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.

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.

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.

Low-grade inflammation and depressive symptoms as predictors of abdominal obesity.

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.

Clustering of metabolic risk factors is associated with high-normal levels of liver enzymes among 6- to 8-year-old children: the PANIC study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Clinical signs of temporomandibular disorders and various pain conditions among children 6 to 8 years of age: the PANIC study.

AIMS: To examine the prevalence and significance of clinically determined signs of temporomandibular disorders (TMD) and pain in different parts of the body as well as the frequency, intensity, and other features of pain in children. METHODS: The subjects were a population-based sample of children 6 to 8 years of age. Complete data on clinical signs of TMD were available for 483 children. Data on pain during the past 3 months, assessed by a questionnaire administered by parents, were available for 424 children. Differences between the prevalence of at least one sign of TMD and the location or frequency of pain were evaluated using the chi-square test, as well as the associations between the prevalence, frequency, and location of pain and gender, the use of medication, and visits to a physician. The relationship of various pain conditions with the risk of having clinical signs of TMD was analyzed using logistic regression. RESULTS: Of the 483 children, 171 (35%) had at least one clinical sign of TMD. Of the 424 children, 226 (53%) had experienced pain during the past 3 months. Pain was most prevalent in the lower limbs (35%) and head (32%). Of the 226 children with pain, 119 (53%) had experienced frequent pain (≥ once a week). No gender differences were found. The risk of having at least one clinical sign of TMD was 3.0 (95% confidence intervals [CI]: 1.1-8.5, P < .05) times higher in children with back pain, 2.7 (95% CI: 1.2-6.0, P < .05) times higher in children with neck-shoulder pain, and 1.6 (95% CI: 1.1-2.5, P < .05) times higher in children with headache compared to children without these pain symptoms. The risk of having at least one clinical sign of TMD was 12.2 (95% CI: 1.4-101.8, P < .01) times higher among children with palpation tenderness in trapezius muscles than among those without it. CONCLUSION: Clinical signs of TMD and pain symptoms are common in children. The relationship of back pain, neck-shoulder muscle palpation tenderness, and headache with clinical signs of TMD suggests that more attention should be paid to stomatognathic function in children with such pain problems.

Adverse childhood experiences and risk of binge drinking and drunkenness in middle-aged finnish men.

Objective. The purpose of this study was to investigate associations between adverse childhood experiences and binge drinking and drunkenness in adulthood using both historical and recalled data from childhood. Methods. Data on childhood adverse experiences were collected from school health records and questionnaires completed in adulthood. Adulthood data were obtained from the baseline examinations of the male participants (n = 2682) in the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) in 1984-1989 from eastern Finland. School health records from the 1930s to 1950s were available for a subsample of KIHD men (n = 952). Results. According to the school health records, men who had adverse childhood experiences had a 1.51-fold (95% CI 1.05 to 2.18) age- and examination-year adjusted odds of binge drinking in adulthood. After adjustment for socioeconomic position in adulthood or behavioural factors in adulthood, the association remained unchanged. Adjustment for socioeconomic position in childhood attenuated these effects. Also the recalled data showed associations with adverse childhood experiences and binge drinking with different beverages. Conclusions. Our findings suggest that childhood adversities are associated with increased risk of binge drinking in adulthood.

Reproducibility of pulse contour analysis in children before and after maximal exercise stress test: the Physical Activity and Nutrition in Children (PANIC) study.

OBJECTIVE: Arterial stiffness index (SI) and reflection index (RI) from digital pulse contour analysis have been shown to be good measures of arterial stiffness and may be useful in the evaluation of endothelial function. Finger skin temperature (FST) is also considered to reflect peripheral circulatory functions. We evaluated the reproducibility of SI, RI and FST before and after the exercise stress test. METHODS: The subjects were 36 children (16 boys, 20 girls) 6-8 years of age. We measured SI, RI and FST at rest both before and after the exercise stress test on a cycle ergometer and repeated these measurements within 5-14 days. The reproducibility of SI, RI and FST was evaluated by calculating intraclass correlation coefficients (ICC), coefficients of variation (CV%) and 95% limits of agreements. RESULTS: SI had a greater reproducibility after the exercise stress test than before it (CV% 4·8 versus 6·3%, ICC 0·548 versus 0·438). RI had a better ICC (0·689 versus 0·416) but a higher CV% (28·6 versus 18·7%) after the exercise stress test than before it. Relative change in response to the exercise stress test in SI (-1·5% at first visit and 0·4% at second visit) was not as dramatic as in RI (-49·3% at first visit and -46·5% at second visit). The reproducibility of FST was also better after the exercise test than before it (CV% 5·7 versus 10·0%, ICC 0·509 versus 0·503). CONCLUSION: In healthy children, the reproducibility of SI, RI and FST was relatively good, especially after the exercise stress test.

The TNF-alpha G-308A polymorphism is associated with C-reactive protein levels: the HERITAGE Family Study.

OBJECTIVE: Pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), stimulate the release of C-reactive protein (CRP). We investigated the association between the TNF-alpha G-308A polymorphism and plasma CRP levels. METHODS: Subjects were 456 White (225 men, 231 women) and 232 Black (83 men, 149 women) healthy adults who underwent a 20-week standardized exercise program in the HERITAGE Family Study. The TNF-alpha gene promoter polymorphism was determined using PCR amplification followed by NcoI digestion. Plasma CRP was measured using a high-sensitivity assay. RESULTS: Genotype frequencies were in Hardy-Weinberg equilibrium. After adjustment for age, smoking, alcohol consumption, maximal oxygen uptake and, in women, hormone use, the AA homozygotes for the G-308A polymorphism had higher baseline CRP levels than other genotypes in White and Black men (P<0.001 and P = 0.044, respectively) and in Black women (P = 0.032). Body mass index partly explained these associations in Blacks. The exercise program results provided further evidence for an association with the polymorphism. Among those with high CRP at baseline (> or = 3.0 mg/L), regular exercise decreased CRP less in AA homozygotes than in other genotypes (P = 0.043). CONCLUSION: The AA genotype of the TNF-alpha G-308A polymorphism is associated with higher plasma CRP levels and less favorable CRP response to regular exercise.

Social disadvantages in childhood and risk of all-cause death and cardiovascular disease in later life: a comparison of historical and retrospective childhood information.

BACKGROUND: Childhood socioeconomic circumstances have been shown to contribute to adult mortality. The purpose of this study was to compare the association between objective historical records and recalled questionnaire-based information on childhood socioeconomic position (SEP) with regard to cardiovascular and all-cause mortality. METHODS: We examined the association between a socially disadvantaged childhood and all-cause mortality, cardiovascular disease (CVD) mortality, coronary heart disease (CHD) mortality, and acute coronary events among male participants in the Kuopio Ischemic Heart Disease (KIHD) Risk Factor Study, a population-based cohort study in eastern Finland with follow-up until 2002. The historical data on childhood factors were collected from school health records (n = 698), mainly from the 1930s to the 1950s. Recall data on socioeconomic conditions in childhood were obtained from the baseline examinations of the KIHD cohort (n = 2,682) in 1984-89. RESULTS: According to original school health records the men who were socially disadvantaged in childhood had a 1.41-fold (95% confidence interval 1.01-1.97) age-adjusted and examination-year-adjusted risk of all-cause death, a 1.32-fold (0.83-2.11) risk of CVD death, a 1.48-fold (0.85-2.57) risk of CHD death, and a 1.50-fold (1.02-2.20) risk of acute coronary events. After adjustment for biological and behavioural risk factors and for the SEP in adulthood the association was attenuated in all-cause death but did not change in CVD death, CHD death, and acute coronary events. On the contrary, the questionnaire-based recalled childhood data on childhood SEP showed no associations with mortality or acute coronary events. CONCLUSIONS: With regard to adult mortality, the use of historical records concerning hygiene and living conditions collected in childhood may either provide more accurate measures of early-life socioeconomic conditions or capture more relevant aspects of childhood socioeconomic disadvantage than retrospective recall data.

Lifestyle management in the metabolic syndrome.

Type 2 diabetes and metabolic syndrome are two of the fastest growing public health problems in both developed and developing countries. Cardiovascular disease is the most prevalent complication of type 2 diabetes and the metabolic syndrome. Overweight, obesity, or weight gain has been shown to be an important risk factor for the development of type 2 diabetes and an important component of the metabolic syndrome. Physical inactivity is another important risk factor for the development of type 2 diabetes. Data from prospective studies have shown that at least 30 min/day of moderate to vigorous physical activity can prevent type 2 diabetes. Moderate or high levels of physical fitness are effective in preventing type 2 diabetes. Results from clinical trials have indicated that lifestyle changes, including dietary modification and increase in physical activity, can prevent type 2 diabetes. Analyses from prospective studies have confirmed that healthy diets are effective and safe ways to prevent type 2 diabetes and the metabolic syndrome. Public health messages, health care professionals, and the health care system should aggressively promote physical activity and responsible nutritional habits during occupation, leisure time, and daily life and prevent overweight and obesity.

Effect of exercise training on plasma levels of C-reactive protein in healthy adults: the HERITAGE Family Study.

AIMS: To study the effect of exercise training on plasma C-reactive protein, a marker of inflammation. METHODS AND RESULTS: We performed a 20 week standardized exercise training programme in 652 sedentary healthy white and black men and women. C-reactive protein was measured with a high sensitivity assay. The study sample was stratified according to baseline C-reactive protein levels using a recommended classification (low <1.0 mg/L, n=265; moderate 1.0-3.0 mg/L, n=225; high >3.0 mg/L, n=162). The median C-reactive protein reduction was 1.34 mg/L in the high baseline C-reactive protein group. C-reactive protein levels did not change in the low or moderate baseline C-reactive protein groups. The difference among the C-reactive protein groups was significant adjusting for all correlates of baseline C-reactive protein (P<0.001) and additionally for changes in body weight, glucose, insulin, LDL cholesterol, HDL cholesterol, triglycerides, systolic and diastolic blood pressure, and maximal oxygen uptake (P<0.001). The C-reactive protein reduction in the high baseline C-reactive protein group was consistent across all population groups (P<0.001 for difference among baseline C-reactive protein groups). CONCLUSION: Plasma C-reactive protein levels are reduced in response to exercise training in sedentary healthy adults with high initial C-reactive protein levels. This finding may partly explain the effectiveness of regular physical activity in the prevention and treatment of cardiovascular and metabolic diseases.

Epidemiology and treatment of the metabolic syndrome.

Recent definitions of the metabolic syndrome from the World Health Organization (WHO) and National Cholesterol Education Program (NCEP) have given us a clearer picture of the prevalence of the metabolic syndrome and the risks it poses for cardiovascular disease and type 2 diabetes. Solid epidemiological and trial evidence support lifestyle changes as the main modifiable risk factors, including abdominal obesity, sedentary lifestyle and a diet rich in saturated fat and low in fiber content, in the treatment of individual components of the metabolic syndrome. Physical activity may prevent the metabolic syndrome as defined by the WHO and NCEP, but the evidence for lifestyle changes using these definitions is still sparse. No trials on the treatment of the metabolic syndrome to prevent diabetes have been published. However, both the Finnish Diabetes Prevention Study and the Diabetes Prevention Program found that moderate lifestyle interventions in persons with impaired glucose tolerance, a condition related to the metabolic syndrome. decreased the incidence of type 2 diabetes by 58%. Some drugs may also prevent diabetes. Further research on lifestyle modifications in the prevention and treatment of the metabolic syndrome, and on how best to promote lifestyle changes, is needed. In the meantime, efforts to curb obesity and overweight, increase physical activity and improve compliance with current dietary recommendations should continue.

Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study.

BACKGROUND: Despite abundant epidemiologic evidence, the role of elevated serum uric acid level as a cardiovascular risk factor is controversial. We assessed the predictive value of serum uric acid levels for cardiovascular and overall mortality. METHODS: A population-based prospective cohort study was performed of 1423 middle-aged Finnish men initially without cardiovascular disease, cancer, or diabetes. The main outcome measure was death from cardiovascular disease and any cause. RESULTS: The mean follow-up was 11.9 years. There were 157 deaths during follow-up, of which 55 were cardiovascular. In age-adjusted analyses, serum uric acid levels in the upper third were associated with a greater than 2.5-fold higher risk of death from cardiovascular disease than levels in the lower third. Taking into account cardiovascular risk factors and variables commonly associated with gout increased the relative risk to 3.73. Further adjustment for factors related to the metabolic syndrome strengthened the risk to 4.77. Excluding the 53 men using diuretics did not alter the results. In age-adjusted analyses, men with serum uric acid levels in the upper third were 1.7-fold more likely to die of any cause than men with levels in the lower third. Adjustment for further risk factors strengthened the association somewhat. CONCLUSIONS: Serum uric acid levels are a strong predictor of cardiovascular disease mortality in healthy middle-aged men, independent of variables commonly associated with gout or the metabolic syndrome. Serum uric acid measurement is an easily available and inexpensive risk marker, but whether its relationship to cardiovascular events is circumstantial or causal remains to be answered.

Leptin and leptin receptor gene polymorphisms and changes in glucose homeostasis in response to regular exercise in nondiabetic individuals: the HERITAGE family study.

We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects. We tested the hypothesis that common exonic variants in the leptin (LEP) and leptin receptor (LEPR) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018). We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010). The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019). The decrease in insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R allele. Similar interaction was observed in blacks (P = 0.046). Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals.

Effects of long-term negative energy balance with exercise on plasma lipid and lipoprotein levels in identical twins.

Plasma lipid and lipoprotein concentrations were measured before and after a 58,000kcal (244MJ) negative energy balance protocol induced entirely by supervised endurance exercise over a 93-day period in seven pairs of young sedentary and healthy male monozygotic twins. The negative energy balance induced significant changes in all measures of body weight and composition except fat free mass. The mean weight loss was 5.0+/-0.6kg, and it was entirely accounted for by the loss of body fat. In response to the program, improvement in the plasma lipid profile was seen including decreases in plasma total (P=0.028) and low density lipoprotein (LDL) (P=0.004) cholesterol; total cholesterol/high density lipoprotein (HDL) cholesterol ratio (P=0.002); and HDL apolipoprotein A-I concentration (P=0.062). Statistically significant within-pair resemblance was found for the changes in total and very low density lipoprotein (VLDL) cholesterol; total, VLDL and LDL triglycerides, and total, VLDL and LDL apolipoprotein B. The findings suggest that favorable changes in the lipid profile can be obtained through chronic negative energy balance achieved by clamping daily energy intake and adding daily moderate intensity exercise even in persons with relatively normal lipid levels at baseline. Furthermore, within-pair resemblance among twin brothers strongly suggests that genetic differences partially account for the variation in the response of lipids and lipoproteins to the negative energy balance protocol.

Sedentary lifestyle, poor cardiorespiratory fitness, and the metabolic syndrome.

PURPOSE: The cross-sectional associations of leisure-time physical activity (LTPA) and cardiorespiratory fitness with the metabolic syndrome (MS) were investigated in a population-based sample of 1069 middle-aged men without diabetes, cardiovascular disease, or cancer. METHODS: LTPA was assessed using a detailed quantitative questionnaire. Maximal oxygen uptake VO(2max) and core and related features of the MS were determined. A modified World Health Organization definition of the MS and factor analysis were used. RESULTS: Men who engaged in at least moderate-intensity (>or=4.5 metabolic equivalents) LTPA <1.0 h.wk-1 were 60% more likely to have the MS than those engaging in >or= 3.0 h.wk-1 even after adjustment for confounders. Low-intensity (<4.5 metabolic equivalents) LTPA was not associated with the metabolic syndrome. Men with a VO(2max) <29.1 mL x kg-1 x min-1 were almost seven times more likely to have the MS than those with a VO(2max) >or=35.5 mL.kg-1.min-1 even after adjusting for confounders. In first-order factor analysis using a promax rotation, the principal factor explained 20% of total variance and had heavy loadings for VO(2max) (-0.57) and at least moderate-intensity LTPA (-0.44), and moderate or heavy loadings for the main components of the MS. The second-order factor analysis generated a principal factor that was strongly loaded on by the main components of the MS and VO(2max) (-0.50) but not LTPA. CONCLUSION: A sedentary lifestyle and especially poor cardiorespiratory fitness are not only associated with the MS but could also be considered features of the MS. Measurement of VO(2max) in sedentary men with risk factors may provide an efficient means for targeting individuals who would benefit from interventions to prevent the MS and its consequences.

Cardiorespiratory fitness and vigorous leisure-time physical activity modify the association of small size at birth with the metabolic syndrome.

OBJECTIVE: Small size at birth has been associated with components of the metabolic syndrome, but little is known about the association with the metabolic syndrome itself or whether leisure-time physical activity (LTPA) and cardiorespiratory fitness modify that association. We studied the association of size at birth with the metabolic syndrome. RESEARCH DESIGN AND METHODS: Birth weight and length, the metabolic syndrome (World Health Organization criteria), LTPA over the previous 12 months, and VO(2max) were assessed in 462 nondiabetic middle-aged Finnish men who were part of a population-based cohort study. RESULTS: Men with a ponderal index (kg/m(3)) at birth in the lower third had higher fasting insulin and glucose levels than men in the upper third in age-adjusted analyses and were at least twofold more likely to have the metabolic syndrome, even in men without cardiovascular disease. Adjustment for childhood or adult socioeconomic status or adult BMI did not attenuate the association. Thinness at birth was even more clearly associated with hyperinsulinemia and the metabolic syndrome in men engaging in <25 min/wk of vigorous LTPA and in men with a VO(2max) <28.6 ml x kg(-1) x min(-1) or <2.44 l/min. In active and fit men, however, the association was absent. CONCLUSIONS: Small size at birth was associated with the metabolic syndrome in middle-aged men already before development of diabetes or cardiovascular disease. Thinness at birth may carry with it lifelong metabolic consequences, but regular strenuous physical activity and maintenance of cardiorespiratory fitness may alleviate or eliminate those consequences.

Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression: the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study.

BACKGROUND: Self-selected supplementation of vitamin E has been associated with reduced coronary events and atherosclerotic progression, but the evidence from clinical trials is controversial. In the first 3 years of the ASAP trial, the supplementation with 136 IU of vitamin E plus 250 mg of slow-release vitamin C twice daily slowed down the progression of carotid atherosclerosis in men but not women. This article examines the 6-year effect of supplementation on common carotid artery (CCA) intima-media thickness (IMT). METHODS AND RESULTS: The subjects were 520 smoking and nonsmoking men and postmenopausal women aged 45 to 69 years with serum cholesterol > or =5.0 mmol/L (193 mg/dL), 440 (84.6%) of whom completed the study. Atherosclerotic progression was assessed ultrasonographically. In covariance analysis in both sexes, supplementation reduced the main study outcome, the slope of mean CCA-IMT, by 26% (95% CI, 5 to 46, P=0.014), in men by 33% (95% CI, 4 to 62, P=0.024) and in women by 14% (not significant). In both sexes combined, the average annual increase of the mean CCA-IMT was 0.014 mm in the unsupplemented and 0.010 mm in the supplemented group (25% treatment effect, 95% CI, 2 to 49, P=0.034). In men, this treatment effect was 37% (95 CI, 4 to 69, P=0.028). The effect was larger in subjects with either low baseline plasma vitamin C levels or CCA plaques. Vitamin E had no effect on HDL cholesterol. CONCLUSIONS: These data replicate our 3-year findings confirming that the supplementation with combination of vitamin E and slow-release vitamin C slows down atherosclerotic progression in hypercholesterolemic persons.