| 1. |
- McCaffery, Jeanne M., et al.
(författare)
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TCF7L2 Polymorphism, Weight Loss and Proinsulin: Insulin Ratio in the Diabetes Prevention Program
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- Aims: TCF7L2 variants have been associated with type 2 diabetes, body mass index (BMI), and deficits in proinsulin processing and insulin secretion. Here we sought to test whether these effects were apparent in high-risk individuals and modify treatment responses. Methods: We examined the potential role of the TCF7L2 rs7903146 variant in predicting resistance to weight loss or a lack of improvement of proinsulin processing during 2.5-years of follow-up participants (N = 2,994) from the Diabetes Prevention Program (DPP), a randomized controlled trial designed to prevent or delay diabetes in high-risk adults. Results: We observed no difference in the degree of weight loss by rs7903146 genotypes. However, the T allele (conferring higher risk of diabetes) at rs7903146 was associated with higher fasting proinsulin at baseline (P, 0.001), higher baseline proinsulin: insulin ratio (p<0.0001) and increased proinsulin: insulin ratio over a median of 2.5 years of follow-up (P = 0.003). Effects were comparable across treatment arms. Conclusions: The combination of a lack of impact of the TCF7L2 genotypes on the ability to lose weight, but the presence of a consistent effect on the proinsulin: insulin ratio over the course of DPP, suggests that high-risk genotype carriers at this locus can successfully lose weight to counter diabetes risk despite persistent deficits in insulin production.
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| 2. |
- McCaffery, Jeanne M., et al.
(författare)
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Genetic Predictors of Change in Waist Circumference and Waist-to-Hip Ratio With Lifestyle Intervention : The Trans-NIH Consortium for Genetics of Weight Loss Response to Lifestyle Intervention
- 2022
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 71:4, s. 669-676
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with waist circumference (WC) and waist-to-hip ratio (WHR) adjusted for BMI (WCadjBMI and WHRadjBMI), but it remains unclear whether these SNPs relate to change in WCadjBMI or WHRadjBMI with lifestyle intervention for weight loss. We hypothesized that polygenic scores (PS) comprised of 59 SNPs previously associated with central adiposity would predict less of a reduction in WCadjBMI or WHRadjBMI at 8-10 weeks in two lifestyle intervention trials, NUGENOB and DiOGenes, and at 1 year in five lifestyle intervention trials, Look AHEAD, Diabetes Prevention Program, Diabetes Prevention Study, DIETFITS, and PREDIMED-Plus. One-SD higher PS related to a smaller 1-year change in WCadjBMI in the lifestyle intervention arms at year 1 and thus predicted poorer response (β = 0.007; SE = 0.003; P = 0.03) among White participants overall and in White men (β = 0.01; SE = 0.004; P = 0.01). At average weight loss, this amounted to 0.20-0.28 cm per SD. No significant findings emerged in White women or African American men for the 8-10-week outcomes or for WHRadjBMI. Findings were heterogeneous in African American women. These results indicate that polygenic risk estimated from these 59 SNPs relates to change in WCadjBMI with lifestyle intervention, but the effects are small and not of sufficient magnitude to be clinically significant.
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| 3. |
- McCaffery, Jeanne M., et al.
(författare)
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Replication of the Association of BDNF and MC4R Variants With Dietary Intake in the Diabetes Prevention Program
- 2017
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Ingår i: Psychosomatic Medicine. - : Lippincott Williams & Wilkins. - 0033-3174 .- 1534-7796. ; 79:2, s. 224-233
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Genomewide association studies (GWAS) have identified consistent associations with obesity, with a number of studies implicating eating behavior as a primary mechanism. Few studies have replicated genetic associations with dietary intake. This study evaluates the association between obesity susceptibility loci and dietary intake. Methods: Data were obtained as part of the Diabetes Prevention Program (DPP), a clinical trial of diabetes prevention in persons at high risk of diabetes. The association of 31 genomewide association studies identified obesity risk alleles with dietary intake, measured through a food frequency questionnaire, was investigated in 3,180 participants from DPP at baseline. Results: The minor allele at BDNF, identified as protective against obesity, was associated with lower total caloric intake (beta = -106.06, SE = 33.13; p = .0014) at experimentwide statistical significance (p = .0016), whereas association of MC4R rs571312 with higher caloric intake reached nominal significance (beta = 61.32, SE = 26.24; p = .0194). Among non-Hispanic white participants, the association of BDNF rs2030323 with total caloric intake was stronger (beta = -151.99, SE = 30.09; p < .0001), and association of FTO rs1421085 with higher caloric intake (beta = 56.72, SE = 20.69; p = .0061) and percentage fat intake (beta = 0.37, SE = 0.08; p =. 0418) was also observed. Conclusions: These results demonstrate with the strength of independent replication that BDNF rs2030323 is associated with 100 to 150 greater total caloric intake per allele, with additional contributions of MC4R and, in non-Hispanic white individuals, FTO. As it has been argued that an additional 100 kcal/d could account for the trends in weight gain, prevention focusing on genetic profiles with high dietary intake may help to quell adverse obesity trends.
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| 4. |
- Papandonatos, George D, et al.
(författare)
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Genetic Predisposition to Weight Loss and Regain With Lifestyle Intervention : Analyses From the Diabetes Prevention Program and the Look AHEAD Randomized Controlled Trials
- 2015
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 64:12, s. 4312-4321
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Tidskriftsartikel (refereegranskat)abstract
- Clinically relevant weight loss is achievable through lifestyle modification, but unintentional weight regain is common. We investigated whether recently discovered genetic variants affect weight loss and/or weight regain during behavioral intervention. Participants at high-risk of type 2 diabetes (Diabetes Prevention Program [DPP]; N = 917/907 intervention/comparison) or with type 2 diabetes (Look AHEAD [Action for Health in Diabetes]; N = 2,014/1,892 intervention/comparison) were from two parallel arm (lifestyle vs. comparison) randomized controlled trials. The associations of 91 established obesity-predisposing loci with weight loss across 4 years and with weight regain across years 2-4 after a minimum of 3% weight loss were tested. Each copy of the minor G allele of MTIF3 rs1885988 was consistently associated with greater weight loss following lifestyle intervention over 4 years across the DPP and Look AHEAD. No such effect was observed across comparison arms, leading to a nominally significant single nucleotide polymorphism x treatment interaction (P = 4.3 x 10-3). However, this effect was not significant at a study-wise significance level (Bonferroni threshold P < 5.8 x 10-4). Most obesity-predisposing gene variants were not associated with weight loss or regain within the DPP and Look AHEAD trials, directly or via interactions with lifestyle.
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| 5. |
- Peaceman, Alan M., et al.
(författare)
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Lifestyle Interventions Limit Gestational Weight Gain in Women with Overweight or Obesity : LIFE-Moms Prospective Meta-Analysis
- 2018
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 26:9, s. 1396-1404
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to evaluate the effects of varied lifestyle intervention programs designed to ameliorate excess gestational weight gain (GWG) in pregnant women with overweight or obesity compared with standard care, including effects on pregnancy outcomes. Methods: Seven clinical centers conducted separate randomized clinical trials to test different lifestyle intervention strategies to modify GWG in diverse populations. Eligibility criteria, specific outcome measures, and assessment procedures were standardized across trials. The results of the separate trials were combined using an individual-participant data meta-analysis. Results: For the 1,150 women randomized, the percent with excess GWG per week was significantly lower in the intervention group compared with the standard care group (61.8% vs. 75.0%; odds ratio [95% CI]: 0.52 [0.40 to 0.67]). Total GWG from enrollment to 36 weeks' gestation was also lower in the intervention group (8.1 ± 5.2 vs. 9.7 ± 5.4 kg; mean difference: −1.59 kg [95% CI:−2.18 to −0.99 kg]). The results from the individual trials were similar. The intervention and standard care groups did not differ in preeclampsia, gestational diabetes, cesarean delivery, or birth weight. Conclusions: Behavioral lifestyle interventions focusing primarily on diet and physical activity among women with overweight and obesity resulted in a significantly lower proportion of women with excess GWG. This modest beneficial effect was consistent across diverse intervention modalities in a large, racially and socioeconomically diverse US population of pregnant women.
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| 6. |
- Phelan, Suzanne, et al.
(författare)
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One-year postpartum anthropometric outcomes in mothers and children in the LIFE-Moms lifestyle intervention clinical trials
- 2020
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 44, s. 57-68
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Tidskriftsartikel (refereegranskat)abstract
- Background/objectives: Excess gestational weight gain (GWG) is a risk factor for maternal postpartum weight retention and excessive neonatal adiposity, especially in women with overweight or obesity. Whether lifestyle interventions to reduce excess GWG also reduce 12-month maternal postpartum weight retention and infant weight-for-length z score is unknown. Randomized controlled trials from the LIFE-Moms consortium investigated lifestyle interventions that began in pregnancy and tested whether there was benefit through 12 months on maternal postpartum weight retention (i.e., the difference in weight from early pregnancy to 12 months) and infant-weight-for-length z scores. Subjects/methods: In LIFE-Moms, women (N = 1150; 14.1 weeks gestation at enrollment) with overweight or obesity were randomized within each of seven trials to lifestyle intervention or standard care. Individual participant data were combined and analyzed using generalized linear mixed models with trial entered as a random effect. The 12-month assessment was completed by 83% (959/1150) of women and 84% (961/1150) of infants. Results: Compared with standard care, lifestyle intervention reduced postpartum weight retention (2.2 ± 7.0 vs. 0.7 ± 6.2 kg, respectively; difference of −1.6 kg (95% CI −2.5, −0.7; p = 0.0003); the intervention effect was mediated by reduction in excess GWG, which explained 22% of the effect on postpartum weight retention. Lifestyle intervention also significantly increased the odds (OR = 1.68 (95% CI, 1.26, 2.24)) and percentage of mothers (48.2% vs. 36.2%) at or below baseline weight at 12 months postpartum (yes/no) compared with standard care. There was no statistically significant treatment group effect on infant anthropometric outcomes at 12 months. Conclusions: Compared with standard care, lifestyle interventions initiated in pregnancy and focused on healthy eating, increased physical activity, and other behavioral strategies resulted in significantly less weight retention but similar infant anthropometric outcomes at 12 months postpartum in a large, diverse US population of women with overweight and obesity.
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| 7. |
- Redman, Leanne M., et al.
(författare)
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Attenuated early pregnancy weight gain by prenatal lifestyle interventions does not prevent gestational diabetes in the LIFE-Moms consortium
- 2021
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227. ; 171
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To examine the effect of lifestyle (diet and physical activity) interventions on the prevalence of GDM, considering the method of GDM ascertainment and its association with early pregnancy characteristics and maternal and neonatal outcomes in the LIFE-Moms consortium. Methods: LIFE-Moms evaluated the effects of lifestyle interventions to optimize gestational weight gain in 1148 pregnant women with BMI ≥ 25 kg/m2 and without known diabetes at enrollment, compared with standard care. GDM was assessed between 24 and 31-weeks gestation by a 2-hour, 75-gram OGTT or by local clinical practice standards. Results: Lifestyle interventions initiated prior to 16 weeks reduced early excess GWG compared with standard care (0.35 ± 0.24 vs 0.43 ± 0.26 kg per week, p=<0.0001) but did not affect GDM diagnosis (11.1% vs 11.6%, p = 0.91). Using the 75-gram, 2-hour OGTT, 13. 0% of standard care and 11.0% of the intervention group had GDM by the IADPSG criteria (p = 0.45). The ‘type of diagnostic test’ did not change the result (p = 0.86). Women who developed GDM were significantly heavier, more likely to have obesity, and more likely to have dysglycemia at baseline. Conclusion: Moderate-to-high intensity lifestyle interventions grounded in behavior change theory initiated between 9 and 16-weeks gestation did not affect the prevalence of GDM despite reducing early GWG. Clinicaltrials.gov: NCT01545934, NCT01616147, NCT01771133, NCT01631747, NCT01768793, NCT01610752, NCT01812694.
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