The association between vitamin D receptor polymorphisms and tissue-specific insulin resistance in human obesity.

BACKGROUND/OBJECTIVES: To investigate (1) the association of four VDR polymorphisms (TaqI/rs731236, ApaI/rs7975232, FokI/rs10735810, and Bsml/rs1544410) with markers of adiposity and tissue-specific insulin resistance at baseline, after weight loss and weight maintenance; (2) the effect of the VDR polymorphisms in the SAT transcriptome in overweight/obese Caucasians of the DiOGenes cohort. METHODS: We included 553 adult obese individuals (mean BMI 34.8 kg/m2), men (n = 197) and women (n = 356) at baseline, following an 8-week weight loss intervention and 26 weeks weight maintenance. Genotyping was performed using an Illumina 660W-Quad SNP chip on the Illumina iScan Genotyping System. Tissue-specific IR was determined using Hepatic Insulin Resistance Index (HIRI), Muscle Insulin Sensitivity Index (MISI), and Adipose Tissue Insulin Resistance Index (Adipo-IR). Expression quantitative trait loci (eQTL) analysis was performed to determine the effect of SNPs on SAT gene expression. RESULTS: None of the VDR polymorphisms were associated with HIRI or MISI. Interestingly, carriers of the G allele of VDR FokI showed higher Adipo-IR (GG + GA 7.8 ± 0.4 vs. AA 5.6 ± 0.5, P = 0.010) and higher systemic FFA (GG + GA: 637.8 ± 13.4 vs. AA: 547.9 ± 24.7 µmol/L, P = 0.011), even after adjustment with age, sex, center, and FM. However, eQTL analysis showed minor to no effect of these genotypes on the transcriptional level in SAT. Also, VDR polymorphisms were not related to changes in body weight and IR as result of dietary intervention (P > 0.05 for all parameters). CONCLUSIONS: The VDR Fokl variant is associated with elevated circulating FFA and Adipo-IR at baseline. Nevertheless, minor to no effect of VDR SNPs on the transcriptional level in SAT, indicating that putative mechanisms of action remain to be determined. Finally, VDR SNPs did not affect dietary intervention outcome in the present cohort.

The Relationship between Circulating Acetate and Human Insulin Resistance before and after Weight Loss in the DiOGenes Study.

Microbially-produced acetate has been reported to beneficially affect metabolic health through effects on satiety, energy expenditure, insulin sensitivity, and substrate utilization. Here, we investigate the association between sex-specific concentrations of acetate and insulin sensitivity/resistance indices (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), circulating insulin and Matsuda Index) in the Diet, Obesity and Genes (DiOGenes) Dietary study at baseline and after a low-calorie diet (LCD, 800 kcal/d). In this analysis, 692 subjects (Body Mass Index >27 kg/m2) were included, who underwent an LCD for 8 weeks. Linear mixed models were performed, which were adjusted for mean acetate concentration, center (random factor), age, weight loss, and fat-free mass (FFM). At baseline, no associations between plasma acetate and insulin sensitivity/resistance indices were found. We found a slight positive association between changes in acetate and changes in HOMA-IR (std 0.130, p = 0.033) in women, but not in men (std -0.072, p = 0.310) independently of age, weight loss and FFM. We were not able to confirm previously reported associations between acetate and insulin sensitivity in this large European cohort. The mechanisms behind the sex-specific relationship between LCD-induced changes in acetate and insulin sensitivity require further study.

Comparison of the portion size and frequency of consumption of 156 foods across seven European countries: insights from the Food4ME study.

There are no standardised serving/portion sizes defined for foods consumed in the European Union (EU). Typical serving sizes can deviate significantly from the 100 g/100 ml labelling specification required by the EU legislation. Where the nutritional value of a portion is specified, the portion size is determined by the manufacturers. Our objective was to investigate the potential for standardising portion sizes for specific foods, thereby ensuring complementarity across countries. We compared portion size for 156 food items measured using a food frequency questionnaire across the seven countries participating in the Food4me study. The probability of consuming a food and the frequency of consumption differed across countries for 93% and 58% of the foods, respectively. However, the individual country mean portion size differed from the average across countries in only 16% of comparisons. Thus, although dietary choices vary markedly across countries, there is much less variation in portion sizes. Our results highlight the potential for standardisation of portion sizes on nutrition labels in the EU.

Effect of a high-protein diet on maintenance of blood pressure levels achieved after initial weight loss: the DiOGenes randomized study.

Randomized trials have shown significant blood pressure (BP) reductions after increased protein compared with carbohydrate intake, but the effect on BP maintenance after initial weight loss is unclear. We examined the effect of a high-protein diet on the maintenance of reduced BP after weight loss in 420 overweight adults from the Diet, Obesity and Genes study. After an 8-week weight-loss period (>8% BW), subjects (42±6 years) were randomized to either a high-protein diet (23-28 en% protein) or a lower-protein control diet (10-15 en% protein) for 26 weeks. BMI after weight loss was 30.3±4.3 kg m(-2), BP was 118/73 mm Hg and 28 subjects (6.5%) used antihypertensive agents. Systolic BP during 26 weeks of weight maintenance dietary intervention increased in both treatment groups, but it was 2.2 mm Hg less (95% CI: -4.6 to 0.2 mm Hg, P=0.08) in the high-protein group than in the lower-protein control group. In 191 (pre)hypertensive subjects (baseline systolic BP⩾120 mm Hg), a larger difference was observed (-4.2 mm Hg (-7.7, -0.7), P=0.02). The effect was attenuated after adjustment for initial BP (-3.4 mm Hg (-6.9, -0.03), P=0.048), and after additional adjustment for weight change (-2.7 mm Hg (-6.1, 0.4), P=0.11). Adjustment for 24-h urinary excretion of sodium and potassium did not change the results. Diastolic BP yielded similar results. These findings suggest that a BP reduction after weight loss is better maintained when the intake of protein is increased at the expense of carbohydrates. This effect is partly mediated by body weight.

Body weight regulation and obesity: dietary strategies to improve the metabolic profile.

This review discusses dietary strategies that may improve the metabolic profile and body weight regulation in obesity. Recent evidence demonstrated that long-term health effects seem to be more beneficial for low-glycemic index (GI) diets compared to high-protein diets. Still, these results need to be confirmed by other prospective cohort studies and long-term clinical trials, and the discrepancy between these study designs needs to be explored in more detail. Furthermore, the current literature is mixed with regard to the efficacy of increased meal frequency (or snacking) regimens in causing metabolic alterations, particularly in relation to body weight control. In conclusion, a growing body of evidence suggests that dietary strategies with the aim to reduce postprandial insulin response and increase fat oxidation, and that tend to restore metabolic flexibility, have a place in the prevention and treatment of obesity and associated metabolic disorders.

Weight loss maintenance in overweight subjects on ad libitum diets with high or low protein content and glycemic index: the DIOGENES trial 12-month results.

BACKGROUND: A high dietary protein (P) content and low glycemic index (LGI) have been suggested to be beneficial for weight management, but long-term studies are scarce. OBJECTIVE: The DIOGENES randomized clinical trial investigated the effect of P and GI on weight loss maintenance in overweight or obese adults in eight centers across Europe. This study reports the 1-year results in two of the centers that extended the intervention to 1 year. METHOD: After an 8-week low-calorie diet (LCD), 256 adults (body mass index >27 kg m(-)(2)) were randomized to five ad libitum diets for 12 months: high P/LGI (HP/LGI), HP/high GI (HP/HGI), low P/LGI (LP/LGI), LP/HGI and a control diet. During the first 6 months, foods were provided for free through a shop system and during the whole 12-month period, subjects received guidance by a dietician. Primary outcome variable was the change in body weight over the 12-month intervention period. RESULTS: During the LCD period, subjects lost 11.2 (10.8, 12.0) kg (mean (95% confidence interval (CI))). Average weight regain over the 12-month intervention period was 3.9 (95% CI 3.0-4.8) kg. Subjects on the HP diets regained less weight than subjects on the LP diets. The difference in weight regain after 1 year was 2.0 (0.4, 3.6) kg (P=0.017) (completers analysis, N=139) or 2.8 (1.4, 4.1) kg (P<0.001) (intention-to-treat analysis, N=256). No consistent effect of GI on weight regain was found. There were no clinically relevant differences in changes in cardiometabolic risk factors among diet groups. CONCLUSION: A higher protein content of an ad libitum diet improves weight loss maintenance in overweight and obese adults over 12 months.

Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults.

INTRODUCTION: Mechanisms for liraglutide-induced weight loss are poorly understood. OBJECTIVE: We investigated the effects of liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese non-diabetic individuals. DESIGN: Participants (N=49, 18-75 years, body mass index: 30-40 kg m(-2)) were randomized to two of three treatments: liraglutide 1.8 mg, 3.0 mg, or placebo in a double-blind, incomplete crossover trial. After 5 weeks, 24-h energy expenditure (EE) and substrate oxidation were measured in a respiratory chamber. Gastric emptying (acetaminophen absorption method), glycemic parameters and appetite were assessed during a 5-h meal test. Ad libitum energy intake during a subsequent lunch was also assessed. RESULTS: Five-hour gastric emptying (AUC(0-300 min)) was found to be equivalent for liraglutide 1.8 versus 3.0 mg (primary end point), and for both liraglutide doses versus placebo, as 90% confidence intervals for the estimated treatment ratios were contained within the prespecified interval (0.80-1.25). However, 1-h gastric emptying was 23% lower than placebo with liraglutide 3.0 mg (P=0.007), and a nonsignificant 13% lower than placebo with liraglutide 1.8 mg (P=0.14). Both liraglutide doses similarly reduced fasting glucose (0.5-0.6 mmol l(-1) versus placebo, P<0.0001), glucose Cmax and 1-h AUC versus placebo; only liraglutide 3.0 mg reduced iAUC(0-300 min) (by ∼26% versus placebo, P=0.02). Glucagon iAUC(0-300 min) decreased by ∼30%, and iAUC(0-60 min) for insulin and C-peptide was ∼20% lower with both liraglutide doses versus placebo. Liraglutide doses similarly increased mean postprandial satiety and fullness ratings, reduced hunger and prospective food consumption and decreased ad libitum energy intake by ∼16%. Liraglutide-associated reductions in EE were partly explained by a decrease in body weight. A relative shift toward increased fat and reduced carbohydrate oxidation was observed with liraglutide. Clinicaltrials.gov ID:NCT00978393. FUNDING: Novo Nordisk. CONCLUSION: Gastric emptying AUC(0-300 min) was equivalent for liraglutide 1.8 and 3.0 mg, and for liraglutide versus placebo, whereas reductions in 1-h gastric emptying of 23% with liraglutide 3.0 mg and 13% with 1.8 mg versus placebo were observed. Liraglutide 3.0 mg improved postprandial glycemia to a greater extent than liraglutide 1.8 mg. Liraglutide-induced weight loss appears to be mediated by reduced appetite and energy intake rather than increased EE.

Fatty acid composition of adipose tissue triglycerides after weight loss and weight maintenance: the DIOGENES study.

Fatty acid composition of adipose tissue changes with weight loss. Palmitoleic acid as a possible marker of endogenous lipogenesis or its functions as a lipokine are under debate. Objective was to assess the predictive role of adipose triglycerides fatty acids in weight maintenance in participants of the DIOGENES dietary intervention study. After an 8-week low calorie diet (LCD) subjects with > 8 % weight loss were randomized to 5 ad libitum weight maintenance diets for 6 months: low protein (P)/low glycemic index (GI) (LP/LGI), low P/high GI (LP/HGI), high P/low GI (HP/LGI), high P/high GI (HP/HGI), and a control diet. Fatty acid composition in adipose tissue triglycerides was determined by gas chromatography in 195 subjects before the LCD (baseline), after LCD and weight maintenance. Weight change after the maintenance phase was positively correlated with baseline adipose palmitoleic (16:1n-7), myristoleic (14:1n-5) and trans-palmitoleic acid (16:1n-7t). Negative correlation was found with baseline oleic acid (18:1n-9). Lower baseline monounsaturated fatty acids (14:1n-5, 16:1n-7 and trans 16:1n-7) in adipose tissue triglycerides predict better weight maintenance. Lower oleic acid predicts lower weight decrease. These findings suggest a specific role of monounsaturated fatty acids in weight management and as weight change predictors.

Circulating ACE is a predictor of weight loss maintenance not only in overweight and obese women, but also in men.

BACKGROUND: Circulating angiotensin-converting enzyme (ACE) was identified as a predictor of weight loss maintenance in overweight/obese women of the Diogenes project. OBJECTIVE: To investigate whether ACE acted also as a predictor in men of the Diogenes study and to compare it with that in women. DESIGN: Subjects, who lost ≥ 8% of body weight induced by low-caloric diet in an 8-week weight loss period, were assigned to weight loss maintenance with dietary intervention for 6 months. SUBJECTS: 125 overweight/obese healthy men from eight European countries who completed whole intervention. MEASUREMENTS: Concentrations and activity of serum ACE at baseline and after the 8-week weight loss, in addition to anthropometric and physiological parameters. RESULTS: Serum ACE concentration decreased by 11.3 ± 10.6% during the weight loss period in men. A greater reduction is associated with less body weight regain during the maintenance period (r=0.227, P=0.012). ACE change was able to predict a weight regain ≤ 20% after 6 months, with an odds ratio of 1.59 (95% confidence interval (CI): 1.09-2.33, P=0.016) for every 10% reduction, which was independent of body mass index and weight loss. The prediction power was weaker in men than in women, but without a significant sex difference (P=0.137). In pooled subjects (N=218), the odds ratio was 1.96 (95% CI: 1.46-2.64, P<0.001). CONCLUSIONS: A greater reduction of ACE during weight loss is favorable for weight maintenance in both men and women. This can offer useful information for personalized advice to improve weight loss maintenance. It also confirms the role of ACE in the metabolic pathways of weight regulation.

Endocrine responses during overnight recovery from exercise: impact of nutrition and relationships with muscle protein synthesis.

Nocturnal endocrine responses to exercise performed in the evening and the potential role of nutrition are poorly understood. To gain novel insight, 10 healthy men ingested carbohydrate with (C+P) and without (C) protein in a randomized order and double-blind manner during 2 hr of interval cycling followed by resistance-type exercise and into early postexercise recovery. Blood samples were obtained hourly throughout 9 hr of postexercise overnight recovery for analysis of key hormones. Muscle samples were taken from the vastus lateralis before and after exercise and then again the next morning (7 a.m.) to calculate mixed-muscle protein fractional synthetic rate (FSR). Overnight plasma hormone concentrations were converted into overall responses (expressed as area under the concentration curve) and did not differ between treatments for either growth hormone (1,464 ± 257 vs. 1,432 ± 164 pg/ml · 540 min) or total testosterone (18.3 ± 1.2 vs. 17.9 ± 1.2 nmol/L · 540 min, C and C+P, respectively). In contrast, the overnight cortisol response was higher with C+P (102 ± 11 nmol/L · 540 min) than with C (81 ± 8 nmol/L · 540 min; p = .02). Mixed-muscle FSR did not differ between C and C+P during overnight recovery (0.062% ± 0.006% and 0.062% ± 0.009%/hr, respectively) and correlated significantly with the plasma total testosterone response (r = .7, p < .01). No correlations with FSR were apparent for the response of growth hormone (r = -.2, p = .4), cortisol (r = .1, p = .6), or the ratio of testosterone to cortisol (r = .2, p = .5). In conclusion, protein ingestion during and shortly after exercise does not modulate the endocrine response or muscle protein synthesis during overnight recovery.

Increased systolic blood pressure after mild cold and rewarming: relation to cold-induced thermogenesis and age.

AIM: Higher winter mortality in elderly has been associated with augmented systolic blood pressure (SBP) response and with impaired defense of core temperature. Here we investigated whether the augmented SBP upon mild cold exposure remains after a rewarming period, and whether SBP changes are linked to thermoregulation. Therefore, we tested the following hypotheses: cold-induced increase in SBP (1) remains augmented after rewarming in elderly compared to young adults (2) is related to non-shivering thermogenesis (NST) upon mild cold (3) is related to vasoconstriction upon mild cold. METHODS: Blood pressure, energy expenditure (EE), skin and core temperature, skin perfusion (abdomen, forearm, both sides of hand) and % body fat were measured in 12 young adults (Y) and 12 elderly (E). Supine subjects were exposed to a thermoneutral baseline 0.5 h (T(air) = 30.1°C), 1 h mild cold (T(air) = 20.7°C), 1 h rewarming (T(air) = 34.8°C) and 1 h baseline (T(air) = 30.5°C). RESULTS: Upon mild cold only the young adults showed significant NST (Y: +2.5 ± 0.6 W m(-2), P < 0.05). No significant age effects in vasoconstriction were observed. After rewarming per cent change in SBP (%ΔSBP) remained significantly increased in both age groups and was augmented in elderly (Y: +5.0% ± 1.2% vs. E: +14.7% ± 3.1%, P < 0.05). Regression analysis revealed that %ΔSBP significantly related to ΔEE upon mild cold (P < 0.01, r(2) = 0.35) and in elderly also to %body fat (P < 0.02, r(2) = 0.57). CONCLUSION: Individual changes in SBP after rewarming correlate negatively to NST. Elderly did not show NST, which explains the greater SBP increase in this group. In elderly a relatively large %body fat protected against the adverse effects of mild cold.

Predictors of lifestyle intervention outcome and dropout: the SLIM study.

BACKGROUND/OBJECTIVES: To evaluate the effect of a 4.1-year (range 3-6 years) lifestyle intervention according to general public health recommendations on glucose tolerance and dropout in a Dutch population with impaired glucose tolerance (IGT). SUBJECTS/METHODS: In the Study on Lifestyle intervention and Impaired glucose tolerance Maastricht, 147 Caucasian IGT subjects were randomized to an intervention group (INT: n=74; 38 male, 36 female) and control group (CON: n=73; 37 male, 36 female). Annually, subjects underwent measurements of body weight, anthropometry, glucose tolerance (oral glucose tolerance test), insulin resistance (homeostasis model assessment-insulin resistance), maximal aerobic capacity (VO(2) max), blood lipids and blood pressure. INT received individual advice regarding a healthy diet and physical activity. RESULTS: INT decreased their saturated fat intake, increased their carbohydrate intake (P<0.05) and VO(2) max (P=0.04) compared with CON. Body weight did not change significantly (P=0.20) between the groups. After an initial decrease, 2-h glucose levels overall increased in INT (+0.11 mmol/l), but significantly less than CON (+1.18 mmol/l; P=0.04). Diabetes incidence was lower in INT versus CON (30 versus 56%, P=0.04). Change in body weight was associated with change in 2-h glucose levels (ß=0.399 mmol/l per kg, P=0.02). Dropouts had a lower aerobic fitness and socioeconomic status, and a higher body mass index (BMI) and 2-h glucose compared with non-dropouts. CONCLUSIONS: Prolonged feasible changes in diet and physical activity prevent deterioration of glucose tolerance and reduce diabetes risk. Low socioeconomic status, low aerobic fitness and high BMI and 2-h glucose are indicative of dropout to the program.

Does adherence to the Mediterranean diet have a protective effect against active and passive smoking?

OBJECTIVE: To investigate the existing evidence about whether adherence to the Mediterranean diet may have a role as an effect modifier of active and passive smoking on human health. STUDY DESIGN: Review. METHODS: An overview of emerging evidence and published studies that cover the interaction between the Mediterranean diet and smoking. RESULTS: Both epidemiological and laboratory studies have shown that the Mediterranean diet has a protective effect against biochemical and molecular processes that lead to cancer, cardiovascular disease and respiratory illness. Based on the high daily intake of vitamins and antioxidants, the Mediterranean diet is comprised of a number of compounds that could alter certain outcomes related to smoking. Studies have indicated that certain diseases attributable to smoking, such as lung cancer, asthma and cardiovascular disease, are inversely associated with certain antioxidants and lipids. CONCLUSIONS: The literature indicates that the existence of a partial interaction between adherence to the Mediterranean diet and the health effects of smoking is possible. Further research is needed to lead to a conclusive statement on this hypothesis.

Gastrointestinal targets to modulate satiety and food intake.

This review discusses the role of enteroendocrine cells in the gastrointestinal tract as chemoreceptors that sense intraluminal contents and induce changes in food intake through the release of signalling substances, such as satiety hormones. Recent evidence supports the concept that chemosensing in the gut involves G protein-coupled receptors (GPCRs) that are known to mediate gustatory signals in the oral cavity. GPCRs can be grouped into several families, depending on the stimuli to which they respond, e.g. proteins, amino acids, carbohydrates, fatty acids, or tastants. Sensing of these stimuli by GPCRs results in hormone secretions of enteroendocrine cells, which participate in the control of food intake. A better understanding of the stimuli that induce the strongest binding with these receptors, and thus induce a strong release of hormones, can be a very useful strategy for the development of novel foods in the treatment of obesity.

Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metabolic syndrome--LIPGENE: a European randomized dietary intervention study.

BACKGROUND: Excessive energy intake and obesity lead to the metabolic syndrome (MetS). Dietary saturated fatty acids (SFAs) may be particularly detrimental on insulin sensitivity (SI) and on other components of the MetS. OBJECTIVE: This study determined the relative efficacy of reducing dietary SFA, by isoenergetic alteration of the quality and quantity of dietary fat, on risk factors associated with MetS. DESIGN: A free-living, single-blinded dietary intervention study. SUBJECTS AND METHODS: MetS subjects (n = 417) from eight European countries completed the randomized dietary intervention study with four isoenergetic diets distinct in fat quantity and quality: high-SFA; high-monounsaturated fatty acids and two low-fat, high-complex carbohydrate (LFHCC) diets, supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) (1.2 g per day) or placebo for 12 weeks. SI estimated from an intravenous glucose tolerance test (IVGTT) was the primary outcome measure. Lipid and inflammatory markers associated with MetS were also determined. RESULTS: In weight-stable subjects, reducing dietary SFA intake had no effect on SI, total and low-density lipoprotein cholesterol concentration, inflammation or blood pressure in the entire cohort. The LFHCC n-3 PUFA diet reduced plasma triacylglycerol (TAG) and non-esterified fatty acid concentrations (P < 0.01), particularly in men. CONCLUSION: There was no effect of reducing SFA on SI in weight-stable obese MetS subjects. LC n-3 PUFA supplementation, in association with a low-fat diet, improved TAG-related MetS risk profiles.

Predictors of weight loss maintenance and attrition during a 6-month dietary intervention period: results from the DiOGenes study.

There is a need to develop tools to predict individual weight loss maintenance and attrition prognosis. We aimed to identify predictors of weight loss maintenance outcome and attrition in subjects from eight European countries in the DiOGenes project. A total of 932 overweight/obese subjects (body mass index: 27-42 kg m(-2) ) were enrolled in an 8-week low-calorie diet (LCD). The 776 subjects (83%) who achieved at least 8% reduction in their initial body weight were randomized into five dietary arms varying in protein content and glycemic index for a 6-month weight maintenance period. Baseline characteristics, weight loss at weeks 1, 3 and 8 of LCD were assessed as predictors of weight loss maintenance and attrition using multivariate regression and correlation models. The multivariate model showed that the 6-month weight loss maintenance was predicted by: 7.889 - 0.343 × weight loss at week 3 + 1.505 × weight loss at week 8 + 2.422 × gender (0 = male and 1 = female gender) (R(2) = 51%, P = 0.0001). A greater weight loss at week 8 was associated with a lower attrition during the subsequent 6-month dietary intervention period (OR = 0.92, 95% CI: 0.88-0.97, P = 0.001). Furthermore, the men showed an increased likelihood for attrition during the dietary intervention period (OR = 1.54, 95% CI: 1.07-2.20, P = 0.02). A greater weight loss during 8 weeks of LCD and female gender predict better 6-month weight maintenance of weight loss, whereas the baseline characteristics did not predict outcome. Attrition could be strongly predicted by gender and weight loss during LCD.

Initial weight loss on an 800-kcal diet as a predictor of weight loss success after 8 weeks: the Diogenes study.

OBJECTIVE: The purpose of this study was to investigate whether pre-treatment subject characteristics and weight change during the first weeks of a low-calorie diet (LCD) can predict weight loss outcomes at the end of a controlled 8-week weight loss period in overweight and obese adults. SUBJECTS: A total of 932 overweight and obese subjects of both genders were included at eight European centers, and underwent an 8-week LCD period. RESULTS: The weight loss at week 8 was positively correlated with initial body weight (Spearman's rho=0.62), height (rho=0.43), body mass index (rho=0.43), waist (rho=0.48) and hip circumference (rho=0.33), sagittal diameter (rho=0.45), fat mass (rho=0.35) and fat-free mass (rho=0.52), and gender (rho=-0.36) (all P<0.01). In the multivariate regression model, adjusted for center, only initial body weight, early weight loss (week 1) and weight loss at week 3 were significant predictors of weight loss outcome at week 8: weight loss (kg) at week 8=0.09+0.046 x baseline body weight (kg)-0.311 x weight loss (kg) at week 1+1.284 x weight loss (kg) at week 3 (R(2)=68%, P<0.0001). A weight loss of > or =2.6 kg at week 1 during the LCD period was identified as the optimal cut-off predictor for at least 10 kg weight loss at week 8. CONCLUSIONS: This study suggests that initial body weight, early weight loss (week 1) and weight loss at week 3 are predictors of final weight loss during an 8-week LCD, and may be used as early biomarkers of subsequent responses to an LCD diet.

Developing a methodology for assigning glycaemic index values to foods consumed across Europe.

There is growing evidence that the glycaemic index (GI) of the diet is important with respect to body weight and metabolic disease risk. However, research is limited by the paucity of GI values for commonly consumed carbohydrate-rich foods in European countries. A new methodology has been developed for consistent assignment of GI values to foods across five European databases used in the Diogenes intervention study. GI values were assigned according to five decreasing levels of confidence (1) Measured values for specific foods; (2) Published values from published sources; (3) Equivalent values where published values for similar foods existed; (4) Estimated values assigned as one of three values representing low/medium/high GI ranges and (5) Nominal values assigned as 70, where no other value could be assigned with sufficient confidence. GI values were assigned to 5105 foods. In food records collected at baseline, the contribution to carbohydrate intake of foods assigned levels 1-2 ranged from 16% to 43% depending on country, and this increased to 53-81% including level 3 foods. The degree of confidence to assigned GI values differed across Europe. This standardized approach of assigning GI values will be made available to other researchers to facilitate further investigation into the effects of dietary GI on health.

Cold-induced vasoconstriction at forearm and hand skin sites: the effect of age.

During mild cold exposure, elderly are at risk of hypothermia. In humans, glabrous skin at the hands is well adapted as a heat exchanger. Evidence exists that elderly show equal vasoconstriction due to local cooling at the ventral forearm, yet no age effects on vasoconstriction at hand skin have been studied. Here, we tested the hypotheses that at hand sites (a) elderly show equal vasoconstriction due to local cooling and (b) elderly show reduced response to noradrenergic stimuli. Skin perfusion and mean arterial pressure were measured in 16 young adults (Y: 18-28 years) and 16 elderly (E: 68-78 years). To study the effect of local vasoconstriction mechanisms local sympathetic nerve terminals were blocked by bretylium (BR). Baseline local skin temperature was clamped at 33 degrees C. Next, local temperature was reduced to 24 degrees C. After 15 min of local cooling, noradrenaline (NA) was administered to study the effect of neural vasoconstriction mechanisms. No significant age effect was observed in vasoconstriction due to local cooling at BR sites. After NA, vasoconstriction at the forearm showed a significant age effect; however, no significant age effect was found at the hand sites. [Change in CVC (% from baseline): Forearm Y: -76 +/- 3 vs. E: -60 +/- 5 (P < 0.01), dorsal hand Y: -74 +/- 4 vs. E: -72 +/- 4 (n.s.), ventral hand Y: -80 +/- 7 vs. E: -70 +/- 11 (n.s.)]. In conclusion, in contrast to results from the ventral forearm, elderly did not show a blunted response to local cooling and noradrenaline at hand skin sites. This indicates that at hand skin the noradrenergic mechanism of vasoconstriction is maintained with age.

Effects of dietary fat modification on skeletal muscle fatty acid handling in the metabolic syndrome.

OBJECTIVE: In the metabolic syndrome (MetS), increased fat storage in 'nonadipose' tissues such as skeletal muscle may be related to insulin resistance ('lipid overflow' hypothesis). The objective of this study was to examine the effects of dietary fat modification on the capacity of skeletal muscle to handle dietary and endogenous fatty acids (FAs). SUBJECTS AND METHODS: In total, 29 men with the MetS were randomly assigned to one of four diets for 12 weeks: a high-fat saturated fat diet (HSFA, n=6), a high-fat monounsaturated fat diet (HMUFA, n=7) and two low-fat high-complex carbohydrate diets supplemented with (LFHCCn-3, n=8) or without (LFHCC, n=8) 1.24 g per day docosahexaenoic and eicosapentaenoic acid. Fasting and postprandial skeletal muscle FA handling was examined by measuring arteriovenous concentration differences across the forearm muscle. [(2)H(2)]-palmitate was infused intravenously to label endogenous triacylglycerol (TAG) and free fatty acids in the circulation and subjects received a high-fat mixed meal (2.6 MJ, 61 energy% fat) containing [U-(13)C]-palmitate to label chylomicron-TAG. RESULTS: Postprandial circulating TAG concentrations were significantly lower after dietary intervention in the LFHCCn-3 group compared to the HSFA group (DeltaiAUC -139+/-67 vs 167+/-70 micromol l(-1) min(-1), P=0.009), together with decreased concentrations of [U-(13)C]-labeled TAG, representing dietary FA. Fasting TAG clearance across forearm muscle was decreased on the HSFA diet, whereas no differences were observed in postprandial forearm muscle FA handling between diets. CONCLUSION: Chronic manipulation of dietary fat quantity and quality did not affect forearm muscle FA handling in men with the MetS. Postprandial TAG concentrations decreased on the LFHCCn-3 diet, which could be (partly) explained by lower concentration of dietary FA in the circulation.