Taylor, M. (Moira)
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- TFAP2B influences the effect of dietary fat on weight loss under energy restriction(Public Library of Science, 2012) Martinez, J.A. (José Alfredo); Harder, M.N. (Marie N.); Saris, W.H.M. (Wim H. M.); Rousseau, F. (Francis); Kunesova, M. (Marie); Sørensen, T.I.A (Thorkild I. A.); Hansen, T. (Torben); Ängquist, L. (Lars); Langin, D. (D.); Pfeiffer, A.F. (A.F.); Banasik, K. (Karina); Astrup, A. (Arne); Stocks, T. (Tanja); Rössner, S. (Stephan); Polak, J. (Jan); Arner, P. (P.); Taylor, M. (Moira); Pedersen, O. (Oluf); Kamatani, Y. (Yoichiro); Holst, C. (C.); Hager, J. (Jörg); Oppert, J.M. (Jean M.); MacDonald, I. (Ian)BACKGROUND: Numerous gene loci are related to single measures of body weight and shape. We investigated if 55 SNPs previously associated with BMI or waist measures, modify the effects of fat intake on weight loss and waist reduction under energy restriction. METHODS AND FINDINGS: Randomized controlled trial of 771 obese adults. (Registration: ISRCTN25867281.) One SNP was selected for replication in another weight loss intervention study of 934 obese adults. The original trial was a 10-week 600 kcal/d energy-deficient diet with energy percentage from fat (fat%) in range of 20-25 or 40-45. The replication study used an 8-weeks diet of 880 kcal/d and 20 fat%; change in fat% intake was used for estimation of interaction effects. The main outcomes were intervention weight loss and waist reduction. In the trial, mean change in fat% intake was -12/+4 in the low/high-fat groups. In the replication study, it was -23/-12 among those reducing fat% more/less than the median. TFAP2B-rs987237 genotype AA was associated with 1.0 kg (95% CI, 0.4; 1.6) greater weight loss on the low-fat, and GG genotype with 2.6 kg (1.1; 4.1) greater weight loss on the high-fat (interaction p-value; p = 0.00007). The replication study showed a similar (non-significant) interaction pattern. Waist reduction results generally were similar. Study-strengths include (i) the discovery study randomised trial design combined with the replication opportunity (ii) the strict dietary intake control in both studies (iii) the large sample sizes of both studies. Limitations are (i) the low minor allele frequency of the TFAP2B polymorphism, making it hard to investigate non-additive genetic effects (ii) the different interventions preventing identical replication-discovery study designs (iii) some missing data for non-completers and dietary intake. No adverse effects/outcomes or side-effects were observed. CONCLUSIONS: Under energy restriction, TFAP2B may modify the effect of dietary fat intake on weight loss and waist reduction.
- PREVIEW study-influence of a behavior modification intervention (PREMIT) in over 2300 people with pre-diabetes: intention, self-efficacy and outcome expectancies during the early phase of a lifestyle intervention(Taylor and Francis Group, 2018) Martinez, J.A. (José Alfredo); Handjiev, S. (Svetoslav); Sando-Pedersen, F. (Finn); Schlicht, W. (Wolfgang); Brand-Miller, J. (Jennie); Pietiläinen, K.H. (Kirsi H.); Raben, A. (Anne); Berendsen, A.A.M. (Agnes A. M.); Silvestre, M.P. (Marta P.); Navas-Carretero, S. (Santiago); Taylor, M. (Moira); Adam, T.C. (Tanja C.); Huttunen-Lenz, M. (Maija); Drummen, M. (Mathijs); Fogelholm, M. (Mikael); Poppitt, S.D. (Sally D.); Hansen, S. (Sylvia); Meinert-Larsen, T. (Thomas); MacDonald, I. (Ian); Christensen, P. (Pia)Purpose: Onset of type 2 diabetes (T2D) is often gradual and preceded by impaired glucose homeostasis. Lifestyle interventions including weight loss and physical activity may reduce the risk of developing T2D, but adherence to a lifestyle change is challenging. As part of an international T2D prevention trial (PREVIEW), a behavior change intervention supported participants in achieving a healthier diet and physically active lifestyle. Here, our aim was to explore the influence of this behavioral program (PREMIT) on social-cognitive variables during an 8-week weight loss phase. Methods: PREVIEW consisted of an initial weight loss, Phase I, followed by a weightmaintenance, Phase II, for those achieving the 8-week weight loss target of ≥ 8% from initial bodyweight. Overweight and obese (BMI ≥25 kg/m2) individuals aged 25 to 70 years with confirmed pre-diabetes were enrolled. Uni- and multivariate statistical methods were deployed to explore differences in intentions, self-efficacy, and outcome expectancies between those who achieved the target weight loss (“achievers”) and those who did not (“non-achievers”). Results: At the beginning of Phase I, no significant differences in intentions, self-efficacy and outcome expectancies between “achievers” (1,857) and “non-achievers” (163) were found. “Non-achievers” tended to be younger, live with child/ren, and attended the PREMIT sessions less frequently. At the end of Phase I, “achievers” reported higher intentions (healthy eating χ2 (1)=2.57; P <0.008, exercising χ2 (1)=0.66; P <0.008), self-efficacy (F(2; 1970)=10.27, P <0.005), and were more positive about the expected outcomes (F(4; 1968)=11.22, P <0.005). Conclusion: Although statistically significant, effect sizes observed between the two groups were small. Behavior change, however, is multi-determined. Over a period of time, even small differences may make a cumulative effect. Being successful in behavior change requires that the “new” behavior is implemented time after time until it becomes a habit. Therefore, having even slightly higher self-efficacy, positive outcome expectancies and intentions may over time result in considerably improved chances to achieve long-term lifestyle changes.
- Genetic polymorphisms and weight loss in obesity: A randomised trial of hypo-energetic high-versus low-fat diets(Public Library of Sciences, 2006) Martinez, J.A. (José Alfredo); Saris, W.H.M. (Wim H. M.); Sørensen, T.I.A (Thorkild I. A.); Boutin, P. (Philippe); Verdich, C. (Camilla); Petersen, M. (Martin); Langin, D. (D.); Dina, C. (Christian); Astrup, A. (Arne); Clement, K. (K.); Petersen, L. (Liselotte); Echwald, S.M. (S.M.); Polak, J. (Jan); Arner, P. (P.); Larsen, L.H. (Lesli H.); Taylor, M. (Moira); Pedersen, O. (Oluf); Stich, V. (Vladimir); Toubro, S. (Soren); Holst, C. (C.); Oppert, J.M. (Jean M.); Froguel, P. (Philippe); MacDonald, I. (Ian)OBJECTIVES: To study if genes with common single nucleotide polymorphisms (SNPs) associated with obesity-related phenotypes influence weight loss (WL) in obese individuals treated by a hypo-energetic low-fat or high-fat diet. DESIGN: Randomised, parallel, two-arm, open-label multi-centre trial. SETTING: Eight clinical centres in seven European countries. PARTICIPANTS: 771 obese adult individuals. INTERVENTIONS: 10-wk dietary intervention to hypo-energetic (-600 kcal/d) diets with a targeted fat energy of 20%-25% or 40%-45%, completed in 648 participants. OUTCOME MEASURES: WL during the 10 wk in relation to genotypes of 42 SNPs in 26 candidate genes, probably associated with hypothalamic regulation of appetite, efficiency of energy expenditure, regulation of adipocyte differentiation and function, lipid and glucose metabolism, or production of adipocytokines, determined in 642 participants. RESULTS: Compared with the noncarriers of each of the SNPs, and after adjusting for gender, age, baseline weight and centre, heterozygotes showed WL differences that ranged from -0.6 to 0.8 kg, and homozygotes, from -0.7 to 3.1 kg. Genotype-dependent additional WL on low-fat diet ranged from 1.9 to -1.6 kg in heterozygotes, and from 3.8 kg to -2.1 kg in homozygotes relative to the noncarriers. Considering the multiple testing conducted, none of the associations was statistically significant. CONCLUSIONS: Polymorphisms in a panel of obesity-related candidate genes play a minor role, if any, in modulating weight changes induced by a moderate hypo-energetic low-fat or high-fat diet.
- Contribution of energy restriction and macronutrient composition to changes in adipose tissue gene expression during dietary weight-loss programs in obese women.(Endocrine Society, 2008) Martinez, J.A. (José Alfredo); Saris, W.H.M. (Wim H. M.); Viguerie, N. (N.); Vidal, H. (Hubert); Klimcakova, E. (E.); Sørensen, T.I.A (Thorkild I. A.); Langin, D. (D.); Clement, K. (K.); Arner, P. (P.); Taylor, M. (Moira); Capel, F. (F.); Vega, N. (Nathalie); Holst, C. (C.); Oppert, J.M. (Jean M.); Dejean, S. (S.)CONTEXT: Hypoenergetic diets are used to reduce body fat mass and metabolic risk factors in obese subjects. The molecular changes in adipose tissue associated with weight loss and specifically related to the dietary composition are poorly understood. OBJECTIVE: We investigated adipose tissue gene expression from human obese women according to energy deficit and the fat and carbohydrate content of the diet. DESIGN AND SETTING: Obese subjects recruited among eight European clinical centers were followed up 10 wk of either a low-fat (high carbohydrate) or a moderate-fat (low carbohydrate) hypoenergetic diet. SUBJECTS: Two sets of 47 women in each dietary arm were selected among 648 subjects matched for anthropometric and biological parameters. MAIN OUTCOME MEASURE: We measured adipose tissue gene expression changes in one set using a candidate gene approach. The other set was used to survey 24,469 transcripts using DNA microarrays. Results were analyzed using dedicated statistical methods. Diet-sensitive regulations were confirmed on the other set of subjects. RESULTS: The two diets induced similar weight loss and similar changes for most of the biological variables except for components of the blood lipid profile. One thousand genes were regulated by energy restriction. We validated an effect of the fat to carbohydrate ratio for five genes (FABP4, NR3C1, SIRT3, FNTA, and GABARAPL2) with increased expression during the moderate-fat diet. CONCLUSIONS: Energy restriction had a more pronounced impact on variations in human adipose tissue gene expression than macronutrient composition. The macronutrient-sensitive regulation of a subset of genes may influence adipose tissue function and metabolic response.
- Men and women respond differently to rapid weight loss: Metabolic outcomes of a multi-centre intervention study after a low-energy diet in 2500 overweight, individuals with pre-diabetes (PREVIEW)(Wiley, 2018) Martinez, J.A. (José Alfredo); Handjiev, S. (Svetoslav); Sando-Pedersen, F. (Finn); Brodie, S. (Shannon); Ritz, C. (Christian); Pastor-Sanz, L. (Laura); Brand-Miller, J. (Jennie); Westerterp-Plantenga, M. (Margriet); Pietiläinen, K.H. (Kirsi H.); Raben, A. (Anne); Handjieva-Darlenska, T. (Teodora); Silvestre, M.P. (Marta P.); Astrup, A. (Arne); Navas-Carretero, S. (Santiago); Taylor, M. (Moira); Sundvall, J. (Jouko); Huttunen-Lenz, M. (Maija); Drummen, M. (Mathijs); Fogelholm, M. (Mikael); Poppitt, S.D. (Sally D.); Hansen, S. (Sylvia); Meinert-Larsen, T. (Thomas); MacDonald, I. (Ian); Christensen, P. (Pia)Aims: The PREVIEW lifestyle intervention study (ClinicalTrials.gov Identifier: NCT01777893) is, to date, the largest, multinational study concerning prevention of type-2 diabetes. We hypothesized that the initial, fixed low-energy diet (LED) would induce different metabolic outcomes in men vs women. Materials and methods: All participants followed a LED (3.4 MJ/810 kcal/daily) for 8 weeks (Cambridge Weight Plan). Participants were recruited from 8 sites in Europe, Australia and New Zealand. Those eligible for inclusion were overweight (BMI ≥ 25 kg/m2 ) individuals with pre-diabetes according to ADA-criteria. Outcomes of interest included changes in insulin resistance, fat mass (FM), fat-free mass (FFM) and metabolic syndrome Z-score. Results: In total, 2224 individuals (1504 women, 720 men) attended the baseline visit and 2020 (90.8%) completed the follow-up visit. Following the LED, weight loss was 16% greater in men than in women (11.8% vs 10.3%, respectively) but improvements in insulin resistance were similar. HOMA-IR decreased by 1.50 ± 0.15 in men and by 1.35 ± 0.15 in women (ns). After adjusting for differences in weight loss, men had larger reductions in metabolic syndrome Z-score, C-peptide, FM and heart rate, while women had larger reductions in HDL cholesterol, FFM, hip circumference and pulse pressure. Following the LED, 35% of participants of both genders had reverted to normo-glycaemia. Conclusions: An 8-week LED induced different effects in women than in men. These findings are clinically important and suggest gender-specific changes after weight loss. It is important to investigate whether the greater decreases in FFM, hip circumference and HDL cholesterol in women after rapid weight loss compromise weight loss maintenance and future cardiovascular health.
- Higher protein intake is not associated with decreased kidney function in pre-diabetic older adults following a one-year intervention-a preview sub-study(MDPI, 2018) Martinez, J.A. (José Alfredo); Simpson, E. (Elizabeth); Andersen, J.R. (Jens Rikardt); Møller, G. (Grith); Swindell, N. (Nils); Ritz, C. (Christian); Mackintosh, K.A. (Kelly A.); Larsen, T.M. (Thomas M.); Raben, A. (Anne); Silvestre, M.P. (Marta P.); Jalo, E. (Elli); Navas-Carretero, S. (Santiago); Taylor, M. (Moira); Dragsted, L.O. (Lars O.); Fogelholm, M. (Mikael); Poppitt, S.D. (Sally D.); Stratton, G. (Gareth); MacDonald, I. (Ian); Christensen, P. (Pia)Concerns about detrimental renal effects of a high-protein intake have been raised due to an induced glomerular hyperfiltration, since this may accelerate the progression of kidney disease. The aim of this sub-study was to assess the effect of a higher intake of protein on kidney function in pre-diabetic men and women, aged 55 years and older. Analyses were based on baseline and one-year data in a sub-group of 310 participants included in the PREVIEW project (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World). Protein intake was estimated from four-day dietary records and 24-hour urinary urea excretion. We used linear regression to assess the association between protein intake after one year of intervention and kidney function markers: creatinine clearance, estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (ACR), urinary urea/creatinine ratio (UCR), serum creatinine, and serum urea before and after adjustments for potential confounders. A higher protein intake was associated with a significant increase in UCR (p = 0.03) and serum urea (p = 0.05) after one year. There were no associations between increased protein intake and creatinine clearance, eGFR, ACR, or serum creatinine. We found no indication of impaired kidney function after one year with a higher protein intake in pre-diabetic older adults.