 6–8 years. 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 β = 0.708, p, final draft, peerReviewed

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.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.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.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.

Obesity and its consequences on cardiometabolic health have been associated to low-grade inflammation. Anthocyanins are anti-inflammatory compounds in diet, and the major group of polyphenols found in wild European blueberries, bilberries (Vaccinium myrtillus). We have studied the effects of a bilberry-rich diet on inflammation and gene expression profile in peripheral blood mononuclear cells (PBMCs) in subjects with features of the metabolic syndrome. In a randomized, controlled dietary intervention study the bilberry group (n=15) consumed bilberries or berry products equivalent to 400 g of fresh berries daily for 8 weeks, while the participants in the control group (n=12) maintained their habitual diets. Inflammatory markers were measured before and after the intervention. The microarray profiling was done from 3 subjects in the bilberry group and further QPCR expression analyses from all subjects in both groups at both timepoints. From 50 differentially expressed transcripts for mRNA (P>0.005), five candidate genes; WDSUB1, COX7B, RGS18, DAPP1 and TICAM1, were randomly selected for QPCR analyses. To further explore the interplay of dietary change and the affected pathways additional genes of LBP, TNFRSF12A, RIPK-1, Ly96 (MD2), TAB-2 (Toll-like receptor pathway); CD19, CD72 (B-cell receptor pathway) MMD, CCR2 (Monocyte and macrophage associated genes) were selected for QPCR analyses. Bilberries tended to decrease plasma concentrations of hsCRP, IL-6 and LPS (lipopolysaccharide, endotoxin). An inflammation score based on these markers and TNF-Alpha showed different trends between the bilberry and control groups. These changes were accompanied by differential expression in PBMCs of MMD and CCR2, transcripts associated with monocyte activation and recruitment, respectively. Our results indicate that high regular bilberry intake may reduce endotoxemia and chronic inflammation, the latter especially by directing the immunity away from overactive innate cell mediated responsiveness. Bilberry consumption may therefore decrease the long term risk of cardiovascular and metabolic diseases

Purpose Previous evidence for the associations of eating frequency and food consumption with clustering of metabolic risk factors among children is limited. We therefore investigated association of the daily number of main meals and snacks and food consumption with a metabolic risk score and individual metabolic risk factors in primary school children. Methods The subjects were a population sample of Finnish girls and boys 6–8 years of age. Dietary factors were measured by a four-day food record. Metabolic risk score was calculated summing up the Z-scores of waist circumference, systolic and diastolic blood pressure, and concentrations of fasting serum insulin and fasting plasma glucose, triglycerides and high-density lipoprotein cholesterol, the latest multiplying by -1. Results Skipping main meals (standardized regression coefficient b =- 0.18, P \ 0.001), a higher consumption of non-root vegetables (b = 0.18, P \ 0.01), low-fat vegetable-oil-based margarine (b = 0.13, P \ 0.01) and sugar-sweetened beverages (b = 0.11, P \ 0.05) and a lower consumption of vegetable oils (b =- 0.10, P \ 0.05) were associated with a higher metabolic risk score after adjustment for age, sex, total physical activity, electronic media time, energy intake and other dietary factors. The consumption of red meat was directly related to the metabolic risk score, but the association was not statistically significant after adjustment for energy intake. Conclusions Eating main meals regularly, decreasing the consumption of sugar-sweetened beverages and low-fat margarine and increasing the consumption of vegetable oils should be emphasized to reduce metabolic risk among children.

Summary 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.

Objective The level of physical activity (PA) of pregnant women in Finland is unknown. Even more limited is our knowledge of PA of women at high risk for gestational diabetes mellitus (GDM). Methods The women (n = 54) were randomly assigned to a lifestyle intervention group (n = 27) including exercise advice by a physiotherapist six times during pregnancy or to a control group (n = 27) without additional exercise advice. Outcomes of the present study were required sample size, timing of counselling and change of PA. PA was retrospectively reported during 12 months before pregnancy and recorded one week monthly during pregnancy. Results Individualized counselling by a physiotherapist resulted in small changes of recreational PA (2.7 MET hours/week, p = 0.056) up to gestational week 25 compared with the similar decreasing tendency of PA in the control group. The women decreased recreational PA after week 30. Sample size of 550 women at high risk for GDM per group would be needed for a PA study. Conclusions The optimal time window for increasing PA must be earlier than in the last trimester of pregnancy. Sample size for a study to increase PA by 2.7 MET hours/week on pregnant women at high risk of GDM should be about 550 per group.

Aim: Abundant evidence suggests that depression is a risk factor for cardiovascular disease and metabolic syndrome. Systemic low-grade inflammation and evolving abdominal obesity are hypothesised to be underlying mechanisms explaining the relationship. To test this hypothesis we examined the association of depressive symptoms and inflammation in developing abdominal obesity. Methods: The subjects were 726 non-diabetic men, 42–60 of age at baseline, participating in the Kuopio Ischemic Heart Disease Risk Factor Study. The follow-up data was collected 11 years after the baseline. Low-grade inflammation was defined as serum C-reactive protein ≥2 mg/l and depressive symptoms were assessed by the Human Population Laboratory Depression Scale. Incident abdominal obesity was defined as waist girth >102 cm. Results: Men with low-grade inflammation and depressive symptoms were more likely (OR 4.28, 95% CI 1.93–12.01) to develop abdominal obesity during the 11-year follow-up than in men not having either of these conditions, adjusting for age, smoking, alcohol consumption, prevalent cardiovascular disease, physical activity and socioeconomic status. These men were also more likely (OR 3.94, 95% CI 1.38–11.26) to develop metabolic syndrome. Conclusions: The presence of systemic low-grade inflammation together with depressive symptoms seems to detect men at a particularly high risk of developing abdominal obesity over a long period of time.

We studied the associations of clustering of metabolic risk factors with plasma levels of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) in healthy prepubertal children.The subjects were a representative population sample of 492 children 6-8 years of age. We assessed body fat percentage (dual-energy X-ray absorptiometry), body mass index, waist circumference, systolic and diastolic blood pressure, glucose, insulin, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, ALT, GGT, and high-sensitivity C-reactive protein (hsCRP) and calculated a continuous metabolic syndrome score variable. We also used factor analysis to examine whether high-normal liver enzymes are a feature of metabolic syndrome among children.Children with overweight or obesity, defined by International Obesity Task Force (IOTF) criteria, had a 2.1-times higher risk of having ALT and a 4.5-times higher risk of having GGT in the highest fifth of its distribution than normal weight children. Children in the highest sex-specific third of metabolic syndrome score, body fat percentage, waist circumference, and insulin had a two to three times higher risk of being in the highest fifth of ALT and GGT. Moreover, children in the highest third of glucose and hsCRP had a 2.5-fold risk of being in the highest fifth of GGT. First-order factor analysis yielded three factors; the first included insulin, glucose, and triglycerides; the second waist circumference, insulin, GGT, and hsCRP; and the third HDL-C, triglycerides, waist circumference, and insulin. Second-order factor analysis yielded a single metabolic syndrome factor, explaining 64.1% of the variance.Clustering of metabolic risk factors, particularly excess body fat, is associated with high-normal levels of ALT and GGT in prepubertal children. High-normal levels of liver enzymes, especially GGT, and systemic low-grade inflammation could be considered features of metabolic syndrome among children. Subtle changes in liver function may play an important role in the pathogenesis of metabolic syndrome beginning in childhood.

Savonen KP, Kiviniemi V, Laaksonen DE, Lakka TA, Laukkanen JA, Tuomainen T-P, Rauramaa R (Kuopio Research Institute of Exercise Medicine, Kuopio, Finland; Kuopio University Hospital, Kuopio; Information Technology Center, University of Eastern Finland, Kuopio Campus, Kuopio; Kuopio University Hospital, Kuopio; Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio Campus; Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus; and Lapland Central Hospital, Rovaniemi, Finland). Two-minute heart rate recovery after cycle ergometer exercise and all-cause mortality in middle-aged men. J Intern Med 2011; doi: 10.1111/j.1365-2796.2011.02434.x Background. A slow heart rate recovery (HRR) after an exercise test is associated with an increased risk of all-cause mortality in asymptomatic individuals, but the data regarding additional prognostic information provided by HRR beyond other exercise test variables are inconsistent. We investigated the prognostic significance of HRR for premature death, particularly in relation to other exercise test variables. Methods. The study subjects were a representative population-based sample of 1102 men (42–61 years of age) without cardiovascular disease, cancer or diabetes. HRR was defined as the difference between maximal HR and HR 2 min after a maximal symptom-limited exercise test using a cycle ergometer. The association between HRR and premature mortality was examined with Cox regression models. Results. During an average follow-up of 18 years, 238 deaths occurred. HRR was an independent predictor of death [for a decrease of 12 beats min−1, relative risk (RR) 1.16, 95% CI 1.02–1.33, P = 0.02] after adjustment for age and established risk factors. When added in a Cox model with chronotropic response (decrease of 12 beats min−1, RR 1.09, 95% CI 0.93–1.27, P = 0.26) or cardiorespiratory fitness (decrease of 12 beats min−1, RR 1.12, 95% CI 0.98–1.30, P = 0.08), the association between a slow HRR and an increased risk of death was clearly weaker. Conclusion. A slow 2-min HRR after a cycle ergometer exercise test was an independent predictor of death in healthy middle-aged men after accounting for demographic and clinical characteristics. However, it was no longer predictive after accounting for chronotropic response and exercise capacity.

Background/Objectives: To predict the health economic consequences of modest reductions in the daily intake of salt (−1.0 g per day) and replacement of saturated fat (SFA, −1.0 energy percent (E%)) with polyunsaturated fat (PUFA, +1.0 E%) in the Finnish population aged 30–74 years. Subjects/Methods: A Markov model with dynamic population structure was constructed to present the natural history of cardiovascular diseases (CVDs) based on the most current information about the age- and sex-specific cardiovascular risk factors, dietary habits and nutrient intake. To predict the undiscounted future health economic consequences of the reduction of dietary salt and SFA, the model results were extrapolated for the years 2010–2030 by replacing the baseline population in the year 2007 with the extrapolated populations from the official Finnish statistics. Finnish costs (€2009, societal perspective) and EQ-5D utilities were obtained from published references. Results: During the next 20 years, a population-wide intervention directed at salt intake and dietary fat quality could potentially lead to 8000–13 000 prevented CVD cases among the Finnish adults compared the situation in year 2007. In addition, the reduced incidence of CVDs could gain 26 000–45 000 quality-adjusted life years and save €150–225 million over the same time period. Conclusion: A modest reduction of salt and replacement of SFA with PUFA in food products can significantly reduce the burden of CVD in the adult Finnish population. This impact may be even larger in the near future due to the ageing of Finnish population.

Heat shock proteins (HSPs) are molecular chaperones which may act protective in cerebrovascular insults and peripheral diabetic neuropathy. We hypothesized that alpha-lipoic acid (LA), a natural thiol antioxidant, may enhance brain HSP response in diabetes. Rats with or without streptozotocin-induced diabetes were treated with LA or saline for 8 weeks. Half of the rats were subjected to exhaustive exercise to investigate HSP induction, and the brain tissue was analyzed. Diabetes increased constitutive HSC70 mRNA, and decreased HSP90 and glucose-regulated protein 75 (GRP75) mRNA without affecting protein levels. Exercise increased HSP90 protein and mRNA, and also GRP75 and heme oxygenase-1 (HO-1) mRNA only in non-diabetic animals. LA had no significant effect on brain HSPs, although LA increased HSC70 and HO-1 mRNA in diabetic animals and decreased HSC70 mRNA in non-diabetic animals. Eukaryotic translation elongation factor-2, essential for protein synthesis, was decreased by diabetes and suggesting a mechanism for the impaired HSP response related to translocation of the nascent chain during protein synthesis. LA supplementation does not offset the adverse effects of diabetes on brain HSP mRNA expression. Diabetes may impair HSP translation through elongation factors related to nascent chain translocation and subsequent responses to acute stress.

Thioredoxin (TRX) is a protein disulfide reductase that plays an important role in many thiol-dependent cellular reductive processes, antioxidant protection, and signal transduction. Moreover, TRX reduces and maintains the function of many proteins during oxidative stress, which is increased in diabetes. The authors recently reported that diabetes impairs brain redox status and TRX response to exercise training. As a continuation of their studies, they hypothesized that alpha-lipoic acid, a natural thiol antioxidant, has a favorable effect on the brain TRX and glutathione (GSH) system in diabetes. Streptozotocin-induced diabetes was used as a chronic model and exhaustive exercise as an acute model for disrupted redox balance. Half the diabetic and nondiabetic animals were subjected to a bout of exhaustive exercise after 8 wk with or without lipoic acid and analyzed for key thiol antioxidants. Lipoic acid neither altered diabetes-induced oxidative stress as assessed by the increased ratio of oxidized to total GSH nor had any impact on the antioxidant protein response to exercise. However, lipoic acid increased mRNA of TRX-interacting protein, an inhibitor of TRX-1, and glutaredoxin-1 in diabetes. Exercise increased TRX-1 mRNA in both diabetic and nondiabetic animals but had no effect on TRX-1 protein. Cytosolic superoxide dismutase mRNA was only increased in diabetes, whereas exercise increased the protein levels in nondiabetic animals. The findings suggest that exhaustive exercise induces mRNA of TRX-1 in the brain and that lipoic acid cannot prevent diabetes-induced disturbances in GSH homeostasis. Because lipoic acid increased TRX-interacting protein transcription in diabetes, high doses may impair TRX-1 homeostasis.

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.

Background and aims Whole-grain cereals and diets with a low glycemic index may protect against the development of type 2 diabetes and heart disease, but the mechanisms are poorly understood. We studied the effect of carbohydrate modification on serum metabolic profiles, including lipids and branched chain amino acids, and dependencies between these and specific gene expression pathways in adipose tissue. Methods and results Twenty subjects with metabolic syndrome were selected from the larger FUNGENUT study population, randomized either to a diet high in oat and wheat bread and potato (OWP) or rye bread and pasta (RP). Serum metabolomics analyses were performed using ultra-performance liquid chromatography coupled to electrospray ionization mass spectrometry (UPLC/MS), gas chromatography (GC) and UPLC. In the OWP group multiple proinflammatory lysophosphatidylcholines increased, while in the RP group docosahexaenoic acid (DHA 22:6n-3) increased and isoleucine decreased. mRNA expression of stress reactions- and adipose tissue differentiation-related genes were up-regulated in adipose tissue in the OWP group. In the RP group, however, pathways related to stress reactions and insulin signaling and energy metabolism were down-regulated. The lipid profiles had the strongest association with the changes in the adipose tissue differentiation pathway when using the elastic net regression model of the lipidomic profiles on selected pathways. Conclusion Our results suggest that the dietary carbohydrate modification alters the serum metabolic profile, especially in lysoPC species, and may, thus, contribute to proinflammatory processes which in turn promote adverse changes in insulin and glucose metabolism.

OBJECTIVE To assess the effects of leisure-time physical activity (LTPA) and resistance training on metabolic syndrome (MetS) and its components in a post hoc analysis of the Finnish Diabetes Prevention Study, a randomized controlled lifestyle counseling trial. RESEARCH DESIGN AND METHODS A cohort of 486 middle-aged overweight men and women with impaired glucose tolerance were followed for an average of 4.1 years. The intervention and control groups were combined in the analyses. LTPA was assessed by questionnaires, dietary intake by food records, and features of the MetS by anthropometric and biochemical measures annually. Resistance training sessions were documented for 137 participants. RESULTS Increased moderate-to-vigorous LTPA, even after adjustments for changes in dietary intakes of total and saturated fat, fiber, and energy, and change in BMI was associated with a greater likelihood for resolution (29.7 vs. 19.1%; P = 0.004 in the upper versus lower third of change) and a lesser likelihood for development (23.5 vs. 44.7%; P = 0.041) of the MetS. Of the components of the MetS, the increase in moderate-to-vigorous LTPA was associated most strongly with improvement of glycemia. Among the 137 participants who participated in resistance training, MetS components were favorable in individuals who were in the upper third of participation rate (median 51 times/year) compared with individuals in the lowest third (median 8.5 times/year). CONCLUSIONS Increased moderate-to-vigorous LTPA was associated with a decreased likelihood of developing the MetS and an increased likelihood of its resolution in individuals at high risk for type 2 diabetes.

Background/Aims: The common polymorphism rs9939609 of the fat mass and obesity-associated gene (FTO) is strongly associated with obesity, but the biological function is still unknown. We compared the FTO gene expression in subcutaneous adipose tissue and peripheral blood mononuclear cells (PBMCs) between overweight and normal weight individuals. We also investigated if mRNA levels of FTO in adipose tissue correlated with the adiposity or inflammatory markers and mRNA levels of genes involved in the response to hypoxia (HIF-1a) and cell death(HMGB1). Results: The mRNA expression of FTO in adipose tissue was greater in obese than normal weight individuals (p < 0.001), but there was no difference in FTO expression in PBMCs. FTO mRNA levels did not correlate with adiposity or inflammatory markers and FTO expression was not influenced by the FTO rs9939609 genotype. FTO mRNA level correlated positively with gene expression levels of HIF-1a and HMGB1 in subcutaneous adipose tissue (r = 0.59, p < 0.001; r = 0.69, p < 0.001, respectively; adjusted for BMI and adipocyte cell size). Conclusions: Altogether, FTO expression appeared not to have a well-defined impact on clinical or biochemical parameters comprising the metabolic syndrome. The correlations with the genes related to hypoxia and cell death suggest novel biological activities for FTO.

This study compared 21 weeks of combined high-intensity strength and endurance training with endurance or strength training only on metabolic risk factors in 40-65-year-old men. The healthy men (n=63) were randomized into endurance (E), strength (S), combined strength and endurance training (SE) and control (C) groups. S and E trained two times a week and SE 2+2 times a week. Systolic (SBP) and diastolic blood pressure decreased significantly both in E (-6+/-8 and -4+/-6 mmHg) and in S (-9+/-8 and -5+/-7 mmHg), but not in SE or C (P=0.003 for the difference in the changes of SBP between the groups). The changes in serum glucose and insulin during an oral glucose tolerance test did not differ between the groups. Only E decreased serum fasting insulin levels (-17+/-27%, P=0.013). Minor changes were observed in blood lipids and lipoproteins in all groups. Both endurance and strength training can modestly improve metabolic health even in relatively lean older men with normal glucose tolerance. Combined strength and endurance training did not produce complementary benefits on metabolic risk factors. Combined training is effective in improving body composition and cardiorespiratory and muscular fitness, however, which is likely to decrease the risk of future metabolic and cardiovascular disease.

As fibras dietéticas parecem contribuir tanto na prevenção quanto no tratamento do diabetes melito tipo 2 (DMT2). Em estudos epidemiológicos a ingestão de fibras insolúveis, e não de fibras solúveis, tem sido inversamente associada à incidência do DMT2. Por outro lado, em estudos pós-prandiais, refeições contendo quantidades suficientes de β-glucano, psyllium, ou goma-guar diminuíram as respostas da insulina e da glicose, tanto em indivíduos saudáveis como em pacientes com DMT2. Dietas enriquecidas com quantidade suficiente de fibras solúveis também parecem melhorar o controle glicêmico de uma forma geral no DMT2. As fibras insolúveis têm pouco efeito sobre as respostas pós-prandiais de insulina e glicose. As fibras da dieta aumentam a saciedade. Em alguns estudos, as fibras solúveis têm se associado com um menor aumento de peso corporal ao longo do tempo. Evidências limitadas, a partir de estudos transversais, sugerem uma associação inversa entre o consumo de fibras dos cereais e de grãos integrais e a prevalência de síndrome metabólica. Apesar da escassez de dados sobre estudos de mais longo prazo que foquem especificamente em fibras dietéticas, seguir a recomendação atual de 25 g de fibras ao dia, a partir de uma dieta rica em grãos integrais, frutas e legumes, provavelmente diminuirá o risco para a obesidade, síndrome metabólica e DMT2. Dietary fiber may contribute to both the prevention and treatment of type 2 diabetes mellitus (T2DM). In epidemiological studies the intake of insoluble fiber, but not the intake of soluble fiber, has been inversely associated with the incidence of T2DM. In contrast, in postprandial studies, meals containing sufficiently quantities of β-glucan, psyllium, or guar gum have decreased insulin and glucose responses in both healthy individuals and patients with T2DM. Diets enriched sufficiently in soluble fiber may also improve overall glycemic control in T2DM. Insoluble fiber has little effect on postprandial insulin and glucose responses. Fiber increases satiety. In some studies, insoluble fiber has been associated with less weight gain over time. Limited cross-sectional evidence suggests an inverse relationship between intake of cereal fiber and whole-grains and the prevalence of the metabolic syndrome. Although long-term data from trials focusing on specifically dietary fiber are lacking, meeting current recommendations for a minimum fiber intake of 25 g/d based on a diet rich in whole grains, fruits and legumes will probably decrease the risk of obesity, the metabolic syndrome and T2DM.

Purpose: Aging alters cardiac autonomic function, which may contribute to a higher risk of cardiac events. Spectral measures of HR variability (HRV) and fractal-like behavior of HR are considered as markers of a healthy heart. The present study examined the effects of combining endurance and strength training compared with endurance or strength training alone on HR dynamics and physical fitness in older previously untrained men aged 40-67 yr. Methods: Subjects were randomized into endurance training (E, n = 23), strength training (S, n = 25), combined endurance and strength training (ES, n = 29), or control group (C, n = 16). Short-term fractal scaling exponent ([alpha]1) and spectral HRV were analyzed from maximal aerobic cycling tests and during supine rest, and leg extension one repetition maximum strength was measured. Results: Aerobic capacity and maximal strength increased in the training groups performing endurance and/or strength training, respectively. Only ES showed a decrease after training in fractal HR behavior during exercise, and the difference was significant between groups (P = 0.019). During supine rest, [alpha]1 only decreased significantly (P = 0.039) in ES from 1.18 (SD = 0.20) to 1.11 (SD = 0.21). The decrease in [alpha]1 at rest from 1.21 (SD = 0.19) to 1.11 (SD = 0.22) also approached significance (P = 0.061) in E. Changes in spectral measures of HRV were minor during the study period and only occurred during exercise. Conclusion: Fractal HR dynamics were improved more by combining strength training with endurance training in our older men compared with endurance training alone, although strength training alone produced no changes in fractal HR behavior. The synergistic effect in fractal HR behavior occurred regardless of changes in aerobic capacity

Good cardiorespiratory fitness has been found to protect against cardiovascular diseases and type 2 diabetes. The purpose of this study was to investigate determinants of directly measured cardiorespiratory fitness (maximal oxygen uptake [Vo 2max ]), including age, body composition, prevalent diseases, cardiovascular and pulmonary functions, biochemical factors, physical activity, nutrition, smoking, and alcohol consumption, in a population-based study of 936 men 42 to 60 years of age. Variables that had the strongest direct associations with Vo 2max (milliliters per minute) in a linear multivariate step-up regression model were body weight, heart rate at maximal exercise, mean intensity and frequency of conditioning physical activity, intake of carbohydrates, blood hemoglobin, and forced expiratory volume in 1 second. The strongest inverse associations with Vo 2max were heart rate at rest, age, fasting serum insulin, waist-to-hip ratio, coronary heart disease, and asthma. This model accounted for 67% of the variation of Vo 2max . In conclusion, mean intensity, frequency, and duration of conditioning physical activity were associated directly with Vo 2max . However, measurements of the function of pulmonary and cardiovascular systems, carbohydrate intake, and body composition were powerful determinants of cardiorespiratory fitness, especially in older middle-aged men.

Hypertrophy of the left ventricle is a diagnostic dilemma in subjects who engage in regular endurance exercise. We studied prospectively whether endurance training in previously sedentary young and middle-aged men and women can alter left ventricular (LV) characteristics. We recruited 33 healthy young and middle-aged subjects (18 women, 15 men, ages 21 to 59 years) to undergo 12 weeks of home-based brisk walking and jogging at a target heart rateor =120 beats/min foror =30 minutes 3 times a week. LV characteristics were measured by cine magnetic resonance imaging. Training intensity as estimated by heart rate correlated positively with the increase in LV myocardial area (r = 0.51, p = 0.005) in the 28 men and women completing the study. In the 13 men and women who trained with heart rate ofor =120 beats/min, LV myocardial area was larger after than before training (17.7 +/- 2.9 vs 16.8 +/- 2.8 cm(2), p0.05). Moreover, in these subjects LV myocardial area increased more (5.5 +/- 9.0% vs -3.0 +/- 5.0%) than in the 15 men and women who trained at a lower intensity (p0.05). LV end-systolic and end-diastolic area and ejection fraction did not change significantly. In conclusion, moderate-to-vigorous endurance training at moderate volumes does not influence LV end-diastolic volume or ejection fraction, but has a minor influence on LV hypertrophy in previously sedentary young and middle-aged men and women.

Viscous fibers, including β-glucan in oat bran, favorably affect satiety as well as postprandial carbohydrate and lipid metabolism. However, effects of fiber viscosity on modulation of satiety-related gut hormone responses are largely unknown. We examined the effects of modified oat bran, with or without its natural viscosity, on sensations of appetite and satiety-related gastrointestinal (GI) hormone responses to establish the relevance of viscosity of β-glucan in oat bran. Twenty healthy, normal-weight participants (16 female, 4 male, aged 22.6 ± 0.7 y) ingested 2 isocaloric (1250 kJ) 300-mL oat bran beverages with low or high viscosity (carbohydrates, 57.9 g; protein, 7.8 g; fat, 3.3 g; fiber, 10.2 g) after a 12-h fast in randomized order. Viscosity of the low-viscosity oat bran beverage was reduced by β-glucanase treatment. Blood samples were drawn before and 15, 30, 45, 60, 90, 120, and 180 min after beverage consumption. The oat bran beverage with low viscosity induced a greater postprandial increase in satiety (P = 0.048) and plasma glucose (P < 0.001), insulin (P = 0.008), cholecystokinin (P = 0.035), glucagon-like peptide 1 (P = 0.037), and peptide YY (P = 0.051) and a greater decrease in postprandial ghrelin (P = 0.009) than the beverage with high-viscosity oat bran. Gastric emptying as measured by paracetamol absorption was also faster (P = 0.034) after low-viscosity oat bran beverage consumption. In conclusion, viscosity differences in oat β-glucan in a liquid meal with identical chemical composition strongly influenced not only glucose and insulin responses, but also short-term gut hormone responses, implying the importance of food structure in the modulation of postprandial satiety-related physiology.

Aims: Recent studies have shown that lack of hope is linked to cardiovascular morbidity and mortality. Little is known, however, about the relationship of hopelessness and the metabolic syndrome. The aim of this study is to examine the association of hopelessness and the metabolic syndrome. Methods: This cross-sectional study examines the relationship between hopelessness and the metabolic syndrome as defined by the National Cholesterol Education Program in a population-based cohort of 1743 non-diabetic men aged 42, 48, 54 and 60 years old at baseline (1984—89). Hopelessness was measured by one's expectations about the future and reaching goals. Results: In simple age-adjusted univariate analyses the prevalence of the metabolic syndrome, many of its components and other cardiovascular risk factors were more common in men with higher levels of hopelessness. In a logistic regression model adjusted for age, smoking, alcohol consumption, cardiovascular disease, adult socioeconomic status and physical activity, men in the highest third were 2.1 (95% CI 1.3—3.2) times more likely to have the metabolic syndrome than those in the lowest third. After further adjusting for body mass index and elevated depressive symptoms the respective figures were 1.9 (95% CI 1.2—3.1) and 2.1 (95% CI 1.4—3.4). Conclusions: Hopelessness was strongly associated with the metabolic syndrome in these middle-aged men, independent of other depressive symptoms and traditional cardiovascular risk factors. These findings suggest that hopelessness is very closely related to the metabolic syndrome. Therefore lifestyle management of the metabolic syndrome should also take into account patients' expectations more thoroughly than hitherto acknowledged.

The transcription factor nuclear factor-kappa-B (NFkappaB) is implicated in inflammatory responses, obesity and the metabolic syndrome, while immune cells appear to play a central role in mediating insulin resistance and can be used as a model to study inflammation and its relationship with insulin resistance. In peripheral blood mononuclear cells of overweight participants with the metabolic syndrome, we evaluated (1) the effect of diet-induced weight loss on the expression of genes involved in NFkappaB activation and (2) their association with insulin sensitivity. The genes studied were: TNF receptors TNFRSF1A and TNFRSF1B, and IL1R1, TLR4, TLR2, ICAM1, CCL5 and IKBKB.We analysed data from 34 overweight participants with abnormal glucose metabolism and the metabolic syndrome, who were randomised to a weight-reduction (n = 24) or control group (n = 10) for 33 weeks. The mRNA expression was measured using real-time PCR. Measures of insulin and glucose homeostasis were assessed by IVGTT and OGTT.In general, the genes studied were downregulated after weight loss intervention. The changes in TLR4, TLR2, CCL5 and TNFRSF1A mRNA expression were associated with an increase in insulin sensitivity index independently of the change in waist circumference (p0.05). The change in IKBKB expression correlated with most of the changes in gene expression in the weight-reduction group.These results suggest that proteins encoded by CCL5, TLR2 and TLR4, and TNFRSF1A might contribute to insulin-resistant states that characterise obesity and the metabolic syndrome.ClinicalTrials.gov NCT 00621205.

OBJECTIVE—We studied the associations of cardiorespiratory fitness with metabolic syndrome in older men and women, because such data are limited in representative population samples. RESEARCH DESIGN AND METHODS—We studied a population sample of 671 men and 676 women aged 57–79 years at baseline of a randomized controlled intervention study. We assessed maximal oxygen uptake (Vo2max) by respiratory gas analysis during a maximal bicycle exercise test. RESULTS—Vo2max had a strong, inverse, and graded association with the risk of having metabolic syndrome as defined by the National Cholesterol Education Program criteria. Men and women in the lowest third of Vo2max had 10.2- and 10.8-fold higher risks and those in the middle third had 2.9- and 4.7-fold higher risks (P < 0.001 all) of metabolic syndrome than those with the highest Vo2max after multivariable adjustments. Factor analysis generated a principal factor that was strongly loaded by the main components of metabolic syndrome and Vo2max (−0.68 in men and −0.70 in women). CONCLUSIONS—Low cardiorespiratory fitness is associated with metabolic syndrome in older men and women. Our findings suggest that low cardiorespiratory fitness could be considered a feature of metabolic syndrome.

Aims Dyslipidaemia and hypertension are features of the metabolic syndrome, but the role of dyslipidaemia in the development of hypertension is less clear. We assessed the association of dyslipidaemia with incident hypertension during a 7-year follow-up in a population-based cohort of middle-aged men without hypertension at baseline. Methods and results In all, 88 of 311 men developed hypertension during the follow-up. A 1-SD increment in triglyceride concentrations was associated with a 1.6-fold [95% CI(confidence interval) 1.2–2.3] increased risk of developing hypertension, independently of features related to the metabolic syndrome. In separate multivariable models, the triglyceride content of high-density lipoprotein (HDL) cholesterol and apolipoprotein B concentrations were also associated with new-onset hypertension. In a stepwise backwards logistic regression model, concentrations of low-density lipoprotein (LDL) cholesterol [odds ratio (OR) 1.3, 95% CI 1.0–1.7 for a 1-SD change] and triglyceride content of HDL cholesterol (OR) 1.5, 95% CI 1.1–1.9) were positively associated with incident hypertension, whereas HDL concentrations (OR 0.7, 95% CI 0.5–0.9) seemed protective. In factor analyses, elevated triglyceride levels and related disturbances in lipid and cholesterol metabolism were associated with new-onset hypertension. Conclusion Dyslipidaemia characteristic of the metabolic syndrome predicts the development of hypertension during a 7-year follow-up of eastern Finnish men, independently of features related to insulin resistance. The recognition of dyslipidaemia and initiation of lifestyle treatment even in the absence of hypertension is likely to reduce the long-term burden of cardiovascular disease.

PURPOSE: This study examined adaptations in body composition and physical fitness during a 21-wk strength and/or endurance training period in 40- to 65-yr-old men. We also compared the usefulness of different methods for the analysis of body composition to detect training-induced adaptations. METHODS: Fifty-three men were randomized into the endurance training (E: N = 14), strength training (S: N = 13), combined strength and endurance training (SE: N = 15), or control (C: N = 11) groups. S and E trained 2 and SE 2 x 2 times a week for strength and endurance. RESULTS: Percentage of fat (fat%) decreased (5-8%) similarly in all training groups. Fat% measured by DXA at baseline and its change correlated with those recorded by bioimpedance (r = 0.90 and 0.66), skinfolds (r = 0.80 and 0.78), and waistline (r = 0.84 and 0.74). Lean mass in legs (DXA) increased only in S (2.0 +/- 1.5%, P < 0.001), but the thickness of vastus lateralis and intermedius measured by ultrasound increased (7-11%) in all training groups, and that of triceps brachii increased in S (22%) and SE (20%). Maximal concentric force increased significantly in S, SE, and E (by 22, 23, and 7%), and maximal oxygen uptake increased in both E (11%) and SE (11%). CONCLUSIONS: Waist circumference and skinfold thickness seem to reasonably assess changes in percent body fat during training. However, only DXA was capable to separate small differences between the groups in training-induced changes in lean body mass. Combined strength and endurance training is of greater value than either alone in optimizing body composition or improving physical fitness in older men.

BACKGROUND: Inflammation may be a mechanism by which high postprandial insulin and glucose responses increase the risk of type 2 diabetes mellitus. OBJECTIVE: We hypothesized that dietary carbohydrates characterized by different postprandial insulin responses may differentially modify cytokine concentrations in plasma and gene expression in subcutaneous adipose tissue. DESIGN: Individuals (n = 47) with the metabolic syndrome were randomly assigned to a 12-wk diet with oat and wheat bread and potato (high postprandial insulin response) or rye bread and pasta (low postprandial insulin response). Postprandial glucose and insulin responses to the oat and wheat bread meal and to the rye bread meal were determined in 19 individuals before intervention. RESULTS: During the 12-wk diet, the change in the gene expression of interleukin (IL)-10 receptor alpha and tumor necrosis factor-alpha in subcutaneous adipose tissue differed between the groups (P = 0.002 and P = 0.083, respectively). Moreover, the change in fasting plasma concentrations of IL-1beta and IL-6 differed between the groups (P = 0.020 and P = 0.055, respectively). In the postprandial challenge, the insulin response to the rye bread meal was lower than that to the oat and wheat bread meal (P < 0.001), whereas there were no differences in the mean blood glucose response. In contrast, plasma glucose concentrations decreased more below fasting concentrations 2.5-3 h after the oat and wheat bread meal than after the rye bread meal. A late postprandial rebound of free fatty acids was detected after the oat and wheat bread meal (P = 0.048). CONCLUSIONS: Long-term intake of cereal foods with differing postprandial insulin responses may be a factor that modulates the inflammatory status in individuals with the metabolic syndrome.

ObjectiveWe examined the expression of ghrelin and ghrelin receptors in peripheral blood mononuclear cells (PBMCs) and evaluated the effect of weight loss or exercise on plasma ghrelin concentrations in subjects with the metabolic syndrome.Design and methodsData from 75 overweight/obese subjects randomized to a weight loss, aerobic exercise, resistance exercise or control group for a 33-week intervention period were analysed. The plasma ghrelin concentrations and indices of insulin and glucose metabolism were assessed, and mRNA expression of ghrelin, its receptors and various cytokines in PBMCs was studied using real-time PCR.ResultsGhrelin and GH secretagogue receptor 1b were expressed in PBMCs of subjects with metabolic syndrome. Ghrelin gene expression correlated positively with the expressions of tumour necrosis factor-α (PPP=0.026) during the study, but was not associated with the plasma ghrelin concentration. Genotype-specific ghrelin gene expression in PBMCs was found for the −604G/A and the −501A/C polymorphisms in the ghrelin gene. At baseline, the plasma ghrelin levels were associated with fasting serum insulin concentrations, insulin sensitivity index and high-density lipoprotein cholesterol. However, longitudinally weight, BMI or waist circumference and acute insulin response in i.v. glucose tolerance test were stronger predictors of the ghrelin concentration. Plasma ghrelin did not change over the study period in the weight reduction group, but it tended to decrease in the control group (P=0.050).ConclusionsGhrelin mRNA expression in PBMCs suggests an autocrine role for ghrelin within an immune microenvironment. Moderate long-term weight loss may prevent a decline in ghrelin concentration over time in individuals with metabolic syndrome.

Inflammation is associated with obesity, the metabolic syndrome, and diabetes. No data are available on the effect of weight reduction on the gene expression of cytokines in immune cells in obesity and the metabolic syndrome. We assessed how long-term weight loss affects expression of cytokines in peripheral blood mononuclear cells (PBMCs) in individuals with impaired glucose metabolism and the metabolic syndrome. Data from 34 subjects randomized to either a weight reduction or a control group for a 33-week period were analyzed. The messenger RNA (mRNA) expression of interleukins (ILs) in PBMCs was measured using real-time polymerase chain reaction. Measures of insulin and glucose metabolism (intravenous and oral glucose tolerance tests), body composition, and circulating adipokines and inflammatory markers were also assessed. Weight reduction resulted in a decrease in the mRNA expression of IL-1beta (IL1B), IL-1 receptor antagonist, and tumor necrosis factor alpha (P < .001) and an increase in expression of IL-6 (IL6) and IL-8 (P < .01). The increase in IL6 expression was associated with a decrease in fasting glycemia (r = -0.53, P < .01). Interestingly, the decrease in IL1B expression was correlated with an increase in insulin sensitivity index (r = -0.68, P < .01). In general, a decrease in circulating levels of adipokines and inflammatory markers was also observed after weight loss. Weight loss altered gene expression of cytokines related to inflammation and the immune response in PBMCs. Changes in IL6 mRNA expression were associated with changes in fasting glycemia. The decrease in IL-1 receptor antagonist expression after weight loss and the strong correlation between the decrease in IL1B expression and the increase in insulin sensitivity suggest a contribution of these genes to insulin-resistant states found in obesity and the metabolic syndrome.