Showing papers by "Arne Astrup published in 2010"
TL;DR: A modest increase in protein content and a modest reduction in the glycemic index led to an improvement in study completion and maintenance of weight loss in this large European study.
Abstract: Background Studies of weight-control diets that are high in protein or low in glycemic index have reached varied conclusions, probably owing to the fact that the studies had insufficient power. Methods We enrolled overweight adults from eight European countries who had lost at least 8% of their initial body weight with a 3.3-MJ (800-kcal) low-calorie diet. Participants were randomly assigned, in a two-by-two factorial design, to one of five ad libitum diets to prevent weight regain over a 26-week period: a low-protein and low-glycemic-index diet, a low-protein and high-glycemic-index diet, a high-protein and low-glycemic-index diet, a high-protein and high-glycemic-index diet, or a control diet. Results A total of 1209 adults were screened (mean age, 41 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 34), of whom 938 entered the low-calorie-diet phase of the study. A total of 773 participants who completed that phase were randomly assigned to one of the five...
736 citations
TL;DR: Exome sequencing of 200 individuals from Denmark with targeted capture of 18,654 coding genes and sequence coverage of each individual exome at an average depth of 12-fold is reported, suggesting that deleterious substitutions are primarily recessive.
Abstract: Targeted capture combined with massively parallel exome sequencing is a promising approach to identify genetic variants implicated in human traits. We report exome sequencing of 200 individuals from Denmark with targeted capture of 18,654 coding genes and sequence coverage of each individual exome at an average depth of 12-fold. On average, about 95% of the target regions were covered by at least one read. We identified 121,870 SNPs in the sample population, including 53,081 coding SNPs (cSNPs). Using a statistical method for SNP calling and an estimation of allelic frequencies based on our population data, we derived the allele frequency spectrum of cSNPs with a minor allele frequency greater than 0.02. We identified a 1.8-fold excess of deleterious, non-syonomyous cSNPs over synonymous cSNPs in the low-frequency range (minor allele frequencies between 2% and 5%). This excess was more pronounced for X-linked SNPs, suggesting that deleterious substitutions are primarily recessive.
319 citations
TL;DR: The scientific evidence for the effects of several dietary manipulations and sustainable strategies for weight loss and body weight stability as well as for treating specific features of the metabolic syndrome are reviewed.
Abstract: Weight loss and subsequent body weight maintenance are difficult for obese individuals despite the wide variety of dietary regimens and approaches. A substantial body of scientific evidence has shown that by simply varying the macronutrient distribution and composition of dietary factors, weight losses of varying amounts, longer-term body weight maintenance periods, better appetite regulation, and changes in features of the metabolic syndrome can be achieved. At present, renewed efforts are underway to increase the protein content of weight-loss diets, simultaneously restrict fat consumption to no more than 30%, favor polyunsaturated fat, have carbohydrates account for between 40 and 50% of total energy intake, and promote the consumption of low-glycemic foods. The present article reviews the scientific evidence for the effects of several dietary manipulations and sustainable strategies for weight loss and body weight stability as well as for treating specific features of the metabolic syndrome.
296 citations
TL;DR: Despite major cultural and dietary regional differences in Europe, interventions addressing effects of dietary factors are feasible with a reasonable attrition and ‘results’ will be limited to baseline characteristics of the study populations included.
Abstract: Diogenes is a Pan-European, randomized, controlled dietary intervention study investigating the effects of dietary protein and glycaemic index on weight (re)gain, metabolic and cardiovascular risk factors in obese and overweight families in eight European centres. The article is methodological in character, and the presentation of 'results' will be limited to baseline characteristics of the study populations included. A total of 891 families with at least one overweight/obese parent underwent screening. The parents started an initial 8-week low-calorie diet and families with minimum one parent attaining a weight loss of > or = 8%, were randomized to one of five energy ad libitum, low-fat (25-30 E%) diets for 6 or 12 months: low protein/low glycaemic index, low protein/high glycaemic index, high protein/low glycaemic index, high protein/high glycaemic index or control (national dietary guidelines). At two centres the families were provided dietary instruction plus free foods for 6 months followed by 6-month dietary instruction only. At the remaining six centres the families received dietary instruction only for 6 months. The median weight loss during the low-calorie diet was 10.3 kg (inter-quartile range: 8.7-12.8 kg, n = 775). A total of 773 adults and 784 children were randomized to the 6-month weight (re)gain prevention phase. Despite major cultural and dietary regional differences in Europe, interventions addressing effects of dietary factors are feasible with a reasonable attrition.
190 citations
TL;DR: LBW subjects developed peripheral insulin resistance and decreased gene expression of PPARGC1A and OXPHOS genes when challenged with fat overfeeding and this work provides the first experimental support in humans that DNA methylation induced by overfeeding is reversible.
Abstract: Context: Low birth weight (LBW) and unhealthy diets are risk factors of metabolic disease including type 2 diabetes (T2D). Genetic, nongenetic, and epigenetic data propose a role of the key metabolic regulator peroxisome proliferator-activated receptor gamma, coactivator 1alpha (PPARGC1A) in the development of T2D. Objective: Our objective was to investigate gene expression and DNA methylation of PPARGC1A and coregulated oxidative phosphorylation (OXPHOS) genes in LBW and normal birth weight (NBW) subjects during control and high-fat diets. Design, Subjects, and Main Outcome Measures: Twenty young healthy men with LBW and 26 matched NBW controls were studied after 5 d high-fat overfeeding (+50% calories) and after a control diet in a randomized manner. Hyperinsulinemic-euglycemic clamps were performed and skeletal muscle biopsies excised. DNA methylation and gene expression were measured using bisulfite sequencing and quantitative real-time PCR, respectively. Results: When challenged with high-fat overfeeding, LBW subjects developed peripheral insulin resistance and reduced PPARGC1A and OXPHOS (P < 0.05) gene expression. PPARGC1A methylation was significantly higher in LBW subjects (P = 0.0002) during the control diet. However, PPARGC1A methylation increased in only NBW subjects after overfeeding in a reversible manner. DNA methylation of PPARGC1A did not correlate with mRNA expression. Conclusions: LBW subjects developed peripheral insulin resistance and decreased gene expression of PPARGC1A and OXPHOS genes when challenged with fat overfeeding. The extent to which our finding of a constitutively increased DNA methylation in the PPARGC1A promoter in LBW subjects may contribute needs to be determined. We provide the first experimental support in humans that DNA methylation induced by overfeeding is reversible.
187 citations
TL;DR: A 16-week formula-diet weight-loss program resulted in a fast and effective weight loss with very few adverse events resulting in a highly significant improvement in symptoms in overweight patients with knee OA.
112 citations
TL;DR: Results show that wholemeal breads increased satiety measures compared to their refined counterparts; however no significant effect on subsequent EI was observed.
111 citations
TL;DR: It is found that the LP/HGI combination increased body fat, whereas the HP/LGI combination was protective against obesity in this sample of children.
Abstract: OBJECTIVE: To investigate the effect of protein and glycemic index (GI) on body composition among European children in the randomized, 6-month dietary intervention DiOGenes (diet, obesity, and genes) family-based study. PATIENTS AND METHODS: In the study, 827 children (381 boys and 446 girls), aged 5 to 18 years, completed baseline examinations. Families with parents who lost ≥8% of their weight during an 8-week run-in low-calorie diet period were randomly assigned to 1 of 5 ad libitum diets: low protein (LP)/low glycemic index (LGI); LP/high GI (HGI); high protein (HP)/LGI; HP/HGI; and control diet. The target difference was 15 GI U between the LGI/HGI groups and 13 protein percentage points between the LP/HP groups. There were 658 children examined after 4 weeks. Advice on food-choice modification was provided at 6 visits during this period. No advice on weight loss was provided because the focus of the study was the ability of the diets to affect outcomes through appetite regulation. Anthropometric measurements and body composition were assessed at baseline, week 4, and week 26. RESULTS: In the study, 465 children (58.1%) completed all assessments. The achieved differences between the GI and protein groups were 2.3 GI U and 4.9 protein percentage points, respectively. The LP/HGI group increased body fat percentage significantly more than the other groups (P = .040; partial η2 = 0.039), and the percentage of overweight/obese children in the HP/LGI group decreased significantly during the intervention (P = .031). CONCLUSIONS: Neither GI nor protein had an isolated effect on body composition. However, the LP/HGI combination increased body fat, whereas the HP/LGI combination was protective against obesity in this sample of children.
90 citations
TL;DR: It is observed that both the prevalence and incidence of overweight/obesity was best predicted by a combination of risk factors, and the importance of looking beyond reported measures of the ‘Big Two’ factors is emphasized.
Abstract: Objective: To compare two traditional (high dietary lipid intake and non-participation in high-intensity physical exercise, namely the ‘Big Two’ factors) versus three nontraditional (short sleep duration, high disinhibition eating behavior, and low dietary calcium intake) risk factors as predictors of excess body weight and overweight/obesity development Method: Adult participants aged 18–64 years of the Quebec Family Study were selected for cross-sectional (n = 537) and longitudinal (n = 283; 6-year follow-up period) analyses The main outcome measure was overweight/obesity, defined as a BMI ≧ 25 kg/m2 Results: We observed that both the prevalence and incidence of overweight/obesity was best predicted by a combination of risk factors However, short sleep duration, high disinhibition eating behavior and low dietary calcium intake seemed to contribute more to the risk of overweight and obesity than high dietary lipid intake and non-participation in high-intensity physical exercise Globally, the risk of being overweight or obese was two-fold higher for individuals having the three nontraditional risk factors combined (OR 605; 95% CI 426–788) compared to those reporting a high percentage of lipids in their diet together with no vigorous physical activity in their daily schedule (OR 295; 95% CI 218–373) Furthermore, the risk of overweight/obesity was also higher for the combination of any two of the nontraditional risk factors than for the combination of the ‘Big Two’ factors Conclusion: These results are concordant with previous reports showing that obesity is a multifactorial condition, and emphasize the importance of looking beyond reported measures of the ‘Big Two’ factors
73 citations
TL;DR: The ability to control body weight loss independent of energy intake or diet composition is reflected in the SAT transcriptome, and a greater mitochondrial energy gene expression is suggested as being beneficial for weight control.
69 citations
TL;DR: The points system provides a useful starting point for designing improved experimental paradigms for the manipulation of dietary intake in future trials, and allowed macronutrient manipulations without compromising dietary flexibility or enforcing energy restrictions.
Abstract: The aim of this study was to describe the development and implementation of a multifaceted, low-fat, weight-loss strategy for a Pan-European randomized controlled dietary intervention study, Diogenes. There were 891 families with at least one overweight/obese parent who underwent screening. Eligible, overweight/obese adults followed an 8-week weight-loss phase with a fixed low-energy diet (800 kcal). On attaining weight loss of > or = 8%, families were randomized to a 6- or 12-month low-fat (25-30%E) diet either based on national dietary guidelines or one of four interventions: low protein (LP)/low glycaemic index (LGI), LP/high GI (HGI), high protein (HP)/LGI and HP/HGI. The impact of each diet in preventing weight (re)gain was tested. A points-based system was used to manipulate dietary protein and carbohydrate. Manipulating carbohydrate composition involved substituting foods with a relatively high or low GI. A questionnaire was designed and completed by study investigators, providing feedback on the dietary intervention methods used to inform future interventions. The points system allowed macronutrient manipulations without compromising dietary flexibility or enforcing energy restrictions. Reported centre/participant differences in the ease of implementing the intervention may reflect dietary diversity and personal preferences for specific weight-management strategies. The points system provides a useful starting point for designing improved experimental paradigms for the manipulation of dietary intake in future trials.
TL;DR: It is suggested that GIP does not affect GE, appetite, energy intake, EE, or the clearance rate of the applied TAG formulation in humans, however, both insulin and GIP lower post-Intralipid FFA concentration, GIP probably via stimulation of insulin secretion, increasing FFA reesterification.
Abstract: We investigated the role of glucose-dependent insulintropic polypeptide (GIP) in the regulation of gastric emptying (GE), appetite, energy intake (EI), energy expenditure (EE), plasma levels of tri...
TL;DR: There is ample evidence to suggest that dietary protein, wholegrain, and fiber promote satiety and either reduce energy absorption or stimulate energy expenditure, and a sufficient intake may also prevent excessive hunger during weight loss diets.
Abstract: Many dietary factors or substances exert effects on the three components of energy balance, and one strategy for tackling weight gain could be to use the inherent properties of these substances. Here, we will review the evidence regarding nutritional factors with a potential impact on energy balance, such as wholegrain foods, dietary fiber and protein content, calcium, and certain spices. There is ample evidence to suggest that dietary protein, wholegrain, and fiber promote satiety and either reduce energy absorption or stimulate energy expenditure. Dietary calcium reduces fat absorption, and a sufficient intake may also prevent excessive hunger during weight loss diets. Chili and mustard have beneficial effects on energy balance, although the quantitative importance of this may be modest. Manipulation of diet composition with an aim to prevent weight gain and weight regain is a promising avenue of research.
TL;DR: 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.
Abstract: Initial weight loss on an 800-kcal diet as a predictor of weight loss success after 8 weeks: the Diogenes study
TL;DR: It is suggested that obese individuals who are homozygous for the TCF7L2 rs7903146 T-risk allele are more sensitive to LF than to HF weight-loss diets.
Maastricht University1, Aarhus University2, Copenhagen University Hospital3, University of Copenhagen4, Paul Sabatier University5, University of Nottingham6, University of Navarra7, University of Paris8, Charles University in Prague9, Steno Diabetes Center10, Health Science University11, Pasteur Institute12, Karolinska University Hospital13
TL;DR: The results should be considered as leads to new hypotheses about effects of specific genetic polymorphisms on fasting and postprandialFat oxidation rates among obese subjects and genotype and FTO was not related to fat oxidation.
Abstract: Both obesity and insulin resistance have been related to low fat oxidation rates, which may be genetically determined. The association between variation in fat oxidation rates among obese subjects and genotype was studied for 42 common single-nucleotide polymorphisms (SNPs) in 26 candidate genes for fat oxidation, insulin resistance, and obesity, including FTO. Energy expenditure (EE) and fat oxidation were measured with indirect calorimetry during fasting and 3 h after a high fat load containing 95 energy% of fat (60% saturated fat, energy content 50% of estimated resting EE) in 722 obese subjects (541 women, 181 men) from 8 European centers. After adjustment for center and gender, -178 A>C CD36 (rs2232169) (P = 0.02), -22510 C>G SLC6A14 (women, rs2011162) (P = 0.03), and T690S C>G PCSK1 (rs6235) (P = 0.02) were related to a reduced fat oxidation, whereas 17 C>G SREBF1 (17 C>G) (P = 0.01) was related to increased fat oxidation in the fasting state. The ability to increase fat oxidation after a high fat load was increased in subjects with -174 G>C IL6 (rs1800795) (P = 0.01). Effect sizes range from 1.1 to 3.1% differences in fat oxidation (expressed as % of EE). FTO rs9939609 was not related to fat oxidation. At the same time, the results are not adjusted for multiple testing, thus none of the associations can be considered statistically significant. The results should therefore only be considered as leads to new hypotheses about effects of specific genetic polymorphisms on fasting and postprandial fat oxidation.
TL;DR: A new methodology has been developed for consistent assignment of GI values to foods across five European databases used in the Diogenes intervention study to facilitate further investigation into the effects of dietary GI on health.
Abstract: 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. © 2010 International Association for the Study of Obesity.
TL;DR: The history of pharmacologic treatment of obesity is characterized by repetition: most drugs that have achieved regulatory approval and reached the markets have subsequently been withdrawn owing to postmarketing discovery of serious adverse effects.
Abstract: The history of pharmacologic treatment of obesity is characterized by repetition: most drugs that have achieved regulatory approval and reached the markets have subsequently been withdrawn owing to postmarketing discovery of serious adverse effects. In 2007, the cannabinoid-receptor antagonist rimonabant was not approved by the Food and Drug Administration (FDA) and was withdrawn from the market in Europe because of an increased risk of depression, anxiety, and suicidal ideation1; the development program for several compounds of the same class that were in phase 3 studies had to be terminated. In January of this year, the European Medicine Agency's Committee . . .
TL;DR: It is found that high versus low calcium intakes from dairy products had no effect on 24-h energy expenditure or substrate oxidation rates, but fecal fat excretion increased approximately 2.5-fold on the high-calcium diets.
TL;DR: TE has a pronounced effect on appetite sensations and a slight effect on energy expenditure at night—both effects can contribute to the strong weight-reducing effect of TE.
Abstract: Tesofensine (TE) is a new drug producing twice the weight loss in obese individuals as seen with currently marketed drugs. It inhibits the presynaptic reuptake of the neurotransmitters noradrenaline, dopamine and serotonin, and is thought to enhance the neurotransmission of all three monoamines. The mechanisms by which it produces weight loss in humans are unresolved. The aim of this study is to investigate the mechanism(s) behind weight reduction by measuring energy expenditure and appetite sensations in overweight and obese individuals. Thirty-two healthy, overweight or moderately obese men were treated with 2.0 mg TE daily for 7 days followed by an additional 7 days with 1.0 mg TE daily or corresponding placebo (PL) in a randomized, controlled trial. They were instructed to maintain habitual food intake and physical activity throughout. Twenty-four-hour energy expenditure (24-h EE), fat oxidation and spontaneous physical activity were measured in a respiration chamber before and after treatment. Body composition was assessed by dual-energy X-ray absorption and appetite was evaluated by visual analogue scales in conjunction with a standardized dinner. Despite efforts to keep body weight and composition constant, TE induced a 1.8 kg weight loss above PL after 2 weeks’ treatment (P<0.0001). TE also induced higher ratings of satiety and fullness and concomitantly lower prospective food intake than placebo. No significant effect of TE on total 24-h EE could be demonstrated compared with PL, but higher energy expenditure was observed during the night period (4.6%; P<0.05) when adjusted for changes in body composition. Furthermore, TE increased 24-h fat oxidation as compared with PL (18 g; P<0.001). TE has a pronounced effect on appetite sensations and a slight effect on energy expenditure at night—both effects can contribute to the strong weight-reducing effect of TE.
TL;DR: Near MC4R variants appear to contribute to body fat, body fat distribution, some metabolic traits, weight development during childhood, but not to energy expenditure.
Abstract: Common variants near melanocortin receptor 4 (MC4R) have been related to fatness and type 2 diabetes. We examined the associations of rs17782313 and rs17700633 in relation to body fat, body fat distribution, metabolic traits, weight development and energy expenditure. Obese young men (n=753, BMI⩾31.0 kg m−2) and a randomly selected group (n=874) identified from a population of 174 800 men were re-examined in three surveys at mean ages 35, 46 and 49 years (S-35, S-46 and S-49). Measurements were available at upto eight times from birth to adulthood. Logistic regression analysis was used to assess odds ratio (OR) for the presence of the carrier allele for a given difference in phenotypic values. Rs17782313 minor C-allele was associated with overall, abdominal and peripheral fatness (range of OR=1.06–1.14 per z-score units) at all three surveys, although only consistently significant at S-35 and S-46. Rs17700633 minor A-allele was also associated with the fatness measures, but significantly so only at S-49 for overall and abdominal fatness (range of OR=1.03–1.15 per z-score units), and peripheral fatness (OR=1.15–1.20 per z-score units). There were only few significant associations with metabolic traits. The rs17782313 C-allele and the rs17700633 A-allele were both associated with lower high-density lipoprotein cholesterol (range of OR=0.64–0.84 per mol l−1), significantly at S-46. The rs17700633 A-allele was significantly associated with insulin (OR=1.25 per 50 pmol l−1), leptin (OR=1.42 per 10 ng μl−1) and insulin sensitivity (OR=0.81 per model unit). The rs17782313 C-allele and the rs17700633 A-allele were both associated with BMI in childhood and adolescence (range of OR=1.04–1.17 per z-score units), significant for the rs17782313 C-allele at the age of 13–19 years and for rs17700633 A-allele at age 7, 10, 13 and 19 years. No significant associations were found for energy expenditure. Near MC4R variants appear to contribute to body fat, body fat distribution, some metabolic traits, weight development during childhood, but not to energy expenditure.
TL;DR: The new rapid method facilitates large scale clinical and nutritional trials with inclusion of diagnostics of chylomicron status and thus creates new opportunities for research in lifestyle diseases and obesity.
Abstract: Background: The lipid content of the chylomicrons is a key biomarker and risk factor of cardiovascular diseases and for the understanding of obesity. A high throughput determination of chylomicrons in human blood plasma is outlined. Methods: The new method, which uses a combination of Nuclear Magnetic Resonance (NMR) analysis and multivariate calibration analysis (chemometrics), is based on a correlation analysis towards the established standard method (ultracentrifugation and colorimetric test kit) and enables extraordinarily fast, inexpensive, and robust prediction of triglyceride (TG) content in chylomicrons. It is the position and shape of the complex lipid methylene resonance band that determines the chylomicron TG status and this information is extracted by the multivariate regression method. Results: The resulting method is a relatively simple multivariate model that facilitates parsimonious and accurate prediction of chylomicron lipids from NMR spectra of blood. The chemometric model predicts the chylomicron TG content with a correlation coefficient (R) of 0.96 when plotted against density gradient ultracentrifugation data. Conclusions: The new rapid method facilitates large scale clinical and nutritional trials with inclusion of diagnostics of chylomicron status and thus creates new opportunities for research in lifestyle diseases and obesity.
TL;DR: The data presented suggest that casein per se did not modulate the postprandial triglyceride response in type 2 diabetes.
Abstract: Background and aims Exaggerated and prolonged postprandial lipemia is potentially atherogenic and associated with type 2 diabetes. Limited data exist regarding the influence of dietary protein on postprandial lipemia in type 2 diabetes. We investigated, over 8-h, the acute effects of casein alone or in combination with carbohydrate on postprandial lipid and incretin responses to a fat-rich meal in type 2 diabetes. Methods and results Eleven type 2 diabetic subjects ingested four test meals in random order: an energy-free soup plus 80g of fat (control-meal); control-meal plus 45g carbohydrates (CHO-meal); control-meal plus 45g of casein (PRO-meal); and PRO-meal plus 45g carbohydrates (CHO+PRO-meal). Triglyceride and retinyl palmitate responses were measured in plasma and in a chylomicron-rich and chylomicron-poor fraction. We found no significant differences in triglyceride responses to PRO- and CHO+PRO-meal compared to the control-meal. However, the addition of casein to the CHO-meal reduced the raised triglyceride response in the chylomicron-rich fraction. Retinyl palmitate responses did not differ significantly between meals in the chylomicron-rich fraction, whereas the PRO-meal increased retinyl palmitate in the chylomicron-poor fraction. PRO- and PRO+CHO-meal increased insulin and glucagon compared to the control-meal. PRO+CHO-meal increased the glucose-dependent insulinotropic peptide response while no change in glucagon-like peptide-1 responses was detected. Conclusions The data presented suggest that casein per se did not modulate the postprandial triglyceride response in type 2 diabetes. When added to carbohydrate, casein suppressed the triglyceride response in the chylomicron-rich fraction, increased insulin and glucagon but did not affect the incretin responses.
TL;DR: It is found that common and rare variation in the GHSR locus are related to increased prevalence of obesity and overweight among Whites, yet there was no consistent relationship with obesity in neither family- nor population-based studies.
Abstract: Background: The growth hormone secretagogue receptor (GHSR) is mediating hunger sensation when stimulated by its natural ligand ghrelin. In the present study, we tested the hypothesis that common and rare variation in the GHSR locus are related to increased prevalence of obesity and overweight among Whites. Methodology/Principal Findings: In a population-based study sample of 15,854 unrelated, middle-aged Danes, seven variants were genotyped to capture common variation in an 11 kbp region including GHSR. These were investigated for their individual and haplotypic association with obesity. None of these analyses revealed consistent association with measures of obesity. A -151C/T promoter mutation in the GHSR was found in two unrelated obese patients. One family presented with complete co-segregation, but the other with incomplete co-segregation. The mutation resulted in an increased transcriptional activity (p,0.02) and introduction of a specific binding for Sp-1-like nuclear extracts relative to the wild type. The -151C/T mutation was genotyped in the 15,854 Danes with a minor allele frequency of 0.01%. No association with obesity in carriers (mean BMI: 2764 kg/m 2 ) versus non-carriers (mean BMI: 2865 kg/m 2 )( p.0.05) could be shown. Conclusions/Significance: In a population-based study sample of 15,854 Danes no association between GHSR genotypes and measures of obesity and overweight was found. Also, analyses of GHSR haplotypes lack consistent associations with obesity related traits. A rare functional GHSR promoter mutation variant was identified, yet there was no consistent relationship with obesity in neither family- nor population-based studies.
TL;DR: The findings suggest that in overweight subjects after weight loss the thrombotic risk profile is improved most favourably by the LF diet compared with the MUFA diet based on the reduction in fibrinogen concentrations.
Abstract: Diet is important in the prevention of CVD, and it has been suggested that a diet high in MUFA is more cardioprotective than a low-fat diet. We hypothesised that the thrombotic risk profile is improved most favourably by a high-MUFA diet compared with a low-fat diet. This was tested in a parallel randomised intervention trial on overweight individuals (aged 28·2 (SD 4·6) years) randomly assigned to a diet providing a moderate amount of fat (35– 45 % of energy; . 20 % of fat as MUFA) (MUFA diet; n 39), to a low-fat (LF; 20– 30 % of energy) diet (n 43), or to a control diet (35 % of energy as fat; n 24) for 6 months after a weight loss of about 10 %. Protein constituted 10– 20 % of energy in all three diets. All foods were provided free of charge from a purpose-built supermarket. Fasting blood samples were collected before and after intervention and analysed for factor VII coagulant activity (FVII:c), fibrinogen, prothrombin fragment 1 þ 2 (F1 þ 2), D-dimer and plasminogen activator inhibitor (PAI). The fibrinogen concentration was significantly lowered by the LF diet, but not by the MUFA diet. Changes in fibrinogen differed significantly between diet groups. BMI and PAI concentration increased and D-dimer concentrations were reduced irrespective of the diets. No changes were observed for FVII:c and F1 þ 2. Our findings suggest that in overweight subjects after weight loss the thrombotic risk profile is improved most favourably by the LF diet compared with the MUFA diet based on the reduction in fibrinogen concentrations.
TL;DR: A diet that provides 1000 mg per day calcium, or a dietary supplement of calcium (and vitamin D), is a cheap means of reducing the risk of pre-eclampsia in women at increased risk and in women with low calcium intakes, and has other health benefi ts while doing no harm.