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1. Effect of Metformin and Lifestyle Interventions on Mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study

Author

Lee, Christine G, Heckman-Stoddard, Brandy, Dabelea, Dana, Gadde, Kishore M, Ehrmann, David, Ford, Leslie, Prorok, Philip, Boyko, Edward J, Pi-Sunyer, Xavier, Wallia, Amisha, Knowler, William C, Crandall, Jill P, Temprosa, Marinella, Group:, Diabetes Prevention Program Research, Bray, George A, Culbert, Iris W, Arceneaux, Jennifer, Chatellier, Annie, Dragg, Amber, Champagne, Catherine M, Duncan, Crystal, Eberhardt, Barbara, Greenway, Frank, Guillory, Fonda G, Herbert, April A, Jeffirs, Michael L, Kennedy, Betty M, Levy, Erma, Lockett, Monica, Lovejoy, Jennifer C, Morris, Laura H, Melancon, Lee E, Ryan, Donna H, Sanford, Deborah A, Smith, Kenneth G, Smith, Lisa L, St. Amant, Julia A, Tulley, Richard T, Vicknair, Paula C, Williamson, Donald, Zachwieja, Jeffery J, Polonsky, Kenneth S, Tobian, Janet, Ehrmann, David A, Matulik, Margaret J, Temple, Karla A, Clark, Bart, Czech, Kirsten, DeSandre, Catherine, Dotson, Brittnie, Hilbrich, Ruthanne, McNabb, Wylie, Semenske, Ann R, Caro, Jose F, Furlong, Kevin, Goldstein, Barry J, Watson, Pamela G, Smith, Kellie A, Mendoza, Jewel, Simmons, Marsha, Wildman, Wendi, Liberoni, Renee, Spandorfer, John, Pepe, Constance, Donahue, Richard P, Goldberg, Ronald B, Prineas, Ronald, Calles, Jeanette, Giannella, Anna, Rowe, Patricia, Sanguily, Juliet, Cassanova-Romero, Paul, Castillo-Florez, Sumaya, Florez, Hermes J, Garg, Rajesh, Kirby, Lascelles, Lara, Olga, Larreal, Carmen, McLymont, Valerie, Mendez, Jadell, Perry, Arlette, Saab, Patrice, Veciana, Bertha, Haffner, Steven M, Hazuda, Helen P, Montez, Maria G, Hattaway, Kathy, Isaac, Juan, Lorenzo, Carlos, Martinez, Arlene, Salazar, Monica, Walker, Tatiana, Hamman, Richard F, Nash, Patricia V, Steinke, Sheila C, Testaverde, Lisa, Truong, Jennifer, and Anderson, Denise R

Subjects
Biomedical and Clinical Sciences, Public Health, Health Sciences, Clinical Sciences, Prevention, Clinical Trials and Supportive Activities, Nutrition, Clinical Research, Cancer, Cardiovascular, Diabetes, Aetiology, 2.2 Factors relating to the physical environment, Good Health and Well Being, Adult, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Life Style, Metformin, Diabetes Prevention Program Research Group, Diabetes Prevention Program Research Group:, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences, Health sciences
Abstract

ObjectiveTo determine whether metformin or lifestyle modification can lower rates of all-cause and cause-specific mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study.Research design and methodsFrom 1996 to 1999, 3,234 adults at high risk for type 2 diabetes were randomized to an intensive lifestyle intervention, masked metformin, or placebo. Placebo and lifestyle interventions stopped in 2001, and a modified lifestyle program was offered to everyone, but unmasked study metformin continued in those originally randomized. Causes of deaths through 31 December 2018 were adjudicated by blinded reviews. All-cause and cause-specific mortality hazard ratios (HRs) were estimated from Cox proportional hazards regression models and Fine-Gray models, respectively.ResultsOver a median of 21 years (interquartile range 20-21), 453 participants died. Cancer was the leading cause of death (n = 170), followed by cardiovascular disease (n = 131). Compared with placebo, metformin did not influence mortality from all causes (HR 0.99 [95% CI 0.79, 1.25]), cancer (HR 1.04 [95% CI 0.72, 1.52]), or cardiovascular disease (HR 1.08 [95% CI 0.70, 1.66]). Similarly, lifestyle modification did not impact all-cause (HR 1.02 [95% CI 0.81, 1.28]), cancer (HR 1.07 [95% CI 0.74, 1.55]), or cardiovascular disease (HR 1.18 [95% CI 0.77, 1.81]) mortality. Analyses adjusted for diabetes status and duration, BMI, cumulative glycemic exposure, and cardiovascular risks yielded results similar to those for all-cause mortality.ConclusionsCancer was the leading cause of mortality among adults at high risk for type 2 diabetes. Although metformin and lifestyle modification prevented diabetes, neither strategy reduced all-cause, cancer, or cardiovascular mortality rates.

Published
2021

3. The Vegetarian/Flexitarian Diet

Author

Miketinas, Derek C., Champagne, Catherine M., Bendich, Adrianne, Series Editor, Bales, Connie W., Series Editor, Temple, Norman J., editor, Wilson, Ted, editor, Jacobs, Jr., David R., editor, and Bray, George A., editor

Published
2023
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4. Obesity: A Disease of Overnutrition

Author

Bray, George A., Champagne, Catherine M., Bendich, Adrianne, Series Editor, Bales, Connie W., Series Editor, Temple, Norman J., editor, Wilson, Ted, editor, Jacobs, Jr., David R., editor, and Bray, George A., editor

Published
2023
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5. Circulating sex hormone binding globulin levels are modified with intensive lifestyle intervention, but their changes did not independently predict diabetes risk in the Diabetes Prevention Program

Author

Aroda, Vanita R, Christophi, Costas A, Edelstein, Sharon L, Perreault, Leigh, Kim, Catherine, Golden, Sherita H, Horton, Edward, Mather, Kieren J, Bray, George A, Gadde, Kishore, Culbert, Iris W, Arceneaux, Jennifer, Chatellier, Annie, Dragg, Amber, Champagne, Catherine M, Duncan, Crystal, Eberhardt, Barbara, Greenway, Frank, Guillory, Fonda G, Herbert, April A, Jeffirs, Michael L, Kennedy, Betty M, Levy, Erma, Lockett, Monica, Lovejoy, Jennifer C, Morris, Laura H, Melancon, Lee E, Ryan, Donna H, Sanford, Deborah A, Smith, Kenneth G, Smith, Lisa L, St, Julia A, Amant, Richard T Tulley, Vicknair, Paula C, Williamson, Donald, Zachwieja, Jeffery J, Polonsky, Kenneth S, Tobian, Janet, Ehrmann, David A, Matulik, Margaret J, Clark, Bart, Czech, Kirsten, DeSandre, Catherine, Hilbrich, Ruthanne, McNabb, Wylie, Semenske, Ann R, Caro, Jose F, Furlong, Kevin, Goldstein, Barry J, Watson, Pamela G, Smith, Kellie A, Mendoza, Jewel, Wildman, Wendi, Liberoni, Renee, Spandorfer, John, Pepe, Constance, Donahue, Richard P, Goldberg, Ronald B, Prineas, Ronald, Calles, Jeanette, Ojito, Juliet, Rowe, Patricia, Cassanova-Romero, Paul, Castillo-Florez, Sumaya, Florez, Hermes J, Giannella, Anna, Kirby, Lascelles, Larreal, Carmen, Lara, Olga, McLymont, Valerie, Mendez, Jadell, Perry, Arlette, Saab, Patrice, Veciana, Beth, Haffner, Steven M, Hazuda, Helen P, Montez, Maria G, Hattaway, Kathy, Lorenzo, Carlos, Martinez, Arlene, Walker, Tatiana, Dabelea, Dana, Hamman, Richard F, Nash, Patricia V, Steinke, Sheila C, Testaverde, Lisa, Anderson, Denise R, Ballonoff, Larry B, Bouffard, Alexis, Bucca, Brian, Calonge, B Ned, Delve, Lynne, Farago, Martha, Hill, James O, Hoyer, Shelley R, Jenkins, Tonya, Jortberg, Bonnie T, Lenz, Dione, and Miller, Marsha

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Diabetes, Cardiovascular, Obesity, Estrogen, Clinical Research, Prevention, Nutrition, Aging, Clinical Trials and Supportive Activities, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, Prevention of disease and conditions, and promotion of well-being, Metabolic and endocrine, Diabetes Mellitus, Type 2, Female, Glucose Intolerance, Humans, Life Style, Male, Metformin, Sex Hormone-Binding Globulin, DPP Research Group, diabetes mellitus, hormone, life style, primary prevention, type 2, Clinical sciences, Public health
Abstract

Sex hormone binding globulin (SHBG) levels are reported to be inversely associated with diabetes risk. It is unknown whether diabetes prevention interventions increase SHBG and whether resultant changes in SHBG affect diabetes risk. The purpose of this analysis was to determine whether intensive lifestyle intervention (ILS) or metformin changed circulating SHBG and if resultant changes influenced diabetes risk in the Diabetes Prevention Program (DPP). This is a secondary analysis from the DPP (1996-2001), a randomized trial of ILS or metformin versus placebo on diabetes risk over a mean follow-up of 3.2 years. The DPP was conducted across 27 academic study centers in the USA. Men, premenopausal and postmenopausal women without hormone use in the DPP were evaluated. The DPP included overweight/obese persons with elevated fasting glucose and impaired glucose tolerance. Main outcomes measures were changes in SHBG levels at 1 year and risk of diabetes over 3 years. ILS resulted in significantly higher increases (postmenopausal women: p

Published
2020

7. The Vegetarian/Flexitarian Diets

Author

Miketinas, Derek, Champagne, Catherine M., Bendich, Adrianne, Series Editor, Bales, Connie W., Series Editor, Wilson, Ted, editor, Temple, Norman J., editor, and Bray, George A., editor

Published
2022
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13. The Type and Amount of Dietary Fat Affect Plasma Factor VIIc, Fibrinogen, and PAI-1 in Healthy Individuals and Individuals at High Cardiovascular Disease Risk: 2 Randomized Controlled Trials

Author

Kris-Etherton, Penny M, Stewart, Paul W, Ginsberg, Henry N, Tracy, Russell P, Lefevre, Michael, Elmer, Patricia J, Berglund, Lars, Ershow, Abby G, Pearson, Thomas A, Ramakrishnan, Rajasekhar, Holleran, Stephen F, Dennis, Barbara H, Champagne, Catherine M, Karmally, Wahida, Ginsberg, Henry, Siddiqui, Maliha, Chen, Niem-Tzu, Holleran, Steve, Johnson, Colleen, Holeman, Roberta, Chirgwin, Karen, Stennett, Kellye, Ganga, Lencey, Towolawai, Tajsudeen, Myers, Minnie, Ngai, Colleen, Fontenez, Nelson, Jones, Jeff, Rodriguez, Carmen, Useche, Norma, Roheim, Paul S, Ryan, Donna, Most, Marlene, Champagne, Catherine, Williamson, Donald, Tulley, Richard, Brock, Ricky, Bodin, Deonne, Kennedy, Betty, Barkate, Michelle, Foust, Elizabeth, York, Deshoin, Kris-Etherton, Penny, Jonnalagadda, Satya, Derr, Janice, Farhat-Wood, Abir, Mustad, Vikkie, Meaker, Kate, Mills, Edward, Tilley, Mary-Ann, Smiciklas-Wright, Helen, Sigman-Grant, Madeleine, Yu, Shaomei, Guinard, Jean-Xavier, Sechevich, Pamela, Reddy, C Channa, Mastro, Andrea M, Cooper, Allen D, Elmer, Patricia, Folsom, Aaron, Van Heel, Nancy, Wold, Christine, Fritz, Kay, Slavin, Joanne, Jacobs, David, Dennis, Barbara, Stewart, Paul, Davis, C, Hosking, James, Anderson, Nancy, Blackwell, Susan, Martin, Lynn, Bryan, Hope, Stewart, W Brian, Abolafia, Jeffrey, Foley, Malachy, Zien, Conroy, Leu, Szu-Yun, Youngblood, Marston, Goodwin, Thomas, Miles, Monica, Wehbie, Jennifer, Pearson, Thomas, Reed, Roberta, Tracy, Russell, Cornell, Elaine, Stewart, Kent, Phillips, Katherine, McGee, Bernestine, Williams, Brenda, Beecher, Gary, Holden, Joanne, Davis, Carol, Ershow, Abby, Gordon, David, Proschan, Michael, and Rifkind, Basil

Published
2020
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18. Isocaloric replacement of ultraprocessed foods was associated with greater weight loss in the POUNDS Lost trial.

Author

Yao, Qisi, de Araujo, Carolina D., Juul, Filippa, Champagne, Catherine M., Bray, George A., Sacks, Frank M., and Vadiveloo, Maya K.

Subjects
WEIGHT loss, REGULATION of body weight, WAIST circumference, FAT, ENERGY dissipation
Abstract

Objective: Higher intake of ultraprocessed foods (UPFs) is associated with obesity. We examined whether replacing UPFs (NOVA 4) with minimally processed foods and culinary ingredients (NOVA 1 + 2) was associated with differential weight change in this secondary prospective analysis of the Preventing Overweight Using Novel Dietary Strategies (POUNDS) Lost trial. Methods: We estimated percent energy intake (%kcal) from the four NOVA groups using 24‐h dietary recalls in a subset of 356 participants. Multivariable‐adjusted substitution models examined whether replacing %kcal from UPFs with NOVA 1 + 2 was associated with greater weight, body fat percentage, trunk fat, and waist circumference reduction at 6 months; changes in parameters were compared among NOVA 1 + 2 tertiles (T). Results: Participants were on average 52.3 years of age, 85% White, 55% female, and 58.2% nonsmoking, with a mean BMI of 32.7 kg/m2. Replacing 10%kcal of UPFs with NOVA 1 + 2 was associated with greater 6‐month weight (ß = 0.51, 95% CI: −0.93 to −0.09, p = 0.02), body fat percentage (ß = 2.7, 95% CI: −5.10 to −0.43, p = 0.02), and trunk fat reduction (ß = 3.9, 95% CI: −7.01 to −0.70, p = 0.02), but not waist circumference reduction. Participants in T3 (−8.33 kg) versus T1 (−5.32 kg) of NOVA 1 + 2 had greater weight loss (p < 0.001). Conclusions: Isocaloric substitution of UPFs with NOVA 1 + 2 was associated with marginally greater weight loss under energy restriction. These modest findings support more research exploring the mechanisms linking UPFs with body weight regulation beyond energy intake. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment: The Diabetes Prevention Program

Author

Pollin, Toni I, Isakova, Tamara, Jablonski, Kathleen A, de Bakker, Paul IW, Taylor, Andrew, McAteer, Jarred, Pan, Qing, Horton, Edward S, Delahanty, Linda M, Altshuler, David, Shuldiner, Alan R, Goldberg, Ronald B, Florez, Jose C, Franks, Paul W, Bray, George A, Culbert, Iris W, Champagne, Catherine M, Eberhardt, Barbara, Greenway, Frank, Guillory, Fonda G, Herbert, April A, Jeffirs, Michael L, Kennedy, Betty M, Lovejoy, Jennifer C, Morris, Laura H, Melancon, Lee E, Ryan, Donna, Sanford, Deborah A, Smith, Kenneth G, Smith, Lisa L, St. Amant, Julia A, Tulley, Richard T, Vicknair, Paula C, Williamson, Donald, Zachwieja, Jeffery J, Polonsky, Kenneth S, Tobian, Janet, Ehrmann, David, Matulik, Margaret J, Clark, Bart, Czech, Kirsten, DeSandre, Catherine, Hilbrich, Ruthanne, McNabb, Wylie, Semenske, Ann R, Caro, Jose F, Watson, Pamela G, Goldstein, Barry J, Smith, Kellie A, Mendoza, Jewel, Liberoni, Renee, Pepe, Constance, Spandorfer, John, Donahue, Richard P, Prineas, Ronald, Rowe, Patricia, Calles, Jeanette, Cassanova-Romero, Paul, Florez, Hermes J, Giannella, Anna, Kirby, Lascelles, Larreal, Carmen, McLymont, Valerie, Mendez, Jadell, Ojito, Juliet, Perry, Arlette, Saab, Patrice, Haffner, Steven M, Montez, Maria G, Lorenzo, Carlos, Martinez, Arlene, Hamman, Richard F, Nash, Patricia V, Testaverde, Lisa, Anderson, Denise R, Ballonoff, Larry B, Bouffard, Alexis, Calonge, B Ned, Delve, Lynne, Farago, Martha, Hill, James O, Hoyer, Shelley R, Jortberg, Bonnie T, Lenz, Dione, Miller, Marsha, Price, David W, Regensteiner, Judith G, Seagle, Helen, Smith, Carissa M, Steinke, Sheila C, VanDorsten, Brent, Lawton, Kathleen E, Arky, Ronald A, Bryant, Marybeth, Burke, Jacqueline P, Caballero, Enrique, Callaphan, Karen M, and Ganda, Om P

Subjects
Diabetes, Nutrition, Clinical Research, Prevention, Genetics, Cardiovascular, Metabolic and endocrine, Adult, Cardiovascular Diseases, Cholesterol, HDL, Cholesterol, LDL, Diabetes Mellitus, Type 2, Dyslipidemias, Female, Genetic Association Studies, Humans, Hypoglycemic Agents, Life Style, Lipid Metabolism, Lipoproteins, Magnetic Resonance Spectroscopy, Male, Metformin, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Triglycerides, Weight Loss, Diabetes Prevention Program Research Group, Developmental Biology
Abstract

Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04-1 × 10(-17)). Except for total HDL particles (r = -0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial |r| = 0.07-0.17, P = 5 × 10(-5)-1 10(-19)). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE ± 0.22 mg/dl/allele, P = 8 × 10(-5), P(interaction) = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE ± 0.22 mg/dl/allele, P = 0.35) or metformin (β = -0.03, SEE ± 0.22 mg/dl/allele, P = 0.90; P(interaction) = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE ± 0.012 ln nmol/L/allele, P = 0.01, P(interaction) = 0.01) but not in the placebo (β = -0.002, SEE ± 0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE ± 0.008 nmol/L/allele, P = 0.12; P(interaction) = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.

Published
2012

29. Prevalence of Distal Symmetrical Polyneuropathy by Diabetes Prevention Program Treatment Group, Diabetes Status, Duration of Diabetes, and Cumulative Glycemic Exposure.

Author

Lee, Christine G., Ciarleglio, Adam, Edelstein, Sharon L., Crandall, Jill P., Dabelea, Dana, Goldberg, Ronald B., Kahn, Steven E., Knowler, William C., Ma, Maxwell T., White, Neil H., Herman, William H., Bray, George A., Gadde, Kishore M., Culbert, Iris W., Arceneaux, Jennifer, Chatellier, Annie, Dragg, Amber, Champagne, Catherine M., Duncan, Crystal, and Eberhardt, Barbara

Subjects
POLYNEUROPATHIES, DIABETES, SYMPTOMS, OLDER people, LOGISTIC regression analysis
Abstract

OBJECTIVE: To assess associations between distal symmetric polyneuropathy (DSPN) and Diabetes Prevention Program (DPP) treatment groups, diabetes status or duration, and cumulative glycemic exposure approximately 21 years after DPP randomization. RESEARCH DESIGN AND METHODS: In the DPP, 3,234 adults ≥25 years old at high risk for diabetes were randomized to an intensive lifestyle (ILS), metformin, or placebo intervention to prevent diabetes. After the DPP ended, 2,779 joined the Diabetes Prevention Program Outcomes Study (DPPOS). Open-label metformin was continued, placebo was discontinued, ILS was provided in the form of semiannual group-based classes, and all participants were offered quarterly lifestyle classes. Symptoms and signs of DSPN were assessed in 1,792 participants at DPPOS year 17. Multivariable logistic regression models were used to evaluate DSPN associations with treatment group, diabetes status/duration, and cumulative glycemic exposure. RESULTS: At 21 years after DPP randomization, 66% of subjects had diabetes. DSPN prevalence did not differ by initial DPP treatment assignment (ILS 21.5%, metformin 21.5%, and placebo 21.9%). There was a significant interaction between treatment assignment to ILS and age (P < 0.05) on DSPN. At DPPOS year 17, the odds ratio for DSPN in comparison with ILS with placebo was 17.4% (95% CI 3.0, 29.3) lower with increasing 5-year age intervals. DSPN prevalence was slightly lower for those at risk for diabetes (19.6%) versus those with diabetes (22.7%) and was associated with longer diabetes duration and time-weighted HbA1c (P values <0.001). CONCLUSIONS: The likelihood of DSPN was similar across DPP treatment groups but higher for those with diabetes, longer diabetes duration, and higher cumulative glycemic exposure. ILS may have long-term benefits on DSPN for older adults. [ABSTRACT FROM AUTHOR]

Published
2024
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38. DNA Methylation Near CPT1A and Changes in Triglyceride-rich Lipoproteins in Response to Weight-loss Diet Interventions

Author

Li, Xiang, primary, Shao, Xiaojian, additional, Xue, Qiaochu, additional, Kou, Minghao, additional, Champagne, Catherine M, additional, Koseva, Boryana S, additional, Heianza, Yoriko, additional, Grundberg, Elin, additional, Bazzano, Lydia A, additional, Bray, George A, additional, Sacks, Frank M, additional, and Qi, Lu, additional

Published
2023
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41. Association between breakfast frequency and physical activity and sedentary time: a cross-sectional study in children from 12 countries

Author

Zakrzewski-Fruer, Julia K., Gillison, Fiona B., Katzmarzyk, Peter T., Mire, Emily F., Broyles, Stephanie T., Champagne, Catherine M., Chaput, Jean-Philippe, Denstel, Kara D., Fogelholm, Mikael, Hu, Gang, Lambert, Estelle V., Maher, Carol, Maia, José, Olds, Tim, Onywera, Vincent, Sarmiento, Olga L., Tremblay, Mark S., Tudor-Locke, Catrine, Standage, Martyn, and for the ISCOLE Research Group

Published
2019
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44. DNA Methylation Near CPT1A and Changes in Triglyceride-rich Lipoproteins in Response to Weight-loss Diet Interventions.

Author

Xiang Li, Xiaojian Shao, Qiaochu Xue, Minghao Kou, Champagne, Catherine M., Koseva, Boryana S., Yoriko Heianza, Grundberg, Elin, Bazzano, Lydia A., Bray, George A., Sacks, Frank M., and Lu Qi

Subjects
DNA methylation, TRIGLYCERIDES, WEIGHT loss
Abstract

Context: Carnitine palmitoyltransferase-1A, encoded by the CPT1A gene, plays a key role in the oxidation of long-chain fatty acids in the mitochondria and may be important in triglyceride metabolism. Previous work has shown that high fat intake was negatively associated with CPT1A methylation and positively associated with CPT1A expression. Objective: We aim to investigate the association of DNA methylation (DNAm) at the CPT1A gene with reductions in triglycerides and triglyceriderich lipoproteins (TRLs) in response to weight-loss diet interventions. Methods: The current study included 538 White participants, who were randomly assigned to 1 of 4 diets varying in macronutrient components. We defined the regional DNAm at CPT1A as the average methylation level over CpGs within 500 bp of the 3 triglyceride-related DNAm sites. Results: Dietary fat intake significantly modified the association between baseline DNAm at CPT1A and 2-year changes in total plasma triglycerides, independent of concurrent weight loss. Among participants assigned to a low-fat diet, a higher regional DNAm level at CPT1A was associated with a greater reduction in total plasma triglycerides at 2 years (P = .01), compared with those assigned to a high-fat diet (P = .64) (P interaction = .018). Further investigation on lipids and apolipoproteins in very low-density lipoprotein (VLDL) revealed similar interaction patterns for 2-year changes in VLDL-triglycerides, VLDL-cholesterol, and VLDL-apolipoprotein B (P interaction = .009, .002, and .016, respectively), but not for VLDL-apoC-III (P interaction = .36). Conclusion: Participants with a higher regional DNAm level at CPT1A benefit more in long-term improvement in triglycerides, particularly in the TRLs and related apolipoproteins when consuming a low-fat weight-loss diet. [ABSTRACT FROM AUTHOR]

Published
2023
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