Associations between weight loss history and factors related to type 2 diabetes risk in the Stop Diabetes study.

BACKGROUND: Frequent weight loss attempts are related to maladaptive eating behaviours and higher body mass index (BMI). We studied associations of several type 2 diabetes (T2D) risk factors with weight loss history, defined as the frequency of prior weight loss attempts, among Finnish adults at increased risk for T2D. METHODS: This study (n = 2684, 80% women) is a secondary analysis of the 1-year StopDia lifestyle intervention with digital intervention group, digital intervention + face-to-face counselling group, or control group. The frequency of prior weight loss attempts was categorized into five groups: no attempts/no attempts to lose weight, but trying to keep weight stable/1-2 attempts/3 or more attempts/ continuous attempts. Data on emotional eating and social/emotional nutrition self-efficacy were collected with a digital questionnaire. We assessed baseline differences between categories of weight loss history as well as the intervention effects. RESULTS: Altogether 84% of participants had attempted weight loss. Those with one or more weight loss attempts had higher BMI, larger waist circumference, and more emotional eating compared to 'no attempts' and 'no attempts to lose weight, but trying to keep weight stable' categories. The 'no attempts' category had the highest baseline fasting insulin, whereas it showed the largest decrease in this measure with the intervention. This change in fasting insulin in the 'no attempts' category was significantly different from all the other categories. Emotional nutrition self-efficacy slightly improved in the 'no attempts' category, which was significantly different from its concomitant decrease in the categories '1-2 attempts' and '3 or more attempts'. The intervention group assignment did not affect the results. CONCLUSIONS: Multiple attempts to lose weight may unfavourably affect T2D risk factors as well as lifestyle intervention outcomes. More research is needed on how weight loss frequency could affect T2D risk factors and how to design lifestyle interventions for individuals with frequent previous weight loss attempts.

Validation of biomarkers of food intake-critical assessment of candidate biomarkers.

Biomarkers of food intake (BFIs) are a promising tool for limiting misclassification in nutrition research where more subjective dietary assessment instruments are used. They may also be used to assess compliance to dietary guidelines or to a dietary intervention. Biomarkers therefore hold promise for direct and objective measurement of food intake. However, the number of comprehensively validated biomarkers of food intake is limited to just a few. Many new candidate biomarkers emerge from metabolic profiling studies and from advances in food chemistry. Furthermore, candidate food intake biomarkers may also be identified based on extensive literature reviews such as described in the guidelines for Biomarker of Food Intake Reviews (BFIRev). To systematically and critically assess the validity of candidate biomarkers of food intake, it is necessary to outline and streamline an optimal and reproducible validation process. A consensus-based procedure was used to provide and evaluate a set of the most important criteria for systematic validation of BFIs. As a result, a validation procedure was developed including eight criteria, plausibility, dose-response, time-response, robustness, reliability, stability, analytical performance, and inter-laboratory reproducibility. The validation has a dual purpose: (1) to estimate the current level of validation of candidate biomarkers of food intake based on an objective and systematic approach and (2) to pinpoint which additional studies are needed to provide full validation of each candidate biomarker of food intake. This position paper on biomarker of food intake validation outlines the second step of the BFIRev procedure but may also be used as such for validation of new candidate biomarkers identified, e.g., in food metabolomic studies.

Physical activity, heart rate variability-based stress and recovery, and subjective stress during a 9-month study period.

The aim of this study was to investigate the association between physical activity (PA) and objective heart rate variability (HRV)-based stress and recovery with subjective stress in a longitudinal setting. Working-age participants (n = 221; 185 women, 36 men) were overweight (body mass index, 25.3-40.1 kg/m2 ) and psychologically distressed (≥3/12 points on the General Health Questionnaire). Objective stress and recovery were based on HRV recordings over 1-3 work days. Subjective stress was assessed with the Perceived Stress Scale and PA level with a questionnaire. Data were collected at three time points: baseline, 10 weeks post intervention, and at the 36-week follow-up. We adopted a latent growth model to investigate the initial level and change in PA, objective stress and recovery, and subjective stress at the three measurement time points. The results showed that initial levels of PA (P < 0.001) and objective stress (P = 0.001) and recovery (P < 0.01) were associated with the change in subjective stress. The results persisted after adjustment for intervention group. The present results suggest that high PA and objectively assessed low stress and good recovery have positive effects on changes in subjective stress in the long-term.

Alkylresorcinols in adipose tissue biopsies as biomarkers of whole-grain intake: an exploratory study of responsiveness to advised intake over 12 weeks.

BACKGROUND/OBJECTIVES: Alkylresorcinols (ARs) have been suggested as biomarkers of whole-grain wheat and rye intake. Plasma AR concentrations have a short half-life; hence, long-term biomarkers are needed. This study evaluated the responsiveness of ARs in adipose tissue biopsies as biomarkers after a whole-grain intake intervention. SUBJECTS/METHODS: Samples and data of 27 participants from a 12-week randomized parallel-group dietary intervention were available. The participants were replacing their habitual diet with a whole-grain-enriched diet (WGDG) or a refined grain diet (RDG) during the intervention. Blood samples and adipose tissue biopsies were collected at baseline and after 12 weeks, and AR concentrations in the plasma and adipose tissues from the participants were compared against estimated whole-grain intake. RESULTS: AR concentrations in the adipose tissue and plasma did not change after 12 weeks in the WGDG group, as no significant increase in whole-grain intake was observed, but was significantly lower than baseline in the RDG group (P<0.05), owing to decreased whole-grain intake in this group. Plasma and adipose tissue AR concentrations were significantly higher in the WGDG group than in the RDG group (P<0.05), and were highly correlated with average whole-grain intake estimated by food records (Spearman's r=0.60-0.72 (P<0.05, n=16) for total and individual AR homolog concentrations in the plasma; r=0.60--0.84, (P<0.05, n=16) for total and individual AR homolog concentrations in the adipose tissue). CONCLUSIONS: In this small pilot study, AR concentrations in adipose tissue responded to reduced intake of whole grain over 12 weeks. Although not significantly different from plasma AR, adipose tissue AR concentrations were highly correlated with whole-grain intake after a 12-week intervention. These results show that adipose tissue AR concentrations have promise as biomarkers of whole-grain wheat and rye intake. Larger studies are needed to evaluate whether they are better long-term biomarkers than AR in the plasma.

Plasma alkylresorcinols C17:0/C21:0 ratio, a biomarker of relative whole-grain rye intake, is associated to insulin sensitivity: a randomized study.

BACKGROUND/OBJECTIVES: Few studies have used biomarkers of whole-grain intake to study its relation to glucose metabolism. We aimed to investigate the association between plasma alkylresorcinols (AR), a biomarker of whole-grain rye and wheat intake, and glucose metabolism in individuals with metabolic syndrome (MetS). SUBJECTS/METHODS: Participants were 30-65 years of age, with body mass index 27-40 kg/m(2) and had MetS without diabetes. Individuals were recruited through six centers in the Nordic countries and randomized to a healthy Nordic diet (ND, n=96), rich in whole-grain rye and wheat, or a control diet (n=70), for 18-24 weeks. In addition, associations between total plasma AR concentration and C17:0/C21:0 homolog ratio as an indication of the relative whole-grain rye intake, and glucose metabolism measures from oral glucose tolerance tests were investigated in pooled (ND+control) regression analyses at 18/24 weeks. RESULTS: ND did not improve glucose metabolism compared with control diet, but the AR C17:0/C21:0 ratio was inversely associated with fasting insulin concentrations (P=0.002) and positively associated with the insulin sensitivity indices Matsuda ISI (P=0.026) and disposition index (P=0.022) in pooled analyses at 18/24 weeks, even after adjustment for confounders. The AR C17:0/C21:0 ratio was not significantly associated with insulin secretion indices. Total plasma AR concentration was not related to fasting plasma glucose or fasting insulin at 18/24 weeks. CONCLUSIONS: The AR C17:0/C21:0 ratio, an indicator of relative whole-grain rye intake, is associated with increased insulin sensitivity in a population with MetS.

Pelvic, perineal and genital reconstructions.

Perineogenital and pelvic surgery is challenging due to the complex anatomy and physiology, multi-organ involvement and microbial environment of this region. In reconstructive surgery local and pedicled flaps are usually applicable. Microvascular flaps are rarely needed. Positioning of the scars, tension in the wound edges and pressure conditions must be taken into account, because failed correction may create more functional and aesthetic problems as the defect itself. This brief review focuses on the reconstructive methods of perineum, genitals and pelvic floor, site by site, with special emphasis on functional details.

DXA estimates of fat in abdominal, trunk and hip regions varies by ethnicity in men.

OBJECTIVE: The aim of this study was to determine whether the quantity of fat is different across the central (that is, android, trunk) and peripheral (that is, arm, leg and gynoid) regions among young African-American (AA), Asian (AS), Hispanic (HI) and non-Hispanic White (NHW) men. SUBJECTS AND METHODS: A cohort of 852 men (18-30 years; mean total body fat percent (TBF%)=18.8±7.9, range=3.7-45.4) were assessed for body composition in five body regions via dual-emission X-ray absorptiometry (DXA). RESULTS: HI men (21.8±8.3) had higher TBF% than AA (17.0±10.0), NHW (17.9±7.2) and AS (18.9±8.0) groups (P-values <0.0001). AS had a lower BMI (23.9±3.4) than all other groups, and NHW (24.7±3.2) had a lower BMI than HI (25.7±3.9) and AA (26.5±4.7; P-values<0.0001). A linear mixed model (LMM) revealed a significant ethnicity by region fat% interaction (P<0.0001). HI men had a greater fat% than NHW for every region (adjusted means (%); android: 29.6 vs 23.3; arm: 13.3 vs 10.6; gynoid: 27.2 vs 23.8; leg: 21.2 vs 18.3; trunk: 25.5 vs 20.6) and a greater fat% than AA for every region except the arm. In addition, in the android and trunk regions, HI had a greater fat% than AS, and AS had a higher fat% than AA. Finally, the android fat% for AS was higher than that of NHW. When comparing the region fat% within ethnicities, the android region was greater than the gynoid region for AS and HI, but did not differ for AA and NHW, and the arm region had the least fat% in all ethnicities. CONCLUSIONS: Fat deposition and body fat patterning varies by ethnicity.

Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome -- a randomized study (SYSDIET).

BACKGROUND: Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. METHODS: We conducted a randomized dietary study lasting for 18-24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m(-2) , 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. RESULTS: Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmol L(-1) 95% CI -0.35; -0.01, P = 0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P = 0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37 ng L(-1) , P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, -0.23, -0.41; -0.05, P = 0.012) were associated with IL-1 Ra. CONCLUSIONS: Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.

Associations of meal frequency and breakfast with obesity and metabolic syndrome traits in adolescents of Northern Finland Birth Cohort 1986.

BACKGROUND AND AIMS: Breakfast consumption and meal frequencies have been linked to the risk of obesity in youth but their associations with metabolic syndrome (MetS) in young populations are yet to be studied. We examined associations of three meal patterns on weekdays--five meals including breakfast, ≤four meals including breakfast and ≤four meals without breakfast--with overweight/obesity and MetS components in Finnish adolescents. METHODS AND RESULTS: A population-based sample of 16-year-old boys and girls (n = 6247) from the Northern Finland Birth Cohort 1986 was used. Adolescents were clinically examined and dietary data were collected using self-administered questionnaires. Overweight/obesity and MetS features were defined according to the International Obesity Task Force cut-offs and the International Diabetes Federation MetS paediatric criteria and their associations with meal patterns assessed using logistic regression, adjusted separately for early life factors (birth size, maternal health) and later childhood factors (health behaviours, weight status, parental education). After adjustment for early life factors, the adolescents who ate five meals/day were at lower risk for overweight/obesity (OR [95% CI] for boys: 0.47 [0.34, 0.65]; girls: 0.57 [0.41, 0.79]), abdominal obesity (OR [95% CI] for boys: 0.32 [0.22, 0.48]; girls: 0.54 [0.39, 0.75]) and hypertriglyceridaemia (boys only). Adjusting for later childhood factors, the five-meal-a-day pattern was associated with decreased odds of overweight/obesity (OR [95% CI] for boys: 0.41 [0.29, 0.58]; girls: 0.63 [0.45, 0.89]) and abdominal obesity in boys (OR 0.32, 95% CI 0.16, 0.63). CONCLUSION: Among 16-year-olds, the five-meal-a-day pattern was robustly associated with reduced risks of overweight/obesity in both genders and abdominal obesity in boys.

Conjugated bile acids associate with altered rates of glucose and lipid oxidation after Roux-en-Y gastric bypass.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (RYGB) induces a more favorable metabolic profile than expected by weight loss alone. In this study, we investigated the effect of RYGB on serum bile acid levels and their relation to clinical outcomes. METHODS: We included 30 obese patients who underwent RYGB (BMI = 46.1 ± 5.9 kg/m(2)). Clinical measurements and laboratory determinations were performed before surgery and 1 year after surgery. Fasting serum bile acids were measured by an enzymatic method and individual bile acids were quantified by HLPC-tandem mass spectrometry. Indirect calorimetry was performed to measure the rates of energy expenditure and substrate oxidation. RESULTS: Fasting total serum bile acid levels increased twofold after RYGB (pre, 3.68 ± 2.03 vs. post, 7.06 ± 9.65 µmol/l, +92 %, p = 0.002). This increase in total bile acids was accompanied by a decrease in conjugated bile acids, which correlated with decreased glucose oxidation (r = 0.571, p = 0.002) and with increased lipid oxidation (r = -0.626, p = 0.0004). The change in taurine-conjugated bile acids correlated with altered DIO2 mRNA expression in adipose tissue (r = -0.498, p = 0.013) potentially linking bile acid conjugation to substrate oxidation through DIO2. CONCLUSIONS: Fasting serum bile acid levels increase after RYGB. More specifically, changes in bile acid conjugation after RYGB associate with altered energy metabolism.

Intergenerational transmission of overweight among Finnish adolescents and their parents: a 16-year follow-up study.

OBJECTIVE: Previous studies have shown strong parental influences on adolescent overweight. However, longitudinal data is scarce on gender-specific effects of parental body mass index (BMI) on offspring overweight. The objective of this study was to examine the associations of parental pre-pregnancy BMI, weight change, BMI and BMI class transition 16 years after pregnancy with the BMI of their 16-year-old children. SUBJECTS AND METHODS: The study population was derived from the general population-based Northern Finland Birth Cohort 1986. A total of 4788 child-mother-father trios (2325 boys, 2463 girls) were analysed. Weight and height of the adolescents were measured and overweight and obesity defined according to the International Obesity Task Force. For the parents, self-reported data were obtained and overweight and obesity defined according to the World Health Organization. Associations of parental BMI status and weight change with offspring BMI were assessed using binary logistic regression analyses stratified by gender and adjusted for parental age and education. RESULTS: Children whose both parents were overweight or obese both before pregnancy and after 16-year follow-up had a strikingly high risk of overweight at age 16 years (boys odds ratio (OR) 5.66 95% confidence interval (CI) 3.12, 10.27; girls OR 14.84 95% CI 7.41, 29.73). Parental pre-pregnancy obesity strongly predicted offspring overweight (mother-son OR 4.36 95% CI 2.50, 7.59; mother-daughter OR 3.95 95% CI 2.34, 6.68; father-son OR 3.17 95% CI 1.70, 5.92; father-daughter OR 5.58 95% CI 3.09, 10.07). CONCLUSION: Parental overweight conveys a major risk for overweight in children for which both parents' long-term overweight (BMI ≥25 kg m(-2) before pregnancy and after 16-year follow-up) was the strongest single predictor. Preventing intergenerational transmission of obesity by helping parents to maintain a healthy weight is an essential target for public health.

A diet high in fatty fish, bilberries and wholegrain products improves markers of endothelial function and inflammation in individuals with impaired glucose metabolism in a randomised controlled trial: the Sysdimet study.

AIMS/HYPOTHESIS: Low-grade inflammation and endothelial dysfunction may play a role in the pathogenesis of type 2 diabetes and cardiovascular disease. We evaluated whether a diet high in fatty fish, bilberries and wholegrain products (Healthy Diet) improves biomarkers reflecting inflammation and endothelial dysfunction in individuals with impaired glucose metabolism. METHODS: We recruited individuals with impaired glucose metabolism and features of the metabolic syndrome into a 12 week, parallel design, dietary intervention trial conducted at the Department of Clinical Nutrition, University of Eastern Finland (Kuopio, Finland). Randomisation was performed by matching according to sex and medians of age, BMI and fasting plasma glucose of the study population at screening. The primary endpoint in the present study was the change in plasma inflammatory markers and the measurements were performed blinded to group assignment. High-sensitivity (hs) C-reactive protein (CRP) and E-selectin responses were also analysed separately in participants not using statins (n = 76). RESULTS: Altogether, 131 individuals were assigned to either the Healthy Diet (n = 44), a whole-grain-enriched diet (WGED) (n = 42) or a control (n = 45) diet, and 104 participants (mean ± SD: age 59 ± 7 years; BMI 31.1 ± 3.5 kg/m(2)) who had completed the study, were analysed (Healthy Diet n = 36, WGED n = 34 and control diet n = 34). Plasma E-selectin decreased only in the Healthy Diet group. This occurred in all group participants (p < 0.05) and also after excluding participants using statins (p < 0.05). Plasma hsCRP levels decreased in the Healthy Diet (median -17%, p < 0.05) and WGED (median -27%, p < 0.01) groups in participants not using statins. Controlling for confounding factors, including BMI or insulin sensitivity, did not alter the results. A greater increase in plasma concentration of very-long-chain n-3 fatty acids and in the intake of fibre during the study was associated with a greater decrease in plasma E-selectin (p < 0.05). The intake of test breads consumed during the Healthy Diet and WGED interventions was inversely associated with the change in hsCRP levels (p < 0.001). CONCLUSIONS/INTERPRETATION: Our results suggest that the combined effect of fatty fish, bilberries and wholegrain products may improve endothelial dysfunction and inflammation in overweight and obese individuals at high risk of developing diabetes.

Association of the FTO gene variant (rs9939609) with cardiovascular disease in men with abnormal glucose metabolism--the Finnish Diabetes Prevention Study.

BACKGROUND AND AIM: The common single nucleotide polymorphism (SNP) in the FTO (fat mass and obesity associated) gene has been consistently associated with an increased risk of obesity. We investigated whether the SNP rs9939609 (T/A) of the FTO is associated with risk factors of cardiovascular diseases (CVD), including serum levels of C - reactive protein (CRP), the chemokine RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted; CCL5), and serum and lipoprotein lipids in the Finnish Diabetes Prevention Study (DPS). Furthermore, we examined whether the rs9939609 increased the CVD risk in the DPS and if these results could be replicated in a larger cross-sectional population-based random sample of Finnish men (the METSIM). METHODS AND RESULTS: In the DPS, altogether 490 (BMI≥25kg/m(2)) subjects with impaired glucose tolerance were genotyped for rs9939609. Cardiovascular morbidity and mortality data were collected during the median follow-up of 10.2 years. The replication study was a population-based cross-sectional study of 6214 men. In the DPS, the AA genotype of rs9939609 was associated, independently of BMI, with increased RANTES (p=0.002) and decreased HDL cholesterol concentrations (p=0.007) in men. During the follow-up, the AA genotype was associated with an adjusted 2.09-fold risk (95% CI 1.17-3.73, p=0.013) of CVD in men. In the METSIM Study, the association with a history of myocardial infarction was replicated in the subgroup of men with type 2 diabetes. CONCLUSION: We suggest that the variation in the FTO gene may contribute to the development of CVD in men with an abnormal glucose metabolism.

Microfibrillar-associated protein 5 is linked with markers of obesity-related extracellular matrix remodeling and inflammation.

OBJECTIVE: Microfibrillar-associated protein 5 (MFAP5) is an extracellular matrix (ECM) glycoprotein, which is colocalized with microfibrils in elastin networks. Its function in adipose tissue (AT) is not known. We have recently shown that the expression of MFAP5 is downregulated in AT along with weight reduction (WR) in persons with metabolic syndrome (MetS). The aim of this work was to study whether the change of MFAP5 mRNA expression in response to WR is associated with markers of adiposity, glucose metabolism and insulin resistance in human AT. DESIGN: Weight reduction intervention study in parallel study design (The Genobin study). Altogether 46 obese subjects with impaired glucose tolerance and features of MetS were randomized to a WR (n=28) or a control group (n=18) lasting for 33 weeks. MEASUREMENTS: Circulating glucose and insulin concentrations were measured and subcutaneous AT biopsies were performed before and after the intervention. The mRNA expression was studied by quantitative real-time PCR (QPCR). RESULTS: QPCR of human AT biopsy samples confirmed that MFAP5 is highly expressed in AT and its expression is decreased during WR. The mRNA expression of MFAP5 correlated positively with body mass index, and the change in MFAP5 mRNA expression during WR correlated positively with the change of body fat mass. Furthermore, the MFAP5 mRNA expression correlated negatively with circulating fasting concentrations of adiponectin and interleukin (IL)-1ß and positively with leptin, insulin and IL-1Ra levels. In addition, the MFAP5 mRNA expression correlated positively with the mRNA expressions of peroxisome proliferator-activated receptor gamma, cyclin D2 and A disintegrin and metalloproteinase domain 12, genes involved in AT remodeling. CONCLUSION: This study demonstrates that MFAP5 is highly expressed in human AT and is correlated with markers of insulin resistance. Furthermore, it is possible that MFAP5 is related to ECM remodeling during development of obesity.

Use of sewer on-line total solids data in wastewater treatment plant modelling.

We describe a neural network model of a municipal wastewater treatment plant (WWTP) in which on-line total solids (TS) sewer data generated by a novel microwave sensor is used as a model input variable. The predictive performance of the model is compared with and without sewer data and with modelling with a traditional linear multiple linear regression (MLR) model. In addition, the benefits of using neural networks are discussed. According to our results, the neural network based MLP (multilayer perceptron) model provides a better estimate than the corresponding MLR model of WWTP effluent TS load. The inclusion of sewer TS data as an input variable improved the performance of the models. The results suggest that increased on-line sensing of WWTPs should be stressed and that neural networks are useful as a modelling tool due to their capability of handling the nonlinear and dynamic data of sewer and WWTP systems.

Dietary carbohydrate modification alters serum metabolic profiles in individuals with the metabolic syndrome.

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.

Link between plasma ceramides, inflammation and insulin resistance: association with serum IL-6 concentration in patients with coronary heart disease.

AIMS/HYPOTHESIS: Ceramides and IL-6 have a role in immune-inflammatory responses and cardiovascular diseases, and are suggested to be involved in insulin and glucose metabolism. We sought to assess the associations of circulating levels of IL-6, TNF-alpha and high-sensitivity C reactive protein (hsCRP), which are inflammatory markers related to insulin resistance (IR), with the plasma lipid metabolites ceramides and diacylglycerols (DAG) in patients with CHD. METHODS: Cross-sectional analyses were carried out on data from 33 patients with CHD. Serum levels of the inflammatory markers and plasma lipid metabolites (lipidomics approach performed by ultra-performance liquid chromatography coupled to electrospray ionisation MS) were measured at the same time point as insulin resistance (IR) (HOMA-IR index). RESULTS: Serum circulating levels of IL-6 were strongly correlated with plasma ceramide concentrations (r = 0.59, p < 0.001). Adjustments for serum TNF-alpha or hsCRP levels, smoking, BMI, age, sex or HOMA-IR did not change the results (p < 0.001). After adjustments for the effect of serum inflammatory markers (TNF-alpha or hsCRP), HOMA-IR and BMI the correlation between plasma DAG and serum IL-6 (r = 0.33) was also significant (p < 0.03). In a linear regression model, circulating levels of both ceramides and TNF-alpha had a significant independent influence on circulating levels of IL-6, altogether accounting for 41% of its variation (p < 0.001). CONCLUSIONS/INTERPRETATION: Our results strongly suggest that the link between ceramides, IR and inflammation is related to the inflammatory marker IL-6. Ceramides may contribute to the induction of inflammation involved in IR states that frequently coexist with CHD.

Association of sequence variations in the gene encoding insulin-like growth factor binding protein 5 with adiponectin.

BACKGROUND: Insulin-like growth factor binding protein 5 (IGFBP5) binds to IGF and thus modulates IGF signaling pathway. We have shown earlier that the IGFBP5 gene was downregulated in the adipose tissue after 12-week carbohydrate diet with low insulinemic response. OBJECTIVE: The aim was to examine the putative contribution of genetic variation of the IGFBP5 gene to the characteristics of metabolic syndrome and incidence of type 2 diabetes (T2DM) in the Finnish Diabetes Prevention Study (DPS). METHODS: DPS is a longitudinal study where 522 subjects with impaired glucose tolerance were randomized to either lifestyle intervention group or control group. DNA was available from 507 subjects (mean body mass index (BMI) 31.2+/-4.5 kg/m(2), age 55+/-7 years). The eight single-nucleotide polymorphisms (SNPs) were selected from HapMap database and genotyped by Taqman allelic discrimination protocol. The main results were confirmed in a larger cross-sectional study population (METSIM). In addition, the gene expression of IGFBP5 was studied in two previously published study populations (FUNGENUT and GENOBIN) of 124 subjects with insulin resistance (BMI 32.2+/-3.5 kg/m(2), age 57.7+/-7.4 years). RESULTS: Three out of eight IGFBP5 markers (rs9341234, rs3276 and rs11575134) were significantly associated with circulating adiponectin concentrations in men. Furthermore, mRNA expression studies of subcutaneous adipose tissue showed that mRNA concentrations of IGFBP5 correlated with adiponectin concentrations in all subjects and in women. None of the IGFBP5 SNPs were associated with T2DM. CONCLUSIONS: Our findings show that IGFBP5 has a gender-specific association with adiponectin, which may modulate the development of metabolic syndrome.

The genetic variation in the tenomodulin gene is associated with serum total and LDL cholesterol in a body size-dependent manner.

We have reported that the sequence variation in the tenomodulin (TNMD) gene is associated with the risk of type 2 diabetes (T2DM), central obesity and serum levels of systemic immune mediators in the Finnish Diabetes Prevention Study (DPS), which is a longitudinal lifestyle intervention study on 522 middle-aged persons with impaired glucose tolerance (IGT). The aim of this study was to investigate whether the association with T2DM, observed in the DPS could be replicated in a larger, cross-sectional population-based random sample of 5298 men (3020 with normoglycaemia, 984 with impaired fasting glucose, 436 with IGT and 811 with T2DM) from the region of Kuopio, eastern Finland. To further explore the putative mechanisms linking TNMD to T2DM and metabolic syndrome, we studied the associations of TNMD sequence variation with lipid abnormalities characteristic to metabolic syndrome. The association with T2DM risk was not replicated, but significant associations were found with serum low-density lipoprotein and total cholesterol in a body mass index-dependent manner. These associations were also observed in the men of DPS, whereas in women these associations were not significant. These results from two independent study populations suggest that the genetic variation in TNMD could modulate cholesterol metabolism in obese men.

Downregulation of genes involved in NFkappaB activation in peripheral blood mononuclear cells after weight loss is associated with the improvement of insulin sensitivity in individuals with the metabolic syndrome: the GENOBIN study.

AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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 (p < 0.05). The change in IKBKB expression correlated with most of the changes in gene expression in the weight-reduction group. CONCLUSIONS/INTERPRETATION: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT 00621205.